Prostatic carcinoma with abundant xanthomatous cytoplasm. Foamy gland carcinoma.
Foamy gland carcinoma, an unusual variant of prostate carcinoma, is characterized by abundant xanthomatous cytoplasm. We studied 38 needle biopsies in which at least one core contained cancer with >20% foamy morphology. On average, each cancer was 72% foamy, and 11 cancers were entirely foamy. In addition to the characteristic cytoplasm, 20 cases had abundant intraluminal dense pink amorphous secretions. Nuclear enlargement and prominent nucleoli were either absent of rare in 23 (61%) and 27 (71%) of foamy gland carcinomas, respectively. High-molecular-weight cyto-keratin stains were done in 20 cases; 19 foamy gland carcinomas were negative, confirming the diagnosis of carcinoma and one case had keratin staining inconsistent with a known benign pattern. Of the 27 cases with associated ordinary gland carcinoma on needle biopsy, 26 (96%) were Gleason sum greater than 4. Subsequent radical prostatectomy (RP) and transurethral resection demonstrating cancer were available in 17 cases. Of the 15 subsequent RPs, only five were organ-confined and only one was Gleason sum less than 5. The cancers in the RP group ranged from 1 to 90% foamy (mean, 39%). Foamy gland carcinoma must be recognized as carcinoma by its abundant foamy cytoplasm, its architectural pattern of crowded or infiltrative glands, and frequently present pink acellular secretions. The more typical features of adenocarcinoma, nuclear enlargement and prominent nucleoli, are frequently absent. Its relatively benign cytology makes this lesion difficult to recognize as carcinoma; 74% of our cases were seen in consultation. Despite its benign cytology, foamy gland carcinoma is best classified as intermediate-grade carcinoma.


Alterations in task-induced activity and resting-state fluctuations in visual and DMN areas revealed in long-term meditators.
Recently we proposed that the information contained in spontaneously emerging (resting-state) fluctuations may reflect individually unique neuro-cognitive traits. One prediction of this conjecture, termed the "spontaneous trait reactivation" (STR) hypothesis, is that resting-state activity patterns could be diagnostic of unique personalities, talents and life-styles of individuals. Long-term meditators could provide a unique experimental group to test this hypothesis. Using fMRI we found that, during resting-state, the amplitude of spontaneous fluctuations in long-term mindfulness meditation (MM) practitioners was enhanced in the visual cortex and significantly reduced in the DMN compared to naïve controls. Importantly, during a visual recognition memory task, the MM group showed heightened visual cortex responsivity, concomitant with weaker negative responses in Default Mode Network (DMN) areas. This effect was also reflected in the behavioral performance, where MM practitioners performed significantly faster than the control group. Thus, our results uncover opposite changes in the visual and default mode systems in long-term meditators which are revealed during both rest and task. The results support the STR hypothesis and extend it to the domain of local changes in the magnitude of the spontaneous fluctuations.


Menstruation Confounding the Correct Interpretation of 99m Tc-RBC Bleeding Scan.
99m Tc-RBC bleeding scan in a 17-year-old adolescent girl showed an increased focal activity in the pelvis. However, SPECT/CT showed that this activity was located in the uterus, which was considered a normal variant considering that the patient was in her fourth day of the menstrual period. Subsequent 99m TcO 4- Meckel scan showed the typical characteristic of ectopic gastric mucosa in the small bowel. Postsurgical pathology confirmed the diagnosis of ectopic gastric mucosa. This case suggested the menstrual period uterus should be included as differential diagnosis of 99m Tc-RBC scan.


Care choices in Europe: To Each According to His or Her Needs?
Growing long-term care (LTC) needs represent a major challenge for our aging societies. Understanding how utilization patterns of different types of care are influenced by LTC policies or changes in the population composition such as age patterns or health can provide helpful insight on how to adequately prepare for this situation. To this aim, this paper explores how individuals choose between different forms of LTC. We exploit variation between countries as well as between individuals within countries using data from the Survey of Health, Ageing, and Retirement in Europe (SHARE). Using nonlinear decomposition techniques, we break down the difference in utilization rates between countries into differences based on observed sociodemographic and need-related characteristics and differences in the impacts of these characteristics, which allows us to identify the drivers behind differences in the formal-informal care mix. Our results show that a substantial fraction of the observed country differences can be explained by differences in impacts. We argue that this is a result of the different incentives provided by the different LTC systems.


Mobile telemonitoring for arrhythmias in outpatients in the Republic of Georgia: a brief report of a pilot study.
As the very first trial of mobile telemedicine in the Republic of Georgia, in June-December 2010 we investigated 35 outpatients with different types of arrhythmia (male/female ratio=16/19; 12-80 years old), among them 5 patients with concomitant epilepsy. The control group comprised 7 clinically healthy sportsmen (soccer players, all men; 15-17 years old), during a 30-min velo ergometer stress test. A three-lead electrocardiogram (ECG) loop recorder (Vitaphone BT 3300; Vitasystems GmbH, Mannheim, Germany) was used in automatic mode, using special LRMA software (MDT, Lázně Bohdaneč, Czech Republic) and a Nokia (Espoo, Finland) model 6730 Symbian phone. Automatically recorded arrhythmia events were transmitted from the loop recorder by Bluetooth(®) (Bluetooth SIG, Inc., Kirkland, WA) to a phone and then by 3G (through our partner mobile operator, MagtiCom Ltd. [Tbilsi, Georgia]) to the Vitasystems server in Germany and were available to Georgian physicians via e-mail/Internet. Arrhythmias were recorded/monitored during 7-68 h of observation. The number of automatically recorded ECG events varied between 3 and 170 per observation, or 0.4-10.7 hourly. Cases of sinus brady- and tachyarrhythmia, sinus node weakness syndrome, atrial fibrillation, supraventricular tachycardia, supraventricular premature complexes, and ventricular premature complexes were correctly recognized by automatic recognition software and recorded. In 3 patients and 1 sportsman previously unspecified (despite multiple investigations), arrhythmias were recorded: paroxysmal tachycardia (n=1), sinus node weakness syndrome (n=1), and ventricular premature complexes (n=2). In 3 cases (all women) light insomnia and nervousness were reported. In 2 patients with neurosis (both elderly men, 1 with epilepsy) we had to stop investigation prematurely because of anxiety/agitation. Mobile telecardiology represents feasible methodology to monitor arrhythmias in outpatients in Georgia, promoting earlier discharge of non-life-threatening cases, improving patients' comfort of life, and increasing their mobility with enhanced safety. Mobile telehealth might also represent significant cost-saving for insurance companies (this is an ongoing study). Finally, in remote areas mobile telemonitoring of patients will improve quality of care by timely provision of a second opinion in cases when local expertise is not sufficient.


Where is emotional feeling felt in the body? An integrative review.
Contemporary research on "embodied emotion" emphasizes the role of the body in emotional feeling. The evidence base on interoception, arguably the most prominent strand of embodied emotion research, places emphasis on the cardiac, respiratory and gastrointestinal systems. In turn, interoception has evidence-based links with improved emotion regulation. Despite the focus on separate bodily systems, it is unclear whether particular interoceptive locations play a greater role in emotional feeling and emotion regulation. Further, according to Gross' "process model", the sooner that regulation of an emotion occurs, the better; hence, it is additionally important to identify the first body areas to activate. These issues are investigated in a two-stage integrative review. The first stage was preliminary, giving an overview of the evidence base to highlight the distribution of measured body areas. This indicated that 86% of publications (n = 88) measured cardiac activity, 26% measured the respiratory system, and six percent the gastrointestinal system. Given the emphasis placed on all three systems in interoception theory and research on emotion, this suggests a dearth of comprehensive findings pertaining to feeling locations. The second stage investigated the core issues of where emotional feelings are felt in the body and time-related implications for regulation. This was based on ten texts, which together suggested that the head, throat and chest are the most consistently detected locations across and within numerous emotional contexts. Caution is required, however, since-among other reasons discussed-measurement was not time-restricted in these latter publications, and direct physiological measurement was found in only a minority of cases.


The wounded blogger: analysis of narratives by women with breast cancer.
The purpose of this article is to analyse the representation of the body in seven blogs by Spanish women with breast cancer. Using both texts and images, we analyse how they reproduce modern and postmodern logic to represent the wounded body. Based on Frank's proposals, this article draws the conclusion that the women bloggers mainly reproduce the modern logic (characterised by the restitution narrative and a predictable, disassociated and monadic body), but there are elements which break with this logic (the quest narrative, the body presented as associated, dyadic and full of desire, and the acceptance of contingency). After applying Frank's categories, we suggest that the contemporary way of experiencing illness may question the clarity of the modern/postmodern divide.


Polyphenol Rich Extract of Garcinia pedunculata Fruit Attenuates the Hyperlipidemia Induced by High Fat Diet.
Fatty foods, the most common diet today are the crux of many metabolic disorders which need urgent attention. Garcinia pedunculata Roxb. (GP, Clusiaceae) is a plant found available in Northeast (NE) region of India, is considered to have versatile therapeutic properties. The people of this region has been using dried pulp of GP fruit for the treatment of different stomach related diseases traditionally. This study aimed at evaluating the potential therapeutic action of the polyphenol-rich methanolic extract of the fruit in experimental induced obese rats. In vitro antioxidant and antidiabetic activity of GP extracts, i.e., fruit extract (GF) and seed extract (GS) were determined by using various methods viz., 1,1-diphenyl-2 picrylhydrazyl (DPPH), 2,2'-Azinobis (3-ethyl benzthiazoline-6-sulphonic acid) (ABTS(•+)), nitroblue tetrazolium (NBT) and α-glucosidase inhibition assay for detection of antihyperglycemic activity. In vivo antilipidemic and antiobesity activities were evaluated by administrating oral dose of GF for 60 days on a high-fat diet (HFD) induced hyperlipidemia in the rat. GF showed higher antioxidant activity than GS by DPPH radical scavenging (IC50 = 4.01 μg/ml), ABTS(•+) (IC50 = 0.82 μg/ml), NBT (IC50 = 0.07 μg/ml) and also showed notable α-glucosidase inhibitory activity (IC50 = 19.26 μg/ml). Furthermore, GF treated rat revealed a reduction in the body weight (~60%), serum total cholesterol (33%), triglycerides (32%), low-density lipoprotein (38%) and liver biomarker enzymes after 60 days HFD fed animals. Simultaneously, GF supplementation significantly protected the HFD induced changes in hematological parameters. Histological observations clearly differentiate the structural changes in liver of HFD and GF treated group. This novel dietary lipid adsorbing agent of GF exhibited prevention of hyperlipidemia induced by HFD in the rat.


