Hepatic paraoxonase 1 ameliorates dysfunctional high-density lipoprotein and atherosclerosis in scavenger receptor class B type I deficient mice.
High-density lipoprotein (HDL) plays an antiatherogenic role by mediating reverse cholesterol transport (RCT), antioxidation, anti-inflammation, and endothelial cell protection. Recently, series of evidence have shown that HDL can also convert to proatherogenic HDL under certain circumstances. Plasma paraoxonase 1 (PON1) as an HDL-bound esterase, is responsible for most of the antioxidant properties of HDL. However, whether PON1 can serve as a therapeutic target of dysfunctional HDL-related atherosclerosis remains unclear. In this study, scavenger receptor class B type I deficient (Scarb1-/- ) mice were used as the animal model with dysfunctional HDL and increased atherosclerotic susceptibility. Hepatic PON1 overexpression and secretion into circulation were achieved by lentivirus injection through the tail vein. We monitored plasma lipids levels and lipoprotein profiles in Scarb1-/- mice, and measured the levels and activities of proteins associated with HDL function. Meanwhile, lipid deposition in the liver and atherosclerotic lesions was quantified. Hepatic genes relevant to HDL metabolism and inflammation were analyzed. The results showed the relative levels of PON1 in liver and plasma were increased by 1.1-fold and 1.6-fold, respectively, and mean plasma PON1 activity was increased by 63%. High-level PON1 increased the antioxidative and anti-inflammatory properties, promoted HDL maturation and macrophage cholesterol efflux through increasing HDL functional proteins components apolipoprotein A1 (APOA1), apolipoprotein E (APOE), and lecithin-cholesterol acyltransferase (LCAT), while decreased inflammatory protein markers, such as serum amyloid A (SAA), apolipoprotein A4 (APOA4) and alpha 1 antitrypsin (A1AT). Furthermore, hepatic PON1 overexpression linked the effects of antioxidation and anti-inflammation with HDL metabolism regulation mainly through up-regulating liver X receptor alpha (LXRα) and its downstream genes. The pleiotropic effects involved promoting HDL biogenesis by raising the level of APOA1, increasing cholesterol uptake by the liver through the APOE-low density lipoprotein receptor (LDLR) pathway, and increasing cholesterol excretion into the bile, thereby reducing hepatic steatosis and aorta atherosclerosis in Western diet-fed mice. Our study reveals that high-level PON1 improved dysfunctional HDL and alleviated the development of atherosclerosis in Scarb1-/- mice. It is suggested that PON1 represents a promising target of HDL-based therapeutic strategy for HDL-related atherosclerotic cardiovascular disease.


Predictive factors of 30-day unplanned readmission after lower extremity bypass.
Thirty-day unplanned readmission after lower extremity bypass represents a large cost burden and is a logical target for cost-containment strategies. We undertook this study to evaluate factors associated with unplanned readmission after lower extremity bypass. This is a retrospective analysis from a prospective institutional registry. All lower extremity bypasses for occlusive disease from January 1995 to July 2011 were included. The primary end point was 30-day unplanned readmission. Secondary end points included graft patency and limb salvage. Of 1543 lower extremity bypasses performed, 84.5% were for critical limb ischemia and 15.5% were patients with intermittent claudication. Twenty-seven patients (1.7%) died in-house and were excluded from further analysis. Of 1516 lower extremity bypasses analyzed, 42 (2.8%) were in patients with a planned readmission within 30 days, and 349 (23.0%), in patients with an unplanned readmission. Most unplanned readmissions were wound related (62.9%). By multivariable analysis, preoperative predictive factors for unplanned readmission were dialysis dependence (odds ratio [OR], 1.73; P = .004), tissue loss indication (OR, 1.62; P = .0004), and history of congestive heart failure (OR, 1.43; P = .03). Postoperative predictors included distal inflow source (OR, 1.38; P = .016), in-hospital wound infection (OR, 8.30; P < .0001), in-hospital graft failure (OR, 3.20; P < .0001), and myocardial infarction (OR, 1.96; P < .04). Neither index length of stay nor discharge disposition independently predicted unplanned readmission. Unplanned readmission was associated with loss of assisted primary patency (hazard ratio, 1.39; 95% confidence interval, 1.08-1.80; P = .01) and long-term limb loss (hazard ratio, 1.68; 95% confidence interval, 1.23-2.29; P = .001). Thirty-day unplanned readmission is a frequent occurrence after lower extremity bypass (23.0%). Stratifying patients by risk factors associated with unplanned readmission is essential for quality improvement and equitable resource allocation when disease-specific bundling strategies are being derived.


TAM receptors Tyro3 and Mer as novel targets in colorectal cancer.
CRC remains the third most common cancer worldwide with a high 5-year mortality rate in advanced cases. Combined with chemotherapy, targeted therapy is an additional treatment option. However as CRC still escapes targeted therapy the vigorous search for new targets is warranted to increase patients´ overall survival. In this study we describe a new role for Gas6/protein S-TAM receptor interaction in CRC. Gas6, expressed by tumor-infiltrating M2-like macrophages, enhances malignant properties of tumor cells including proliferation, invasion and colony formation. Upon chemotherapy macrophages increase Gas6 synthesis, which significantly attenuates the cytotoxic effect of 5-FU chemotherapy on tumor cells. The anti-coagulant protein S has similar effects as Gas6.In CRC patient samples Tyro3 was overexpressed within the tumor. In-vitro inhibition of Tyro3 and Mer reduces tumor cell proliferation and sensitizes tumor cells to chemotherapy. Moreover high expression of Tyro3 and Mer in tumor tissue significantly shortens CRC patients´ survival. Various in vitro models were used to investigate the role of Gas6 and its TAM receptors in human CRC cells, by stimulation (rhGas6) and knockdown (siRNA) of Axl, Tyro3 and Mer. In terms of a translational research, we additionally performed an expression analysis in human CRC tissue and analyzed the medical record of these patients. Tyro3 and Mer represent novel therapeutic targets in CRC and warrant further preclinical and clinical investigation in the future.


Early detection of thermoacoustic instabilities in a cryogenic rocket thrust chamber using combustion noise features and machine learning.
We present a data-driven method for the early detection of thermoacoustic instabilities. Recurrence quantification analysis is used to calculate characteristic combustion features from short-length time series of dynamic pressure sensor data. Features like recurrence rate are used to train support vector machines to detect the onset of instability a few hundred milliseconds in advance. The performance of the proposed method is investigated on experimental data from a representative LOX/H 2 research thrust chamber. In most cases, the method is able to timely predict two types of thermoacoustic instabilities on test data not used for training. The results are compared with state-of-the-art early warning indicators.


Exosomal miR-21 determines lung-to-brain metastasis specificity through the DGKB/ERK axis within the tumor microenvironment.
Brain metastasis affects 20-40 % of lung cancer patients, severely diminishing their quality of life. This research focuses on miR-21, overexpressed in these patients and inversely associated with DGKB in the ERK/STAT3 pathway, suggesting a dysregulated pathway with therapeutic potential. The objective was to investigate miR-21's role in lung cancer patients with brain metastases and whether targeting this pathway could improve treatment outcomes. We also examined the miR-21 content in tumor spheres-derived extracellular vesicles (EVs) and their influence on ERK/STAT3 signaling and metastasis. Tumor spheres were created from metastatic lung cancer cells. We studied miR-21 levels in these spheres, their impact on macrophage polarization, and the transition of nonmetastatic lung cancer cells. Furthermore, we analyzed miR-21 content in EVs derived from these spheres and their effect on ERK/STAT3 signaling and metastasis potential. We found tumor spheres had high miR-21 levels, promoting macrophage polarization and, epithelial-mesenchymal transition. These spheres-derived EVs, enriched with miR-21, accelerated ERK/STAT3 signaling and metastasis. Silencing miR-21 and inhibiting ERK signaling with ulixertinib notably mitigated these effects. Moreover, ulixertinib reduced brain metastasis incidence and increased survival in a mouse model and led to reduced tumor sphere generation and miR-21 levels in EVs. Our study highlights the exacerbation of lung-to-brain metastasis via miR-21-rich EV secretion. This underlines the therapeutic promise of targeting the miR-21/ERK/STAT3 pathway with ulixertinib for managing brain metastasis from lung cancer.


Evaluation of a lactate sensor for rapid repeated measurements of blood lactate concentration.
In critically ill patients, serial measurements of blood lactate may indicate adequacy of therapy and predict development of multi-organ failure. We studied the accuracy, precision, and repeatability of the newly developed 800 Series Lactate Sensor (Ciba Corning Diagnostic Corp., Medfield, U.S.A.). Lactate levels determined with the sensor were compared with the standard laboratory method (Abbott TDX) in 75 paired arterial blood samples from 20 patients. Agreement between methods was determined and the mean coefficient of variation calculated for repeated measurements. The bias of the sensor was -0.38 mmol/l (CI -0.23 to -0.53), and the precision +/- 0.67. The coefficient of variation for repeated measurements was 1.95% with the sensor, and 11.5% with the TDX (P = 0.007). The new sensor offers a more reproducible, rapid method of measuring lactate, vital for serial measurements. The relatively wide limits of agreement between the methods reflect the greater variability of the TDX assay.


Extraordinarily complex crystal structure with mesoscopic patterning in barium at high pressure.
Elemental barium adopts a series of high-pressure phases with such complex crystal structures that some of them have eluded structure determination for many years. Using single-crystal synchrotron X-ray diffraction and new data analysis strategies, we have now solved the most complex of these crystal structures, that of phase Ba-IVc at 19 GPa. It is a commensurate host-guest structure with 768 atoms in the representative unit, where the relative alignment of the guest-atom chains can be represented as a two-dimensional pattern with interlocking S-shaped 12-chain motifs repeating regularly in one direction and repeating with constrained disorder in the other. The existence of such patterning on the nanometre scale points at medium-range interactions that are not fully screened by the itinerant electrons in this metal. On the basis of first-principles electronic structure calculations, pseudopotential theory and an analysis of the lattice periodicities and interatomic distances, we rationalize why the Ba phases with the common densely packed crystal structures become energetically unfavourable in comparison with the complex-structured Ba-IVc phase, and what the role of the well-known pressure-induced s-d electronic transfer is.


