Speaking to a common tune: Between-speaker convergence in voice fundamental frequency in a joint speech production task.
Recent research on speech communication has revealed a tendency for speakers to imitate at least some of the characteristics of their interlocutor's speech sound shape. This phenomenon, referred to as phonetic convergence, entails a moment-to-moment adaptation of the speaker's speech targets to the perceived interlocutor's speech. It is thought to contribute to setting up a conversational common ground between speakers and to facilitate mutual understanding. However, it remains uncertain to what extent phonetic convergence occurs in voice fundamental frequency (F0), in spite of the major role played by pitch, F0's perceptual correlate, as a conveyor of both linguistic information and communicative cues associated with the speaker's social/individual identity and emotional state. In the present work, we investigated to what extent two speakers converge towards each other with respect to variations in F0 in a scripted dialogue. Pairs of speakers jointly performed a speech production task, in which they were asked to alternately read aloud a written story divided into a sequence of short reading turns. We devised an experimental set-up that allowed us to manipulate the speakers' F0 in real time across turns. We found that speakers tended to imitate each other's changes in F0 across turns that were both limited in amplitude and spread over large temporal intervals. This shows that, at the perceptual level, speakers monitor slow-varying movements in their partner's F0 with high accuracy and, at the production level, that speakers exert a very fine-tuned control on their laryngeal vibrator in order to imitate these F0 variations. Remarkably, F0 convergence across turns was found to occur in spite of the large melodic variations typically associated with reading turns. Our study sheds new light on speakers' perceptual tracking of F0 in speech processing, and the impact of this perceptual tracking on speech production.


Vulnerability of Quebec drinking-water treatment plants to cyanotoxins in a climate change context.
Cyanobacteria are a growing concern in the province of Quebec due to recent highly publicised bloom episodes. The health risk associated with the consumption of drinking water coming from contaminated sources was unknown. A study was undertaken to evaluate treatment plants' capacity to treat cyanotoxins below the maximum recommended concentrations of 1.5 microg/L microcystin-LR (MC-LR) and the provisional concentration of 3.7 microg/L anatoxin-a, respectively. The results showed that close to 80% of the water treatment plants are presently able to treat the maximum historical concentration measured in Quebec (5.35 microg/L MC-LR equ.). An increase, due to climate change or other factors, would not represent a serious threat because chlorine, the most popular disinfectant, is effective in treating MC-LR under standard disinfection conditions. The highest concentration of anatoxin-a (2.3 microg/L) measured in natural water thus far in source water is below the current guideline for treated waters. However, higher concentrations of anatoxin-a would represent a significant challenge for the water industry as chlorine is not an efficient treatment option. The use of ozone, potassium permanganate or powder activated carbon would have to be considered.


Preparation and Sound Absorption Properties of a Barium Titanate/Nitrile Butadiene Rubber-Polyurethane Foam Composite with Multilayered Structure.
Barium titanate/nitrile butadiene rubber (BT/NBR) and polyurethane (PU) foam were combined to prepare a sound-absorbing material with an alternating multilayered structure. The effects of the cell size of PU foam and the alternating unit number on the sound absorption property of the material were investigated. The results show that the sound absorption efficiency at a low frequency increased when decreasing the cell size of PU foam layer. With the increasing of the alternating unit number, the material shows the sound absorption effect in a wider bandwidth of frequency. The BT/NBR-PU foam composites with alternating multilayered structure have an excellent sound absorption property at low frequency due to the organic combination of airflow resistivity, resonance absorption, and interface dissipation.


[The estradiol and estrone esters of [103Ru]ruthenocenecarboxylic acid. Synthesis, excretion and organ distribution (author's transl)].
The synthesis of the estradiol-17beta and estrone esters of ferrocenecarboxylic acid is described. The exchange reaction of these compounds with [103Ru]RuCl3 produced the corresponging [103Ru]ruthenocene compounds. The excretion and organ distribution of these estrogen esters in mice were quite different from those of [103Ru]ruthenocenecarboxylic acid and its methyl ester. The 103Ru-labelled estrogen esters are compared to 125I or 135I-labelled derivatives with respect to possible applications.


Molecular testing of chronic myeloid leukaemia in low resource areas.
Most cancer cases occur in areas of low resources. The diagnosis, treatment and monitoring of cancers is especially challenging in these locations. Unique partnerships exist between non-profit organisations and pharmaceutical companies to provide free drugs to CML patients throughout the world if the diagnosis can be rigorously and unambiguously established. But there lies the rub: How do you perform molecular diagnostics in areas where even electricity is unreliable? Here we describe the evolution of testing patients from low resource areas, which, when merged with a remarkable effort to bring tyrosine kinase inhibitors to patients across the globe, have led to survival outcomes similar to cases in industrialised countries.


Induction of light emission by luminescent bacteria treated with UV light and chemical mutagens.
Intensity of light emission by luminescent bacteria in response to UV irradiation and chemical mutagens was tested. We demonstrated that luminescence of six strains of marine bacteria (belonging to four species: Photobacterium leiognathi, P. phosphoreum, Vibrio fischeri and V. harveyi) is significantly increased by UV irradiation relatively shortly after dilution of cultures. Such a stimulation of luminescence was abolished in cells treated with chloramphenicol 15 min before UV irradiation, indicating that effective gene expression is necessary for UV-mediated induction of light emission. These results suggest that stimulation of luminescence in UV-irradiated bacterial cells may operate independently of the quorum sensing regulation. A significant induction of luminescence was also observed upon treatment of diluted cultures of all investigated strains with chemical mutagens: sodium azide (SA), 2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine x 2HCl (ICR-191), 4-nitro-o-phenylenediamine (NPD), 4-nitroquinolone-N-oxide (NQNO), 2-aminofluorene (2-AF), and benzo[alpha]pyrene. These results support the proposal that genes involved in bioluminescence belong to the SOS regulon. The use of bacterial luminescence systems in assays for detection of mutagenic compounds is discussed in the light of this proposal.


From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells.
The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs), was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine. Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.


Membrane-Active Thermoresponsive Block Copolymers Containing a Diacylglycerol-Based Segment: RAFT Synthesis, Doxorubicin Encapsulation, and Evaluation of Cytotoxicity against Breast Cancer Cells.
Herein, we report the formation of drug delivery systems from original thermoresponsive block copolymers containing lipid-based segments. Two acrylate monomers derived from palmitic- or oleic-acid-based diacylglycerols (DAGs) were synthesized and polymerized by the reversible addition-fragmentation chain transfer (RAFT) method. Well-defined DAG-based polymers with targeted molar masses and narrow molar mass distributions were next used as macro-chain transfer agents (macro-CTAs) for the polymerization of N-isopropylacrylamide (NIPAAm) or N-vinylcaprolactam (NVCL). The obtained amphiphilic block copolymers were formed into polymeric nanoparticles (PNPs) with and without encapsulated doxorubicin and characterized. Their biological assessment indicated appropriate cytocompatibility with the representatives of normal cells. Furthermore, compared to the free drug, increased cytotoxicity and apoptosis or necrosis induction in breast cancer cells was documented, including a highly aggressive and invasive triple-negative MDA-MB-231 cell line.


Analysis of physiological response to two virtual environments: driving and flying simulation.
As virtual reality technology continues to attract significant attention in clinical psychology, especially in the treatment of phobias, physiological monitoring is increasingly considered as an objective measurement tool for studying participants. There are few studies, however, of the normal physiological response to virtual environments or reactions to different virtual environments. The goal of this study is to analyze nonphobic participants' physiological reactions to two virtual environments: driving and flying. Eleven nonphobic participants were exposed to each virtual environment for 15 min. Heart rate, skin resistance, and skin temperature were measured during physiological monitoring, and the Presence and Simulator Sickness Questionnaire scores were obtained after each exposure. This study found that skin resistance and heart rate variability can be used to show arousal of participants exposed to the virtual environment experience and that such measures generally returned to normal over time. The data suggest that skin resistance and heart rate can be used as objective measures in monitoring the reaction of non-phobic participants to virtual environments. We also noted that heart rate variability could be useful for assessing the emotional states of participants.


Comparison of four electronic root canal length measurement devices.
The objective of this study is to evaluate the performance of four electronic root canal length measurement devices (ERCLMDs) [Root ZX, Raypex 6, ProPex II, and VDW Gold with ERCLMD] in wet and dry root canals with different major foramen diameters, in association with three file positions within the final 1 mm of canals. Fifty roots were divided into five groups that were instrumented apically to the terminus diameter using K-files 15, 20, 30, 40, and 60. ERCLMD measurements were made when the file tip was at major foramen, 0.5 mm and 1.0 mm short of the foramen, when the apex touched to the surface of saline or was immersed 3 mm into saline, and when the canal was dry or was irrigated with saline. The differences between the electronic lengths and the actual lengths were calculated. The data were analyzed using the three-, two-, and one-way ANOVA and the LSD test (p < .05). Overall, the four ERCLMDs demonstrated 12.8% unstable and beyond the foramen measurements (11.3%). About 85% of the beyond the foramen measurements had foramen diameters 0.40 and 0.60. ERCLMD comparisons related to the file positions in the foramen diameters showed significant differences between ERCLMDs in each foramen diameter (p < .05). All ERCLMDs provided highly accurate measurements within the final 1 mm of the foramen. Wet or dry canals and apex conditions did not adversely affect the accuracy of the ERCLMDs' readings. ProPex II located the file positions in the teeth with different foramen diameters more accurately than the other ERCLMDs.