Probing the valence orbitals of transition metal-silicon diatomic anions: ZrSi, NbSi, MoSi, PdSi and WSi.
Evolution of electronic properties and the nature of bonding of the 4d-transition metal silicides (ZrSi, NbSi, MoSi and PdSi) are discussed, revealing interesting trends in the transition metal-silicon interactions across the period. The electronic properties of select transition metal silicide diatomics have been determined by anion photoelectron imaging spectroscopy and theoretical methods. The electron binding energy spectra and photoelectron angular distributions obtained by 2.33 eV (532 nm) photons have revealed the distinct features of these diatomics. The theoretical calculations were performed at the density functional theory (DFT) level using the unrestricted B3LYP hybrid functional and at the ab initio unrestricted coupled cluster singles and doubles (triplets) (UCCSD(T)) methods to assign the ground electronic states of the neutral and anionic diatomics. The excited electronic states were calculated by the DFT (TD-DFT)/UB3LYP method. We have observed that the valence molecular orbital configuration of the ZrSi and NbSi anions are significantly different from that of the MoSi and PdSi anions. By combining our experimental and theoretical results, we report that the composition of the highest occupied molecular orbitals shift from a majority of transition metal s- and d-orbital contribution in ZrSi and NbSi, to mainly silicon p-orbital contribution for MoSi and PdSi. We expect these observed atomic scale transition metal-silicon interactions to be of increasing importance with the miniaturization of devices approaching the sub-nanometer size regime.


Possible explanations for why some countries were harder hit by the pandemic influenza virus in 2009 - a global mortality impact modeling study.
A global pandemic mortality study found prominent regional mortality variations in 2009 for Influenza A(H1N1)pdm09. Our study attempts to identify factors that explain why the pandemic mortality burden was high in some countries and low in others. As a starting point, we identified possible risk factors worth investigating for Influenza A(H1N1)pdm09 mortality through a targeted literature search. We then used a modeling procedure (data simulations and regression models) to identify factors that could explain differences in respiratory mortality due to Influenza A(H1N1)pdm09. We ran sixteen models to produce robust results and draw conclusions. In order to assess the role of each factor in explaining differences in excess pandemic mortality, we calculated the reduction in between country variance, which can be viewed as an effect-size for each factor. The literature search identified 124 publications and 48 possible risk factors, of which we were able to identify 27 factors with appropriate global datasets. The modelling procedure indicated that age structure (explaining 40% of the mean between country variance), latitude (8%), influenza A and B viruses circulating during the pandemic (3-8%), influenza A and B viruses circulating during the preceding influenza season (2-6%), air pollution (pm10; 4%) and the prevalence of other infections (HIV and TB) (4-6%) were factors that explained differences in mortality around the world. Healthcare expenditure, levels of obesity, the distribution of antivirals, and air travel did not explain global pandemic mortality differences. Our study found that countries with a large proportion of young persons had higher pandemic mortality rates in 2009. The co-circulation of influenza viruses during the pandemic and the circulation of influenza viruses during the preceding season were also associated with pandemic mortality rates. We found that real time assessments of 2009 pandemic mortality risk factors (e.g. obesity) probably led to a number of false positive findings.


KI-catalyzed arylation of benzothiazoles from the coupling of aryl aldehydes with benzothiazoles in neat water.
A KI-catalyzed oxidative coupling of benzothiazoles with aryl aldehydes has been developed using TBHP as an oxidant in neat water under metal free conditions. Various 2-aryl benzothiazoles were prepared in 36-79% yields for 28 examples. The mechanistic studies suggested that this transformation proceeded via a radical process.


Metabolism of methanol by Rhodopseudomonas acidophila.
Rhodopseudomonas acidophila strain 10050, grown anaerobically in the light on methanol, contained a methanol and formaldehyde dehydrogenase which could be coupled to phenazine methosulphate; an NAD-linked formaldehyde dehydrogenase which required GSH for activity; and an NAD-linked formate dehydrogenase. The specific activities of these enzymes varied in a non-coordinate manner when the organism was grown on different alcohols, formate or succinate. The affinity of the phenazine methosulphate linked methanol dehydrogenase for methanol was increased 10-fold if the cell-free extract was prepared and assayed in the absence of oxygen. Pulse-labelling experiments with [14C5methanol and [14C]bicarbonate indicated that fixation of carbon dioxide occurred via the ribulose diphosphate cycle and C3 + CO 2 fixation reaction(s). No evidence was obtained for operation of a reduced C1 fixation sequence. This conclusion was borne out by the enzyme content of cell-free extracts of the organism.


Patients' views of routine quality of life assessment following a diagnosis of early-stage non-small cell lung cancer.
There is an increasing interest in the quality of life (QoL) evaluation following video-assisted thoracoscopic anatomical lung resection or stereotactic ablative body radiotherapy for early-stage non-small-cell lung cancer (NSCLC). A qualitative interview study was conducted to gain insight into the optimal methods of assessing and discussing QoL in clinical practice. A prospective observational longitudinal study of patients with early-stage NSCLC was conducted where repeated QoL measures were administered either online or on paper. A subset of participants was invited for qualitative interviews after the 6-month assessment or at the end of the study. The semi-structured interviews were transcribed verbatim and thematically analysed. Twenty-three patients were interviewed. Generally, patients were content with recruitment and data collection procedures. Most opted to complete the assessments on paper instead of online; this choice was influenced by the level of technology literacy. Some found the questionnaires too generic to reflect their experiences. Barriers to questionnaire completion were mostly practical, and many acknowledged benefits of QoL assessment including allowing them to express problems and health issues, and following changes over time. Generally, participants would like to discuss QoL results during clinical consultations, but reported this rarely happened. Lung cancer patient interviews confirm the acceptability of repeated QoL assessments, but online data capture is limited. Patients highlight the importance of discussing QoL aspects with their clinical team. Future strategies are needed to optimize the routine collection of patient-reported outcomes in clinical practice.


Pre-registration diploma students: a quantitative study of entry characteristics and course outcomes.
Nurse education has been transformed over the last decade and continuing change is likely. Nurse educators are responsible for meeting the quality assurance standards of local stakeholders and student retention and progress are important aspects of this process. As part of a monitoring exercise, an enquiry was set up to review pre-registration selection and recruitment strategies and to establish if there were any significant relationships between the characteristics of pre-registration diploma entrants and their academic achievement or completion rates. A multi-factorial tree-based technique was used for this purpose. This is one of the first British studies to consider both academic performance and completion rates for pre-registration diploma students. Four cohorts (N = 355) were studied. There was marked heterogeneity in student characteristics with a wide age distribution, a significant proportion of mature entrants with previous care experience, and considerable diversity in terms of education. Education and age were significant predictors of academic achievement: entrants with a minimum of two A levels and mature women with recent study experience did particularly well. Younger recruits with modest educational qualifications on entry performed less well in their assessments of theoretical knowledge. Younger students tended to leave more regularly, and well-qualified entrants showed a greater tendency to complete, although these relationships were not statistically significant. Multi-factorial analysis demonstrated that organisational and course characteristics have a conjoint influence on course outcomes. Although the study is concerned with Project 2000 in the United Kingdom, there are lessons to be drawn concerning the selection and support of non-traditional recruits into nursing.


Blocking agents of Ca2+-activated K+ channels in cultured medullary thick ascending limb cells.
Ca2+-activated K+ channels with estimated single channel conductances of 127 +/- 2 pS were identified in the apical cell membrane of clone A3 of cultured medullary thick ascending limb (MTAL) cells. Both Ba2+ and the scorpion toxin, charybdotoxin (CTX), are slow blockers of the channels. An application of 0.1 microM Ba2+ to the intracellular face caused a 50% reduction in fractional open time (fv). Ba2+ block is both concentration and voltage dependent. Concentrations of CTX as low as 2 nM in the extracellular solution caused a significant reduction in fv. Tetraethylammonium (TEA) and quinine are fast blockers of Ca2+-activated K+ channels in MTAL cells. TEA, 400 microM, in the extracellular solution caused a voltage-dependent reduction in channel amplitude, whereas it takes 10 mM in the intracellular solution to reduce channel amplitude by 30%. Micromolar amounts of quinine applied to the intracellular face caused the channels to flicker rapidly between open and blocked states. These results suggest that K+ channels in MTAL cells are homologous to those found in muscle cells, and that these blocking agents may be used to probe the nature of K+ conductances in several nephron segments.


Regional organisational audit of district departments of public health.
Organisational audit of public health in the United Kingdom is rare. To provide a framework for a structured organisational audit in district public health departments in one region organisational factors contributing to efficient, high quality work were identified and compared between districts, enabling each department to identify its organisational strengths and weaknesses. A draft list of organisational factors, based on the King's Fund organisational audit programme, were rated by 52 public health physicians and trainees in 12 district public health departments in South East Thames region for their importance on a scale of 0 (not relevant) to 5 (vital). Factors with average ratings of > 4, judged to be "vital" and proxies for standards, were then used to compare each district's actual performance, as reported by its director of public health in a self reported questionnaire. In all, 37 responses were received to the rating questionnaire (response rate 71%) and 12 responses to the directors' questionnaire. Of the 54 factors identified as vital factors, 20(37%) were achieved in all 12 districts and 16(30%) in all but one district; 18 were not being achieved by two (33%) districts or more. Overall, vital factors were not being achieved in 9% of cases. The authors concluded that most departments are achieving most vital organisational factors most of the time, but improvement is still possible. The results have been used as a basis for planning the organisation of public health departments in several of the newly formed commissioning agencies. This was the first regional audit of public health of its kind performed in the region and it provided valuable experience for planning future regional audit activity.


