Genetics of ascites resistance and tolerance in chicken: a random regression approach.
Resistance and tolerance are two complementary mechanisms to reduce the detrimental effects of parasites, pathogens, and production diseases on host performance. Using body weight and ascites data on domesticated chicken Gallus gallus domesticus, we demonstrate the use of random regression animal model and covariance functions to estimate genetic parameters for ascites resistance and tolerance and illustrate the way individual variation in resistance and tolerance induce both genotype re-ranking and changes in variation of host performance along increasing ascites severity. Tolerance to ascites displayed significant genetic variance, with the estimated breeding values of tolerance slope ranging from strongly negative (very sensitive genotype) to weakly negative (less sensitive). Resistance to ascites had heritability of 0.34. Both traits are hence expected to respond to selection. The two complementary defense strategies, tolerance and resistance, were genetically independent. Ascites induced changes to the correlations between ascites resistance and body weight, with the genetic correlations being weak when birds were ascites-free but moderately negative when both healthy and affected birds were present. This likely results because ascites reduces growth, and thus high ascites incidence is genetically related to low adult body weight. Although ascites induced elevated phenotypic and genetic variances in body weight of affected birds, heritability displayed negligible changes across healthy and affected birds. Ascites induced moderate genotype re-ranking in body weight, with the genetic correlation of healthy birds with mildly affected birds being unity but with severely affected birds 0.45. This study demonstrates a novel approach for exploring genetics of defense traits and their impact on genotype-by-environment interactions.


Masculine toughness and the categorical perception of onset sibilant clusters.
Evidence from production studies demonstrate that /s/-retraction, a sound change in American English where /s/ approaches [ʃ], is progressing in apparent time and highly context-dependent, occurring overwhelmingly in /str/ clusters. This study reports findings from a phoneme categorization task, suggesting that listeners perceive sibilants in /str/ clusters less categorically than in /spr/ and /skr/ clusters and are becoming less categorical in apparent time for all clusters. Indicators of masculine toughness, including the model talker's voice and face and the listener's endorsement of masculine stereotypes, additionally contribute to a less categorical perception of sibilants in these environments.


Featural and temporal attention selectively enhance task-appropriate representations in human primary visual cortex.
Our perceptions are often shaped by focusing our attention towards specific features or periods of time irrespective of location. Here we explore the physiological bases of these non-spatial forms of attention by imaging brain activity while subjects perform a challenging change-detection task. The task employs a continuously varying visual stimulus that, for any moment in time, selectively activates functionally distinct subpopulations of primary visual cortex (V1) neurons. When subjects are cued to the timing and nature of the change, the mapping of orientation preference across V1 systematically shifts towards the cued stimulus just prior to its appearance. A simple linear model can explain this shift: attentional changes are selectively targeted towards neural subpopulations, representing the attended feature at the times the feature was anticipated. Our results suggest that featural attention is mediated by a linear change in the responses of task-appropriate neurons across cortex during appropriate periods of time.


A study of the anisotropy and tension/compression behavior of human cervical tissue.
The cervix plays a crucial role in maintaining a healthy pregnancy, acting as a mechanical barrier to hold the fetus in utero during gestation. Altered mechanical properties of the cervical tissue are suspected to play a critical role in spontaneous preterm birth. Both MRI and X-ray data in the literature indicate that cervical stroma contains regions of preferentially aligned collagen fibers along anatomical directions (circumferential/longitudinal/radial). In this study, a mechanical testing protocol is developed to investigate the large-strain response of cervical tissue in uniaxial tension and compression along its three orthogonal anatomical directions. The stress response of the tissue along the different orthogonal directions is captured using a minimal set of model parameters generated by fitting a one-dimensional time-dependent rheological model to the experimental data. Using model parameters, mechanical responses can be compared between samples from patients with different obstetric backgrounds, between samples from different anatomical sites, and between the different loading directions for a single specimen. The results presented in this study suggest that cervical tissue is mechanically anisotropic with a uniaxial response dependent on the direction of loading, the anatomical site of the specimen, and the obstetric history of the patient. We hypothesize that the directionality of the tissue mechanical response is primarily due to collagen orientation in the cervical stroma, and provides an interpretation of our mechanical findings consistent with the literature data on preferential collagen alignment.