A review of vision-based motion analysis in sport.
Efforts at player motion tracking have traditionally involved a range of data collection techniques from live observation to post-event video analysis where player movement patterns are manually recorded and categorized to determine performance effectiveness. Due to the considerable time required to manually collect and analyse such data, research has tended to focus only on small numbers of players within predefined playing areas. Whilst notational analysis is a convenient, practical and typically inexpensive technique, the validity and reliability of the process can vary depending on a number of factors, including how many observers are used, their experience, and the quality of their viewing perspective. Undoubtedly the application of automated tracking technology to team sports has been hampered because of inadequate video and computational facilities available at sports venues. However, the complex nature of movement inherent to many physical activities also represents a significant hurdle to overcome. Athletes tend to exhibit quick and agile movements, with many unpredictable changes in direction and also frequent collisions with other players. Each of these characteristics of player behaviour violate the assumptions of smooth movement on which computer tracking algorithms are typically based. Systems such as TRAKUS, SoccerMan, TRAKPERFORMANCE, Pfinder and Prozone all provide extrinsic feedback information to coaches and athletes. However, commercial tracking systems still require a fair amount of operator intervention to process the data after capture and are often limited by the restricted capture environments that can be used and the necessity for individuals to wear tracking devices. Whilst some online tracking systems alleviate the requirements of manual tracking, to our knowledge a completely automated system suitable for sports performance is not yet commercially available. Automatic motion tracking has been used successfully in other domains outside of elite sport performance, notably for surveillance in the military and security industry where automatic recognition of moving objects is achievable because identification of the objects is not necessary. The current challenge is to obtain appropriate video sequences that can robustly identify and label people over time, in a cluttered environment containing multiple interacting people. This problem is often compounded by the quality of video capture, the relative size and occlusion frequency of people, and also changes in illumination. Potential applications of an automated motion detection system are offered, such as: planning tactics and strategies; measuring team organisation; providing meaningful kinematic feedback; and objective measures of intervention effectiveness in team sports, which could benefit coaches, players, and sports scientists.


The presence of an intron relieves gene repression caused by promoter-proximal four-bp specific sequences in yeast.
Introns can enhance gene expression in eukaryotic cells in a process called intron-mediated enhancement (IME). The levels of enhancement are affected not only by the intron sequence but also by coding sequences (CDSs). However, the parts of CDSs responsible for mediating IME have not yet been identified. In this study, we identified an IME-mediating sequence by analyzing three pairs of IME-sensitive and -insensitive CDSs in Saccharomyces cerevisiae. Expression of the CDSs yCLuc, yRoGLU1, and KmBGA1 was enhanced by the presence of an intron (i.e., they were IME sensitive), but the expression of each corresponding codon-changed CDS, which encoded the identical amino acid sequence, was not enhanced (i.e., they were IME insensitive). Interestingly, the IME-insensitive CDSs showed higher expression levels that were like intron-enhanced expression of IME-sensitive CDSs, suggesting that expression of IME-sensitive CDSs was repressed. A four-nucleotide sequence (TCTT) located in the promoter-proximal position of either the untranslated or coding region was found to be responsible for repression in IME-sensitive CDSs, and repression caused by the TCTT sequence was relieved by the presence of an intron. Further, it was found that the expression of intron-containing yeast-native genes, UBC4 and MPT5, was repressed by TCTT in the CDS but relieved by the introns. These results indicate that TCTT sequences in promoter-proximal positions repress gene expression and that introns play a role in relieving gene repression caused by sequences such as TCTT.


Dielectric analysis of the upper critical solution temperature behaviour of a poly(acrylamide-co-acrylonitrile) copolymer system in water.
A copolymer consisting of acrylamide (AAm) and acrylonitrile (AN) in aqueous solution was investigated using broadband dielectric spectroscopy at frequencies between 10-1 Hz and 106 Hz in the temperature range from 2 °C to 60 °C. This system shows an UCST phase behavior. The phase transition and aggregation behavior is monitored by both the temperature and frequency dependence of the complex conductivity σ*(f, T), where the AN fraction and the concentration of the solution were varied. Additionally, the dielectric data are compared with the results obtained from dynamic light scattering measurements. The temperature dependence of the DC conductivity (σDC) of the copolymer solution is monitored and the phase transition temperature (PTT) of the poly(AAm-co-AN) copolymer is deduced from a change in the T-dependence of the DC conductivity. The change in σDC can be explained by decreased effective charge carrier mobility and a reduction of the effective charge number density at temperatures below the phase transition temperature of the poly(AAm-co-AN) solution. A pronounced interfacial polarization effect on the frequency dependence of the real part of the conductivity (σ') is observed at temperatures below the phase transition temperature. The charge carriers are blocked at the formed aggregates giving rise to this interfacial polarization. The dependence of the interfacial polarization on the acrylonitrile fraction in the copolymer and the concentration of the solution is studied in detail and conclusions concerning the internal structures of the copolymer aggregates are drawn.


Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis.
We applied a genome-wide microarray analysis to three transgenic mouse models of liver cancer in which targeted overexpression of c-Myc, E2f1, and a combination of the two was driven by the albumin promoter. Although gene expression profiles in HCC derived in all three transgenic lines were highly similar, oncogene-specific gene expression signatures were identified at an early dysplastic stage of hepatocarcinogenesis. Overexpression of E2f1 was associated with a strong alteration in lipid metabolism, and Srebp1 was identified as a candidate transcription factor responsible for lipogenic enzyme induction. The molecular signature of c-Myc overexpression included the induction of more than 60 genes involved in the translational machinery that correlated with an increase in liver mass. In contrast, the combined activity of c-Myc and E2f1 specifically enhanced the expression of genes involved in mitochondrial metabolism--particularly the components of the respiratory chain--and correlated with an increased ATP synthesis. Thus, the results suggest that E2f1, c-Myc, and their combination may promote liver tumor development by distinct mechanisms. In conclusion, determination of tissue-specific oncogene expression signatures might be useful to identify conserved expression modules in human cancers.


Use of mesenchymal stem cell therapy in COVID-19 related strokes.
Coronavirus disease 2019 (COVID-19) has affected a broad demographics, eliciting a more significant effect on specific groups such as males, African Americans, and Hispanic minorities. Treatment of COVID-19 often requires antiviral drugs or monoclonal antibodies. However, immunotherapies such as mesenchymal stem cells and mesenchymal stem cells-derived exosomal vesicles should be evaluated as treatment options for COVID-19. Mesenchymal stem cell therapy offers regenerative, anti-inflammatory, and immunomodulatory properties that can speed up the recovery from COVID-19. Mesenchymal stem cell therapy can also benefit COVID-19 patients who suffer from strokes, as COVID-19 increases the risk of strokes due to increased cytokines and clotting factors. Most stroke cases that occur in COVID-19 patients are ischemic strokes. Therefore, with the help of mesenchymal stem cell therapy and mesenchymal stem cells-derived exosomes, COVID-19-induced stroke patients might benefit from dual-ended treatment. The objective of this review was to discuss COVID-19 and stroke incidence and the available treatment options.


Rhodium-Catalyzed Enantioselective Reductive Arylation: Convenient Access to 3,3-Disubstituted Oxindoles.
A rhodium-Josiphos(L*) catalyzed enantioselective intramolecular hydroarylation reaction is described. The reductive cyclization of o-bromoaniline-derived acrylamides provides convenient access to 3,3-disubstituted oxindoles in good yields and with excellent enantioselectivity across a range of substrates. We propose that the key cyclization proceeds via a rhodium(III) intermediate. Overall, this method represents an unusual mode of reactivity for rhodium catalysis and is complementary to palladium(0)-catalyzed α-arylation methods.


How whales used to filter: exceptionally preserved baleen in a Miocene cetotheriid.
Baleen is a comb-like structure that enables mysticete whales to bulk feed on vast quantities of small prey, and ultimately allowed them to become the largest animals on Earth. Because baleen rarely fossilises, extremely little is known about its evolution, structure and function outside the living families. Here we describe, for the first time, the exceptionally preserved baleen apparatus of an entirely extinct mysticete morphotype: the Late Miocene cetotheriid, Piscobalaena nana, from the Pisco Formation of Peru. The baleen plates of P. nana are closely spaced and built around relatively dense, fine tubules, as in the enigmatic pygmy right whale, Caperea marginata. Phosphatisation of the intertubular horn, but not the tubules themselves, suggests in vivo intertubular calcification. The size of the rack matches the distribution of nutrient foramina on the palate, and implies the presence of an unusually large subrostral gap. Overall, the baleen morphology of Piscobalaena likely reflects the interacting effects of size, function and phylogeny, and reveals a previously unknown degree of complexity in modern mysticete feeding evolution.


A double-blind cross-over study of nifedipine retard in patients with Raynaud's phenomenon.
The effectiveness of nifedipine retard as a treatment for Raynaud's phenomenon was assessed in 15 patients in a placebo controlled double blind study. An associated connective tissue disease was evident in 7 patients. Changes in finger and forearm blood flow (venous occlusion plethysmography), digital skin temperature and digital systolic pressure were measured acutely before and after a 2-week treatment period. Subjective assessment of efficacy was based on patient diary data. In addition alpha 2-adrenoceptor density on platelets was measured before and after chronic nifedipine therapy in both the patient group and in an age-and-sex-matched control group. No significant haemodynamic changes were observed. Nifedipine retard significantly reduced the frequency (p less than 0.05) with no change in either the duration or severity of vasospastic attacks. Side effects were common following nifedipine retard. A reduction in alpha 2-adrenoceptor density on platelets was observed in patients compared to a control group (p less than 0.05). Alpha 2-adrenoceptor density was unchanged following a 2-week treatment period with nifedipine retard. This study concludes that nifedipine retard is not effective in the treatment of Raynaud's phenomenon over a short time course. Patients with Raynaud's phenomenon have reduced alpha 2-adrenoceptor densities on their platelets.