Importance of radiobiological studies for the advancement of boron neutron capture therapy (BNCT).
Boron neutron capture therapy (BNCT) is a tumour selective particle radiotherapy, based on the administration of boron carriers incorporated preferentially by tumour cells, followed by irradiation with a thermal or epithermal neutron beam. BNCT clinical results to date show therapeutic efficacy, associated with an improvement in patient quality of life and prolonged survival. Translational research in adequate experimental models is necessary to optimise BNCT for different pathologies. This review recapitulates some examples of BNCT radiobiological studies for different pathologies and clinical scenarios, strategies to optimise boron targeting, enhance BNCT therapeutic effect and minimise radiotoxicity. It also describes the radiobiological mechanisms induced by BNCT, and the importance of the detection of biomarkers to monitor and predict the therapeutic efficacy and toxicity of BNCT alone or combined with other strategies. Besides, there is a brief comment on the introduction of accelerator-based neutron sources in BNCT. These sources would expand the clinical BNCT services to more patients, and would help to make BNCT a standard treatment modality for various types of cancer. Radiobiological BNCT studies have been of utmost importance to make progress in BNCT, being essential to design novel, safe and effective clinical BNCT protocols.


The prognostic impact of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patients with advanced colorectal cancer treated with first-line chemotherapy.
Colorectal cancer is the second most frequently diagnosed malignancy and one of the leading causes of cancer-related death in Poland. Many reports of different types of cancer have indicated that blood count parameters may serve as a source of prognostic or predictive information. To assess the association between these parameters and clinical outcome in patients with advanced colorectal cancer. We retrospectively analysed a database of 295 patients with advanced colorectal cancer treated with first-line palliative chemotherapy at our institution from January 2008 to December 2012. Blood-based parameters were measured before the first cycle of treatment. The median progression-free survival (PFS) was 6.7 months, and the median overall survival was 17.6 months. A high neutrophil-to-lymphocyte ratio (NLR) and a high platelet-to-lymphocyte ratio (PLR) were associated with a shorter survival (hazard ratio (HR): 1.88, p < 0.0001 for the NLR and HR: 1.39, p = 0.0054 for the PLR), but for the PLR, we observed only a not significant trend toward a worse PFS (HR = 1.25, p = 0.07 for the PLR and HR = 1.55, p = 0.0004 for the NLR). A high lymphocyte-to-monocyte ratio (LMR) was associated with a better prognosis (HR = 0.58, p ≤ 0.0001) and a longer PFS (HR = 0.73, p = 0.011). The blood-based parameters are readily available, reliable, and low-cost biomarkers, which can be easily incorporated into routine practice to predict the prognosis in patients with advanced colorectal cancer.


The correlation between Google trends and salmonellosis.
Salmonella infection (salmonellosis) is a common infectious disease leading to gastroenteritis, dehydration, uveitis, etc. Internet search is a new method to monitor the outbreak of infectious disease. An internet-based surveillance system using internet data is logistically advantageous and economical to show term-related diseases. In this study, we tried to determine the relationship between salmonellosis and Google Trends in the USA from January 2004 to December 2017. We downloaded the reported salmonellosis in the USA from the National Outbreak Reporting System (NORS) from January 2004 to December 2017. Additionally, we downloaded the Google search terms related to salmonellosis from Google Trends in the same period. Cross-correlation analysis and multiple regression analysis were conducted. The results showed that 6 Google Trends search terms appeared earlier than reported salmonellosis, 26 Google Trends search terms coincided with salmonellosis, and 16 Google Trends search terms appeared after salmonellosis were reported. When the search terms preceded outbreaks, "foods" (t = 2.927, P = 0.004) was a predictor of salmonellosis. When the search terms coincided with outbreaks, "hotel" (t = 1.854, P = 0.066), "poor sanitation" (t = 2.895, P = 0.004), "blueberries" (t = 2.441, P = 0.016), and "hypovolemic shock" (t = 2.001, P = 0.047) were predictors of salmonellosis. When the search terms appeared after outbreaks, "ice cream" (t = 3.077, P = 0.002) was the predictor of salmonellosis. Finally, we identified the most important indicators of Google Trends search terms, including "hotel" (t = 1.854, P = 0.066), "poor sanitation" (t = 2.895, P = 0.004), "blueberries" (t = 2.441, P = 0.016), and "hypovolemic shock" (t = 2.001, P = 0.047). In the future, the increased search activities of these terms might indicate the salmonellosis. We evaluated the related Google Trends search terms with salmonellosis and identified the most important predictors of salmonellosis outbreak.


G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers.
Expression levels of the chemokine receptor, CC chemokine receptor 5 (CCR5), at the cell surface determine cell susceptibility to HIV entry and infection. Cellular activation by CCR5 itself, but also by unrelated receptors leads to cross-phosphorylation and cross-internalization of CCR5. This study addresses the underlying molecular mechanisms of homologous and heterologous CCR5 regulation. As shown by bioluminescence resonance energy transfer experiments, CCR5 formed constitutive homo- as well as heterooligomeric complexes together with C5aR but not with the unrelated AT(1a)R in living cells. Stimulation with CCL5 of RBL cells, which co-expressed CCR5 together with an N-terminally truncated CCR5-DeltaNT mutant, resulted in both protein kinase C (PKC)- and G protein-coupled receptor (GPCR) kinase (GRK)-mediated cross-phosphorylation of the mutant unligated receptor, as determined by phosphosite-specific monoclonal antibody. Similarly, both PKC and GRK cross-phosphorylated CCR5 in a heterologous manner after C5a stimulation of RBL-CCR5/C5aR cells, whereas AT(1a)R stimulation resulted only in classical PKC-mediated CCR5 phosphorylation. Co-expression of CCR5-DeltaNT together with a phosphorylation-deficient CCR5 mutant that neither binds beta-arrestin nor undergoes internalization partially restored the CCL5-induced association of beta-arrestin with the homo-oligomeric receptor complex and augmented cellular uptake of (125)I-CCL5. Co-expression of C5aR, but not of AT(1a)R, promoted CCR5 co-internalization upon agonist stimulation by a mechanism independent of CCR5 phosphorylation. Co-internalization of phosphorylated CCR5 was also observed in C5a-stimulated macrophages. Finally, co-expression of a constitutively internalized C5aR-US28(CT) mutant led to intracellular accumulation of CCR5 in the absence of ligand stimulation. These results show that GRKs and beta-arrestin are involved in heterologous receptor regulation by cross-phosphorylating and co-internalizing unligated receptors within homo- or hetero-oligomeric protein complexes.


Primary care practitioners' detection of youth violence involvement.
Youth violence is a widespread public health problem. Despite recommendations to address youth violence by the American Academy of Pediatrics, it is unclear how often primary care practitioners (PCPs) do so. To determine PCPs' documentation of violence involvement. Children 11 to 17 years old were enrolled while attending a clinic. They completed questionnaires assessing violence involvement confidentially without the knowledge of the PCP. The primary outcome, documented reference to violence involvement, was determined by chart review. A total of 165 youth participated: mean age = 14.5 years (standard deviation = 1.7), 43% male, 46% white. In all, 14.5% of charts documented any violence involvement. Of the 20% of youth who reported serious violence involvement, PCPs documented violence issues 19.4% of the time. Factors associated with documentation included nonwhite race (P < .05), having public (or no) insurance (P < .001), visit type (routine checkup (P < .05), and clinic site (P < .001). PCPs infrequently document discussion of violence-related issues, specifically in youth who are demonstrating risk.


Stress MR imaging for evaluation of popliteal artery entrapment.
The popliteal artery entrapment (PAE) syndrome has been recognized as a cause of arterial occlusion in young people. It is the result of an anomaly of the relationship between the popliteal artery and the gastrocnemius muscle. Eight young health volunteers (16 legs) and six patients (10 legs) with suspected PAE underwent magnetic resonance (MR) imaging. Gradient-echo images were obtained in axial planes with the leg at rest and during active plantar flexion against resistance. Imaging at rest allowed identification of PAE signs in only one leg, which had an anomalous medial course of the popliteal artery. In the other cases, only the stress technique was able to show signal loss in the popliteal artery due to muscular compression (two legs) or the presence of accessory muscle slip around the vessel (two legs), as confirmed at surgery. MR imaging is therefore a useful technique for the diagnosis of PAE because of its capability of combining information obtainable with other modalities.


Effects of consumption of edible oils for a period of 4 months on the ultrastructure of the aorta of spontaneously hypertensive rats.
Edible oils have different effects on lipid profiles and on the propensity for producing lipid peroxidation products. These two properties of edible oils can affect arterial structure, ultimately leading to atherosclerosis. Hypertension is said to be a predisposing factor for atherosclerosis and can accelerate its process. This paper investigates the effects of three edible oils, namely soya bean oil, palm oil and ghee, on the ultrastructure of the aortas of spontaneously hypertensive rats at the end of a 4 month feeding period. It was found that ghee produced significant structural changes to the aortic wall when compared with palm oil or soya bean oil, and that no noticeable structural differences were seen to occur on the aortas of the palm oil-fed and soya bean oil-fed groups of rats. This study suggests that the consumption of ghee, rather than palm or soya bean oil, is more likely to lead to the development of atherosclerosis.


Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1.
Leukocyte functional antigen 1 (LFA-1), with intercellular adhesion molecule ligands, mediates T cell adhesion, but the signaling pathways and functional effects imparted by LFA-1 are unclear. Here, intracellular phosphoprotein staining with 13-dimensional flow cytometry showed that LFA-1 activation induced phosphorylation of the beta(2) integrin chain and release of Jun-activating binding protein 1 (JAB-1), and mediated signaling of kinase Erk1/2 through cytohesin-1. Dominant negatives of both JAB-1 and cytohesin-1 inhibited interleukin 2 production and impaired T helper type 1 differentiation. LFA-1 stimulation lowered the threshold of T cell activation. Thus, LFA-1 signaling contributes to T cell activation and effects T cell differentiation.