Salt-Induced Dissolution of Protein Aggregates.
Protein aggregation is mediated by a complex interplay of noncovalent interactions and is associated with a broad range of aspects from debilitating human diseases to the food industry and therapeutic biotechnology. Deciphering the intricate roles of noncovalent interactions is of paramount importance for the design of effective inhibitory and disaggregation strategies, which remains a formidable challenge. By using a combination of spectroscopic and microscopic tools, here we show that the surfactant-mediated protein aggregation can be modulated by an intriguing interplay of hydrophobic and electrostatic effects. Additionally, our results illuminate the unique role of salt as a potent disaggregation inducer that alters the protein-surfactant electrostatic interactions and triggers the dissolution of preformed protein aggregates resulting in restoring the native protein structure. This unusual salt-induced dissolution and refolding offers a unique approach to regulating the balance between protein self-assembly and disassembly and will offer a potent strategy to design electrostatically targeted inhibitors.


[Optimizing MaxEnt model in the prediction of species distribution.]
Maximum Entropy (MaxEnt) model has been widely used in recent years. However, MaxEnt is highly inclined to produce misleading results if it is not well optimized. We summarized the researches about the model optimization for sampling bias correction, model complexity tuning, presence-absence threshold selection, and model evaluation. Spatial filtering performs best for sampling bias correction, while restricted background method shows the lowest efficacy. Model complexi-ty is mainly determined by three factors: The number of environmental variables, model feature types, and regularization multiplier. Variables filtering is needed when sample size is less than the number of environment variables. The criterion of variables selection should focus on their ecological significance rather than the co-linearity between them. The choice of feature types has relatively limi-ted effects on predictive performance of the model, therefore it is advised to choose simpler models. To control overfitting, it is necessary to conduct species-specific tuning on regularization multiplier, which was usually bigger than the default setting. There are three criteria called objectivity, equality and discriminability for selecting threshold to convert continuous predication (e.g. probability of presence) into binary results. Maximizing the sum of sensitivity and specificity is a sound method for threshold selection. Model evaluation methods could be classified into two main types: Threshold-independent and threshold-dependent. Among the threshold-independent evaluations, information criteria may offer significant advantages over AUC and COR. True Skill Statistics is a better index for threshold-dependent evaluations, because it takes both omission and commission errors into account, and is robust to pseudo-absence assumption and species prevalence.


Paget disease of the male breast.
Paget disease of the breast is an uncommon tumor of the nipple-areola complex that usually presents as an erythematous and erosive lesion. We report the case of a 61-year-old man that presented with a three-year history of an erythematous lesion of the right areola, first treated with topical corticosteroids without benefit. He was then referred to our dermatology department and the clinical suspicion of Paget disease was considered. The diagnosis was later confirmed by biopsy. This case report highlights the importance of clinical recognition of this entity along with other diseases that mimic these skin changes in order to allow earlier diagnosis and proper follow-up.


The expression of Pax6 variants is subject to posttranscriptional regulation in the developing mouse eyelid.
Pax6 is a pivotal transcription factor that plays a role during early eye morphogenesis, but its expression and function in eyelid development remain unknown. In this study, the expression patterns of Pax6 mRNA and protein were examined in the developing mouse eyelid at embryonic days 14.5, 15.5, and 16.5. The function of Pax6 in eyelid development was determined by comparing it to that in the eyes-open-at-birth mutant mouse. In the normally developing eyelid, Pax6 and Pax6(5a) mRNA levels were low at E14.5, increased at E15.5, and then declined at E16.5, accompanied by a change in the Pax6/Pax6(5a) ratio. Pax6 protein was mainly located in the mesenchyme and conjunctiva. It was expressed at low levels in the epidermis at E14.5, severely reduced at E15.5, but re-expressed in the keratinocyte cells of the periderm at E16.5. In contrast, Pax6 and the Pax6/Pax6(5a) ratio were considerably higher with strong nuclear expression in the mutant at E15.5. Next, we examined the relationship of Pax6 to epidermal cell proliferation, migration, and the associated signalling pathways. The Pax6 protein in the developing eyelid was negatively correlated with epidermal cell proliferation but not migration, and it is in contrast to the activation of the EGFR-ERK pathway. Our in vivo data suggest that Pax6 expression and the Pax6/Pax6(5a) ratio are at relatively low levels in the eyelid, and acting as a transcription factor, Pax6 is required for the initiation of eyelid formation and for differential development of the keratinised cells in the closed eyelid. The Pax6 protein is likely to be controlled by the EGFR-ERK pathways. An abnormal increase in Pax6 expression and the Pax6/Pax6(5a) ratio due to alteration of the pathway activity could suppress epidermal cell proliferation leading to the eyes-open-at-birth defect. This study offers insight into the function of the Pax6 protein in eyelid development.