Arachidonic acid affects biofilm formation and PGE2 level in Candida albicans and non-albicans species in presence of subinhibitory concentration of fluconazole and terbinafine.
Candida albicans utilizes arachidonic acid (AA) released during the course of infection (Candidiasis) from phospholipids of infected host cell membranes and synthesizes extracellular prostaglandin(s) which play an important role in hyphae formation and host cell damage. C. albicans biofilms secrete significantly more prostaglandin(s) and evidence suggests that Candida biofilms have dramatically reduced susceptibility to majority of antifungal drugs. AA influences the saturation level of lipids and fluidity of yeast cell membranes. Therefore the aim of this study was to evaluate the effect of AA alone or in combination with antifungal agents on biofilm formation and production of prostaglandin (PGE2) in C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. albicans amphotericin B resistant strain (AmBR). Maximum biofilm formation was found to be in the case of C. albicans compared to C. non-albicans species. However, among the non-albicans species C. tropicalis exhibited highest biofilm formation. Treatment with AA in combination with subinhibitory concentrations of fluconazole and terbinafine separately exhibited significant (p<0.05) reduction in biofilm formation against C. glabrata, C. parapsilosis, C. tropicalis and AmBR as compared to their individual effect. Further, these two antifungal agents in combination with AA caused an increase in production of prostaglandin from fungal cell itself which was significant (p<0.05) in case of all the strains tested.


Characteristics of breast cancer survivors that predict partners' participation in research.
Psycho-oncology couples' research frequently includes fewer than 50 % of those eligible. This research examined individual and relationship characteristics associated with recruitment and retention of breast cancer survivors' partners. Investigators asked survivors from the Moving Beyond Cancer trial for permission to invite their partners to a parallel, longitudinal study. Of 384 survivors with male partners, 280 survivors provided consent to contact partners, and 164 partners completed both assessments. Backward stepwise regression indicated that greater family income and support from a partner and helpful other increased the likelihood of survivor consent to contact her partner. Greater family income, better survivor physical and emotional quality of life, and white ethnicity increased the likelihood of partner participation. Breast cancer patients who are ethnic minorities, have lower socioeconomic status, or have poorer physical and mental quality of life appear less likely to participate in psycho-oncology couples' research, whereas women with supportive partners might be overrepresented.


Endothelium and hemorheology.
Hemorheological alterations which can be found in ischaemic vascular diseases are well known and widely studied; less clear is the relationship between these alterations and endothelial function. Our studies showed that modifications in endothelial function caused by physical stress are associated with a worsening in hemorheological parameters mainly in patients affected by ischaemic vascular diseases: major vascular alterations have been found in patients with very high levels of plasma markers endothelial dysfunction. The control of the basal tone of the vessels is given by the complex interaction between vasoconstrictor and vasodilator endothelial factors and when this equilibrium is broken we have the endothelial dysfunction. From a methodological point of view we can find an endothelial dysfunction index determining the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, which is one of the more powerful endogenous vasodilators and whose synthesis is catalysed by nitric oxide synthase (NOS), can be determined by the ratio between blood concentrations of citrulline and arginine (the co-product and the precursor of the way of NO synthesis), which represents the level of activity of the enzyme. A very affordable index of the endothelial dysfunction is the asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOS; in fact several studies demonstrated a strong relationship between ischaemic vascular diseases and high levels of plasma ADMA. Evaluation of these parameters is measured by means of high performance liquid chromatography (HPLC): this technique provides very affordable results and allows to obtain evaluations of substances in very small concentrations, like ADMA.


Intrinsic site-selectivity of ubiquitin dimer formation.
The post-translational modification of proteins with ubiquitin can take on many forms, including the decoration of substrates with polymeric ubiquitin chains. These chains are linked through one of the seven lysine residues in ubiquitin, with the potential to form a panoply of linkage combinations as the chain length increases. The ensuing structural diversity of modifications serves a variety of signaling functions. Still, some linkages are present at a much higher level than others in cellulo. Although ubiquitination is an enzyme-catalyzed process, the large disparity of abundancies led us to the hypothesis that some linkages might be intrinsically faster to form than others, perhaps directing the course of enzyme evolution. Herein, we assess the kinetics of ubiquitin dimer formation in an enzyme-free system by measuring the rate constants for thiol-disulfide interchange between appropriate ubiquitin variants. Remarkably, we find that the kinetically expedient linkages correlate with those that are most abundant in cellulo. As the abundant linkages also appear to function more broadly in cellulo, this correlation suggests that the more accessible chains were selected for global roles.


Tumor-infiltrating cells as a prognostic factor in Hodgkin's lymphoma: a quantitative tissue microarray study in a large retrospective cohort of 267 patients.
The present study aimed to describe the general tissular composition of the immune infiltrate observed in Hodgkin's lymphoma (HL) and its possible relationship with clinical and survival prognostic factors. In this retrospective study of 267 HL patients, the relative proportions of infiltrating T lymphocytes (CD4+, CD8+), natural killer cells (CD 56+, CD 57+), cytotoxic cells (Granzyme B+, TIA-1+) and dendritic cells (CD 21+, S-100+) were quantified immunohistochemically with tissue microarray technology. Our results confirm the predominance of CD4 + T lymphocytes in the background of tumoral cells, in addition to a high number of cytotoxic lymphocytes (CD8, CD 57 and TIA-1). Patients with low numbers of infiltrating CD8, CD 56, CD 57+cells and high numbers of Granzyme B and TIA-1+cells presented a significantly unfavourable clinical course (presence of leukocytosis, B symptoms, advanced clinical stage (III/IV), non-responding patients). A reduced infiltration of CD4+T lymphocytes was related with the presence of Epstein - Barr virus. Significantly longer survival times were observed in patients with a high level of infiltrating CD 57, as well as a low level of Granzyme B and TIA-1+cells (log-rank test). When evaluated in a multivariate model, high levels of infiltrating TIA-1 and Granzyme B+cells were shown to be independent prognostic factors that negatively influenced overall survival. The presence of TIA-1+cells was found to be the only unfavorable prognostic factor of event-free survival and disease-free survival. The overall detection of tumor-infiltrating cells in HL confirms the importance of cytotoxic T lymphocyte infiltration (Granzyme B and TIA-1+cells) in these patients. Independently of the classical clinical and pathological features, these cells appear to be an unfavourable prognostic factor in HL and, more particularly, the presence of cytotoxic TIA-1+cells.


First Occurrence of Sternochetus mangiferae (Fabricius) (Coleoptera: Curculionidae) in Brazil.
Specimens of the mango stone weevil Sternochetus mangiferae (Fabricius) (Coleoptera: Curculionidae) were found in fruits of mango from a tree in the residential area of the Rio de Janeiro, RJ. This is the first report of the S. mangiferae in Brazil, currently regulated as an absent quarantine pest in the country. A taxonomist specialized in Curculionidae confirmed the identification based on morphological diagnostics characteristics. This detection is a relevant finding, because Brazil is a major producer and exporter of mango and the main areas of mango for exportation are located very far from this detection point. This pest damages seed and embryo of mango fruits and it causes reduction of fruit size and its premature dropping. The detection was notified to the Plant Health Department, division of the Brazilian Ministry of Agriculture, Livestock and Food Supply (MAPA), which is the National Plant Protection Organization of Brazil.


Adenosine receptors are coupled negatively to release of tachykinin(s) from enteric nerve endings.
Adenosine receptors capable of modulating tachykininergic transmission were characterized in functional studies using both field-stimulated and cholecystokinin octapeptide-stimulated contractile responses of atropinized guinea pig longitudinal muscle-myenteric plexus preparations. These tetrodotoxin-sensitive responses, which were mediated by release of one or more tachykinins, were inhibited by adenosine analogs in a concentration-dependent manner. The rank order of potencies of the analogs as inhibitors of the responses to cholecystokinin octapeptide was N6-cyclopentyladenosine greater than 5'-N-ethylcarboxamidoadenosine much greater than 2-phenylaminoadenosine (CV 1808). Schild analysis of the antagonism of the presynaptic inhibitory effects of 5'-N-ethylcarbocamidoadenosine and N6-cyclopentyladenosine on cholecystokinin octapeptide-stimulated responses using the A1 selective antagonists 1,3-dipropyl-8-(4-sulfophenyl)xanthine and 1,3-dipropyl-8-(cyclopentyl)xanthine yielded linear isoboles with unit slopes indicating competitive antagonism. The affinity of the antagonists for the receptor site(s) involved in inhibition of tachykininergic transmission was similar to those established previously for cholinergic transmission. The rank order of potency of adenosine analogs as inhibitors of the field-stimulated responses was such that N6-cyclopentyladenosine = 5'-ethylcarboxamidoadenosine. Reverse-phase high-performance liquid chromatography analysis performed on lysates of isolated myenteric nerve endings demonstrated the presence of substance P and neurokinin-A. Neurokinin-B was undetectable. These studies indicate that adenosine receptor(s) on myenteric nerve endings are coupled negatively to tachykinin release and that they are probably identical to those involved in the modulation of acetylcholine release.


The IDA-LIKE peptides IDL6 and IDL7 are negative modulators of stress responses in Arabidopsis thaliana.
Small signalling peptides have emerged as important cell to cell messengers in plant development and stress responses. However, only a few of the predicted peptides have been functionally characterized. Here, we present functional characterization of two members of the IDA-LIKE (IDL) peptide family in Arabidopsis thaliana, IDL6 and IDL7. Localization studies suggest that the peptides require a signal peptide and C-terminal processing to be correctly transported out of the cell. Both IDL6 and IDL7 appear to be unstable transcripts under post-transcriptional regulation. Treatment of plants with synthetic IDL6 and IDL7 peptides resulted in down-regulation of a broad range of stress-responsive genes, including early stress-responsive transcripts, dominated by a large group of ZINC FINGER PROTEIN (ZFP) genes, WRKY genes, and genes encoding calcium-dependent proteins. IDL7 expression was rapidly induced by hydrogen peroxide, and idl7 and idl6 idl7 double mutants displayed reduced cell death upon exposure to extracellular reactive oxygen species (ROS). Co-treatment of the bacterial elicitor flg22 with IDL7 peptide attenuated the rapid ROS burst induced by treatment with flg22 alone. Taken together, our results suggest that IDL7, and possibly IDL6, act as negative modulators of stress-induced ROS signalling in Arabidopsis.