Autotaxin and LPA1 and LPA5 receptors exert disparate functions in tumor cells versus the host tissue microenvironment in melanoma invasion and metastasis.
Autotaxin (ENPP2/ATX) and lysophosphatidic acid (LPA) receptors represent two key players in regulating cancer progression. The present study sought to understand the mechanistic role of LPA G protein-coupled receptors (GPCR), not only in the tumor cells but also in stromal cells of the tumor microenvironment. B16F10 melanoma cells predominantly express LPA5 and LPA2 receptors but lack LPA1. LPA dose dependently inhibited invasion of cells across a Matrigel layer. RNAi-mediated knockdown of LPA5 relieved the inhibitory effect of LPA on invasion without affecting basal invasion. This suggests that LPA5 exerts an anti-invasive action in melanoma cells in response to LPA. In addition, both siRNA-mediated knockdown and pharmacologic inhibition of LPA2 reduced the basal rate invasion. Unexpectedly, when probing the role of this GPCR in host tissues, it was found that the incidence of melanoma-derived lung metastasis was greatly reduced in LPA5 knockout (KO) mice compared with wild-type (WT) mice. LPA1-KO but not LPA2-KO mice also showed diminished melanoma-derived lung metastasis, suggesting that host LPA1 and LPA5 receptors play critical roles in the seeding of metastasis. The decrease in tumor cell residence in the lungs of LPA1-KO and LPA5-KO animals was apparent 24 hours after injection. However, KO of LPA1, LPA2, or LPA5 did not affect the subcutaneous growth of melanoma tumors. These findings suggest that tumor and stromal LPA receptors, in particular LPA1 and LPA5, play different roles in invasion and the seeding of metastasis.


[Early hearing loss detection by otoemissions. Analysis of the results in 200 consecutive children reviewed].
We present a retrospective study of 200 consecutive children explored in our hospital between november 2005 and april 2006, as a part of the protocole or program of early identification hearing loss stablished several years ago in our Comunity. In case of suspected hypoacusia after performing otoacoustic emissions, children must be sent to PEATC 3 months later.


Liposomes embedded with differentiating factors as a new strategy for enhancing DPSC osteogenic commitment.
Human dental pulp stem cell (DPSC) differentiation toward the osteoblastic phenotype is enhanced when culture media are supplemented with differentiating factors, i.e. ascorbic acid, β-glycerophosphate and dexamethasone. Liposomes, spherical vesicles formed by a phospholipid bilayer, are frequently used as carriers for drugs, growth factors and hydrophobic molecules. The aim of this work was to speed up DPSC commitment to the osteogenic lineage by embedding differentiating factors within liposomes. Firstly, liposomes were prepared by rehydrating a phospholipidic thin film and characterised in terms of dimensions. Secondly, liposome-exposed DPSCs were characterised by their immunophenotypic profile. Levels of CD90 were significantly decreased in the presence of liposomes filled with ascorbic acid, β-glycerophosphate and dexamethasone (Lipo-Mix) with respect to normal differentiation medium (DM), while CD73 and CD29 expression were enhanced, suggesting osteogenic commitment. Additionally, an appreciable extracellular matrix deposition is detected. Thirdly, the Lipo-Mix formulation better increases alkaline phosphatase activity and levels of Collagen I secretion with respect to DM. In parallel, the new liposome formulation is capable of decreasing the release of H2O2 and of triggering a precocious antioxidant cell response, redressing the redox balance required upon mesenchymal stem cell commitment to osteogenesis. It can be therefore hypothesised that Lipo-Mix could represent a suitable tool for clinical regenerative purposes in the field of tissue engineering by speeding up DPSC osteogenic commitment, mineralised matrix deposition and remodelling.


Molecular Insight into Binding Behavior of Caffeine with Lactoferrin: Spectroscopic, Molecular Docking, and Simulation Study.
The majority of bioactive substances in the human diet come from polyphenols. Here, we use spectroscopy, molecular docking, molecular dynamics simulations, and in vitro digestion to look at the relationship between caffeine (CAF) and bovine lactoferrin (BLF). The correlation analysis of the CAF-BLF fluorescence quenching process revealed that the reaction was spontaneous and that the CAF-BLF fluorescence quenching process may have been static. The predominant intrinsic binding forces were hydrogen bonds and van der Waals forces, which were also supported by molecular docking and molecular dynamics simulations. Through fourier infrared and circular dichroism spectroscopy experiments, it was found that CAF changed the secondary structure of BLF and might bind to the hydrophobic amino acids of BLF. Compared with BLF, CAF-BLF showed inhibitory effects on digestion in simulated in vitro digestion. It will be helpful to better understand the interaction between CAF and BLF and provide the basis for the development of innovative dairy products.


Surgical management of astigmatism with toric intraocular lenses.
Correction of corneal astigmatism is a key element of cataract surgery, since post-surgical residual astigmatism can compromise the patient's uncorrected visual acuity. Toric intraocular lenses (IOLs) compensate for corneal astigmatism at the time of surgery, correcting ocular astigmatism. They are a predictable treatment. However, accurate measurement of corneal astigmatism is mandatory for choosing the correct toric IOL power and for planning optimal alignment. When calculating the power of toric IOLs, it is important to consider anterior and posterior corneal astigmatism, along with the surgically induced astigmatism. Accurate toric lens alignment along the calculated meridian is also crucial to achieve effective astigmatism correction. There are several techniques to guide IOL alignment, including the traditional manual marking technique and automated systems based on anatomic and topographic landmarks. The aim of this review is to provide an overview on astigmatism management with toric IOLs, including relevant patient selection criteria, corneal astigmatism measurement, toric IOL power calculation, toric IOL alignment, clinical outcomes and complications.


Integrated Microarray and RNAseq Transcriptomic Analysis of Retinal Pigment Epithelium/Choroid in Age-Related Macular Degeneration.
We report for the first time an integrated transcriptomic analysis of RPE/choroid dysfunction in AMD (mixed stages) based on combining data from publicly available microarray (GSE29801) and RNAseq (GSE135092) datasets aimed at increasing the ability and power of detection of differentially expressed genes and AMD-associated pathways. The analysis approach employed an integrating quantitative method designed to eliminate bias among different transcriptomic studies. The analysis highlighted 764 meta-genes (366 downregulated and 398 upregulated) in macular AMD RPE/choroid and 445 meta-genes (244 downregulated and 201 upregulated) in non-macular AMD RPE/choroid. Of these, 731 genes were newly detected as differentially expressed (DE) genes in macular AMD RPE/choroid and 434 genes in non-macular AMD RPE/choroid compared with controls. Over-representation analysis of KEGG pathways associated with these DE genes mapped revealed two most significantly associated biological processes in macular RPE/choroid in AMD, namely the neuroactive ligand-receptor interaction pathway (represented by 30 DE genes) and the extracellular matrix-receptor interaction signaling pathway (represented by 12 DE genes). Furthermore, protein-protein interaction (PPI) network identified two central hub genes involved in the control of cell proliferation/differentiation processes, HDAC1 and CDK1. Overall, the analysis provided novel insights for broadening the exploration of AMD pathogenesis by extending the number of molecular determinants and functional pathways that underpin AMD-associated RPE/choroid dysfunction.


Gradient-type algorithms for partial singular value decomposition.
It is often desirable to calculate only a few terms of the SVD expansion of a matrix, corresponding to the largest or smallest singular values. Two algorithms, based on gradient and conjugate gradient search, are proposed for this purpose. SVD is computed term by term in a decreasing or increasing order of singular values. The algorithms are simple to implement and are especially advantageous with large matrices.


Development of additional autoimmune diseases in a population of patients with primary Sjögren's syndrome.
To investigate whether patients with primary Sjögren's syndrome (pSS) have an increased tendency to develop other autoimmune diseases. A retrospective case note review was carried out on 114 patients in whom a diagnosis of pSS had been made in a department of rheumatology from 1979 onwards. The year of diagnosis of pSS was recorded, plus the diagnosis and year of diagnosis of any other identified autoimmune disease. Of the 114 patients with pSS, seven (6%) were male and 107 (94%) female. Mean age at diagnosis of pSS was 53 years (range 21 to 83). Patients were followed up for an average of 10.5 years (range 0 to 23). Thirty eight patients (33.3%) were diagnosed as having another autoimmune disease, while nine (7.9%) had two or more. Thirteen additional autoimmune diseases were identified. Twenty five diagnoses (51.0%) were made before the diagnosis of pSS, three (6.1%) within the same year, and 21 (42.9%) after the diagnosis. Hypothyroidism was the most common autoimmune disease (n = 16). Although pSS is a relatively benign condition, affected individuals have an increased tendency to develop additional autoimmune diseases. Patients with pSS should be monitored on a regular basis for such diseases.


Anti-Inflammatory, Anti-Arthritic and Anti-Nociceptive Activities of Nigella sativa Oil in a Rat Model of Arthritis.
This study investigated the preventive efficacy of the crude oil extracted from Nigella sativa seeds in a rat model of arthritis induced by using complete Freund's adjuvant (CFA). Nigella sativa oil at 1.82 mL/kg or 0.91 mL/kg (corresponding to 1596 and 798 mg/kg, respectively) was orally administered for 25 days from the day of immunization. One immunized group was treated orally with indomethacin (3 mg/kg) as a reference drug. Body weight growth rate, paw swelling, arthritis score, mechanical allodynia, locomotor activity and anxiety-like behavior were observed, and the levels of Interleukin 6 (IL-6), C-reactive protein, albumin and total cholesterol in plasma were measured on days 15 and 25. Nigella sativa oil showed anti-inflammatory, anti-arthritic and anti-nociceptive activities that were significant as compared to untreated arthritic rats but less than indomethacin. These results indicated that Nigella sativa oil significantly attenuated adjuvant-arthritis in rats and the higher dose (1.82 mL/kg) prevented the development of arthritis with an inhibition of 56%.


Imaging high-energy electrons propagating in a crystal.
It has recently become possible to focus a beam of high-energy electrons to a spot smaller than an atom, with vast potential for the study of condensed matter. We devise an experiment that can image, with subangstrom resolution, the distribution of such an electron beam as it scatters within an atomic lattice. Our experiments reveal the acute sensitivity of the scattered electron distribution to 0.1 Å shifts of the impact point. Scattering due to plasmon excitations is also examined. Implications for the study of the atomic and electronic structure of condensed matter are discussed.