Extramedullary plasmacytoma of the nasal cavity and ethmoidal sinus in human immunodeficiency virus-positive patient.
Extramedullary plasmacytoma (EMP) occurring in the nose and paranasal sinus regions are rare with a male preponderance in the fifth and seventh decades of life. We report a case of EMP of the nasal cavity and ethmoid sinus in a 28-year-old female with human immunodeficiency virus infection.


New phenylpropenoids, bis(1-phenylethyl)phenols, bisquinolinone alkaloid, and anti-inflammatory constituents from Zanthoxylum integrifoliolum.
Five new compounds, including two new phenylpropenoids, (R,E)-1-[4-(3-hydroxyprop-1-enyl)phenoxy]-3-methylbutane-2,3-diol (1) and 4-hydroxy-3-(3-methyl-2-butenyl)cinnamyl alcohol (2), two new bis(1-phenylethyl)phenols, 2,6-bis(1-phenylethyl)phenol (3) and 2,4-bis(1-phenylethyl)phenol (4), and a new bisquinolinone alkaloid, 18-demethylparaensidimerin C (5), together with 17 known compounds have been isolated from the stem wood of Zanthoxylum integrifoliolum. The structures of these new compounds were determined through spectral analyses including extensive 2D nuclear magnetic resonance data. Among the isolates, N-methylflindersine (7), (-)-simulanol (10), and evofolin-C (16) exhibited potent inhibition against N-formylmethionylleucylphenylalanine-induced superoxide production with IC(50) values less than 12 microM.


Current and future treatments of alopecia areata and trichotillomania in children.
Treatment options for hair disorders are generally very limited. These options are even more limited in children due to the lack of trials and clinical research. Moreover, physicians are sometimes scared to treat children with drugs without safety data, especially because most hair disorders are benign. The objective of this paper is to review current and future treatments for alopecia areata and trichotillomania, two disorders that are sometimes encountered in differential diagnosis or even occur together and probably affect the mental condition of the patient involved more than others. Hair disorders are very stressful in paediatric population. Both physicians and families are often unsatisfied leading to non-compliance. New drugs with less side- effects are needed to increase the percentage of cure. It is also crucial to refine genetic studies on alopecia areata in order to identify new potential drugs worth studying. Moreover, studies on trichotillomania should not be evaluated only by psychiatrics, but also by dermatologists.


Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours.
Ellagitannins (ETs) from pomegranate juice (PJ) are reported to have numerous biological properties, but their absorption and metabolism in humans are poorly understood. To investigate the pharmacokinetics of pomegranate ETs, 18 healthy volunteers were given 180 mL of PJ concentrate, and blood samples were obtained for 6 h afterwards. Twenty-four-hour urine collections were obtained on the day before (-1), the day of (0), and the day after (+1) the study. Ellagic acid (EA) was detected in plasma of all subjects with a maximum concentration of 0.06 +/- 0.01 micromol/L, area under concentration time curve of 0.17 +/- 0.02 (micromol x h) x L(-1), time of maximum concentration of 0.98 +/- 0.06 h, and elimination half-life of 0.71 +/- 0.08 h. EA metabolites, including dimethylellagic acid glucuronide (DMEAG) and hydroxy-6H-benzopyran-6-one derivatives (urolithins), were also detected in plasma and urine in conjugated and free forms. DMEAG was found in the urine obtained from 15 of 18 subjects on d 0, but was not detected on d -1 or +1, demonstrating its potential as a biomarker of intake. Urolithin A-glucuronide was found in urine samples from 11 subjects on d 0 and in the urine from 16 subjects on d +1. Urolithin B-glucuronide was found in the urine of 3 subjects on d 0 and in the urine of 5 subjects on d +1. Urolithins, formed by intestinal bacteria, may contribute to the biological effects of PJ as they may persist in plasma and tissues and account for some of the health benefits noted after chronic PJ consumption. Whether genetic polymorphisms in EA-metabolizing enzymes (e.g., catechol-O-methyl transferase and glucuronosyl transferase) are related to variations in response to PJ remains to be established.


Transplantable adenocarcinomas from color-rectal tumors induced by infusion of N-methyl-N'-nitro-N-nitrosoguanidine in ACI/N rats.
Two transplantable strains of adenocarcinoma were established from the carcinomas of the colon and rectum induced by infusion of N-methyl-N'-nitro-N-nitrosoguanidine in inbred ACI/N rats, The tumors are solid type, not converted to ascite form yet, either papillary or tubulo-papillary adenocarcinomas, and particularly grow slowly, showing 2 to 4 months of survival in animals transplanted subcutaneously. Besides histological resemblance of the tumors to human adenocarcinoma of the large intestine, marked mucin production in tumor was noted in one of these strains.


[Management of endometrioma, recto-vaginal and bladder endometriosis].
Endometriosis is a frequent, benign, chronic disease associated with pain and/or infertility. Classically the lesions are found on the pelvic peritoneum, ovary (endometrioma), rectovaginal septum and bladder. Management of endometrioma has evolved over the last few years to individualised treatment. Indeed endometrioma cystectomy can decrease pain and the risk of recurrence but is also associated with a decrease in ovarian reserve. A multi-disciplinary team should manage recto-vaginal or bladder endometriosis. Surgical resection of these lesions must be as complete as possible and can be complex.


Muscular hypertrophy of the left diaphragmatic crus: an unusual cause of a paraspinal "mass".
We present a case of marked muscular hypertrophy of the muscular portion of the diaphragm and of the diaphragmatic crura in a professional opera singer. In this case the right and left crus each measured 20 mm in maximum thickness. The left crus, by nature of its vertical orientation in the sagittal plane, produced marked deviation of the inferior left paraspinal line near the diaphragm mimicking a retrocrural or paraspinal mass on the posteroanterior chest radiograph. The correct diagnosis was made by computed tomography. Muscular hypertrophy of the diaphragmatic crura should be included in the differential diagnosis of retrocrural or paraspinal masses at the level of the diaphragm.


Leflunomide for the treatment of rheumatoid arthritis and autoimmunity.
Leflunomide, a new oral immunomodulatory agent, is effective for the treatment of rheumatoid arthritis. Its mechanism of action in suppressing inflammation is based in its inhibition of dihydroorotate dehydrogenase, an enzyme responsible for de novo synthesis of pyrimidine containing ribonucleotides. It is the first disease-modifying antirheumatic drug approved for treatment of rheumatoid arthritis with an indication for retardation of joint damage by radiography. Side effects are generally mild and include diarrhea, rashes, reversible alopecia, and elevation of hepatic transaminases. Despite the concern about hepatotoxicity, combination use with methotrexate in treating patients with rheumatoid arthritis has been shown to be safe. Other autoimmune diseases in which leflunomide has been used successfully include Felty syndrome, vasculitis, Sjogren syndrome, Wegener granulomatosis, and bullous pemphigoid.


Insights into a Novel blaKPC-2-Encoding IncP-6 Plasmid Reveal Carbapenem-Resistance Circulation in Several Enterobacteriaceae Species from Wastewater and a Hospital Source in Spain.
Untreated wastewater, particularly from hospitals and other healthcare facilities, is considered to be a reservoir for multidrug-resistant bacteria. However, its role in the spread of antibiotic resistances in the human population remains poorly investigated. We used whole genome sequencing to analyze 25 KPC-2-producing Enterobacteriaceae isolates from sewage water collected during a 3-year period and three clinical Citrobacter freundii isolates from a tertiary hospital in the same collection area in Spain. We detected a common, recently described, IncP-6 plasmid carrying the gene blaKPC-2 in 21 isolates from both sources. The plasmid was present in diverse environmental bacterial species of opportunistic pathogens such as C. freundii, Enterobacter cloacae, Klebsiella oxytoca, and Raoultella ornithinolytica. The 40,186 bp IncP-6 plasmid encoded 52 coding sequences and was composed of three uniquely combined regions that were derived from other plasmids recently reported in different countries of South America. The region harboring the carbapenem resistance gene (14 kb) contained a Tn3 transposon disrupted by an ISApu-flanked element and the core sequence composed by ISKpn6/blaKPC-2/ΔblaTEM-1/ISKpn27. We document here the presence of a novel promiscuous blaKPC-2 plasmid circulating in environmental bacteria in wastewater and human populations.


Effect of intensive insulin therapy on progression of overt nephropathy in patients with type 1 diabetes mellitus.
To assess the effects of chronic (long-term) intermittent intravenous insulin therapy (CIIIT) on the progression of overt nephropathy in patients with type 1 diabetes mellitus. We undertook a retrospective longitudinal three-center study of 31 patients with type 1 diabetes mellitus and overt nephropathy, who were receiving intensive subcutaneous insulin therapy (four insulin injections daily) and weekly CIIIT. All study patients had follow-up consultations weekly for at least 12 months (mean duration, 37.0 +/- 4.6 months). Each patient had monthly hemoglobin A(1c) (by high-performance liquid chromatography) and semiannual creatinine clearance determinations. The hemoglobin A(1c) levels declined significantly from 8.6 +/- 0.6% to 7.6 +/- 0.3% (P = 0.0062) during the study period. The creatinine clearance remained essentially unchanged (from 46.1 +/- 3.0 mL/min per 1.73 m 2 at baseline to 46.0 +/- 3.9 mL/min per 1.73 m 2 at the end of the observation period, with an average annualized slope increase of 3.39 +/- 1.5 mL/min per year--no significant difference). The addition of CIIIT to intensive subcutaneous insulin therapy in patients with type 1 diabetes mellitus seems to arrest or appreciably reduce the progression of overt diabetic nephropathy, as well as substantially improve their glycemic control.