Effects of gonadotropin-releasing hormone analogs on cis-platinum-induced spermatogenic damage.
In order to test the hypothesis that pretreatment with gonadotropin-releasing hormone (GnRH) analogs might ameliorate cytotoxic drug-induced testicular damage, mature male Wistar rats were pretreated for 2 weeks with a GnRH superactive agonist or a pure GnRH antagonist prior to, and for 1 week after, a 5 mg/kg intraperitoneal dose of cis-platinum. Despite inhibition of testicular function by both GnRH analogs prior to cis-platinum administration, there was no evidence of protection or enhanced recovery of spermatogenesis at 6 and 12 weeks after cis-platinum treatment, and spermatogenesis was significantly further depressed at both time-points by both GnRH agonist and antagonist pretreatment. This suggests that pretreatment with GnRH analogs in the rat does not protect spermatogenesis from cis-platinum-induced testicular damage within up to two spermatogenic cycles and that hypogonadism at the time of cytotoxic drug treatments may aggravate testicular damage.


Pharmacodynamic evaluation and physical/chemical analysis of two formulations of propofol used in target-controlled infusion.
There are several formulations of propofol available to the anesthesiologist for clinical use. The aim of this study was to analyze the physicochemical properties, pharmacodynamic effect, and pharmaceutical and clinical equivalence of the reference drug propofol as well as a similar formulation. Sixteen volunteers were enrolled in this randomized, double-blind, and paired study of Diprivan and Propovan formulations. Formulations were given as target-controlled infusion with target concentration of 3.0 μg.mL(-1) for 15 minutes. Variables studied were the area under the curve (AUC) of the bispectral index (BIS) graph regarding time, minimum BIS reached and time to reach it, and recovery time. The two formulations were sent to analysis of particle size of lipid emulsion, surface potential, and active principle quantification. There was no difference between the formulations when comparing AUC, minimum BIS reached and time to reach it. The similar formulation recovery time was lower compared to the reference formulation (eight and 10 min, respectively, p=0.014). Mean particle size of lipid emulsion, surface potential, and active ingredient quantification were similar for both formulations. There was no clinically significant difference between the use of propofol, reference Diprivan, and the similar Propovan during infusion. However, the recovery time was longer with the reference drug. Although analysis of both formulations studied show similar results regarding its physicochemical characterization, further studies should be conducted to justify this difference.


Poly[(μ(3)-rac-5-eth-oxy-carbonyl-6-hy-droxy-6-methyl-4-phenyl-4,5,6,7-tetra-hydro-benzo[c]isoxazol-3-olato)potassium].
The title compound, [K(C(17)H(18)NO(5))](n), reveals the relative configuration (4R*,5S*,6R*) whereas its crystals are racemic. The cyclo-hexane ring adopts a half-chair conformation and the isoxazole ring has an envelope conformation. The ethyl fragment of the eth-oxy-carbonyl group at position 5 is disordered in a 0.547 (7):0.453 (7) ratio. The K(+) ion is surrounded by five O atoms from three ligands at distances ranging from 2.606 (2) to 3.028 (2) Å, generating a three-dimensional network. The crystal packing displays inter-molecular O-H⋯N and O-H⋯O hydrogen bonds in which the hy-droxy group acts as a double proton donor.


The risk of lower mental outcome in infantile spasms increases after three weeks of hypsarrhythmia duration.
To assess the correlation between hypsarrhythmia duration and mental outcome in infantile spasms (IS) the medical records of 48 infants with IS were reviewed retrospectively and psychological assessments undertaken at follow-up at the age of 3 to 13 years. We found 18 (38%) cryptogenic IS cases with typical hypsarrhythmia and 30 symptomatic with modified hypsarrhythmia-further classified into 15 cases as multifocal, 10 as pseudoperiodic and 5 as unilateral hypsarrhythmia. A short treatment lag (one to two weeks) occurred in 25, three to four weeks in 10 cases. Spasms ceased within one month after treatment in 23 infants. At follow-up 15 children had normal mental outcome (borderline included). A correlation between hypsarrhythmia duration longer than three weeks and lower mental outcome was found using the logistic regression model. The duration of hypsarrhythmia represents a sensitive prognostic parameter in IS; the risk of mental retardation increases after three weeks of hypsarrhythmia.


Multicontrast Pocket Colposcopy Cervical Cancer Diagnostic Algorithm for Referral Populations.
Objective and Impact Statement. We use deep learning models to classify cervix images-collected with a low-cost, portable Pocket colposcope-with biopsy-confirmed high-grade precancer and cancer. We boost classification performance on a screened-positive population by using a class-balanced loss and incorporating green-light colposcopy image pairs, which come at no additional cost to the provider. Introduction. Because the majority of the 300,000 annual deaths due to cervical cancer occur in countries with low- or middle-Human Development Indices, an automated classification algorithm could overcome limitations caused by the low prevalence of trained professionals and diagnostic variability in provider visual interpretations. Methods. Our dataset consists of cervical images (n=1,760) from 880 patient visits. After optimizing the network architecture and incorporating a weighted loss function, we explore two methods of incorporating green light image pairs into the network to boost the classification performance and sensitivity of our model on a test set. Results. We achieve an area under the receiver-operator characteristic curve, sensitivity, and specificity of 0.87, 75%, and 88%, respectively. The addition of the class-balanced loss and green light cervical contrast to a Resnet-18 backbone results in a 2.5 times improvement in sensitivity. Conclusion. Our methodology, which has already been tested on a prescreened population, can boost classification performance and, in the future, be coupled with Pap smear or HPV triaging, thereby broadening access to early detection of precursor lesions before they advance to cancer.


First-principles investigation of stable lead-free halide perovskite materials CsSnClxBryI3-x-yfor solar cell applications.
Perovskite solar cells based on hybrid organic-inorganic lead halide materials have attracted immense interest in recent years due to their enhanced power conversion efficiency. However, the toxic lead element and unstable property of the material limit their applications. With first-principles calculations based on density functional theory, we studied a series of ten lead-free perovskite materials made of cesium, tin, and halogen elements, chlorine (Cl), bromine (Br), and iodine (I). We found that the relative concentrations of the halogen atoms determine the crystal structures and the relative stability of the halide perovskites. Chlorine tends to increase the structural stability, while iodine plays the role of reducing the band gaps of the mixed halide perovskites. Considering the stability and the requirement of suitable band gaps, we identify that, among the ten lead-free halide perovskites, CsSnCl2I, CsSnBr2I, CsSnClBrI, CsSnClI2, CsSnBrI2, and CsSnI3are the appropriate choices for solar cell applications.


Immunologic characterization of patients with chronic mucocutaneous candidiasis disease.
Even if initial immunologic screen is normal, a high index of suspicion for immunodeficiency should guide the evaluation and management of patients with recurrent episodes of mucocutaneous candidiasis. Although rare, a diagnosis of chronic mucocutaneous disease should always be considered in order to improve their outcome.


The efficiency of oxidative phosphorylation and the rapid control by thyroid hormone of nicotinamide nucleotide reduction and transhydrogenation in intact rat liver mitochondria.
In confirmation of previous work enhancement of the fluorescence emission of reduced nicotinamide nucleotides in intact rat liver mitochondria was found to depend on incubation conditions. Under standard conditions the enhancement is constant at 4.8-fold in states 3 and 4 and is not altered by thyroidectomy of the animal 6 weeks prior to experiment. The ADP-induced (state 4----state 3----state 4) fluorescence changes are significantly different in intact mitochondria from normal and hypothyroid animals and reflect the decreased rate and efficiency of oxidative phosphorylation after thyroidectomy. Incubation of liver homogenates in vitro for 15 min with 1 microM triiodothyronine before isolating mitochondria significantly restores their ADP response towards normal. Direct addition of hormone to isolated mitochondria was ineffective. Enzymatic measurement of mitochondrial extracts shows that thyroidectomy leads to increases in the contents of NAD(H) by 22% and NADP(H) by 33%. With glutamate as substrate ADP-induced changes in the reduced/oxidized ratio of NAD+ are not significantly altered in hypothyroid preparations. By contrast the NADP+ ratio remains substantially more reduced in state 3 than it does in normal mitochondria. The hypothesis is advanced that the decreased efficiency of hypothyroid preparations in phosphorylating ADP may be the result of increased energy-linked transhydrogenase activity. This is needed to supply NADPH via the glutathione peroxidase for reducing endogenously formed peroxides. Direct reduction of mitochondrial glutathione with dithiothreitol had no substantial effect on ADP/O ratios or on ADP-induced redox cycles in either normal or thyroidectomised preparations. This decisively eliminates the possibility that lowered phosphorylation efficiency is the result of a leak of reducing equivalents via glutathione peroxidase.


Simulation of oxygen carrier mediated oxygen transport to C3A hepatoma cells housed within a hollow fiber bioreactor.
A priori knowledge of the dissolved oxygen (O2) concentration profile within a hepatic hollow fiber (HF) bioreactor is important in developing an effective bioartificial liver assist device (BLAD). O2 provision is limiting within HF bioreactors and we hypothesize that supplementing a hepatic HF bioreactor's circulating media with bovine red blood cells (bRBCs), which function as an O2 carrier, will improve oxygenation. The dissolved O2 concentration profile within a single HF (lumen, membrane, and representative extra capillary space (ECS)) was modeled with the finite element method, and compared to experimentally measured data obtained on an actual HF bioreactor with the same dimensions housing C3A hepatoma cells. Our results (experimental and modeling) indicate bRBC supplementation of the circulating media leads to an increase in O2 consumed by C3A cells. Under certain experimental conditions (pO2,IN) = 95 mmHg, Q = 8.30 mL/min), the addition of bRBCs at 5% of the average in vivo human red blood cell concentration (% hRBC) results in approximately 50% increase in the O2 consumption rate (OCR). By simply adjusting the operating conditions (pO2,IN) = 25 mmHg, Q = 1.77 mL/min) and increasing bRBC concentration to 25% hRBC the OCR increase is approximately 10-fold. However, the improved O2 concentration profile experienced by the C3A cells could not duplicate the full range of in vivo O2 tensions (25-70 mmHg) typically experienced within the liver sinusoid with this particular HF bioreactor. Nonetheless, we demonstrate that the O2 transport model accurately predicts O2 consumption within a HF bioreactor, thus setting up the modeling framework for improving the design of future hepatic HF bioreactors.