A case of cutaneous inflammatory myofibroblastic tumor.
Pseudo-inflammatory tumors are also known as plasma cell granuloma, inflammatory pseudo-tumor and inflammatory myofibroblastic tumor, and these tumors are a group of highly variable proliferations of myofibroblastic cells that are associated with a prominent inflammatory infiltrate. This tumor is known to most commonly occur in the lungs, bladder and gastrointestinal system with only a few cases having been reported in the skin. A previously healthy 26-year-old man presented with a 6-year history of an intermittently pruritic lesion on his back. On the histologic examination, there were spindle cells in fascicles and a mixed inflammatory cellular infiltrate of plasma cells and lymphocytes. A diagnosis of inflammatory fibroblastic tumor was made and the nodule was surgically removed. We report here on an additional case of this rare cutaneous entity, and it is probably the first such report from Korea.


Osmotic effects on feline spermatozoa from normospermic versus teratospermic donors.
Effects of osmolality stresses on the sperm of normospermic (>60% normal sperm/ejaculate) versus teratospermic (<40% normal sperm) domestic cats and the normospermic leopard cat and the teratospermic clouded leopard were studied. Spermatozoa were exposed to various anisotonic solutions in a single step or returned to near isotonic conditions in a single step after exposure to anisotonic solutions. The percentage of sperm motility was measured subjectively, and dual fluorescent stains were used to assess membrane integrity by flow cytometry. The percentage of sperm motility declined (P < 0.05) in domestic cat sperm exposed to osmolalities <200 and >450 mOsm. Spermatozoa from all felines underwent marked (P < 0.05) membrane disruption following a hypotonic stress, but sperm from teratospermic donors experienced greater (P < 0.05) membrane disruption in response to decreased osmolality. While feline spermatozoa appeared to be highly resistant to hypertonic (600, 1200, and 2400 mOsm) conditions, with >85% of the cells maintaining intact membranes, severe membrane disruption occurred when cells were returned to isotonicity in a single step. There was no difference (P > 0.05) between a 1- and 5-min exposure to various anisotonic solutions. Similarly, sperm from normospermic and teratospermic domestic cats responded identically after exposure to ionic or nonionic solute. Results demonstrate that: (1) spermatozoa from teratospermic males are more vulnerable to a hypotonic stress than sperm from normospermic counterparts; (2) in response to small deviations in osmolality, feline sperm experience a more rapid decline in motility than membrane integrity; and (3) an abrupt return to isotonicity after a hypertonic stress causes extensive sperm membrane damage regardless of ejaculate quality.


Massive scrotal edema as a complication of abdominoplasty.
Massive scrotal edema is an unreported complication of abdominoplasty. This patient's postoperative decompensation of medial thigh and scrotal lymphatic return may well have been due to an occult lymphedema tarda or previously compromised lymphatics from the fibrosis of venous stasis disease and obesity.


Building the capacity of public health programmes to become data rich, information rich and action rich.
Good quality, timely data are the cornerstone of health systems, but in many countries these data are not used for evidence-informed decision making and/or for improving public health. The SORT IT (Structured Operational Research and Training Initiative) model has, over 8 years, trained health workers in low- and middle-income countries to use data to answer important public health questions by taking research projects through to completion and publication in national or international journals. The D2P (data to policy) training initiative is relatively new, and it teaches health workers how to apply 'decision analysis' and develop policy briefs for policy makers: this includes description of a problem and the available evidence, quantitative comparisons of policy options that take into account predicted health and economic impacts, and political and feasibility assessments. Policies adopted from evidence-based information generated through the SORT IT and D2P approaches can be evaluated to assess their impact, and the cycle repeated to identify and resolve new public health problems. Ministries of Health could benefit from this twin-training approach to make themselves 'data rich, information rich and action rich', and thereby use routinely collected data in a synergistic manner to improve public health policy making and health care delivery.


Structural analyses of covalent enzyme-substrate analog complexes reveal strengths and limitations of de novo enzyme design.
We report the cocrystal structures of a computationally designed and experimentally optimized retro-aldol enzyme with covalently bound substrate analogs. The structure with a covalently bound mechanism-based inhibitor is similar to, but not identical with, the design model, with an RMSD of 1.4 Å over active-site residues and equivalent substrate atoms. As in the design model, the binding pocket orients the substrate through hydrophobic interactions with the naphthyl moiety such that the oxygen atoms analogous to the carbinolamine and β-hydroxyl oxygens are positioned near a network of bound waters. However, there are differences between the design model and the structure: the orientation of the naphthyl group and the conformation of the catalytic lysine are slightly different; the bound water network appears to be more extensive; and the bound substrate analog exhibits more conformational heterogeneity than typical native enzyme-inhibitor complexes. Alanine scanning of the active-site residues shows that both the catalytic lysine and the residues around the binding pocket for the substrate naphthyl group make critical contributions to catalysis. Mutating the set of water-coordinating residues also significantly reduces catalytic activity. The crystal structure of the enzyme with a smaller substrate analog that lacks naphthyl ring shows the catalytic lysine to be more flexible than in the naphthyl-substrate complex; increased preorganization of the active site would likely improve catalysis. The covalently bound complex structures and mutagenesis data highlight the strengths and weaknesses of the de novo enzyme design strategy.


Investigating the effect of compression on solute transport through degrading municipal solid waste.
The effect of applied compression on the nature of liquid flow and hence the movement of contaminants within municipal solid waste was examined by means of thirteen tracer tests conducted on five separate waste samples. The conservative nature of bromide, lithium and deuterium tracers was evaluated and linked to the presence of degradation in the sample. Lithium and deuterium tracers were non-conservative in the presence of degradation, whereas the bromide remained effectively conservative under all conditions. Solute diffusion times into and out of less mobile blocks of waste were compared for each test under the assumption of dominantly dual-porosity flow. Despite the fact that hydraulic conductivity changed strongly with applied stress, the block diffusion times were found to be much less sensitive to compression. A simple conceptual model, whereby flow is dominated by sub-parallel low permeability obstructions which define predominantly horizontally aligned less mobile zones, is able to explain this result. Compression tends to narrow the gap between the obstructions, but not significantly alter the horizontal length scale. Irrespective of knowledge of the true flow pattern, these results show that simple models of solute flushing from landfill which do not include depth dependent changes in solute transport parameters are justified.


Barriers to contraceptive access after health care reform: experiences of young adults in Massachusetts.
To explore how Massachusetts' 2006 health insurance reforms affected access to sexual and reproductive health (SRH) services for young adults. We conducted 11 focus group discussions across Massachusetts with 89 women and men aged 18 to 26 in 2009. Most young adults' primary interaction with the health system was for contraceptive and other SRH services, although they knew little about these services. Overall, health insurance literacy was low. Parents were primary decision makers in health insurance choices or assisted their adult children in choosing a plan. Ten percent of our sample was uninsured at the time of the discussion; a lack of knowledge about provisions in Chapter 58 rather than calculated risk analysis characterized periods of uninsurance. The dynamics of being transitionally uninsured, moving between health plans, and moving from a location defined by insurance companies as the coverage area limited consistent access to contraception. Notably, staying on parents' insurance through extended dependency, a provision unique to the post-reform context, had implications for confidentiality and access. Young adults' access to and utilization of contraceptive services in the post-reform period were challenged by unanticipated barriers related to information and privacy. The experience in Massachusetts offers instructive lessons for the implementation of national health care reform. Young adult-targeted efforts should address the challenges of health service utilization unique to this population.


Estrogen Receptor, Inflammatory, and FOXO Transcription Factors Regulate Expression of Myasthenia Gravis-Associated Circulating microRNAs.
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate important intracellular biological processes. In myasthenia gravis (MG), a disease-specific pattern of elevated circulating miRNAs has been found, and proposed as potential biomarkers. These elevated miRNAs include miR-150-5p, miR-21-5p, and miR-30e-5p in acetylcholine receptor antibody seropositive (AChR+) MG and miR-151a-3p, miR-423-5p, let-7a-5p, and let-7f-5p in muscle-specific tyrosine kinase antibody seropositive (MuSK+) MG. In this study, we examined the regulation of each of these miRNAs using chromatin immunoprecipitation sequencing (ChIP-seq) data from the Encyclopedia of DNA Elements (ENCODE) to gain insight into the transcription factor pathways that drive their expression in MG. Our aim was to look at the transcription factors that regulate miRNAs and then validate some of those in vivo with cell lines that have sufficient expression of these transcription factors This analysis revealed several transcription factor families that regulate MG-specific miRNAs including the Forkhead box or the FOXO proteins (FoxA1, FoxA2, FoxM1, FoxP2), AP-1, interferon regulatory factors (IRF1, IRF3, IRF4), and signal transducer and activator of transcription proteins (Stat1, Stat3, Stat5a). We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). AChR+ MG miRNAs showed a stronger overall regulation by the FOXO transcription factors, and of this group, miR-21-5p, let-7a, and let 7f were found to possess ESR1 binding sites. Using a murine macrophage cell line, we found activation of NF-κB -mediated inflammation by LPS induced expression of miR-21-5p, miR-30e-5p, miR-423-5p, let-7a, and let-7f. Pre-treatment of cells with the anti-inflammatory drugs prednisone or deflazacort attenuated induction of inflammation-induced miRNAs. Interestingly, the activation of inflammation induced packaging of the AChR+-specific miRNAs miR-21-5p and miR-30e-5p into exosomes, suggesting a possible mechanism for the elevation of these miRNAs in MG patient serum. In conclusion, our study summarizes the regulatory transcription factors that drive expression of AChR+ and MuSK+ MG-associated miRNAs. Our findings of elevated miR-21-5p and miR-30e-5p expression in immune cells upon inflammatory stimulation and the suppressive effect of corticosteroids strengthens the putative role of these miRNAs in the MG autoimmune response.