HCV activity in an isolated community in north east India.
Prevalence of anti-HCV among the people at risk and general population were reported across the globe. We investigated HCV activity among the members of "Lisu" community settled in a remote and isolated area of Changlang District, Arunachal Pradesh during 1999-2000. The families were scattered with 380 households. Blood samples were collected from 76 (35 males and 45 females) apparently healthy individuals from randomly selected 10% families. Sera were processed for detection for antibody to HCV by using 3rd generation ELISA kit. All the persons were within the age of 18-98 years and 75% of them were uneducated and 92% were cultivators. The prevalence of anti-HCV was found to be very high (7.89%). Since the HCV activity is high in an isolated community, transmission dynamics study will be interesting for this epidemiologically important viral disease.


Capacitive Neutralization Dialysis for Direct Energy Generation.
Capacitive neutralization dialysis energy (CNDE) is proposed as a novel energy-harvesting technique that is able to utilize waste acid and alkaline solutions to produce electrical energy. CNDE is a modification based on neutralization dialysis. It was found that a higher NaCl concentration led to a higher open-circuit potential when the concentrations of acid and alkaline solutions were fixed. Upon closing of the circuit, the membrane potential was used as a driving force to move counter ions into the electrical double layers at the electrode-liquid interface, thereby creating an ionic current. Correspondingly, in the external circuit, electrons flow through an external resistor from one electrode to the other, thereby generating electrical energy directly. The influence of external resistances was studied to achieve greater energy extraction, with the maximum output of 110 mW/m2 obtained by employing an external resistance of 5 Ω together with the AC-coated electrode.


Immunohistochemical localization of glutaredoxin and thioredoxin in human endometrium: a possible association with pinopodes.
The human endometrium is only receptive for blastocyst implantation during a short period of the menstrual cycle. Pinopodes have been suggested to be markers of uterine receptivity, but little is known about their function and the biochemical processes taking place in them. In this study, we have examined the presence of glutaredoxin (Grx) and thioredoxin (Trx) and their co-localization with pinopodes in the normal human endometrium. Endometrial biopsies were obtained from fertile women with normal menstrual cycles. The biopsies were examined by scanning electron microscopy for detection of pinopodes and by immunohistochemistry for the expression of Grx and Trx. The pinopodes showed strong immunostaining for Grx. Increasing levels of Grx immunoreactivity were seen in the luminal and glandular epithelial cells concomitant with pinopode formation. Trx immunostaining was most intense in the ciliated cells of the luminal and glandular epithelium, while the staining was moderate to strong in a majority of the other cells, both epithelial and stromal. Trx levels did not change during the secretory phase of the cycle. The intense immunostaining concomitant with the presence of pinopodes suggests that Grx plays an important role during implantation, possibly by protecting the epithelial cells from apoptotic actions of the trophoblast cells.


Pathophysiology of acute pancreatitis: potential application from experimental models and human medicine to dogs.
The cellular events leading to pancreatitis have been studied extensively in experimental models. Understanding the cellular events and inciting causes of the multisystem inflammatory cascades that are activated with this disease is of vital importance to advance diagnosis and treatment of this condition. Unfortunately, the pathophysiology of pancreatitis in dogs is not well understood, and extrapolation from experimental and human medicine is necessary. The interplay of the inflammatory cascades (kinin, complement, cytokine) is extremely complex in both initiating leukocyte migration and perpetuating disease. Recently, nitric oxide (NO) and altered microcirculation of the pancreas have been proposed as major initiators of inflammation. In addition, the role of the gut is becoming increasingly explored as a cause of oxidative stress and potentiation of systemic inflammation in pancreatitis.