Management of primary Sjögren's syndrome: recent developments and new classification criteria.
For many years primary Sjögren's syndrome (pSS) has been considered an orphan disease, since no specific therapies were recognized as being capable of contrasting the development and progression of this disorder. The treatment of oral and ocular features, as well as of the systemic organ involvement, has been entrusted to the joint management of different subspecialty physicians, like ophthalmologists, otolaryngologists, dentists and rheumatologists. These latter subspecialty doctors are usually more involved in the treatment of systemic extraglandular involvement and, to do it, they have long been using the conventional therapies borrowed by the treatment schedules adopted in other systemic autoimmune diseases. The increasing knowledge of the biological pathways that are operative in patients with pSS, and the parallel development of molecular biology technology, have allowed the production and availability of a number of biological agents able to positively act on different disease mechanisms, and thus are candidates for testing in therapeutic trials. Meanwhile, the scientific community has made a great effort to develop new accurate and validated classification criteria and outcome measures to be applied in the selection of patients to be included and monitored in therapeutic studies. Some of the new-generation biotechnological agents have been tested in a number of open-label and randomized controlled trials that have produced in many cases inconclusive or contradictory results. Behind the differences in trial protocols, adopted outcome measures and predefined endpoints, reasons for such unsatisfactory results can be found in the large heterogeneity of clinical subtypes in the examined cohorts. The future challenge for a substantial advancement in the therapeutic approach to pSS could be to identify the pathologic mechanisms, outcome tools and biomarkers that characterize the different subsets of the disease in order to test carefully selected target therapies with the highest probability of success in each different clinical phenotype.


Distribution of targets for avian retrovirus DNA integration in vivo.
The targeting of DNA integration in retrovirus-infected cells is a central yet very poorly understood aspect of the biology of the virus. To investigate this problem, we have assessed the use of specific sites for integration targets of avian leukosis virus (ALV) DNA within defined regions of turkey embryo fibroblast (TEF) cellular DNA. For this purpose, we developed an assay of sufficient sensitivity and specificity to allow detection and location of single integration events in a population of 5 million cells. Targets selected for study were either regions cloned by virtue of a previous integration event or clones chosen at random from cellular DNA. By use of this approach, we found that all genomic regions tested contained integration targets, with a frequency that varied from approximately 0.2 to 4 times that expected for random integration. Within regions, the frequency of use of specific sites varied considerably, with some sites used up to 280 times random frequency. When one region was introduced into cells at moderately high copy number by transfection, it provided integration targets in a pattern very much like that seen with the same sequence in vitro. On the basis of our sampling, we conclude that most or all regions of the TEF genome are accessible to ALV retroviral integration. As with integration in vitro, integration specificity seems to be determined largely by local structural features rather than accessibility of specific regions.


ATP-dependent translocation of proteins along single-stranded DNA: models and methods of analysis of pre-steady state kinetics.
Processive DNA helicases are able to translocate along single-stranded DNA (ssDNA) with biased directionality in a nucleoside triphosphate-dependent reaction, although translocation is not generally sufficient for helicase activity. An understanding of the mechanism of protein translocation along ssDNA requires pre-steady state transient kinetic experiments. Although ensemble experimental approaches have been developed recently for the study of translocation of proteins along DNA, quantitative analysis of the complete time-courses from these experiments, which is needed to obtain quantitative estimates of translocation kinetic parameters (rate constants, processivity, step sizes and ATP coupling) has been lacking. We discuss three ensemble transient kinetic experiments that can be used to study protein translocation along ssDNA, along with the advantages and limitations of each approach. We further describe methods to analyze the complete kinetic time-courses obtained from such experiments performed with a series of ssDNA lengths under "single-round" conditions (i.e. in the absence of re-binding of dissociated protein to DNA). These analysis methods utilize a sequential "n-step" model for protein translocation along ssDNA and enable quantitative determinations of the rate constant, processivity and step size for translocation through global non-linear least-squares fitting of the full time-courses.


Evidence for temporal population replacement and the signature of ecological adaptation in a major Neotropical malaria vector in Amazonian Peru.
The major Neotropical malaria vector, Anopheles darlingi, was reintroduced into the Iquitos, Loreto, Peru area during the early 1990s, where it displaced other anophelines and caused a major malaria epidemic. Since then, case numbers in Loreto have fluctuated, but annual increases have been reported since 2012. The population genetic structure of An. darlingi sampled before and after the introduction of long-lasting insecticidal nets (LLINs) was investigated to test the hypothesis of temporal population change (2006 vs. 2012). Current samples of An. darlingi were used to test the hypothesis of ecological adaptation to human modified (highway) compared with wild (riverine) habitat, linked to forest cover. In total, 693 An. darlingi from nine localities in Loreto, Peru area were genotyped using 13 microsatellite loci. To test the hypothesis of habitat differentiation in An. darlingi biting time patterns, HBR and EIR, four collections of An. darlingi from five localities (two riverine and three highway) were analysed. Analyses of microsatellite loci from seven (2006) and nine settlements (2012-2014) in the Iquitos area detected two distinctive populations with little overlap, although it is unclear whether this population replacement event is associated with LLIN distribution or climate. Within the 2012-2014 population two admixed subpopulations, A and B, were differentiated by habitat, with B significantly overrepresented in highway, and both in near-equal proportions in riverine. Both subpopulations had a signature of expansion and there was moderate genetic differentiation between them. Habitat and forest cover level had significant effects on HBR, such that Plasmodium transmission risk, as measured by EIR, in peridomestic riverine settlements was threefold higher than in peridomestic highway settlements. HBR was directly associated with available host biomass rather than forest cover. A population replacement event occurred between 2006 and 2012-2014, concurrently with LLIN distribution and a moderate El Niño event, and prior to an increase in malaria incidence. The likely drivers of this replacement cannot be determined with current data. The present-day An. darlingi population is composed of two highly admixed subpopulations, which appear to be in an early stage of differentiation, triggered by anthropogenic alterations to local habitat.


Application of Composite Hydrogels to Control Physical Properties in Tissue Engineering and Regenerative Medicine.
The development of biomaterials for the restoration of the normal tissue structure⁻function relationship in pathological conditions as well as acute and chronic injury is an area of intense investigation. More recently, the use of tailored or composite hydrogels for tissue engineering and regenerative medicine has sought to bridge the gap between natural tissues and applied biomaterials more clearly. By applying traditional concepts in engineering composites, these hydrogels represent hierarchical structured materials that translate more closely the key guiding principles required for improved recovery of tissue architecture and functional behavior, including physical, mass transport, and biological properties. For tissue-engineering scaffolds in general, and more specifically in composite hydrogel materials, each of these properties provide unique qualities that are essential for proper augmentation and repair following disease and injury. The broad focus of this review is on physical properties in particular, static and dynamic mechanical properties provided by composite hydrogel materials and their link to native tissue architecture and, ultimately, tissue-specific applications for composite hydrogels.


Comparison of epicardial vs. endocardial reimplantation in pacemaker-dependent patients with device infection.
Reimplantation of cardiac implantable electronic devices (CIEDs) after extraction due to device infection is a major issue in pacemaker-dependent patients. We compared in-hospital and long-term outcomes with two techniques: epicardial reimplantation (EPI) before CIED extraction and temporary pacing (TP) with a view to delayed endocardial reimplantation. Two cohorts of consecutive pacemaker-dependent patients who underwent transvenous lead extraction at our tertiary centre were included in this retrospective cohort study. According to successive policies, either the EPI or the TP approach was used. In-hospital complications occurred at similar rates in the EPI (n = 59) and TP (n = 52) cohorts (37.3% vs. 32.7%, respectively; P = 0.61). Thirteen (25.0%) patients in the TP cohort eventually were reimplanted epicardially, mainly because of infection of the temporary lead. Finally, 65 patients were discharged with an epicardial device and 37 with an endocardial device. Median follow-up was 41.7 (interquartile range 34.1-51.5) months. No difference was observed in long-term mortality according to the reimplantation strategy, but use of TP was associated with a reduced risk of late endocarditis and device reintervention (hazard ratio (HR) 0.25, 95% confidence interval (CI) 0.09-0.069, P = 0.01), whereas epicardial device reimplantation was associated with an increased risk (HR 3.62, 95% CI 1.07-12.21, P = 0.04). We observed similar in-hospital outcomes in our EPI and TP cohorts. Twenty-five percent of the patients initially paced by a TP strategy finally needed an epicardial device, mainly because of infection of their TP lead. Use of TP resulted in lower rates of late endocarditis and device reintervention.


New amorphous hole blocking materials for high efficiency OLEDs.
Two new amorphous molecular materials, 2,5-bis(2',5'-dimethyl-4-triphenylsilyl-phenyl)-[1,3,4]oxadiazole (BDTSO) and 2,5-bis(2',5'-dimethyl-4-triphenylsilyl-phenyl)-[1,3,4]thiadiazole (BDTST) were synthesized and investigated as hole blocking materials (HBM) for organic light-emitting diodes. The efficiency of electroluminescent device was improved by using BDTSO instead of BAlq. The current and power efficiency of the device using BDTSO as HBM is 39.6 cd/A and 13.1 lm/W at 10 mA/cm2, respectively, which is higher compared to the same values for devices using BDTST and BAq which are typically used as HBM.


The predicted primary structure of the peplomer protein E2 of the porcine coronavirus transmissible gastroenteritis virus.
The complete nucleotide sequence of cloned cDNAs containing the E2 glycoprotein-encoding region of the genome of transmissible gastroenteritis virus (TGEV) has been determined. A single large translatable frame of 4.3 kb starting at 8.2 kb from the 3' end of the genome was identified. Its deduced amino acid sequence contains the characteristic features of a coronavirus peplomer protein: the precursor polypeptide of TGEV E2 is 1447 residues long (i.e. 285 longer than the avian infectious bronchitis coronavirus spike protein); partial N-terminal sequencing demonstrated that a putative secretory signal sequence of 16 amino acids is absent in the virion-associated protein; the predicted mol. wt. of the apoprotein is 158K; most of the 32 potential N-glycosylation sites available in the sequence are presumed to be functional to account for the difference between this and the experimentally determined value (200K to 220K); a typical hydrophobic sequence near the C terminus is likely to be responsible for anchoring the peplomer to the virion envelope.