Paper 1: The EUROCAT network--organization and processes.
The European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe, funded by the European Union, which has been in operation for more than 30 years. It currently surveys more than 1.7 million births per year, including 31% of births in the European Union, and includes almost all population-based European congenital anomaly registries as its members. EUROCAT member registries collect data, ascertained from multiple sources, on all major structural congenital and chromosomal anomalies. EUROCAT surveillance relates to three areas: prevalence, primary prevention, and prenatal screening. This article describes the history of EUROCAT and gives an overview of the current methodology and work of EUROCAT covering the database content and management, coding and classification of anomalies, core surveillance, prevalence tables, statistical monitoring. The monitoring of new developments in prenatal diagnosis, medication during pregnancy, use of folic acid, and investigation of clusters and exposures are overseen by working groups responsible for organizing research and producing regular reports. The EUROCAT Web site includes current data on prevalence rates and prenatal detection rates-an example of information useful to clinicians, public health service managers, and patients.


[Influence of environmental conditions on human hematologic constants].
A blood investigation was carried out on 3,030 volunteer blood donors and the results treated on a computer by multivariant analysis. The authors noted a depressor effect of the urban environment on the red and white cells, a rise in small lymphocytes and a reduction in monocytes in patients living in industrial areas. This stimulation of the lymphocyte system may be compared with the experimental results obtained by the same authors in animals.


Optimization of the arthroscopic indentation instrument for the measurement of thin cartilage stiffness.
Structural alterations associated with early, mostly reversible, degeneration of articular cartilage induce tissue softening, generally preceding fibrillation and, thus, visible changes of the cartilage surface. We have already developed an indentation instrument for measuring arthroscopic stiffness of cartilage with typical thickness >2 mm. The aim of this study was to extend the applicability of the instrument for the measurement of thin (<2 mm) cartilage stiffness. Variations in cartilage thickness, which will not be known during arthroscopy, can nonetheless affect the indentation measurement, and therefore optimization of the indenter dimensions is necessary. First, we used theoretical and finite element models to compare plane-ended and spherical-ended indenters and, then, altered the dimensions to determine the optimal indenter for thin cartilage measurements. Finally, we experimentally validated the optimized indenter using bovine humeral head cartilage. Reference unconfined compression measurements were carried out with a material testing device. The spherical-ended indenter was more insensitive to the alterations in cartilage thickness (20% versus 39% in the thickness range 1.5-5 mm) than the plane-ended indenter. For thin cartilage, the optimal dimensions for the spherical-ended indenter were 0.5 mm for diameter and 0.1 mm for height. The experimental stiffness measurements with this indenter correlated well with the reference measurements (r = 0.811, n = 31, p < 0.0001) in the cartilage thickness range 0.7-1.8 mm. We conclude that the optimized indenter is reliable and well suited for the measurement of thin cartilage stiffness.


Cytosolic progesterone receptors in the oviducts of reproductively active and quiescent turkeys (Meleagris gallopavo).
Cytosolic progesterone receptors (PRcs) from the reproductive tract of the female turkey were analyzed by high-performance liquid chromatography using a diethylaminoethyl (DEAE) ion-exchange column. PRcs from oviduct tissue of laying, incubating, photorefractory and short-day turkey hens were compared. In general, three types of PRcs were identified: Receptor I, a partially displaceable species that was eluted at a 0.13 M salt concentration; and Receptors II and III, which were two specific binding species eluting at 0.23 M and 0.26 M, respectively. In the subdivided tissue from the laying hen oviduct, Receptor I was the major PRc species of the isthmus and Receptor III was the only receptor present in the uterus. The infundibulum and magnum each contained a small amount of Receptor II and a substantial amount of Receptor III. The whole oviduct of incubating hens contained a greater proportion of Receptor I than Receptor II or III, and these last two receptor types were present in equal quantity. The whole oviduct of the short-day hens had an equal distribution of the three receptor types. In the presence of sodium molybdate, an inhibitor of phosphatase and protease, only one sharp Receptor II species was seen in the magnum and uterus of the laying hen oviduct and in the whole oviducts of incubating and short-day hens. The transformation of Receptor II to Receptor III in the absence of sodium molybdate was facilitated by the aging of cytosol at 0-4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)


The pathophysiology of acquired premature ejaculation.
The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE.


[Contributions by food demand studies to the development of public policies in nutrition].
Food choice in diet composition is a determinant of individual health status. Currently, there are gradually fewer conditions involving food scarcity and more involving excess food. Changes in income and relative prices generate measurable effects on the population's food intake patterns. Economic models have significant explanatory power for food demand, and the interactions between consumption, income, and prices are usually expressed as elasticity. However, the construction of some studies shows important shortcomings, especially for public policy application. This conceptual article discusses the potential contribution of food demand studies, suggesting improvements in the structural design of such studies with the inclusion of current nutritional concepts for redirecting the nutritional transition from under-nutrition to healthy eating, avoiding the present trend towards epidemic obesity.


Precision knockdown of EGFR gene expression using radio frequency electromagnetic energy.
Electromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect cells at the molecular level. Here we report a technology that can record the specific RFE signal of a given molecule, in this case the siRNA of epidermal growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR siRNA RFE signal have a 30-70% reduction of EGFR mRNA expression and ~60% reduction in EGFR protein expression vs. control treated cells. Specificity for EGFR siRNA effect was confirmed via RNA microarray and antibody dot blot array. The EGFR siRNA RFE decreased cell viability, as measured by Calcein-AM measures, LDH release and Caspase 3 cleavage, and increased orthotopic xenograft survival. The outcomes of this study demonstrate that an RFE signal can induce a specific siRNA-like effect on cells. This technology opens vast possibilities of targeting a broader range of molecules with applications in medicine, agriculture and other areas.


The 5-HT immunoreactive innervation of the Helix procerebrum.
In the procerebrum of terrestrial snails, 5-HT is a key modulatory substance of the generation of synchronous oscillatory activity and odor learning capability. In this study, we have analyzed the characteristics of the 5-HT-immunoreactive (5-HT-IR) innervation of the distinct anatomical regions of the procerebrum of Helix pomatia, applying correlative light- and electron microscopic immunocytochemistry. A dense network of 5-HT-IR innervation was demonstrated in the cell body layer, meanwhile a varicose fiber system of different density occurred in the different neuropil regions. At the ultrastructural level, labeled varicosities were found to contact both procerebral cell bodies, and different unlabeled axon profiles in the neuropils. The labeled structures established mostly close non-specialized membrane contacts with the postsynaptic profiles. The overall dense distribution of 5-HT-IR innervation supports a general modulatory role of 5-HT in processing different olfactory events.


Natural Therapies of the Inflammatory Bowel Disease: The Case of Rutin and its Aglycone, Quercetin.
Inflammatory bowel disease (IBD), commonly represented by ulcerative colitis and Crohn's disease, is a form of chronic inflammatory disorders of the gastrointestinal system. Its current drug treatment includes the use of antibiotics, 5-aminosalicylates, corticosteroids, immune-modifying agents and biologics such as anti-TNF agents and adhesion molecules blockers. These drugs have inherent problems of efficacy as many IBD sufferers need surgical intervention at some stage, high cost especially for the protein-based drugs, loss of efficacy and unwanted side effects. The discovery of novel drugs including those from natural sources that overcome the above mentioned drawbacks of the current therapy is therefore of great interest. While the flavonoid quercetin with proven antiinflammatory effect failed to show activity in vivo, its glycoside rutin has recently proven to possess a significant IBD therapeutic potential in experimental animals. In this communication, the pharmacological and pharmacokinetic profiles of rutin along with its ability to serve as a prodrug that deliver the bioactive quercetin close to the IBD site are discussed. Potential mechanisms of action far beyond antioxidant effects such as suppression of proinflammatory mediators' release and expression of inflammatory proteins (e.g. adhesion molecules, cyclooxygenase, nitric oxide synthase, etc.) are also scrutinized.


Molecular dynamics and molecular docking studies on E166A point mutant, R274N/R276N double mutant, and E166A/R274N/R276N triple mutant forms of class A β-lactamases.
Bacterial resistance to β-lactams antibiotics is a serious threat to human health. The most common cause of resistance to the β-lactams is the production of β-lactamase that inactivates β-lactams. Specifically, class A extended-spectrum β-lactamase produced by antibiotic resistant bacteria is capable of hydrolyzing extended-spectrum Cephalosporins and Monobactams. Mutations in class A β-lactamases play a crucial role in substrate and inhibitor specificity. In this present study, the E166A point mutant, R274N/R276N double mutant, and E166A/R274N/R276N triple mutant class A β-lactamases are analyzed. Molecular dynamics (MD) simulations are done to understand the consequences of mutations in class A β-lactamases. Root mean square deviation, root mean square fluctuation, radius of gyration, solvent accessibility surface area, hydrogen bond, and essential dynamics analysis results indicate notable loss in stability for mutant class A β-lactamases. MD simulations of native and mutant structures clearly confirm that the substitution of alanine at the position of 166, Asparagine at 274 and 276 causes more flexibility in 3D space. Molecular docking results indicate the mutation in class A β-lactamases which decrease the binding affinity of Cefpirome and Ceftobiprole which are third and fifth generation Cephalosporins, respectively. MD simulation of Ceftobiprole-native and mutant type Class A β-lactamases complexes reveal that E166A/R274N/R276N mutations alter the structure and notable loss in the stability for Ceftobirole-mutant type Class A β-lactamases complexes. Ceftobiprole is currently prescribed for patients with serious bacterial infections; this phenomenon is the probable cause for the effectiveness of Ceftobiprole in controlling bacterial infections.


Immunotherapeutic advancements for glioblastoma.
Immunotherapy seeks to improve the body's immune response to a tumor. Currently, the principal mechanisms employed are: (1) to improve an aspect of the immune response (e.g., T cell activation) and (2) to encourage the targeting of particular antigens. The latter is typically achieved by exposing the immune system to the antigen in question, in vivo, or in vitro followed by re-introduction of the primed cells to the body. The clinical relevance of these approaches has already been demonstrated for solid tumors such as melanoma and prostate cancer. The central nervous system was previously thought to be immune privileged. However, we know now that the immune system is highly active in the brain and interacts with brain tumors. Thus, harnessing and exploiting this interaction represents an important approach for treating malignant brain tumors. We present a summary of progress in this area, focusing particularly on immune-checkpoint inhibition, vaccines, and T cell engineering.