The impact of implementation of the Bethesda System for Reporting Thyroid Cytopathology on the quality of reporting, "risk" of malignancy, surgical rate, and rate of frozen sections requested for thyroid lesions.
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been anticipated to improve communication between pathologists and clinicians and thereby patient outcomes. In the current study, the impact of TBSRTC on various quality and outcome measures was assessed. The current study included all patients who underwent fine-needle aspiration (FNA) of the thyroid between April 2006 and April 2009. Before implementation, the authors used generic diagnostic categories; after implementation, TBSRTC was used. Quality of reporting, diagnostic categories, rate of surgery, rates of frozen section, the "risk" of malignancy after a cytologic diagnosis, and errors before and after implementation of TBSRTC were compared using the chi-square and Fisher exact tests. Multilevel likelihood ratios and the receiver operating characteristic were used to compare the accuracy of FNA before and after implementation. A total of 1671 FNAs (957 obtained before and 714 obtained after implementation of TBSRTC) were obtained from 1339 patients. Of these, 301 patients (191 before and 110 after implementation) underwent subsequent surgical resection. Before implementation, the reports were more ambiguous (3.7% vs 0.5%; P < .05) and implicit (5.1% vs 2.7%; P < .05) than after implementation. The overall rate of surgery decreased after implementation of TBSRTC (24.5% vs 19.6%; P < .05). The overall risk of malignancy did not appear to be affected by implementation of TBSRTC, but it decreased significantly after a benign FNA diagnosis compared with a diagnosis of an atypical lesion or follicular neoplasm. The rate of frozen section remained unchanged. The diagnostic accuracy was not found to be significantly different before compared with after implementation of TBSRTC. Implementation of TBSRTC appears to improve the quality of reporting by lowering the number of ambiguous and implicit diagnoses and decreases the overall surgery rates, particularly for benign lesions, but it does not appear to have any effect on the accuracy of FNA of the thyroid, false-positive rates, or the frequency of intraoperative consultations.


The wave of the future: genetic profiling in treatment selection.
Chemotherapy treatment recommendations traditionally have been based on the anatomic site of origin and the histology of the tumor. More recently, treatment options are transitioning to targeted therapies, in which drug selection is based on mutations present in an individual tumor. Genomic testing is a developing area that involves testing tumors to determine their molecular or genetic characteristics, then matching those characteristics to treatments that specifically target them.


Cardiac ion channel gene mutations in sudden infant death syndrome.
Sudden infant death syndrome (SIDS) is multifactorial and may result from the interaction of a number of environmental, genetic, and developmental factors. We studied three major genes causing long QT syndrome in 42 Japanese SIDS victims and found five mutations, KCNQ1-K598R, KCNH2-T895M, SCN5A-F532C, SCN5A-G1084S, and SCN5A-F1705S, in four cases; one case had both KCNH2-T895M and SCN5A-G1084S. All mutations were novel except for SCN5A-F532C, which was previously detected in an arrhythmic patient. Heterologous expression study revealed significant changes in channel properties of KCNH2-T895M, SCN5A-G1084S, and SCN5A-F1705S, but did not in KCNQ1-K598R and SCN5A-F532C. Our data suggests that nearly 10% of SIDS victims in Japan have mutations of the cardiac ion channel genes similar to in other countries.


Comparative pharmacokinetics and pharmacodynamics of amikacin and ceftazidime in tricuspid and aortic vegetations in experimental Pseudomonas endocarditis.
A factor in the higher medical cure rates for endocarditis in the right as opposed to the left side of the heart in humans may be a difference in antimicrobial pharmacokinetics within vegetations. Rabbits with combined tricuspid and aortic endocarditis due to Pseudomonas aeruginosa received single intravenous doses of either ceftazidime (50 mg/kg) or amikacin (15 or 40 mg/kg). For each antibiotic regimen, areas under the time-concentration curves and percent vegetation penetrances were significantly greater for tricuspid than aortic vegetations (P less than .001). Time-concentration curves for aortic vegetations paralleled those for plasma; curves for the tricuspid vegetations resembled those for subcutaneous fibrin clots. The times above the minimum bactericidal concentration for tricuspid vegetations were significantly longer than those achieved within aortic vegetations for ceftazidime (P less than .01) and amikacin at 15 mg/kg (P less than .001). Antimicrobial pharmacokinetics and pharmacodynamics may be more favorable within tricuspid than aortic vegetations; this difference may, in part, explain more salutary outcomes in bacterial endocarditis involving the right side of the heart.


Multi-Targeting Anticancer Agents: Rational Approaches, Synthetic Routes and Structure Activity Relationship.
We live in a world with complex diseases such as cancer which cannot be cured with one-compound one-target based therapeutic paradigm. This could be due to the involvement of multiple pathogenic mechanisms. One-compound-various-targets stratagem has become a prevailing research topic in anti-cancer drug discovery. The simultaneous interruption of two or more targets has improved the therapeutic efficacy as compared to the specific targeted based therapy. In this review, six types of dual targeting agents along with some interesting strategies used for their design and synthesis are discussed. Their pharmacology with various types of the molecular interactions within their specific targets has also been described. This assemblage will reveal the recent trends and insights in front of the scientific community working in dual inhibitors and help them in designing the next generation of multi-targeted anti-cancer agents.


Structure of Atg5.Atg16, a complex essential for autophagy.
Atg5 is covalently modified with a ubiquitin-like modifier, Atg12, and the Atg12-Atg5 conjugate further forms a complex with the multimeric protein Atg16. The Atg12-Atg5.Atg16 multimeric complex plays an essential role in autophagy, the bulk degradation system conserved in all eukaryotes. We have reported here the crystal structure of Atg5 complexed with the N-terminal region of Atg16 at 1.97A resolution. Atg5 comprises two ubiquitin-like domains that flank a helix-rich domain. The N-terminal region of Atg16 has a helical structure and is bound to the groove formed by these three domains. In vitro analysis showed that Arg-35 and Phe-46 of Atg16 are crucial for the interaction. Atg16, with a mutation at these residues, failed to localize to the pre-autophagosomal structure and could not restore autophagy in Atg16-deficient yeast strains. Furthermore, these Atg16 mutants could not restore a severe reduction in the formation of the Atg8-phosphatidylethanolamine conjugate, another essential factor for autophagy, in Atg16-deficient strains under starvation conditions. These results taken together suggest that the direct interaction between Atg5 and Atg16 is crucial to the performance of their roles in autophagy.


Evaluation of the Lyra Direct Strep Assay To Detect Group A Streptococcus and Group C and G Beta-Hemolytic Streptococcus from Pharyngeal Specimens.
The Lyra Direct strep assay was compared to culture for its ability to detect Streptococcus group A and β-hemolytic groups C/G using rapid antigen-negative pharyngeal specimens (n = 161). The Lyra assay correctly detected all β-hemolytic streptococci (group A, n = 19; group C/G, n = 5). In batch mode, the Lyra assay reduced intralaboratory turnaround time by 60% (18.1 h versus 45.0 h) but increased hands-on time by 96% (3 min 16 s versus 1 min 40 s per specimen).


Recent Trends and Hotspots in Knee Arthroplasty: A Bibliometric Analysis and Visualization Study of the Last Five-Year Publications.
Bibliometric analysis is one of the most prevalent methods for analyzing and predicting the research trends of particular subjects. Through a bibliometric analysis, this study sought to look into and depict the hotspots and research trends in knee arthroplasty research over the previous five years. The Web of Science Core Collection database was used to find research articles on knee arthroplasty published between 2018 and 2022. The VOS viewer, Cite Space, and Bibliometrix were used to carry out the bibliometric study and network visualization. During the previous five years, 7,422 included knee arthroplasty publications were cited 57,087 times. The United States and the Journal of Arthroplasty were the top countries and journals regarding the number of articles. The top 10 global high-impact documents were determined using the citation ranking and citation burst. The most frequently referenced article revealed that the epidemiological characteristics of knee arthroplasty, perioperative care in knee arthroplasty, prosthetic joint infections, and opioid medications were the hot topics in knee arthroplasty research. Keyword burst analysis showed that the research trends in knee arthroplasty through 2022 were racial disparity, limb alignment, tibial slope, and meniscectomy. The analysis of the subject areas revealed the close connections and relationships between different subject areas, as demonstrated by the figures. The knee arthroplasty research community is highly productive and centralized. Recent hotspots in knee arthroplasty research were unicompartmental knee arthroplasty, periprosthetic joint infection, kinematic alignment, outpatient total knee arthroplasty (TKA), bariatric surgery, payment model, tranexamic acid, Robotic-Assisted TKA, patient-reported outcome measures, metaphyseal cone, opioid use, and patient-specific instrumentation. Research trends in knee arthroplasty research were racial disparity, limb alignment, tibial slope, and meniscectomy.


Extensive coil embolization of a giant coronary artery aneurysm in an octogenarian: a case report.
Coronary artery aneurysms (CAA) are often diagnosed incidentally on coronary angiography or imaging modalities done for other reasons. 'Giant' CAA by definition exceeds 20 mm in diameter or four times the diameter of normal coronary artery. The management of patients with CAAs is challenging due to poorly understood mechanism, variable presentation, and lack of clear-cut societal recommendations. Though conservative management is preferred in asymptomatic patients, massive size or interval growth may make intervention necessary. We describe a case of successful coil embolization of a giant coronary aneurysm in an elderly 84-year-old male. Patient, who presented for a follow-up computed tomography angiography to evaluate a previously repaired abdominal aortic aneurysm 2 years back, was found to have interval growth of right coronary artery aneurysm from 4 cm in diameter to 7 × 8 cm in its greatest dimensions. The rationale for treatment was to prevent sudden death from continued growth and eventual rupture of aneurysm in addition to potential risk of thromboembolism and compression of adjacent structures. This case demonstrates the safe and successful use of extensive coil embolization technique to treat a 'giant' CAA in an elderly patient when surgical risks were prohibitive.