Use of classification regression tree in predicting oral absorption in humans.
The purpose of this study is to explore the use of classification regression trees (CART) in predicting, in the dose-independent range, the fraction dose absorbed in humans. Since the results from clinical formulations in humans were used for training the model, a hypothetical state of drug molecules already dissolved in the intestinal fluid was adopted. Therefore, the molecular attributes affecting dissolution were not considered in the model. As a result, the model projects the highest achievable fraction dose absorbed, providing a reference point for manipulating the formulations or solid states to optimize oral clinical efficacy. A set of approximately 1260 structures and their human oral pharmacokinetic data, including bioavailability and/or absorption and/or radio-labeled studies, were used, with 899 compounds as the training set and 362 the test set. The numerical range of the fraction dose absorbed, 0 to 1, was divided into 6 classes with each class having a size of approximately 0.16. A set of 28 structural descriptors was used for modeling oral absorption without considering active transport. Then, a separate branch was created for modeling oral absorption involving active transport. The AAE of the training set was 0.12 and those of five test sets ranged from 0.17 to 0.2. In terms of classification, two test sets of unpublished, proprietary compounds showed 79% to 86% prediction when the predicted values fallen within +/- one class of real values were considered predicted. Overall, the computational errors from all the test sets of diverse structures were similar and reasonably acceptable. As compared to artificial membranes for ranking drug absorption potential, prediction by the CART model is considered fast and reasonably accurate for accelerating drug discovery. One can not only improve continuously the accuracy of CART computations by expanding the chemical space of the training set but also calculate the statistical errors associated with individual decision paths resulting from the training set to determine whether to accept individual computations of any test sets.


Patient satisfaction constructs.
The purpose of this paper is to examine the five-factor structure of patients' satisfaction constructs toward private healthcare service providers. This research is a cross-sectional study. A questionnaire-based survey was conducted with previous and current Bangladeshi patients. Exploratory factor analysis was employed to extract the underlying constructs. Five underlying dimensions that play a significant role in structuring the satisfaction perceived by Bangladeshi private healthcare patients are identified in this study. Practical implications - The main contribution of this study is identifying the dimensions of satisfaction perceived by Bangladeshi patients regarding private healthcare service providers. Healthcare managers adopt the five identified underlying construct items in their business practices to improve their respective healthcare efficiency while ensuring overall customer satisfaction.


QUANTITATIVE ANALYSIS OF THE POTENTIAL ROLE OF BASAL CELL HYPERPLASIA IN THE RELATIONSHIP BETWEEN CLONAL EXPANSION AND RADON CONCENTRATION.
Applying the two-stage clonal expansion model to epidemiology of lung cancer among uranium miners, it has been revealed that radon acts as a promoting agent facilitating the clonal expansion of already mutated cells. Clonal expansion rate increases non-linearly by radon concentration showing a plateau above a given exposure rate. The underlying mechanisms remain unclear. Earlier we proposed that progenitor cell hyperplasia may be induced upon chronic radon exposure. The objective of the present study is to test whether the induction of hyperplasia may provide a quantitative explanation for the plateau in clonal expansion rate. For this purpose, computational epithelium models were prepared with different number of basal cells. Cell nucleus hits were computed by an own-developed Monte-Carlo code. Surviving fractions were estimated based on the number of cell nucleus hits. Cell division rate was computed supposing equilibrium between cell death and cell division. It was also supposed that clonal expansion rate is proportional to cell division rate, and therefore the relative increase in cell division rate and clonal expansion rate are the same functions of exposure rate. While the simulation results highly depend on model parameters with high uncertainty, a parameter set has been found resulting in a cell division rate-exposure rate relationship corresponding to the plateau in clonal expansion rate. Due to the high uncertainty of the applied parameters, however, further studies are required to decide whether the induction of hyperplasia is responsible for the non-linear increase in clonal expansion rate or not. Nevertheless, the present study exemplifies how computational modelling can contribute to the integration of observational and experimental radiation protection research.


[Bacteriological and clinical studies of biapenem (L-627) in pediatrics].
Bacteriological and clinical studies in the pediatric field have been performed on biapenem (L-627), a newly-developed carbapenem antibiotic, and the following results were obtained. 1. In the pharmacokinetic study, the plasma concentration of L-627 showed dose-dependant change: Cmax was 14.6 micrograms/ml and AUC was 15.4 micrograms.hr/ml with the administration of 6 mg/kg, while Cmax was 49.2 micrograms/ml and AUC was 60.1 micrograms.hr/ml with the administration of 12 mg/kg. After the administration of 6 mg/kg, the urinary concentration reached maximum within 2 hours and the cumulative urinary excretion rate in the first 6 hours was 49.4%. 2. Antibacterial activities of L-627 against 27 strains of clinical isolates were determined. MICs of L-627 against such Gram-positive cocci as Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes were sufficiently low, and those against such Gram-negative rods as Haemophilus influenzae, Escherichia coli and Bordetella pertussis were satisfactory and as low as those of imipenem or ceftazidime. 3. Clinical efficacies of L-627 were evaluated in 36 cases of bacterial infections. The overall efficacy rate was 100%, and excellent responses in 26 cases and good in 10 cases were obtained. As for bacteriological efficacies, all strains except 1 of B. pertussis were eradicated and a high eradication rate of 96.6% was obtained. 4. No side effects were observed in 37 evaluated cases. As abnormal laboratory test results, eosinophilia was noted in 2 cases (5.4%), but they returned to normal values rapidly after the drug was discontinued. From these results, it has been concluded that L-627 is a safe and effective drug to be used in treatment of pediatric infectious diseases.


Perforator topography of the deep inferior epigastric perforator flap in 100 cases of breast reconstruction.
The anatomic topography of the perforators within the rectus muscle and the anterior fascia largely determines the time needed to harvest the perforator free flap and the difficulty of the procedure. In 100 consecutive cases, the topographic patterns of the perforators were investigated. In 65 percent, a short intramuscular course was seen. In 16 percent, a perforator at the tendinous intersection was encountered. In 9 percent, the largest perforator was found to have a long intramuscular course. In 5 percent, a subfascial course was found, and in another 5 percent, a paramedian course was found. In 74 percent of flaps, just one perforator was used, whereas two perforators were dissected in 20 percent. Only in 6 percent of flaps were three perforators used. A long intramuscular course (>4 cm) lengthens the dissection substantially, especially when the intramuscular course is in a step-wise pattern. The subfascial course requires precarious attention at the early stage of the perforator dissection when splitting the fascia. The perforators at the tendinous intersections are the most accessible and require a short but intense dissection in the fibrotic tissue of intersection. A paramedian perforator, medial to the rectus muscle, is a septocutaneous rather than a musculocutaneous perforator. The straightforward dissection almost extends up to the midline. Therefore, dissection always is performed at one side and, if no good perforators are present, continued at the intact contralateral side. The size of these perforators and their location in the flap determine the choice. One perforator with significant flow can perfuse the whole flap. If in doubt, two perforators can be harvested, especially if they show a linear anatomy so that muscle fibers can be split. The only interference with the muscle exists in splitting the muscle fibers. A perforator that lies in the middle of the flap is preferable. For a large flap, a perforator of the medial row provides better perfusion to zone 4 than one of the lateral row because of the extra choke vessel for the lateral row perforators. The clinical appearance of the perforators is the key element in the dissection of the perforator flap. Perforator topography determines the overall length and difficulty of the procedure.


Characterizing the Antimicrobial Activity of N2,N4-Disubstituted Quinazoline-2,4-Diamines toward Multidrug-Resistant Acinetobacter baumannii.
We previously reported a series of N2,N4-disubstituted quinazoline-2,4-diamines as dihydrofolate reductase inhibitors with potent in vitro and in vivo antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. In this work, we extended our previous study to the Gram-negative pathogen Acinetobacter baumannii We determined that optimized N2,N4-disubstituted quinazoline-2,4-diamines are strongly antibacterial against multidrug-resistant A. baumannii strains when the 6-position is replaced with a halide or an alkyl substituent. Such agents display potent antibacterial activity, with MICs as low as 0.5 μM, while proving to be strongly bactericidal. Interestingly, these compounds also possess the potential for antibiofilm activity, eradicating 90% of cells within a biofilm at or near MICs. Using serial passage assays, we observed a limited capacity for the development of resistance toward these molecules (4-fold increase in MIC) compared to existing folic acid synthesis inhibitors, such as trimethoprim (64-fold increase) and sulfamethoxazole (128-fold increase). We also identified limited toxicity toward human cells, with 50% lethal doses (LD50s) of ≤23 μM for lead agents 4 and 5. Finally, we demonstrated that our lead agents have excellent in vivo efficacy, with lead agent 5 proving more efficacious than tigecycline in a murine model of A. baumannii infection (90% survival versus 66%), despite being used at a lower dose (2 versus 30 mg kg-1). Together, our results demonstrate that N2,N4-disubstituted quinazoline-2,4-diamines have strong antimicrobial and antibiofilm activities against both Gram-positive organisms and Gram-negative pathogens, suggesting strong potential for their development as antibacterial agents.