Humanized FcRn mouse models for evaluating pharmacokinetics of human IgG antibodies.
A key element for the successful development of novel therapeutic antibodies is to fully understand their pharmacokinetic and pharmacodynamic behavior before performing clinical trials. While many in vitro modeling approaches exist, these simply cannot substitute for data obtained from appropriate animal models. It was established quite early that the unusual long serum half-life of immunoglobulin G's (IgGs) and Fc domains are due to their rescue and recycling by the neonatal Fc receptor (FcRn). The diverse roles of FcRn became apparent after isolation and cloning. Interesting are the significant species differences between rodent and human FcRn reactivity, rendering wild type rodents an inadequate model for studying IgG serum half-life. With the advance of genetic engineering mouse models have been established expressing human FcRn, and lacking mouse FcRn protein. These models have become highly relevant tools for serum half-life analysis of Fc-containing compounds.


Water fluoridation: a response to critics in Australia and New Zealand.
Recent questions about the effectiveness of water fluoridation have come from Diesendorf in Australia and Colquhoun in New Zealand. This report examines the arguments of both authors in detail and finds errors in each. Diesendorf employed an outdated view of how fluoride exerts its anticariogenic action and took a number of quotations out of context. Colquhoun's data are questionable. Neither author has produced evidence to challenge the established safety and effectiveness of water fluoridation.


How β-Cyclodextrin-Functionalized Biochar Enhanced Biodenitrification in Low C/N Conditions via Regulating Substrate Metabolism and Electron Utilization.
Biodenitrification plays a vital role in the remediation of nitrogen-contaminated water. However, influent with a low C/N ratio limits the efficiency of denitrification and causes the accumulation/emission of noxious intermediates. In this study, β-cyclodextrin-functionalized biochar (BC@β-CD) was synthesized and applied to promote the denitrification performance of Paracoccus denitrificans when the C/N was only 4, accompanied by increased nitrate reduction efficiency and lower nitrite accumulation and nitrous oxide emission. Transcriptomic and enzymatic activity analyses showed BC@β-CD enhanced glucose degradation by promoting the activities of glycolysis (EMP), the pentose phosphate pathway (PPP), and the tricarboxylic acid (TCA) cycle. Notably, BC@β-CD drove a great generation of electron donors by stimulating the TCA cycle, causing a greater supply of substrate metabolism to denitrification. Meanwhile, the promotional effect of BC@β-CD on oxidative phosphorylation accelerates electron transfer and ATP synthesis. Moreover, the presence of BC@β-CD increased the intracellular iron level, causing further improved electron utilization in denitrification. BC@β-CD helped to remove metabolites and induced positive feedback on the metabolism of P. denitrificans. Collectively, these effects elevated the glucose utilization for supporting denitrification from 36.37% to 51.19%. This study reveals the great potential of BC@β-CD for enhancing denitrification under low C/N conditions and illustrates a potential application approach for β-CD in wastewater bioremediation.


Polyampholyte-Wrapped Carbon Nanotubes: Preparation and Internalization by Embryonic Fibroblast Cells.
The cytotoxicity and cellular uptake of carbon nanotubes (CNTs) has recently attracted considerable interest because of the issue of biosphere-nanomaterial interactions. The biocompatibility of CNTs is determined by the metal impurities in the CNTs, the size of the CNTs and the CNT dispersion states; in particular, the type of surface modifications on the CNTs affects how they interact with cells and determines their cytotoxicity and cellular uptake. In this study, biocompatible single-walled carbon nanotubes (SWNTs) wrapped with a water-soluble copolymer, poly[2-(dimethylamino)ethyl methacrylate-co-methacrylic acid] (PDM), were prepared. We report that these SWNTs have enhanced water dispersibility and cellular internalization but no significant cytotoxic activity against mouse embryonic fibroblast NIH-3T3 cells.