Chlamydia pneumoniae and its role in chronic obstructive pulmonary disease.
The diverging of T-helper (Th) cells into predominantly Th1 and Th2 subsets on the basis of their cytokine profiles has decisively improved our understanding of the pathogenesis of many chronic infectious diseases. Recent data suggest that the presence of interferon-gamma and the subsequent suppression of interleukin-4 production leads to a Th1-type response that is required for the resolution of infections caused by intracellular pathogens. The ability of the macrophages to respond aggressively during early antigen contact seems to be one crucial factor in the development of an appropriate Th-cell response. Several host-related factors can affect macrophage function and the polarization of T-cell responses, ie the shift from a Th1 response to a Th2 one, and thus dramatically deteriorate the resolution of infections caused by intracellular agents such as Chlamydia pneumoniae. Chronic C. pneumoniae infection has been associated with several common chronic diseases, quite recently with chronic obstructive pulmonary disease. Chronic C. pneumoniae infection may amplify smoking-associated inflammation in the bronchi and may be a contributory factor in the development of irreversible pathological changes.


Cellulose Fibers Constructed Convenient Recyclable 3D Graphene-Formicary-like δ-Bi2O3 Aerogels for the Selective Capture of Iodide.
Radioiodine is highly radioactive and acutely toxic, which can be a serious health threat, and requires effective control. To fully utilize an adsorbent and reduce the overall production cost, successive recycling applications become necessary. Here, 3D formicary-like δ-Bi2O3 (FL-δ-Bi2O3) aerogel adsorbents were synthesized using a one-pot hydrothermal method. In this hybrid structure, abundant flowerlike δ-Bi2O3 (MR-δ-Bi2O3) microspheres were inlaid into the interconnected ant nest channel, forming a 3D hierarchical structure, which is applied as an efficient adsorbent with easy recovery for radioiodine removal. Notably, the FL-δ-Bi2O3 aerogel adsorbent exhibited a very high uptake capacity of 2.04 mmol/g by forming an insoluble Bi4I2O5 phase. Moreover, the FL-δ-Bi2O3 worked in a wide pH range of 4-10 and displayed fast uptake kinetics and excellent selectivity due to the 3D porous interconnected network and larger specific surface area. Importantly, the recycling process is easy, using only tweezers to directly move the 3D aerogel adsorbents from one reaction system to another. Therefore, the FL-δ-Bi2O3 aerogel may be a promising practical adsorbent for the selective capture of radioactive iodide.


The relationship between morbidity and intensity of Schistosoma japonicum infection of a community in Jiangxi Province, China.
Seven hundred and eighty-five individuals from an area endemic for Schistosoma japonicum had parasitological and physical examinations done. A morbidity questionnaire was also administered to each participant. Among those with S. japonicum infection, there was a significant increase in diarrhea, blood in the stool and weakness during the previous two weeks. The severity of the disease appears to be related to the history of schistosomiasis japonicum and these results give further justification for treatment of the infected individuals and those severe morbidity groups in community based chemotherapy programs designed to reduce morbidity in endemic areas.


Ultrastable Tb-Organic Framework as a Selective Sensor of Phenylglyoxylic Acid in Urine.
Industrial pollution and harmful chemicals seriously affect environment and human health. Styrene is a common air toxicant with widespread exposure sources, including smoking, automobile exhaust, and plastic pollutants. Phenylglyoxylic acid (PGA) is a typical biomarker for exposed styrene. Therefore, it is crucial to quickly identify and quantitatively detect PGA. Herein, an ultrastable terbium metal-organic framework (Tb-MOF 1) was developed, and the luminescence film (1/PLA) consisting of polylactic acid (PLA) and 1 was fabricated as a sensor for rapid detection of PGA. The sensor possesses the advantages of efficient detection [limit of detection (LOD) is 1.05 × 10-4 mg/mL] and rapid response speed (less than 10 s) for PGA in urine. Furthermore, this sensor exhibits high stability, outstanding anti-interference ability, and excellent recyclability. Based on this film technology, a paper-based probe was then developed for portable and convenient detection. The probe could easily distinguish different concentrations of PGA under the naked eye toward practical sensing applications. Meanwhile, photoinduced electron transfer was demonstrated to be responsible for the luminescence sensing. Hence, this study indicates that Tb-MOF is a promising material to detect PGA for evaluating the effect of styrene on the body.


Predicting the energetics of osmolyte-induced protein folding/unfolding.
A primary thermodynamic goal in protein biochemistry is to attain predictive understanding of the detailed energetic changes that are responsible for folding/unfolding. Through use of recently determined free energies of side-chain and backbone transfer from water to osmolytes and Tanford's transfer model, we demonstrate that the long-sought goal of predicting solvent-dependent cooperative protein folding/unfolding free-energy changes (m values) can be achieved. Moreover, the approach permits dissection of the folding/unfolding free-energy changes into individual contributions from the peptide backbone and residue side chains.


Use of FDA approved medications for Alzheimer's disease in mild dementia is associated with reduced informal costs of care.
ABSTRACTBackground:The use of FDA approved medications for Alzheimer's disease [AD; FDAAMAD; (cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists)] has been associated with symptomatic benefit with a reduction in formal (paid services) and total costs of care (formal and informal costs). We examined the use of these medications and their association with informal costs in persons with dementia. Two hundred eighty participants (53% female, 72% AD) from the longitudinal, population-based Dementia Progression Study in Cache County, Utah (USA) were followed up to ten years. Mean (SD) age at baseline was 85.6 (5.5) years. Informal costs (expressed in 2015 dollars) were calculated using the replacement cost method (hours of care multiplied by the median wage in Utah in the visit year) and adjusted for inflation using the Medical Consumer Price Index. Generalized Estimating Equations with a gamma log-link function were used to examine the longitudinal association between use of FDAAMAD and informal costs. The daily informal cost for each participant at baseline ranged from $0 to $318.12, with the sample median of $9.40. Within the entire sample, use of FDAAMAD was not significantly associated with informal costs (expβ = 0.73, p = 0.060). In analyses restricted to participants with mild dementia at baseline (N = 222), use of FDAAMAD was associated with 32% lower costs (expβ = 0.68, p = 0.038). Use of FDAAMAD was associated with lower informal care costs in those with mild dementia only.


Information order effects in clinical psychological diagnoses.
Despite the wide application and long history of diagnostic systems, several sources of diagnostic errors remain in the criterion-based diagnosing of mental disorders. The aim of this study was to investigate whether the presentational order of diagnosis-relevant information and pretreatment reports predict diagnostic errors. One hundred twenty psychotherapists participated in the present online study. The study employed a 2 (symptom presentation: core symptoms at vignette's beginning vs. core symptoms at the end of the case vignette) × 2 (pretreatment report: receiving a pretreatment report with an incongruent diagnosis to the case vignette vs. receiving no pretreatment report) between-subjects experimental design, with random assignment. Participants were asked to make diagnoses after reading three case vignettes describing patients with different disorder constellations. Additionally, participants rated their confidence in the diagnoses and their estimation of the severity of each diagnosed condition. Results indicated that order of symptom descriptions predicted the correctness of diagnostic decisions, with a recency effect causing more fully correct diagnostic decisions in cases where diagnostic information was presented last. Receiving incongruent pretreatment reports was predictive for diagnostic errors. In conclusion, the results of this study indicate that diagnoses of mental disorders can depend on the way symptoms are presented or reported. Therapists' diagnostic decisions are not influenced by pretreatment reports. Diagnostic decisions are affected by information order effects. Diagnostic accuracy of psychotherapists is debatable. High rate of misdiagnoses in case vignette with comorbid disorders.


The role of telemedicine in fostering health-care innovations to address problems of access, specialty shortages and changing patient care needs.
The integration of advanced technologies into health-care services promises to aid society in its transition to a coordinated, systems approach which is focused on disease prevention, enhanced wellness, chronic disease management, decision support, quality and patient safety. By incorporating such technologies, clinicians will be able to manage the growing volumes of medical information, research and decision support analytical tools. The deployment of advanced technologies will minimize the barriers of distance and geography to enhance access and facilitate the delivery of integrated health care. This will support and enhance the goals of the US federal Healthy People 2010 initiative.


The effect of ergocalciferol on uremic pruritus severity: a randomized controlled trial.
Hemodialysis (HD) patients have a high prevalence of pruritus. 25-Hydroxy vitamin D deficiency is common in this population and may play a role in its etiology. Because of this, we studied whether vitamin D2 treatment with ergocalciferol is effective for relief of uremic pruritus severity as measured by pruritus severity surveys. In this double-blind, placebo-controlled, randomized trial, the effect of 12 weeks of ergocalciferol administration on uremic pruritus severity was evaluated. Fifty HD patients randomly received either ergocalciferol 50,000 international units (IU) or placebo once weekly for 12 weeks. Pruritus severity surveys were completed every 2 weeks by all patients starting from baseline until 12 weeks and serve as the main outcome variable. Twenty-five study participants were randomized to ergocalciferol therapy and 25 were randomized to placebo. At baseline, the only significant difference between the two groups was time on dialysis and white blood cell count. Both groups experienced a decrease in pruritus scores from the beginning to the end of study (percent change -38.9% in the treatment group vs. -47.5% in the placebo group). By intention to treat, the treatment × time effect was not statistically significant (F = 0.71, df = (1, 282), P = .34), indicating that the pruritus score was not significantly lower in the treatment group than the placebo group throughout the study. In conclusion, we did not find ergocalciferol to be effective for the treatment of uremic pruritus.


Expression of a putative stem cell marker Musashi-1 in endometrium.
Firstly to examine the expression characteristics of Musashi (Msi)-1 in fetal endometrium, reproductive normal endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, next, to focus on exploring the possibility that Msi-1 serves as a marker of the endometrial stem cells in-situ. Immunohistochemical staining was performed to detect the expression of Msi-1 in 20 cases of fetal endometrium, 20 cases of normal endometrium, 20 cases of endometrial hyperplasia and 50 cases of endometrioid adenocarcinoma respectively. In fetal endometrium, Msi-1 positive cells were observed from the 12th week in epithelium, but the number of Msi-1 positive cells decreased with an increase in gestational age. In reproductive normal endometrium, Msi-1 expression presented as dispersed single cell and cell groups in the stroma adjacent to the myometrium. In endometrial hyperplasia and endometrioid adenocarcinoma, Msi-1 expression significantly increased and was more widely distributed. Msi-1 positive cells mainly lie in the stroma of normal endometrium, and the distribution pattern is consistent with that of the speculated endometrial stem cells. The high expression of Msi-1 in fetal endometrium and endometrioid adenocarcinoma suggests that Msi-1 positive cells have several characteristics of stem cells, such as high proliferative potentiality and multipotency. Considering these factors, this makes Msi-1 potentially a promising stem cell marker.