Insecticide selectivity to two species of Trichogramma in three different hosts, as determined by IOBC/WPRS methodology.
The use of Trichogramma species is a potential key strategy in integrated pest management. However, its effectiveness depends on the use of chemicals that do not interfere with parasitism and parasite population growth. Here, a study was made of the effects of synthetic insecticides on Trichogramma pretiosum and Trichogramma exiguum in different hosts (Ephestia kuehniella, Plutella xylostella and Spodoptera frugiperda) and the influence of International Organisation for Biological Control (IOBC/WPRS) methodology in selectivity studies using different Trichogramma species. The insecticides used were commercial formulations (triflumuron at a concentration of 0.2 mL L(-1) water, etofenprox at a concentration of 0.47 mL L(-1) water and endosulfan at a concentration of 7.5 mL L(-1) water); the control treatment consisted of distilled water. Eggs attached to cardboard cards were offered to parasitoids inside glass cages. Parasitised eggs, parasitism and adult emergence rates and parasitism reduction were evaluated. Endosulfan and etofenprox, classified as class-4 toxic products, were extremely toxic to the parasitoids. Triflumuron, classified as a non-toxic product, was selective to the parasitoids in eggs of all hosts. The methodology recommended by IOBC/WPRS influenced results regarding the use of different species of parasitoids, and the use of a single parasitoid species in their experiment is questionable.


The level of physical activity as an intervening factor in the cognitive state of primary care older adults.
This study proposed to evaluate the level of physical activity and the cognitive state of elderly users of Primary Care Facilities (UBS) of the Municipality of Maringá, State of Paraná, Brazil. This is a descriptive, cross-sectional, epidemiological study with 654 elderly men and women UBS users. A sociodemographic questionnaire, the Mini Mental State Examination (MMSE) and the short version of the International Physical Activity Questionnaire (IPAQ) were employed. Data was analyzed using the Kolmogorov-Smirnov, Chi-square, Kruskal-Wallis and Mann-Whitney "U" tests, with a significance level of p<0.05. However, they evidenced a high score in temporal orientation (Md = 5.0), spatial orientation (Md = 5.0), immediate memory (Md = 3.0), recall (Md = 3.0) and language (Md = 8.0). When comparing the mental state according to the level of physical activity of the elderly, we observed that very active/active individuals had better attention and calculation (p = 0.036), recall (p = 0.001) and general cognitive status (p = 0.002) against irregularly active and sedentary elderly. Adequate levels of physical activity may be related to better scores of cognitive functions of elderly subjects.


Comparison of two different doses of intrathecal dexmedetomidine as adjuvant with isobaric ropivacaine in lower abdominal surgery.
To augment the subarachnoid block utility, the efficacy of newer molecules as an adjuvant is investigated constantly. Considering the favorable profile of dexmedetomidine, it could have a potential role as an adjuvant to ropivacaine. We evaluated the efficacy of two different doses of dexmedetomidine as an adjuvant to isobaric ropivacaine, intrathecally. Ninety patients scheduled for lower abdominal surgery under spinal anesthesia were randomized into three groups to receive 2.5 ml of isobaric ropivacaine (0.75%, 7.5 mg/ml) added to 5 µg (10 µg/ml) or 10 µg (20 µg/ml) of dexmedetomidine or 0.5 ml of normal saline in group A, B or C, respectively. Block characteristics were compared as a primary outcome. One-way analysis of variance test, Fisher's exact test/Chi-square test, whichever appropriate. A P < 0.05 was considered significant. Time to achieve desired block was least in group B and maximum in group C. The sensory-motor blockade remained significantly prolonged in group B compared to other groups. Hemodynamic parameters remained stable in all three groups. Among the investigated doses, dexmedetomidine augments the efficacy of intrathecal ropivacaine in a dose-dependent manner, without any untoward side effects.


[Electromyographic analysis of the role of the otolith apparatus in regulation of postural disorders in humans with extrapyramidal pathology].
In 30 patients with cervical dystonia in the posture of orthostasis, an obvious change of the electromyographic pattern was shown both at rest and in different functional tests. The analysis has shown an enhanced excitability of motoneurons and a disorder of the cortical control, as well as enhancement of the irradiation process between paired structures controlling activity of opposite muscular groups. After treatment with intratympanal administration of an ototoxical preparation on the opposite side in respect to head turn direction, normalising of the cortical control and diminishing of the excitation irradiation. The data obtained suggest a significant role of the vestibular otolithic apparatus in regulation of postural disorders in extrapyramidal pathology.


Bioaffinity chromatography on monolithic supports.
Affinity chromatography on monolithic supports is a powerful analytical chemical platform because it allows for fast analyses, small sample volumes, strong enrichment of trace biomarkers and applications in microchips. In this review, the recent research using monolithic materials in the field of bioaffinity chromatography (including immunochromatography) is summarized and discussed. After giving an introduction into affinity chromatography, information on different biomolecules (antibodies, enzymes, lectins, aptamers) that can act as ligands in bioaffinity chromatography is presented. Subsequently, the history of monoliths, their advantages, preparation and formats (disks, capillaries and microchips) as well as ligand immobilization techniques are mentioned. Finally, analytical and preparative applications of bioaffinity chromatography on monoliths are presented. During the last four years 37 papers appeared. Protein A and G are still most often used as ligands for the enrichment of immunoglobulins. Antibodies and lectins remain popular for the analysis of mainly smaller molecules and saccharides, respectively. The highly porous cryogels modified with ligands are applied for the sorting of different cells or bacteria. New is the application of aptamers and phages as ligands on monoliths. Convective interaction media (epoxy CIM disks) are currently the most used format in monolithic bioaffinity chromatography.


Physical activity and risk of hot flashes among women in midlife.
Hot flashes commonly affect women during menopause and are among the primary menopausal complaints for which women seek medical treatment. Recent evidence of the potential risks posed by hormone therapies has led to interest in nonhormonal interventions, including physical activity. Studies evaluating the therapeutic effects of physical activity for relief of hot flashes have been limited by small sample size, problems with hot flash classification, and assumptions regarding the timing of risk and effect. The current study evaluated the association between physical activity prior to the time of the last menstrual period (LMP) and hot flashes in a large sample maintaining an appropriate sequence of physical activity and menopausal symptoms. This study included 512 perimenopausal and postmenopausal women who participated in a population-based study of midlife health in the Baltimore metropolitan area. Questionnaires assessed self-reported physical activity levels at various ages as well as frequency and severity of hot flashes. Multiple logistic regression was used to evaluate the association between physical activity prior to LMP and each of the hot flash outcomes. Highly active women between the ages of 35 and 40 were significantly more likely to report moderate to severe hot flashes (OR = 1.70, p = 0.01) and daily hot flashes (OR = 1.79, p < 0.01) than minimally active women in unadjusted models. Adjustment for age and smoking status did not substantially alter these results. Frequent physical activity in midlife may be associated with risk of greater severity and frequency of menopausal hot flashes.


Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma.
Hypoxia is a critical driver of cancer pathogenesis, directly inducing malignant phenotypes such as epithelial-mesenchymal transition, stem cell-like characteristics and metabolic transformation. However, hypoxia-associated phenotypes are often observed in cancer in the absence of hypoxia, a phenotype known as pseudohypoxia, which is very well documented in specific tumour types, including in paraganglioma/pheochromocytoma (PPGL). Approximately 40% of the PPGL tumours carry a germ line mutation in one of a number of susceptibility genes of which those that are found in succinate dehydrogenase (SDH) or in von Hippel-Lindau (VHL) genes manifest a strong pseudohypoxic phenotype. Mutations in SDH are oncogenic, forming tumours in a select subset of tissues, but the cause for this remains elusive. Although elevated succinate levels lead to increase in hypoxia-like signalling, there are other phenotypes that are being increasingly recognised in SDH-mutated PPGL, such as DNA hypermethylation. Further, recently unveiled changes in metabolic re-wiring of SDH-deficient cells might help to decipher cancer related roles of SDH in the future. In this review, we will discuss the various implications that the malfunctioning SDH can have and its impact on cancer development.


Autologous vein-coated stent for exclusion of a coronary artery aneurysm: case report with postimplantation intravascular ultrasound characteristics.
This report describes the successful use of an autologous cephalic vein-coated coronary stent to exclude an aneurysm of the distal right coronary artery. Post-implantation angiography confirmed successful exclusion of the aneurysm with no evidence of leakage. Intravascular ultrasonography showed complete apposition of the stent to the arterial wall proximal and distal to the aneurysm. The vein could be seen clearly around the stent. Symmetrical stent expansion (minimal luminal diameter, 2.8 mm) was verified. Increased echogenicity in the excluded aneurysm indicated early thrombus formation. Evidently, this is the 1st report of the successful use of an autologous cephalic vein-coated coronary stent to exclude an aneurysm of the distal right coronary artery.


High-throughput screening by droplet microfluidics: perspective into key challenges and future prospects.
In two decades of development, impressive strides have been made for automating basic laboratory operations in droplet-based microfluidics, allowing the emergence of a new form of high-throughput screening and experimentation in nanoliter to femtoliter volumes. Despite advancements in droplet storage, manipulation, and analysis, the field has not yet been widely adapted for many high-throughput screening (HTS) applications. Broad adoption and commercial development of these techniques require robust implementation of strategies for the stable storage, chemical containment, generation of libraries, sample tracking, and chemical analysis of these small samples. We discuss these challenges for implementing droplet HTS and highlight key strategies that have begun to address these concerns. Recent advances in the field leave us optimistic about the future prospects of this rapidly developing technology.


[Histamine intolerance--possible dermatologic sequences].
Although histamine intolerance (HIT) is not very frequently encountered, it can have serious consequences. Food intolerance is a non allergic hypersensitivity to food that does not include the immune system even though the symptoms are similar to those of IgE-mediated allergic reactions. HIT apparently develops as a result of an impaired diamine oxidase (DAO) activity due to gastrointestinal disease or through DAO inhibition, as well as through a genetic predisposition which was proven in a number of patients. The intake of histamine-rich foods as well as alcohol or drugs which cause either the release of histamine or the blocking of DAO can lead to various disorders in many organs (gastrointestinal system, skin, lungs, cardiovascular system and brain), depending on the expression of histamine receptors. Dermatologic sequels can be rashes, itch, urticaria, angioedema, dermatitis, eczema and even acne, rosacea, psoriasis, and other. Recognizing the symptoms due to HIT is especially important in treating such patients. The significance of HIT in patients with atopic dermatitis in whom the benefit of a low histamine diet has been proven is becoming increasingly understood recently. Because of the possibility of symptoms affecting numerous organs, a detailed history of symptoms following the intake of histamine-rich foods or drugs that interfere with histamine metabolism is essential for making the diagnosis of HIT. Considering that such symptoms can be the result of multiple factors, the existence of HIT is usually underestimated, but considerable expectations are being made from future studies.