Preventive surgery - tenosynovectomy and synovectomy.
The goal of preventative rheumatoid hand surgery is the eradication of the diseased synovium or tenosynovium before irreparable joint or tendon destruction occurs. Although there is general agreement that both dorsal and flexor tenosynovectomy are reliable and effective procedures to prevent the complications of tenosynovitis, the case for synovectomy is less well established. We have discussed the indications for both tenosynovectomy and synovectomy and described the surgical techniques used for dorsal tenosynovectomy and flexor tenosynovectomy in the wrist, palm, and digits. In addition, the treatment of both extensor and flexor tendon ruptures has been presented.


Endoscopy and polyps-diagnostic and therapeutic advances in management.
Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options.


Time-dependent hierarchical regulation analysis: deciphering cellular adaptation.
Cells adapt to changes in their environment by the concerted action of many different regulatory mechanisms. Examples of such mechanisms are feedback inhibition by intermediates of metabolism, covalent modification of enzymes and changes in the abundance of mRNAs and proteins. These mechanisms act in parallel at different levels in the cellular hierarchy while regulating a single process. Existing hierarchical regulation analysis determines the relative importance of these mechanisms when the cell regulates a transition from one steady-state to another. Here, the analysis is extended to the regulation of time-dependent phenomena, for which two methods are introduced and illustrated with a kinetic model incorporating transcription and translation of metabolic enzymes.


[Descriptive analytical study on patient mobilization of the Internal Medicine Department of the USL - IRCCS of Reggio Emilia (MOBINT)].
Hospitalisation represents a significant risk factor for the decline in the general conditions of the elderly. Loss of autonomy in elderly inpatients, together with immobilisation, has been defined as 'Hospital-Acquired Disability' and affects 65% of this class of patients. Less than half of them will regain independent mobilisation. Included among the negative effects are: falls, increased percentage of admission to nursing homes, longer hospital admissions, increased mortality and morbitity. Despite these facts, elderly patients remain in bed for 83-95% of their hospital stay; they rarely walk or are mobilised. Only on an international level has this issue been analysed OBJECTIVES: To analyse active mobilisation in inpatients. Prospective analytical and descriptive study performed from December 2018 - May 2019 in the Clinical Medicine department of the AUSL of Reggio Emilia. Descriptive analysis of the data has been performed. A total of 1725 patients were screened for the study. After applying the inclusion criteria, 295 patients were enrolled in the study, 9 of which were then excluded for failure to be mobilised. 66.4% of these patients were mobilized the morning during hygiene-rounds. According to the nurse, they appeared in a stable state, alert and oriented (88.1%) and used a variety of aids (from 1 to 3) (57.3%). The frequency of mobilisations were: 44.4% once a day, 31.2% twice, 24.4% three times or more. This study highlighted that mobilisation is strictly correlated to first assistance, frequently relying on health care assistants, and is mostly applied to oriented patients who only need one assistant. Further studies are required to investigate connections between patient's features and mobilisation.


Gestational Phthalate Exposure and Preschool Attention Deficit Hyperactivity Disorder in Norway.
Prenatal phthalate exposure has been linked to altered neurobehavioral development in both animal models and epidemiologic studies, but whether or not these associations translate to increased risk of neurodevelopmental disorders is unclear. We used a nested case-cohort study design to assess whether maternal urinary concentrations of 12 phthalate metabolites at 17 weeks gestation were associated with criteria for Attention Deficit Hyperactivity Disorder (ADHD) classified among 3-year-old children in the Norwegian Mother, Father and Child Cohort Study (MoBa). Between 2007 and 2011, 260 children in this substudy were classified with ADHD using a standardized, on-site clinical assessment; they were compared with 549 population-based controls. We modeled phthalate levels both linearly and by quintiles in logistic regression models adjusted for relevant covariates and tested for interaction by child sex. Children of mothers in the highest quintile of di-iso-nonyl phthalate (∑DiNP) metabolite levels had 1.70 times the odds of being classified with ADHD compared with those in the lowest quintile (95% confidence interval [CI] = 1.03 to 2.82). In linear models, there was a trend with the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP); each natural log-unit increase in concentration was associated with 1.22 times the odds of ADHD (95% CI = 0.99 to 1.52). In boys, but not girls, mono-n-butyl phthalate exposure was associated with increased odds of ADHD (odds ratio [OR] 1.42; 95% CI = 1.07 to 1.88). Additional adjustment for correlated phthalate metabolites attenuated estimates. These results suggest gestational phthalate exposure may impact the behavior of children as young as 3 years.