[The application of artificial neural networks to predict individual risk of essential hypertension].
To establish models to predict individual risk of essential hypertension and to evaluate and explore new forecasting methods. To select data of 3054 community residents from an epidemiological survey and divided them into 4:1 (2438 cases and 616 cases) ratio in accordance with the balance of age and sex to filter variables, and to establish, test and evaluate the prediction models. Using artificial neural network (ANN) and logistic regression analysis to establish models while applying ROC to evaluate the prediction models. Forecast results of the models applying to the test set proved that ANN had lower specificity but better veracity and sensitivity than logistic regression. In particular, the Youden's index of the ANN2 came up to 0.8399 which was distinctly higher than the other two models. When the area was under the ROC curve of logistic regression, the ANN, and ANN2 models equaled to 0.732 +/- 0.026, 0.900 +/- 0.014 and 0.918 +/- 0.013 respectively, which proved that the ANN model was better in the prediction about individual health risk of essential hypertension. Our results showed that ANN method seemed better than logistic regression in terms of predicting the individual risk from hypertension thus supplied a new method to solve the forecast of individual risk.


[Impact of cytomegalovirus infection on the course of tuberculosis in children and adolescents].
Sixty-five children and adolescents with respiratory tuberculosis were examined to determine the proportion of cytomegalovirus infection among patients with tuberculosis and its impact on the occurrence and course of different forms of tuberculosis. The number of children and adolescents infected with cytomegalovirus among the patients with respiratory tuberculosis (66.2%) was found to be three times more than that among those not infected with tuberculosis (21.0). The absolute majority (91.3%) of the examinees with the complicated course of a tuberculous process were carriers of cytomegalovirus. They were found to have both antigens and antibodies to cytomegalovirus 9 times more frequently than patients with the smooth course of tuberculosis, which is indicative of the activity of cytomegalovirus infection. The findings suggest that cytomegalovirus infection has an impact on the occurrence and pattern of a tuberculous process.


Drug-induced hepatotoxicity linked to zoledronic acid in the treatment of an elderly man with primary osteoporosis.
Zoledronic acid (ZA), an intravenous bisphosphonate, has been widely used for the treatment of osteoporosis. ZA is generally well tolerated, and ZA-related hepatotoxicity is rare. We report a case of hepatotoxicity after ZA infusion in an elderly male patient with primary osteoporosis. The patient had femoral neck and vertebral fractures, and 3 days after ZA 5-mg infusion, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased 23.4- and 15.3-fold, respectively, compared with pre-treatment values. Hepatoprotective agents were administered, and liver enzymes were back to near normal range 9 days later. This case report shows the possible hepatic adverse effects related to ZA infusion. The mechanism of hepatotoxicity caused by ZA is not clear. Acute-phase reaction after ZA infusion may play a role in hepatotoxicity, which should be taken into consideration, especially for the elderly.


Adaptive divergence and the evolution of hybrid trait mismatch in threespine stickleback.
Selection against mismatched traits in hybrids is the phenotypic analogue of intrinsic hybrid incompatibilities. Mismatch occurs when hybrids resemble one parent population for some phenotypic traits and the other parent population for other traits, and is caused by dominance in opposing directions or from segregation of alleles in recombinant hybrids. In this study, we used threespine stickleback fish (Gasterosteus aculeatus L.) to test the theoretical prediction that trait mismatch in hybrids should increase with the magnitude of phenotypic divergence between parent populations. We measured morphological traits in parents and hybrids in crosses between a marine population representing the ancestral form and twelve freshwater populations that have diverged from this ancestral state to varying degrees according to their environments. We found that trait mismatch was greater in more divergent crosses for both F1 and F2 hybrids. In the F1, the divergence-mismatch relationship was caused by traits having dominance in different directions, whereas it was caused by increasing segregating phenotypic variation in the F2. Our results imply that extrinsic hybrid incompatibilities accumulate as phenotypic divergence proceeds.


Microbial community succession in response to sludge composting efficiency and heavy metal detoxification during municipal sludge composting.
This study researched microbial community succession in response to sludge composting efficiency and heavy metal detoxification during municipal sludge co-composting with spent mushroom and spent bleaching. The change law of key physicochemical properties, the heavy metals contents and forms during composting were analyzed, and the passivation of heavy metals after composting was explored. High-throughput sequencing was used to analyze the microbial community structure of treat 2 during composting, and the correlation analysis of microbial community structure with heavy metal contents and forms were carried out. The results showed that the sludge of each treatment reached composting maturity after 26 days of composting. Organic matter content, electrical conductivity, pH and seed germination index of treat 2 were all in line with the standard limit of agricultural sludge. Because of the presence of compost bacteria addition, the passivating heavy metals performance of treat 2 satisfied the standard limit of agricultural sludge after composting, which was superior to that of treat 1 and treat 3. The diversity of microbial communities in treat 2 decreased during composting. Extensive bacteria such as Bacillus, Geobacter, Lactobacillus, and Pseudomonas, which possessed the abilities of heavy metal passivation and organic oxidizing, were dominant in treat 2 during the heating stage. However, as composting proceeded, Tuberibacillus with ability of organic oxidizing gradually became the most dominant species at the thermophilic and cooling stages. Changes in microbial function varied from changes of microbial community in treat 2, subsequently affected the performances of heavy metal passivation and organic oxidizing during composting.


Cytoenzymologic investigations on carcinomas of the cervix uteri.
A study was carried out on 85 patients with lesions of the cervix uteri: 45 carcinomas and 40 dysplasias. A large battery of cytoenzymatic tests was used to determine their potential value in the diagnosis of carcinomas. An increase of LDH, G6PDH, 6PGDH and NADH2-TR activities and a loss of alpha-GP-ase I activity were demonstrated in malignant cells. It is suggested that the cytoenzymologic techniques may offer help in the distinction between normal, dyskaryotic and malignant cells of vaginal fluid. In individual patients these techniques are useful in understanding the evolution of dysplastic lesions and in the diagnosis of carcinoma. These techniques, however, cannot be used as a general screening test for malignancy.


Factors affecting the sensitivity of T-47D human breast cancer cells to tamoxifen.
Cell proliferation kinetics during growth of an estrogen receptor-positive human breast carcinoma cell line, T-47D, was defined, and some factors which modify its response to tamoxifen were investigated in vitro. T-47D cells were estrogen responsive when grown in charcoal-stripped fetal calf serum, but the addition of 17 beta-estradiol did not fully restore the growth rate to that observed in the same concentration of fetal calf serum. Tamoxifen had both a low-dose, estrogen-reversible, growth-inhibitory effect and a high-dose, estrogen-irreversible, growth-inhibitory and cytotoxic effect on T-47D cells. Tamoxifen-induced growth inhibition was associated with a decrease in the percentage of S-phase cells and, to a lesser extent, G2-M-phase cells and an increase in G0-G1-phase cells. Plateau-phase cells were considerably less sensitive than were exponentially growing cells, and this was accompanied by a fall in unoccupied estrogen receptor content from 4407 +/- 655 (S.E.) sites/cell in exponentially growing cultures to 1420 +/- 315 sites/cell in plateau-phase cultures. T-47D cells were more sensitive to tamoxifen cytostasis when grown in fetal calf serum rather than charcoal-stripped fetal calf serum. However, with both types of growth medium, the sensitivity to tamoxifen was inversely related to the serum concentration, e.g., the 50%-inhibitory dose concentration increased 75-fold as the fetal calf serum concentration was increased from 0.25 to 10%. Addition of insulin to the culture medium had no effect on the growth rate, estrogen receptor content, or tamoxifen sensitivity of T-47D cells. These results illustrate that the conditions under which cells are cultured markedly affect their sensitivity to tamoxifen and highlight the need to specify these conditions when reporting effects of this drug.


Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.
With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.


Efficacy and Tolerability of a Cosmetic Skin Care Product With Trans-4-t-butylcyclohexanol and Licochalcone A in Subjects With Sensitive Skin Prone to Redness and Rosacea.

BACKGROUND: Sensitive skin and rosacea are skin conditions, which may affect the quality of life of the patients considerably. In vitro and in vivo data indicated that the combination of trans-t-butylcyclohexanol and licochalcone A is an effective combination for alleviating the increased sensitivity of rosacea subtype I.

OBJECTIVE: Objective of this open dermocosmetic study was to investigate the efficacy and tolerability of a skin care product containing the anti-inflammatory licochalcone A and the TRPV1 antagonist trans-t-butylcyclohexanol in subjects with sensitive skin prone to redness and rosacea.

METHODS: 1221 subjects with sensitive skin and rosacea stage 0-II applied the test product twice daily for 4 weeks. Clinical assessment of sensitive skin and rosacea symptoms were performed at baseline and after 4 weeks. Additionally, at treatment end the test subjects filled a self-assessment questionnaire.

RESULTS: After 4 weeks of application, both, clinical and subjective assessment have shown improvement of all symptoms of sensitive skin and rosacea in a significant number of subjects (P less than 0.001). The test product was efficacious and very well tolerated also when used in conjunction with pharmacological treatments of the skin condition under scrutiny.

Conclusions: The study confirmed the good tolerability and efficacy of the skin care product in the management of sensitive skin prone to redness and rosacea when used alone or in combination with other therapies.

J Drugs Dermatol. 2017;16(6):605-611.
.