Postnatal care service utilization and its determinants in East Gojjam Zone, Northwest Ethiopia: A mixed-method study.
The days and weeks after childbirth are crucial for both the mother and her newborn child leading for the majority of maternal and perinatal mortalities. The World Health Organization recommends at least three postnatal visits within 42 days after birth. However, postnatal care utilization remains low worldwide. Quantitative findings revealed low utilization of postnatal care in Ethiopia, however, no study explored the barriers for postnatal care. This study aimed to assess the barriers to postnatal care service utilization in East Gojjam Zone, Northwest Ethiopia. A community-based, mixed type cross-sectional study was conducted from December 15, 2018, to February 15, 2019. The quantitative data was gathered using the interviewer-administered interviewing technique from 751 women who gave birth within one year prior to the study selected by multistage sampling. The qualitative data were collected from purposively sampled women, facility leaders, and health extension workers using in-depth interviews and focused group discussions. The quantitative and qualitative data were analyzed using logistic regression and by the thematic content analysis method, respectively. The study revealed that postnatal care service utilization was 34.6%. The odds of using PNC services were greater in women aged 25-34 years and used maternity waiting home. In contrast, women who were muslim religion followers, had normal or instrumental birth, not aware of the PNC services and whose partners were not supportive of the use of MCH services were less likely to use PNC services. According to the qualitative findings, lack of awareness, traditional beliefs and religious practices, distance and transportation, environmental exposure, and waiting time were identified as barriers to PNC service utilization. The study showed low utilization of PNC services in East Gojjam zone, northwest Ethiopia. Improvements in personal health education, in construction of relevant infrastructure, and to transport, are needed to remove or reduce barriers to PNC service use in East Gojjam Zone, Northwest Ethiopia.


The Phospholipid N-Methyltransferase and Phosphatidylcholine Synthase Pathways and the ChoXWV Choline Uptake System Involved in Phosphatidylcholine Synthesis Are Widely Conserved in Most, but Not All Brucella Species.
The brucellae are facultative intracellular bacteria with a cell envelope rich in phosphatidylcholine (PC). PC is abundant in eukaryotes but rare in prokaryotes, and it has been proposed that Brucella uses PC to mimic eukaryotic-like features and avoid innate immune responses in the host. Two PC synthesis pathways are known in prokaryotes: the PmtA-catalyzed trimethylation of phosphatidylethanolamine and the direct linkage of choline to CDP-diacylglycerol catalyzed by the PC synthase Pcs. Previous studies have reported that B. abortus and B. melitensis possess non-functional PmtAs and that PC is synthesized exclusively via Pcs in these strains. A putative choline transporter ChoXWV has also been linked to PC synthesis in B. abortus. Here, we report that Pcs and Pmt pathways are active in B. suis biovar 2 and that a bioinformatics analysis of Brucella genomes suggests that PmtA is only inactivated in B. abortus and B. melitensis strains. We also show that ChoXWV is active in B. suis biovar 2 and conserved in all brucellae except B. canis and B. inopinata. Unexpectedly, the experimentally verified ChoXWV dysfunction in B. canis did not abrogate PC synthesis in a PmtA-deficient mutant, which suggests the presence of an unknown mechanism for obtaining choline for the Pcs pathway in Brucella. We also found that ChoXWV dysfunction did not cause attenuation in B. suis biovar 2. The results of these studies are discussed with respect to the proposed role of PC in Brucella virulence and how differential use of the Pmt and Pcs pathways may influence the interactions of these bacteria with their mammalian hosts.


A central role of nucleosomes in lupus nephritis.
Lupus nephritis is characterized by the presence of subendothelial and subepithelial immune complexes and thickening of the glomerular basement membranes (GBM). Electron-dense structures (EDS) in mesangium and GBM have been demonstrated to constitute target structures for nephritogenic autoantibodies in vivo. Whether these antibodies bind nucleosomal antigens within the EDS or cross-react with components of the GBM has not been resolved. Data recently published point at intra-GBM-associated nucleosomes as target for the nephritogenic autoantibodies. Colocalization IEM has demonstrated that autoantibodies and experimental antibodies against DNA, histones, or transcription factors like TATA box-binding protein colocalize in the EDS. By using terminal transferase in situ nick-end labeling in combination with immune electron microscopy to detect DNA specifically in human and murine SLE kidneys, we were able to detect DNA within the EDS of nephritic glomeruli that corresponded with the detected autoantibodies.


Association of kallistatin with carotid intima-media thickness in women with polycystic ovary syndrome.
Kallistatin is a secreted protein that acts as a tissue kallikrein inhibitor. It has anti-inflammatory, antioxidant and vasoprotective properties. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with low-grade chronic inflammation and multiple risk factors for cardiovascular diseases. The aims of this study were to ascertain whether circulating kallistatin levels are altered in women with PCOS, and whether there is an association between kallistatin and carotid intima-media thickness (cIMT) as well as inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). This cross-sectional study included 75 women with PCOS and 75 age- and BMI-matched controls without PCOS. Circulating kallistatin and TNF-α levels were measured using ELISA. Metabolic and hormonal parameters, hs-CRP levels and cIMT were also determined. All subjects underwent the 2-hour oral glucose tolerance test (2-h OGTT). Circulating kallistatin levels were significantly elevated in women with PCOS compared to controls (6.31±2.09 vs. 4.79±2.26 ng/mL, P<0.001). Inflammatory markers hs-CRP and TNF-α were found to be elevated in women with PCOS. Kallistatin levels positively correlated with insulin, insulin resistance index (HOMA-IR), free androgen index, hs-CRP, TNF-α and cIMT in both PCOS and control groups. Kallistatin levels did not show correlation with BMI, blood pressure, fasting blood glucose, 2-h OGTT or HbA1c. Multiple linear regression analysis revealed that kallistatin is an independent predictor for cIMT (β=0.131, 95% CI: 0.114-0.150, P=0.019). Kallistatin levels may provide useful information regarding cardiovascular risk in women with PCOS.


Characterizing growth and carcass composition differences in pigs with varying weaning weights and postweaning performance.
The unprecedented increase in litter size over the last decade has led to a perceived increase in the number of fallback pigs (Sus scrofa). However, there is little peer-reviewed data available regarding the biological differences between fallback pigs and their normal cohorts. Therefore, the objective of this experiment was to identify differences in the biology and physiology, and thus the growth and metabolism, between pigs with varying weaning weights (WW) and postweaning performance. To accomplish this objective, a total of 120 barrows (PIC C22/C29 × 337) were used in growth and comparative slaughter experiments. Pigs were selected from a population of 960 weanling pigs to represent the 10% lightest, median, and heaviest pigs at weaning (n = 40 pigs per WW category). Eight pigs from each WW category were harvested on d 5 postweaning as the initial slaughter group (ISG). The remaining 96 barrows were housed in individual crates, fed ad libitum quantities of a common diet during a 27-d growth study, and were harvested on d 33 or 34 postweaning. After the completion of the live animal component of the experiment, pigs within each WW category were further stratified into the slowest, median, or fastest 33% ADG categories. This resulted in a total of 9 treatments in a nested design. Fallback pigs were designated as those belonging to the slowest ADG category from either the lightest or median WW categories. Data were analyzed using the GLIMMIX procedure of SAS with the fixed effects of WW category and WW(ADG). Although feed intake was maximized (P < 0.0001) by WW(ADG) category, feed efficiency was not different (P = 0.30). When equalized per unit of BW, WW(ADG) category greatly affected (P < 0.02) eviscerated carcass, organ, and metabolic BW, but not (P = 0.28) empty BW. There were no differences (P > 0.12) in tissue nutrient concentrations, ratios, or energy content among pigs in the growth experiment. All tissue deposition rates, which were calculated as the difference between tissue nutrient concentrations of the growth experiment and initial slaughter groups, were maximized (P < 0.0002) by WW(ADG), even when equalized per unit of BW. In conclusion, WW and ADG affect tissue accretion rates, but not feed efficiency or carcass composition in nursery pigs.


SARS-CoV-2 epidemic after social and economic reopening in three US states reveals shifts in age structure and clinical characteristics.
In the United States, state-level re-openings in spring 2020 presented an opportunity for the resurgence of SARS-CoV-2 transmission. One important question during this time was whether human contact and mixing patterns could increase gradually without increasing viral transmission, the rationale being that new mixing patterns would likely be associated with improved distancing, masking, and hygiene practices. A second key question to follow during this time was whether clinical characteristics of the epidemic would improve after the initial surge of cases. Here, we analyze age-structured case, hospitalization, and death time series from three states - Rhode Island, Massachusetts, and Pennsylvania - that had successful re-openings in May 2020 without summer waves of infection. Using a Bayesian inference framework on eleven daily data streams and flexible daily population contact parameters, we show that population-average mixing rates dropped by >50% during the lockdown period in March/April, and that the correlation between overall population mobility and transmission-capable mobility was broken in May as these states partially re-opened. We estimate the reporting rates (fraction of symptomatic cases reporting to health system) at 96.0% (RI), 72.1% (MA), and 75.5% (PA); in Rhode Island, when accounting for cases caught through general-population screening programs, the reporting rate estimate is 94.5%. We show that elderly individuals were less able to reduce contacts during the lockdown period when compared to younger individuals. Attack rate estimates through August 31 2020 are 6.4% (95% CI: 5.8% ‒ 7.3%) of the total population infected for Rhode Island, 5.7% (95% CI: 5.0% ‒ 6.8%) in Massachusetts, and 3.7% (95% CI: 3.1% ‒ 4.5%) in Pennsylvania, with some validation available through published seroprevalence studies. Infection fatality rates (IFR) estimates for the spring epidemic are higher in our analysis (>2%) than previously reported values, likely resulting from the epidemics in these three states affecting the most vulnerable sub-populations, especially the most vulnerable of the ≥80 age group.