Ethnopharmacologic study of Chinese rhubarb.
This paper deals with an interdisciplinary study covering historic, botanical, phytochemical, pharmacological and clinical aspects of rhubarb and related species, to lay stress on the correlation between plant phylogeny, chemical constituents and purgative activity. It was found that the official rhubarbs were exclusively restricted in the Sect. Palmata, e.g. Rheum palmatum, R. palmatum var. tanguticum, R. officinale; the following criteria may serve as their standard, viz., the presence of sennoside derivatives and rhein, the occurrence of the reduced form of rhein and aloe-emodin, the leaves with any kind of palmate incision. Comprehensive multivariate analyses showed that there is a very close relationship between the leaf incision, existence of sennosides or rhein and purgative activity.


The effect of ethnicity on facial anthropometry in Northern Iran.
The evaluation and measurement of human body dimensions are achieved by physical anthropometry. Cephalometery is a branch of anthropometry science in which the head and face anatomical dimensions are measured. This research was conducted in view of the importance of anthropometric indices of the face in forensic medicine, surgery, paediatrics and medical imaging. This descriptive and cross-sectional study was set up to determine and compare the face shapes in Fars and Turkman ethnic groups of 808 normal 17- to 20-year-old males and females in Gorgon, North Iran (Fars group 407, male 200 and female 207; Turkman group 401, male 198 and female 203). The length and width of faces were determined by using classic cephalometery technique with Martin spreading callipers, and the shape of faces in the ethnic group of Fars and Turkman in both sexes was compared. The dominant type of face shape in both the native Fars and Turkman females was euryprosopic (37.7 and 51.7 percent, respectively). The dominant type of face shape in the native Fars and Turkman males was mesoprosopic (44 and 38.4 percent, respectively). This study determined the possible effect of ethnicity on the diversity of face shapes in young males and females in this region.


Improvement of the far-infrared optical property for glasses by plasma-assisted dispersion of fluorocarbon species into the shallow surface.
Owing to global warming together with the demands for thermal energy storage in diverse fields, there is demand for transparent glasses achieving reflection of the short-wave far-infrared (IR) light from solar radiation while also absorbing the longer wavelength part. Here, we performed the plasma-assisted ion implantation using a desktop-type low-pressure fluorocarbon plasma generator system to improve the optical properties of transparent soda-lime glasses. Investigations using positron annihilation techniques for the plasma-treated glass demonstrated that the fluorocarbon species occupy the sub-nanoscale interstitial sites available in the glass network of the soda-lime glass as the intrinsic open spaces, forming an implantation layer in the shallow-surface region around a depth of 50 nm. As revealed by optical spectroscopy, the subsurface layer, due to the implanted fluorocarbon species, significantly cuts off the short-wave far-IR light around a wavelength of ∼3 µm and also acts as the absorber of the longer wavelength region from 7 to 12 µm. Plasma treatment could be a promising tool to improve the optical properties in the IR light region for various materials.


[Erythrocyte interaction during aggregation according to scanning electron microscope findings].
Scanning electron microscopy was used to study red cell aggregation caused by intravascular injection of dextran (m. w. 500 000). Two types of aggregates were revealed. Type 1 was represented by aggregates of red cells with no substantial change in the form while type 2 by aggregates with the wrinkling of the surface of red cells and enlarged area of red cell surface contacts. Both types are prone to disaggregation after injection of rheopolyglucin.