The effect of water on gold supported chiral graphene nanoribbons: rupture of conjugation by an alternating hydrogenation pattern.
In the last few years we have observed a breakpoint in the development of graphene-derived technologies, such as liquid phase filtering and their application to electronics. In most of these cases, they imply exposure of the material to solvents and ambient moisture, either in the fabrication of the material or the final device. The present study demonstrates the sensitivity of graphene nanoribbon (GNR) zigzag edges to water, even in extremely low concentrations. We have addressed the unique reactivity of (3,1)-chiral GNR with moisture on Au(111). Water shows a reductive behaviour, hydrogenating the central carbon of the zigzag segments. By combining scanning tunnelling microscopy (STM) with simulations, we demonstrate how their reactivity reaches a thermodynamic limit when half of the unit cells are reduced, resulting in an alternating pattern of hydrogenated and pristine unit cells starting from the terminal segments. Once a quasi-perfect alternation is reached, the reaction stops regardless of the water concentration. The hydrogenated segments limit the electronic conjugation of the GNR, but the reduction can be reversed both by tip manipulation and annealing. Selective tip-induced dehydrogenation allowed the stabilization of radical states at the edges of the ribbons, while the annealing of the sample completely recovered the original, pristine GNR.


[Electrocardiogram in acute period of myocardial infarction: from ischemia severity and size of myocardial injury to clinical outcome].
Electrocardiogram (ECG) registered in acute period of myocardial infarction (MI) can be used not only for diagnostic purposes, but also for prediction of extent of myocardial injury and assessment of prognosis. This review covers assessment of acute ischemia in MI using Sclarovsky-Birnbaum classification and Anderson-Wilkins score, prediction of myocardial injury and necrosis size using changes of repolarization and depolarization and relation of these characteristics to clinical outcome. The importance of ECG-assessment during reperfusion, particularly using continuous ECG-monitoring, is also discussed.


Diagenesis of carbonate sediments: interaction of magnesium in sea water with mineral grains.
Samples of natural fine-grained carbonate sediment from Florida Bay, Florida, undergo mole-for-mole cation exchange with aqueous solutions of MgCl(2) and CaCl(2) in the laboratory. The exchange reaction, which involves the surface of the grains of sediment, can be essentially described by a simple mass action-law equation. Enrichment of Mg++ beyond the amounts found within particle interiors should take place on the surface of CaCo(3) sediments immersed in sea water; it may be on both exchangeable and unexchangeable sites.


Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis.
The blood-brain barrier (BBB) provides a constant homeostatic brain environment that is essential for proper neural function. An unusually low rate of vesicular transport (transcytosis) has been identified as one of the two unique properties of CNS endothelial cells, relative to peripheral endothelial cells, that maintain the restrictive quality of the BBB. However, it is not known how this low rate of transcytosis is achieved. Here we provide a mechanism whereby the regulation of CNS endothelial cell lipid composition specifically inhibits the caveolae-mediated transcytotic route readily used in the periphery. An unbiased lipidomic analysis reveals significant differences in endothelial cell lipid signatures from the CNS and periphery, which underlie a suppression of caveolae vesicle formation and trafficking in brain endothelial cells. Furthermore, lipids transported by Mfsd2a establish a unique lipid environment that inhibits caveolae vesicle formation in CNS endothelial cells to suppress transcytosis and ensure BBB integrity.


Cerebral hemispheric lateralization in cardiac autonomic control.
To identify cerebral hemispheric lateralization in cardiac autonomic control. Eight patients undergoing an intracarotid amobarbital sodium test as a presurgical evaluation of temporal lobe epilepsy. Power spectral analysis of heart rate variability before and after intracarotid amobarbital injection. University hospital and research center. The changes in the ratio of low-frequency (LF) (sympathetic) to high-frequency (HF) (parasympathetic) power (LF/HF ratio), a measure of sympathovagal balance, after hemispheric inactivation. The LF/HF ratio changed as follows: right preinactivation = 3.81 +/- 0.96, postinactivation = 3.40 +/- 1.23; left preinactivation = 2.74 +/- 0.49, postinactivation = 4.34 +/- 0.59 (mean +/- SEM). The test of interaction between laterality and inactivation using a 2-way repeated-measures analysis of variance was statistically significant (P = .001). The increased ratio on the left side (1.61 +/- 0.70) was statistically significant (P = .03), but the decrease on the right side (-0.40 +/- 0.46) was not (P < or = .70). These findings suggest that there is a cerebral lateralization in cardiac autonomic control and that the right cerebral hemisphere predominantly modulates sympathetic activity. This study may help identify subgroups of patients with intracranial disease at high risk of cardiac complications.


DNA-PK Inhibitor, M3814, as a New Combination Partner of Mylotarg in the Treatment of Acute Myeloid Leukemia.
Despite significant advances in the treatment of acute myeloid leukemia (AML) the long-term prognosis remains relatively poor and there is an urgent need for improved therapies with increased potency and tumor selectivity. Mylotarg is the first AML-targeting drug from a new generation of antibody drug conjugate (ADC) therapies aiming at the acute leukemia cell compartment with increased specificity. This agent targets leukemia cells for apoptosis with a cytotoxic payload, calicheamicin, carried by a CD33-specific antibody. Calicheamicin induces DNA double strand breaks (DSB) which, if left unrepaired, lead to cell cycle arrest and apoptosis in cancer cells. However, repair of DSB by the non-homologous end joining pathway driven by DNA-dependent protein kinase (DNA-PK) can reduce the efficacy of calicheamicin. M3814 is a novel, potent and selective inhibitor of DNA-PK. This compound effectively blocks DSB repair, strongly potentiates the antitumor activity of ionizing radiation and DSB-inducing chemotherapeutics and is currently under clinical investigation. Suppressing DSB repair with M3814 synergistically enhanced the apoptotic activity of calicheamicin in cultured AML cells. Combination of M3814 with Mylotarg in two AML xenograft models, MV4-11 and HL-60, demonstrated increased efficacy and significantly improved survival benefit without elevated body weight loss. Our results support a new application for pharmacological DNA-PK inhibitors as enhancers of Mylotarg and a potential new combination treatment option for AML patients.


Physiologic field triage criteria for identifying seriously injured older adults.
To evaluate the ability of out-of-hospital physiologic measures to predict serious injury for field triage purposes among older adults and potentially reduce the undertriage of seriously injured elders to non-trauma hospitals. This was a retrospective cohort study involving injured adults 55 years and older transported by 94 emergency medical services (EMS) agencies to 122 hospitals (trauma and non-trauma) in 7 regions of the western United States from January 1, 2006 to December 31, 2008. We evaluated initial out-of-hospital Glasgow Coma Scale (GCS) score, systolic blood pressure (SBP), respiratory rate, heart rate, shock index (SBP ÷ heart rate), out-of-hospital procedures, mechanism of injury, and patient demographics. The primary outcome was "serious injury," defined as Injury Severity Score (ISS) ≥ 16, as a measure of trauma center need. We used multivariable regression models, fractional polynomials and binary recursive partitioning to evaluate appropriate physiologic cut-points and the value of different physiologic triage criteria. A total of 44,890 injured older adults were evaluated and transported by EMS, of whom 2,328 (5.2%) had ISS ≥ 16. Nonlinear associations existed between all physiologic measures and ISS ≥ 16 (unadjusted and adjusted p ≤ 0.001 for all,), except for heart rate (adjusted p = 0.48). Revised physiologic triage criteria included GCS score ≤ 14; respiratory rate < 10 or > 24 breaths per minute or assisted ventilation; and SBP < 110 or > 200 mmHg. Compared to current triage practices, the revised criteria would increase triage sensitivity from 78.6 to 86.3% (difference 7.7%, 95% CI 6.1-9.6%), reduce specificity from 75.5 to 60.7% (difference 14.8%, 95% CI 14.3-15.3%), and increase the proportion of patients without serious injuries transported to major trauma centers by 60%. Existing out-of-hospital physiologic triage criteria could be revised to better identify seriously injured older adults at the expense of increasing overtriage to major trauma centers.


Short stay pyeloplasty: variables affecting pain and length of stay.
Pyeloplasty is increasingly performed on a short stay basis. We sought to determine what patient and treatment variables affect postoperative pain and length of stay, and whether an open approach could be considered "minimally invasive." We performed a retrospective review of patients younger than 10 years who underwent open pyeloplasty between 2001 and 2007. All patients received ketorolac every 6 hours and acetaminophen with codeine as needed. Data extracted from the medical records included morphine and codeine usage, patient age and gender, incision type, operative time, stent usage and outcome data (pain scores and length of stay). Multiple regression analyses were used to determine the association between variables and outcomes. A total of 51 patients met the inclusion criteria. Patient age and gender, operative time and stent usage had no significant correlation with mean or median pain scores. Children who received morphine had significantly higher mean, median and maximum pain scores and length of stay (33 vs 23 hours) than those who did not receive morphine. Multiple regression analyses revealed that morphine usage and dorsal lumbotomy incision were independently associated with higher mean, median and maximum pain scores, and a nephroureteral catheter was correlated with a higher maximum pain score. The only variable associated with length of stay was morphine usage. Morphine usage was the most significant variable associated with increased pain scores and increased length of stay. Ketorolac and acetaminophen/codeine provide better pain control, and allow children to return home within 24 hours. With mean pain scores less than 1 this series demonstrates that open pyeloplasty can be "minimally invasive."