Structural and biochemical analyses indicate that a bacterial persulfide dioxygenase-rhodanese fusion protein functions in sulfur assimilation.
Hydrogen sulfide (H2S) is a signaling molecule that is toxic at elevated concentrations. In eukaryotes, it is cleared via a mitochondrial sulfide oxidation pathway, which comprises sulfide quinone oxidoreductase, persulfide dioxygenase (PDO), rhodanese, and sulfite oxidase and converts H2S to thiosulfate and sulfate. Natural fusions between the non-heme iron containing PDO and rhodanese, a thiol sulfurtransferase, exist in some bacteria. However, little is known about the role of the PDO-rhodanese fusion (PRF) proteins in sulfur metabolism. Herein, we report the kinetic properties and the crystal structure of a PRF from the Gram-negative endophytic bacterium Burkholderia phytofirmans The crystal structures of wild-type PRF and a sulfurtransferase-inactivated C314S mutant with and without glutathione were determined at 1.8, 2.4, and 2.7 Å resolution, respectively. We found that the two active sites are distant and do not show evidence of direct communication. The B. phytofirmans PRF exhibited robust PDO activity and preferentially catalyzed sulfur transfer in the direction of thiosulfate to sulfite and glutathione persulfide; sulfur transfer in the reverse direction was detectable only under limited turnover conditions. Together with the kinetic data, our bioinformatics analysis reveals that B. phytofirmans PRF is poised to metabolize thiosulfate to sulfite in a sulfur assimilation pathway rather than in sulfide stress response as seen, for example, with the Staphylococcus aureus PRF or sulfide oxidation and disposal as observed with the homologous mammalian proteins.


Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate.
The protein XTC-MIF, a Xenopus homologue of activin A and a potent mesoderm-inducing factor, can induce responding animal pole explants to form several different cell types in a dose-dependent manner, higher doses eliciting more dorso-anterior tissues. This graded response, characteristic of classically postulated morphogens, may underlie pattern formation, but the response of intact animal caps to XTC-MIF provides only a crude indication of trends. Here we report the effects of XTC-MIF on dispersed blastomeres rather than intact animal caps. Under these conditions, responding cells distinguish sharply between doses of pure XTC-MIF differing by less than 1.5-fold. Two different response thresholds have been found, defining three cell states. This suggests that XTC-MIF has an instructive effect. Notochord and muscle are both induced in the same narrow dose-range. Mixing treated with untreated cells does not seem to shift the dose thresholds, showing that at least some cells can stably record the received dose of inducing factor.


Effect of HIV aspartyl protease inhibitors on experimental infection with a cystogenic Me49 strain of Toxoplasma gondii.
Toxoplasmosis is a zoonotic disease of major significant perspectives in public health and veterinary medicine. So far, the available drugs control only the active infection, once the parasite encysts in the tissues, they lose their efficacy. Cytokines; IFN-γ and IL-10, play a critical role in the modulation of toxoplasmic encephalitis and neuro-inflammation in chronic toxoplasmosis. Antiretroviral protease inhibitors applied in the treatment of acquired immunodeficiency syndrome, revealed activity against multiple parasites. Aluvia (lopinavir/ritonavir) (L/R); an aspartyl protease inhibitor, had efficiently treated T. gondii RH strain infection. We investigated the potential activity of L/R against experimental T. gondii infection with a cystogenic Me49 strain in mice, considering the role of IFN-γ and IL-10 in the neuropathology versus pyrimethamine-sulfadiazine combination therapy. Three aluvia regimens were applied; starting on the day of infection (acute phase), 2-week PI (early chronic phase) and eight weeks PI (late chronic phase). L/R reduced the brain-tissue cyst burden significantly in all treatment regimens. It impaired the parasite infectivity markedly in the late chronic phase. Ultrastructural changes were detected in Toxoplasma cyst membrane and wall, bradyzoite membrane and nuclear envelope. The signs of bradyzoite paraptosis and cytoplasmic lipid droplets were observed. L/R had significantly reduced the brain-homogenate levels of IFN-γ and IL-10 in its three regimens however, they could not reach the normal level in chronic phases. Cerebral hypercellularity, perivascular inflammatory response, lymphoplasmacytic infiltrates and glial cellular reaction were ameliorated by L/R treatment. Herein, L/R was proved to possess promising preventive and therapeutic perspectives in chronic cerebral toxoplasmosis.


Central haemodynamics in different stages of hypertension.
Central and systemic haemodynamics were investigated in 53 juvenile hypertensives (JH) and in 43 older hypertensives aged over 30 (OH). The cardiac index at rest was significantly higher in JH, stage I and II according to the WHO, than in OH, stage I and II. Hyperkinetic circulation was present in systolic as well as in systolic-diastolic hypertension. Peripheral vascular resistance was at rest in JH relatively elevated (in relation to the given cardiac output) and normalized during heavy muscular work. In OH, peripheral vascular resistance was elevated at rest, but did not normalize during exercise. Mean and end-diastolic pulmonary artery pressure are at rest and during exercise higher in OH, regardless of the stage of hypertension, while in JH they are normal. Mean and diastolic pulmonary artery pressure correlate with systolic pressure in systemic circulation at rest and during exercise both in JH and in OH. In OH, left heart filling pressure is during exercise higher in patients with signs of ischaemic heart disease.


The situation in Eastern Europe.
The administrative structure for the management of patients with sexually transmitted disease is described. The association of dermatology and venerology had psychological advantages for patients attending a combined clinic, but because it was considered that the future development of venereology might suffer an Institute of Venereology has been founded in Poland. The functions of this Institute are described and the organization of undergraduate and postgraduate medical training is outlined.


Atheroprotective effects of statins in patients with unstable angina by regulating the blood-borne microRNA network.
Experimental studies have demonstrated several effects of statins in acute coronary syndrome (ACS) that may extend their clinical benefit beyond the lipid profile modification itself. However, the precise underlying mechanism remains to be elucidated. microRNAs (miRNAs) serve significant roles in the pathophysiology of atherosclerotic plaque progression. The present study investigated the protective role of statins in patients with unstable angina (UA) by regulating the circulating miRNA network. miRNA array results demonstrated that there were 21 differentially expressed miRNAs in non‑statin‑treated patients with UA (n=8) compared with non‑coronary artery disease controls (n=8), and 33 differentially expressed miRNAs in statin‑treated patients with UA (n=8) compared with non‑statin patients. TargetScan and miRanda programs were used to predict miRNAs target genes. miRNAs target genes in vascular endothelial cells and monocytes were clustered based on the CGAP SAGE library via the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform, and miRNA target genes in platelets were clustered based on a UP tissue‑specific library via the DAVID platform. The PANTHER database via DAVID platform was used to perform signaling pathway analysis. The miRNA‑gene/pathway network was visualized by Cytoscape software. Bioinformatic analysis suggested that statin‑induced miRNAs functions were primarily enriched in angiogenesis, integrin and platelet derived growth factor signaling pathways in UA patients. In endothelial cells and platelets, statin‑induced miRNAs primarily targeted the integrin signaling pathway, and in monocytes primarily targeted cytoskeletal regulation by the Rho GTPase signaling pathway. These results revealed that statins may serve systematic protective roles in UA patients by influencing the circulating miRNA regulatory network. Further studies are required to verify the functions of statin‑induced miRNAs in endothelial cells, platelets and monocytes.


Multicomponent T2 analysis of articular cartilage with synovial fluid partial volume correction.
To investigate the use of a three-pool model to account for the confounding effects of synovial fluid on multicomponent T2 analysis of articular cartilage using Multicomponent Driven Equilibrium Single Shot Observation of T1 and T2 (mcDESPOT). mcDESPOT was performed on the knee of eight asymptomatic volunteers and eight patients with osteoarthritis at 3.0T with multicomponent T2 maps created using the two-pool model and a three-pool model containing a nonexchanging synovial fluid water pool. The fraction of the fast-relaxing water component (FF ) and the T2 relaxation times for the fast-relaxing (T2F ) and slow-relaxing (T2S ) water components were measured in the superficial and deep layers of patellar cartilage using the two-pool and three-pool models in asymptomatic volunteers and patients with osteoarthritis and were compared using Wilcoxon signed rank tests. Within the superficial layer of patellar cartilage, FF was 22.5% and 25.6% for asymptomatic volunteers and 21.3% and 22.8% for patients with osteoarthritis when using the two-pool and three-pool models, respectively, while T2S was 73.9 msec and 62.0 msec for asymptomatic volunteers and 72.0 msec and 63.1 msec for patients with osteoarthritis when using the two-pool and three-pool models, respectively. For both asymptomatic volunteers and patients with osteoarthritis, the two-pool model provided significantly (P < 0.05) lower FF and higher T2S than the three-pool model, likely due to the effects of synovial fluid partial volume averaging. The effects of partial volume averaging between superficial cartilage and synovial fluid may result in biased multicomponent T2 measurements that can be corrected using an mcDESPOT three-pool model containing a nonexchanging synovial fluid water pool.


Nanoscale phase separation in DSPC-cholesterol systems.
The lipid arrangement of eukaryotic cell membranes has been shown to be heterogeneous, with domains enriched in cholesterol and saturated phospholipids, coexisting with a continuous phase that is enriched in unsaturated phospholipids. While the existence of these domains is well-established, there is still a lack of consensus regarding domain size and the factors influencing it. In this work, we investigate model membranes consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-cholesterol (Chol) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC, 18:1-16:0)-DSPC-Chol with a steady-state fluorescence assay and report the influence of phospholipid chain saturation and chain length on domain size. The spectral shifts of 1-myristoyl-2-[12-[(5-dimethylamino-1-naphthalenesulfonyl)amino]dodecanoyl]-sn-glycero-3-phosphocholine (DAN-PC) and a Förster resonance energy transfer (FRET) assay were used, along with an analytical model, to estimate domain sizes. A region of nanoscale domain existence was observed in both ternary systems; however, the domains formed in the system containing the asymmetric lipid (POPC, 18:1-16:0) were larger than those formed in the diunsaturated lipid (DOPC, 18:1-18:1). This is a new finding, as domains were not previously known to exist in similar POPC-based systems.