Assessment of the Contamination of Some Foodstuffs by Escherichia coli O157 in Benin, West Africa.
Escherichia coli O157 is a pathogenic bacterium causing haemorrhagic colitis. It represents a serious public health problem in Northern America and Europe, which can plague Africa. Most cases of mentioned poisoning were related to contaminated meat products and vegetables. The present work aimed to estimate the prevalence of E. coli O157 in meat and vegetables in Benin. For this purpose, 6 lots of faeces samples from pigs and 8 from cattle were collected at the farms on the outskirts of Cotonou. Similarly, 20 samples of carcasses, 20 samples of intestines and stomach, and 20 surfaces samples of slaughtering equipment were taken. Vegetables and environment materials in gardens have also been sampled for 84 samples. Bacteriological analyses revealed a percentage of contamination of 50% for pig faeces and 25% for cattle ones. All the meats from stalling parks have been contaminated by this bacterium. For vegetables, 14.6% of samples were contaminated by E. coli O157. The presence of this pathovar in animal breeding and slaughtering environment and in the gardens shows that Benin is not aware of the risks of foodborne illness associated with the consumption of contaminated products. Therefore, it urges including that germ in a systematic search during safety control of food products in Benin.


Perceived challenges and barriers for medical students in the COVID-19 crisis.
Unpredictable and immediate changes, especially in the clinical and practical fields of medical sciences following the coronavirus disease (COVID-19) epidemic, have posed many challenges for medical students. This study was conducted to identify the experiences and students' understanding of the challenges in the COVID-19 crisis. The present qualitative research was conducted by performing semi-structured interviews with the students along with holding a student panel. The study population consisted of 30 clinical and basic medical students of Babol, Iran and Kermanshah universities of medical sciences who were selected by purposive sampling method. Data were collected based on students' perceived experiences of challenges, obstacles, and problems in the COVID-19 crisis. The data analysis process was performed by conducting interviews and information obtained from the panel using v10 R150410 software. Finally, the related factors and components were identified. Challenges and perceived obstacles of medical students in the COVID-19 crisis were identified in the form of eight factors including student life factors, interaction and communication, psychological factors, educational technology, factors related to the professors, limitations of educational and research planning, crisis management, and educational evaluation. Identifying the challenges of medical education perceived by students in this study and adopting appropriate strategies to overcome existing barriers open new opportunities for expanding the scope of the curriculum, providing education, and promoting community health to universities; moreover, the challenges of medical education and any skill-based discipline, such as medical sciences in the COVID-19 pandemic will require much attention and investigation in cognitive sciences.


Transrectal ultrasound versus cystography in the evaluation of anatomical stress urinary incontinence.
Thirty-two female patients with clinical and urodynamic findings of genuine stress urinary incontinence were evaluated before and 6 months after surgery for stress urinary incontinence. Twenty-nine control patients had identical evaluations before and 6 months after surgery which did not involve the urethrovesical junction. Twenty-four patients with primary bladder instability had similar evaluations and served as a second control group. Anatomical landmarks indicating support to the urethrovesical junction were evaluated by the position of the urethra at the most dependent point in the bladder on straining and the urethral descent on straining to beneath the posterior ramus of the symphysis pubis on bead chain cystography. The urethrovesical junction drop on straining was evaluated by transrectal ultrasonography. Cystographic and ultrasonographic tests for the position of the urethrovesical junction at the most dependent position in the bladder during straining were very sensitive in women with stress urinary incontinence (94 and 87% respectively) but much less specific (45 and 48% respectively). When evaluating anatomical support to the urethrovesical junction and its descent on straining, these tests were both highly sensitive (97 and 94% respectively) and specific (76 and 96% respectively) in women with genuine stress urinary incontinence. Simple clinical tests for support of the urethrovesical junction, such as the Q tip test, are non-specific in patients with stress urinary incontinence. Transrectal ultrasonography is a simple and quick out-patient procedure. The availability of ultrasound equipment in most clinics and the high sensitivity and specificity of the test make it an attractive and cost-effective alternative to X-ray cystography in the pre-operative evaluation of anatomical support to the urethrovesical junction.


Improving the accuracy of synovial fluid analysis in the diagnosis of prosthetic joint infection with simple and inexpensive biomarkers: C-reactive protein and adenosine deaminase.
The aims of this study were to increase the diagnostic accuracy of the analysis of synovial fluid in the differentiation of prosthetic joint infection (PJI) by the addition of inexpensive biomarkers such as the levels of C-reactive protein (CRP), adenosine deaminase (ADA), alpha-2-macrogloblulin (α2M) and procalcitonin. Between January 2013 and December 2015, synovial fluid and removed implants were requested from 143 revision total joint arthroplasties. A total of 55 patients met inclusion criteria of the receipt of sufficient synovial fluid, tissue samples and removed implants for analysis. The diagnosis of PJI followed the definition from a recent International Consensus Meeting to create two groups of patients; septic and aseptic. Using receiver operating characteristic curves we determined the cutoff values and diagnostic accuracy for each marker. There were 23 PJIs and 32 patients with aseptic loosening. The levels of total leucocyte count, proportion of polymorphonuclear leucocytes (PMNs), CRP, ADA and α2M in the synovial fluid were all significantly higher in those with a PJI than in those with aseptic loosening. The levels of procalcitonin were comparable in the two groups. Cutoff values for the optimal performance in the diagnosis of infection were: total leucocyte count > 1463 cells/μL (sensitivity (Sens) 100%, specificity (Spec) 71.9%, positive predictive value (PPV) 71.9%, negative predictive value (NPV) 100%); proportion of PMNs > 81% (Sens 78.3%, Spec 75.0%, PPV 69.2%, NPV 82.8%); CRP > 6.7mg/L (Sens 78.3%, Spec 93.8%, PPV 90.0%, NPV 85.7%); ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%) and α2M > 958 mg/L (Sens 47.8%, Spec 96.9%, PPV 91.7%, NPV 72.1%). The addition of a raised level of CRP or ADA to the total leukocyte count increased the specificity: total leukocyte count > 1463 cells/μL and CRP > 6.7mg/L (Sens 78.3%, Spec 100%, PPV 100%, NPV 86.5%) or with ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%). The total leucocyte count in the synovial fluid offers great negative predictive value in the diagnosis of PJI and the addition of more specific markers such as CRP and ADA improves the positive predictive value. Thus the addition of simple and inexpensive markers to the measurement of the leucocyte count in the synovial fluid may reduce the number of equivocal results which demand more expensive investigation. Cite this article: Bone Joint J 2017;99-B:351-7.


[Urinary flow measurement at home prior to examination for intravesical obstruction].
Fifty patients referred with the diagnosis of prostatic hypertrophy were sent written instructions for simple home flow measurement. Forty-one patients came to outpatient interview and carried out uroflowmeterflow, home flow as water cystometry supplemented by simultaneous pressure-flow examination. Thirty-one patients achieved conclusive flows. No significant differences were observed between home flow (mean 6.7 ml/second, range 2.2-21.8 ml/second) and uroflowmeterflow (mean 5.9 ml/second, range 1.8-14.7 ml/second) assessed by Pratt's test (p greater than 0.05). The positive predictive values were 88% and 85%, respectively. The conclusion of this investigation is that simple home flow measurement is a useful parameter in the prehospital assessment of patients with suspected infravesical obstruction.


Immunization coverage: role of sociodemographic variables.
Children are considered fully immunized if they receive one dose of BCG, three doses of DPT and polio vaccine each, and one measles vaccine. In India, only 44% of children aged 12-23 months are fully vaccinated and about 5% have not received any vaccination at all. Even if national immunization coverage levels are sufficiently high to block disease transmission, pockets of susceptibility may act as potential reservoirs of infection. This study was done to assess the immunization coverage in an urban slum area and determine various sociodemographic variables affecting the same. A total of 210 children were selected from study population using WHO's 30 cluster sampling method. Coverage of BCG was found to be the highest (97.1%) while that of measles was the lowest. The main reason for noncompliance was given as child's illness at the time of scheduled vaccination followed by lack of knowledge regarding importance of immunization. Low education status of mother, high birth order, and place of delivery were found to be positively associated with low vaccination coverage. Regular IEC activities (group talks, role plays, posters, pamphlets, and competitions) should be conducted in the community to ensure that immunization will become a "felt need" of the mothers in the community.


An ability to improvise.
What is your job? I am a Kenyan-born emergency nurse in the medical emergency response team in Galkayo, Somalia. My role is to provide mobile and rapid medical emergency response capacity, advanced life support intervention and to work with humanitarian workers and the local community on a case-by-case basis.


Extreme ultraviolet Talbot interference lithography.
Periodic nanopatterns can be generated using lithography based on the Talbot effect or optical interference. However, these techniques have restrictions that limit their performance. High resolution Talbot lithography is limited by the very small depth of focus and the demanding requirements in the fabrication of the master mask. Interference lithography, with large DOF and high resolution, is limited to simple periodic patterns. This paper describes a hybrid extreme ultraviolet lithography approach that combines Talbot lithography and interference lithography to render an interference pattern with a lattice determined by a Talbot image. As a result, the method enables filling the arbitrary shaped cells produced by the Talbot image with interference patterns. Detailed modeling, system design and experimental results using a tabletop EUV laser are presented.


Heme oxygenase-1, a novel target for the treatment of diabetic complications: focus on diabetic peripheral neuropathy.
Diabetic neuropathy is a complex disorder induced by long standing diabetes. Many signaling pathways and transcription factors have been proposed to be involved in the development and progression of related processes. Years of research points to critical role of oxidative stress, neuroinflammation and apoptosis in the pathogenesis of neuropathy in diabetes. Heme oxygenase-1 (HO-1) is heat-shock protein induced under conditions of different kinds of stress and has been implicated in cellular defense against oxidative stress. HO-1 degrades heme to biliverdin, carbon monoxide (CO) and free iron. Biliverdin and CO are gaining particular interest because these two have been found to mediate most of anti-inflammatory, antioxidant and anti-apoptotic effects of HO-1. Although extensively studied in different kinds of cancers and cardiovascular conditions, role of HO-1 in diabetic neuropathy is still under investigation. In this paper, we review the unique therapeutic potential of HO-1 and its role in mitigating various pathological processes that lead to diabetic neuropathy. This review also highlights the therapeutic approaches such as pharmacological and natural inducers of HO-1, gene delivery of HO-1 or its reaction products that in future, could lead to progression of HO-1 activators through the preclinical stages of drug development to clinical trials.