Chemotherapy Use and Survival Among Young and Middle-Aged Patients With Colon Cancer.
Treatment options for patients with young-onset colon cancer remain to be defined and their effects on prognosis are unclear. To investigate receipt of adjuvant chemotherapy by age category (18-49, 50-64, and 65-75 years) and assess whether age differences in chemotherapy matched survival gains among patients diagnosed as having colon cancer in an equal-access health care system. This cohort study was based on linked and consolidated data from the US Department of Defense's Central Cancer Registry and Military Heath System medical claims databases. There were 3143 patients aged 18 to 75 years with histologically confirmed primary colon adenocarcinoma diagnosed between 1998 and 2007. This study was conducted from December 2015 to August 2016. Patients who underwent surgery and postoperative systemic chemotherapy. The primary outcome measure of the study was overall survival of patients who only received surgery and those who received both surgery and postoperative systemic chemotherapy. Of the 3143 patients, 1841 were men (58.6%). Young (18-49 years) and middle-aged (50-64 years) patients were 2 to 8 times more likely to receive postoperative systemic chemotherapy compared with older patients (65-75 years) across all tumor stages. Middle-aged patients with stage I (odds ratio, 5.04; 95% CI, 2.30-11.05) and stage II (odds ratio, 2.42; 95% CI, 1.58-3.72) disease were more likely to receive postoperative chemotherapy compared with older patients. Both groups were more likely to receive multiagent chemotherapy than were older patients (patients aged 18-49 years: odds ratio, 2.48; 95% CI, 1.42-4.32 and patients aged 50-64 years: odds ratio, 2.66; 95% CI, 1.70-4.18). Among patients who received surgery and postoperative systemic chemotherapy, no significant differences were observed in survival among age groups (the 95% CIs of hazard ratios included 1 for young and middle-aged patients compared with older patients for all tumor stages). In an equal-access health care system, we found potential overuse of chemotherapy among young and middle-aged adults with colon cancer. The addition of postoperative systemic chemotherapy did not result in matched survival improvement.


A-to-I RNA Editing in the Earliest-Diverging Eumetazoan Phyla.
The highly conserved ADAR enzymes, found in all multicellular metazoans, catalyze the editing of mRNA transcripts by the deamination of adenosines to inosines. This type of editing has two general outcomes: site specific editing, which frequently leads to recoding, and clustered editing, which is usually found in transcribed genomic repeats. Here, for the first time, we looked for both editing of isolated sites and clustered, non-specific sites in a basal metazoan, the coral Acropora millepora during spawning event, in order to reveal its editing pattern. We found that the coral editome resembles the mammalian one: it contains more than 500,000 sites, virtually all of which are clustered in non-coding regions that are enriched for predicted dsRNA structures. RNA editing levels were increased during spawning and increased further still in newly released gametes. This may suggest that editing plays a role in introducing variability in coral gametes.


[Choice of the kind of bone cavity replacement in the treatment of patients with chronic osteomyelitis].
Results of surgical treatment of 197 patients with osteomyelitis by bone autoplasty, plasty with Osteoset T and combined kinds of plasty were analyzed. Persistent positive effect was obtained in 89.8% of cases in patients after bone plasty, in 86.9% of cases after plasty with Osteoset T and in 85.3% of cases after using combined kinds of plasty. The proposed succession of actions in decision on different kinds of bone plasty and bone-muscular plasty in patients with chronic osteomyelitis is in line with the requirements of the national directions on traumatology and orthopedics and allows the interventions in question to be performed with minimal risk for the patients.


Bone morphogenetic protein-3b (BMP-3b) gene expression is correlated with differentiation in rat calvarial osteoblasts.
BMP-3b (also called GDF-10) is a novel BMP-3-related protein recently discovered in rat femur tissue. Gene expression of BMP-3b in osteoblastic cells and its regulation by prolonged culture, BMP-2 and transforming growth factor beta1 (TGF-beta1) were examined. The BMP-3b gene was highly expressed in rat osteoblasts obtained from calvarial bones but not in the osteoblastic cell lines (MC3T3-E1 and U2-OS). BMP-3b mRNA increased during osteoblastic differentiation in prolonged culture and was associated with increased alkaline phosphatase (ALPase) activity. When BMP-2, an enhancer of ALPase activity, was added to the primary osteoblast culture, BMP-3b mRNA increased 6.9-fold after 24 h. In contrast, TGF-beta1 treatment, which suppresses ALPase activity, rapidly and completely inhibited gene expression of BMP-3b. The regulation of BMP-3 mRNA differed from that of BMP-3b, even though both proteins share 81% identity. These findings indicate that BMP-3b gene expression is regulated by osteoblastic differentiation and BMP-3b functions in highly differentiated osteoblasts.


Small cell lung cancer cell line derived from a primary tumor with a characteristic deletion of 3p.
Chemotherapy plus surgery is feasible and potentially effective in selected patients with small cell lung cancer (SCLC) and provides a unique opportunity to study SCLC early in its biological history. The in vitro characteristics of a SCLC cell line derived from a resected lung primary tumor after treatment with 3 courses of chemotherapy is described. The original SCLC cell line UMC-SCLC-1 exhibited features of classic SCLC with typical morphology and growth characteristics, high levels of dopa decarboxylase, bombesin-like peptides, neuron-specific enolase and calcitonin, and the presence of neurosecretory granules and demonstrated the deletion of the short arm of chromosome 3. After multiple passages, UMC-SCLC-1 gradually changed its culture characteristics to a cell line, UMC-SCLC-1A, with morphological features of large cell anaplastic carcinoma, an altered growth pattern, decrease in calcitonin, and increase in radioresistance but retained the other biochemical markers of classic SCLC (bombesin and dopa decarboxylase production). Serial DNA content analyses showed that increased aneuploidy during continuous culture in vitro was associated with the morphological changes. Both UMC-SCLC-1 and UMC-SCLC-1A demonstrated the deletion of chromosome 3p, amplification and abundant expression of N-myc, and increased expression of c-raf. Chemotherapy sensitivities were stable throughout multiple passages and correlated with in vivo response. UMC-SCLC-1A represents a unique SCLC cell line with heterogeneous properties of both classic and morphological variant SCLC cell lines. In addition, the characteristic deletion of 3p, previously described in cultures derived from metastatic lesions and heavily pretreated patients, is seen in a primary lesion early in the natural history of SCLC.


Pain in cancer and psychological methods of its correction.
Physical pain can be a major component of cancer patient's suffering but suffering itself covers much more different sides of a human being than physical manifestations and often happens in the absence of physical pain. Suffering or total pain include physical pain, social pain, psychological pain and spiritual pain, which have a mutual influence on each other. The efficacy of treatment of total pain in cancer patients may be increased by additional use of psychological methods of its correction.


Noninvasive positive pressure ventilation as a weaning strategy for intubated adults with respiratory failure.
Noninvasive positive pressure ventilation (NPPV) provides ventilatory support without the need for an invasive airway. Interest has emerged in using NPPV to facilitate earlier removal of the endotracheal tube and decrease complications associated with prolonged intubation. To summarize the evidence comparing NPPV and invasive positive pressure ventilation (IPPV) weaning on clinical outcomes in intubated adults with respiratory failure. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 2, 2003), MEDLINE (January 1966 to July 2003) and EMBASE (January 1980 to July 2003) for randomized controlled trials comparing NPPV and IPPV weaning. Additional data sources included personal files, conference proceedings and author contact. Randomized and quasi-randomized studies comparing early extubation with immediate application of NPPV to IPPV weaning in intubated adults with respiratory failure. Two reviewers independently assessed trial quality and abstracted data according to prespecified criteria. Sensitivity and subgroup analyses were planned to assess the impact of (i) excluding quasi-randomized trials and (ii) the etiology of respiratory failure on outcomes. We identified eleven trials, of which five were included, involving 171 participants with predominantly chronic obstructive pulmonary disease. Overall, the included studies were of moderate to good quality. Compared to the IPPV strategy, the NPPV strategy decreased mortality (RR 0.41, 95% CI 0.22 to 0.76), the incidence of ventilator associated pneumonia (RR 0.28, 95% CI 0.09 to 0.85), intensive care unit length of stay (WMD -6.88 days, 95% CI -12.60 to -1.15), hospital length of stay (WMD -7.33 days, 95%CI -14.05 to -0.61), total duration of mechanical support (WMD -7.33 days, 95% CI -11.45 to -3.22) and the duration of endotracheal mechanical ventilation (WMD -6.79 days, 95% CI -11.70 to -1.87). There was no effect of NPPV on weaning failures or the duration of mechanical support related to weaning and insufficient data to pool adverse events or quality of life. Excluding a single quasi-randomized trial maintained the significant reduction in mortality and ventilator associated pneumonia. Subgroup analyses suggested that the mortality benefit of the NPPV approach is greater in patients with chronic obstructive pulmonary disease. Summary estimates from five studies of moderate to good quality demonstrated a consistent positive effect on overall mortality. At present, use of NPPV to facilitate weaning in mechanically ventilated patients, with predominantly chronic obstructive lung disease, is associated with promising, although insufficient, evidence of net clinical benefit.


Project among African-Americans to explore risks for schizophrenia (PAARTNERS): recruitment and assessment methods.
The Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) is a multi-site, NIMH-funded study that seeks to identify genetic polymorphisms that confer susceptibility to schizophrenia among African-Americans by linkage mapping and targeted association analyses. Because deficits in certain dimensions of cognitive ability are thought to underlie liability to schizophrenia, the project also examines cognitive abilities in individuals affected by schizophrenia and their extended family members. This article describes PAARTNERS study design, ascertainment methods and preliminary sample characteristics. We aim to recruit a sample of 1260 African-American families, all of whom have at least one proband with schizophrenia or schizoaffective disorder. The data collection protocol includes a structured Diagnostic Interview for Genetic Studies, Family Interview for Genetic Studies, focused neurocognitive assessment, medical records review, and the collection of blood or buccal cells for genetic analyses. We have currently completed study procedures for 106 affected sib-pair, 457 case-parent trio and 23 multiplex families. A total of 289 probands have completed the best estimate final diagnosis process and 1153 probands and family members have been administered the computerized neuropsychological battery. This project lays the foundation for future analysis of cognitive and behavioral endophenotypes. This novel integration of diagnostic, neurocognitive and genetic data will also generate valuable information for future phenotypic and genetic studies of schizophrenia.