Management of Spinal Bone Metastases With Radiofrequency Ablation, Vertebral Reinforcement and Transpedicular Fixation: A Retrospective Single-Center Case Series.
Spine is a frequent site of bone metastases, with a 8.5 months median survival time after diagnosis. In most cases treatment is only palliative. Several advanced techniques can ensure a better Quality of Life (QoL) and increase life expectancy. Radiofrequency ablation (RFA) uses alternating current to produce local heating and necrosis of the spinal lesion, preserving the healthy bone. RFA is supported by vertebral reinforcement through kyphoplasty and vertebroplasty in order to stabilize the fracture with polymethylmethacrylate (PMMA) injection, restoring vertebral body height and reducing the weakness of healthy bone. The aim of this study is to demonstrate the efficacy and advantages of RFA plus vertebral reinforcement through PMMA vertebroplasty and fixation in patients affected by bone spinal metastases. We retrospectively analyzed 54 patients with thoraco-lumbar metastatic vertebral fractures admitted to our Unit between January 2014 and June 2020. Each patient underwent RFA followed by PMMA vertebroplasty and transpedicle fixation. We evaluated pain relief through the Visual Analogue Scale (VAS) Score and PMMA vertebral filling based on the mean Saliou filling score. Analysis of variance (ANOVA) was used to test pain relief with statistical significance for p<0.05. A total of 54 patients (median age 63,44 years; range 34-86 years), with a total of 63 infiltrated vertebrae, were treated with RFA, PMMA vertebroplasty and transpedicular screw fixation; average operative time was 60.4 min (range 51-72). The preoperative average VAS score decreased significantly from 7.81 to 2.50 (p < 0.05) after 12 months. Based on Saliou filling score, filling was satisfactory (12-18) in 20 vertebrae (31,7%), mediocre (6-11) in 33 vertebrae (52,4%), inadequate (0-5) in 10 vertebrae (15,9%). A consistent PMMA filling of vertebral bodies was successfully achieved with significant pain relief. Concomitant RFA, PMMA vertebroplasty and pedicle screw fixation represent a safe and effective technique for the management of spinal metastases, improving clinical outcome and pain control.


Fratricide: a forensic psychiatric perspective.
Analyses of fratricide rates based on national homicide data have provided some general information pertaining to offenders and victims of sibling homicide but are limited by data constraints to examining a few major variables. Exploring fratricide from a forensic psychiatric perspective could uncover other related factors and provide insight into why some individuals murder their siblings. In a retrospective study of data from coroners' files on domestic homicide pertaining to individuals killed by their siblings over a 10-year period in Quebec, Canada, we identified several specific offender and victim characteristics and circumstances surrounding offenses. The impact of mental illness and substance abuse on fratricidal behavior is indicated, underscoring the importance of identifying existing psychopathology. From a forensic psychiatric perspective, we identify characteristic patterns and discuss potential dynamics operating in fratricide. We raise some issues relevant to treatment and prevention, including the fact that most cases are alcohol-related, impulsive, and unpredictable until the moment they occur.


CONTRAST-TO-NOISE RATIO IS A USEFUL PREDICTOR OF EARLY DISPLACEMENT OF LARGE SUBMACULAR HEMORRHAGE BY INTRAVITREAL SF6 GAS INJECTION.
To investigate predictors of early displacement of submacular hemorrhage (SMH) by simple intravitreal SF6 gas injection. This retrospective study included 16 eyes of 16 consecutive patients (age: 74.5 ± 7.7 years; 15 men) with large SMH treated with simple intravitreal SF6 gas before inception of subretinal tissue plasminogen activator injection at our institution. The SMH displacement was graded at 1-week posttreatment as 0, 1, or 2. Central retinal thickness, central choroidal thickness, SMH height, SMH area, disease duration, use of anticoagulant or antiplatelet drugs, and contrast-to-noise ratio (CNR) of SMH on optical coherence tomography images were recorded. Correlations between displacement grading and baseline parameter were analyzed. Univariable correlation analysis revealed association of the 1-week displacement grading with the CNR (P = 0.004; r = -0.68) and SMH height (P = 0.03; r = -0.55). The CNR was most strongly associated with 1-week displacement on multivariable correlation analysis (P = 0.01; β = -0.60). Findings of the present study showed that the CNR of SMH was a useful predictor of early displacement of large SMH after simple intravitreal SF6 gas injection. When vitrectomy with subretinal injection of tissue plasminogen activator is difficult in patients with large SMH, with low CNR on optical coherence tomography, simple intravitreal SF6 gas injection may be a treatment option.


Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.
Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy. 171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS). Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho=0.361, p<0.001) with each other, while presenting significant differences across age groups (all p values<0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p=0.558) or after completion (p=0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p=0.487) or after (p=0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p=0.499; OS: p=0.220) or IGFBP-3 (DFI: p=0.900; OS: p=0.406) serum levels. IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer.


Abdominal Wall Evisceration Coupled With Iliac Vascular Injury After Blunt Trauma.
Abdominal evisceration after blunt trauma is uncommon and rarely survivable when coupled with a concomitant iliac vascular injury. Blunt abdominal injury is rarely a cause of abdominal evisceration but may, on occasion, present in patients affected by a unique or high-energy traumatic injury. In these instances, major vascular injury is exceedingly rare but is associated with a high mortality rate. Damage to important vessels that may present more subtly, such as iliac arterial injury, can still be lethal and are important to evaluate in the trauma workup for blunt evisceration. We report the case of a 20-year-old woman who survived an abdominal wall and vascular injury in a motor vehicle accident. Management of this unusual association is discussed.


Mechanical Characteristics, Testing, and Future Perspective of Nickel-Titanium Rotary Instruments.
The main drawback of several studies is the limited analysis performed for the comparison of nickel-titanium (NiTi) rotary systems. Most often, research articles in this area are focalized on the static characteristics such as static cyclic fatigue, torsional loads, and flexibility, not considering their reciprocal interaction and all dynamic factors.1 Recent evidence in the literature defines the reciprocal interaction between these parameters as a fundamental element in the study of their mechanical characteristics.2 However, static mechanical behavior is fundamental to assess the basic performance of NiTi instruments, but its interpretation during clinical practice is pointless as it does not resemble the real clinical scenario.1,3,4 Results arising from static tests, certainly valid as a first approach to the evaluation of an instrument recently introduced on the market, and comparative evaluations, should be considered in a general and more complete view, considering their reciprocal relationships.3-6 For these reasons, different types of researches that investigate both static and dynamic performance of NiTi instruments should be strongly recommended in order to give to original research and in vitro study an actual clinical significance, certainly much more indicative in view of a subsequent clinical application of NiTi rotary instruments.7-9.


Safe handling of hip replacement patients.
This article aims to promote understanding of the potential causes of dislocation in post-operative hip replacements as well as the dangers of back injury to nurses handling these patients. A questionnaire survey of orthopaedic surgeons revealed where practice could be changed from the traditional 'lift only' procedure in compliance with the new EC safety regulations for manual handling.


Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.
The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain) and two progenitor strains SHR-Lx (n = 13) and BXH2/Cub (n = 18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains.


Effects of relative humidity and spraying medium on UV decontamination of filters loaded with viral aerosols.
Although respirators and filters are designed to prevent the spread of pathogenic aerosols, a stockpile shortage is anticipated during the next flu pandemic. Contact transfer and reaerosolization of collected microbes from used respirators are also a concern. An option to address these potential problems is UV irradiation, which inactivates microbes by dimerizing thymine/uracil in nucleic acids. The objective of this study was to determine the effects of transmission mode and environmental conditions on decontamination efficiency by UV. In this study, filters were contaminated by different transmission pathways (droplet and aerosol) using three spraying media (deionized water [DI], beef extract [BE], and artificial saliva [AS]) under different humidity levels (30% [low relative humidity {LRH}], 60% [MRH], and 90% [HRH]). UV irradiation at constant intensity was applied for two time intervals at each relative humidity condition. The highest inactivation efficiency (IE), around 5.8 logs, was seen for DI aerosols containing MS2 on filters at LRH after applying a UV intensity of 1.0 mW/cm(2) for 30 min. The IE of droplets containing MS2 was lower than that of aerosols containing MS2. Absorption of UV by high water content and shielding of viruses near the center of the aggregate are considered responsible for this trend. Across the different media, IEs in AS and in BE were much lower than in DI for both aerosol and droplet transmission, indicating that solids present in AS and BE exhibited a protective effect. For particles sprayed in a protective medium, RH is not a significant parameter.


[Testicular cancer with inferior vena caval embolus causing pulmonary embolism following chemotherapy: a case report].
A 21-year-old male presented with right scrotal discomfort. Right high orchiectomy revealed non-seminoma and he was diagnosed with stage I non-seminoma. Since acute myeloid leukemia (AML) was diagnosed incidentally, no adjuvant therapy was given and he received chemotherapy for AML. One year later, he complained of lumbago and general malaise. Complete remission of AML had been achieved and bone marrow puncture revealed no signs of recurrence. Computed tomography showed retroperitoneal lymph node swelling, inferior vena caval embolus distal to the hepatic vein, and multiple lung nodules. Metastasis of testicular neoplasm was suspected and chemotherapy with Bleomycin, Etoposide, and Cisplatin was started. On the fourth day of chemotherapy, the patient complained of sudden dyspnea and acutely went into shock. Pulmonary embolism was diagnosed and an inferior vena cava filter was placed. Chemotherapy was continued for four courses and the tumor showed complete remission. He has been free of disease for 24 months. In rare cases of testicular cancer with inferior vena caval embolus, the physician should be aware of the possibility of causing pulmonary embolism after chemotherapy.