Catha Edulis Active Principle, Cathinone, Suppresses Motor Coordination, Accelerates Anxiety and Alters the Levels of Dopamine and its Metabolites in the Limbic Areas of Male Swiss Albino Mice.
Cathinone, the active principle of khat (Catha edulis), stimulates, excites and produces euphoric feelings in khat users. Locomotor and rearing activities, either individual or in groups, of male Swiss albino mice were decreased significantly compared to the control. Motor coordination tests (rotarod, rope climb and grip tests) have shown decreased motor performance in the mice treated with cathinone compared to the control. The elevated plus maze test has shown significant anxiety in the mice compared to the control. Contents of dopamine and its metabolite, homovanillic acid, were increased in the limbic areas compared to the control group. In contrast, contents of 3,4-dihydroxyphenyl acetic acid were depleted significantly and dose dependently compared to the control group in the limbic areas of mice. In conclusion, natural cathinone has depleted motor coordination, accelerated anxiety in mice and altered the contents of dopamine and its metabolites.


[Health status survey in a district with many immigrant children].
In Norway, prophylactic child health care is organized through local mother and child clinics, each of which serves a given population. This study summarizes the findings from the routine check-up of four-year-olds in a district with a high proportion of immigrant families. The sample consisted of 70 children, 33 of them from immigrant families. The ordinary check-up was supplemented by information obtained by means of a questionnaire, which was filled in by the public health nurse and the doctor in consultation with the parents. A validated scale, or checklist (BCL), for ordinary behavioural problems among pre-school children was also included. The findings must be interpreted with caution, one reason being the large socio-economic differences between the immigrant and the Norwegian families included in the study. Nevertheless, the difference between the eating habits of the two groups of children was striking, in spite of the emphasis placed on diet at the clinic. Another important finding was the poor knowledge of Norwegian among the immigrant children, which was obviously associated with the poor language skills of the mothers. Therefore, an important element of the preventive health work among immigrant children should be to encourage the mothers to attend courses in Norwegian.


Self-care ability and institutional/non-institutional care of the elderly.
This paper discusses the relationship between demographic change, health status, self-care ability, and the needs of the elderly for medico-social care. The author introduces ASKORUSS, an instrument used to assess self-care ability and the need for assistance. ASKORUSS organizes the results of the assessment in a visually accessible and compelling way and can be used to determine the patient's needs for level of care, treatment, and rehabilitation. The instrument also can be used to evaluate the efficacy of an institution and its services, the outcomes of the care provided, as well as other purposes.


Asymmetric staining of Ctenomys chromosomes after treatment with AluI restriction nuclease.
After treatment with the endonuclease AluI for 6 or 24 h, chromosomes of two populations of the South American rodent Ctenomys presented an asymmetric banding pattern after Giemsa staining. These asymmetric patterns were chromosome specific (each chromosome of a pair showed different banding pattern) but constant from cell to cell and between homologous chromosomes of the populations analysed. The nature of this peculiar staining is discussed in the light of the interaction between endonucleases and DNA in chromatin of fixed chromosomes.


The C-terminal cysteine annulus participates in auto-chaperone function for Salmonella phage P22 tailspike folding and assembly.
Elongated trimeric adhesins are a distinct class of proteins employed by phages and viruses to recognize and bind to their host cells, and by bacteria to bind to their target cells and tissues. The tailspikes of E. coli phage K1F and Bacillus phage Ø29 exhibit auto-chaperone activity in their trimeric C-terminal domains. The P22 tailspike is structurally homologous to those adhesins. Though there are no disulfide bonds or reactive cysteines in the native P22 tailspikes, a set of C-terminal cysteines are very reactive in partially folded intermediates, implying an unusual local conformation in the domain. This is likely to be involved in the auto-chaperone function. We examined the unusual reactivity of C-terminal tailspike cysteines during folding and assembly as a potential reporter of auto-chaperone function. Reaction with IAA blocked productive refolding in vitro, but not off-pathway aggregation. Two-dimensional PAGE revealed that the predominant intermediate exhibiting reactive cysteine side chains was a partially folded monomer. Treatment with reducing reagent promoted native trimer formation from these species, consistent with transient disulfide bonds in the auto-chaperone domain. Limited enzymatic digestion and mass spectrometry of folding and assembly intermediates indicated that the C-terminal domain was compact in the protrimer species. These results indicate that the C-terminal domain of the P22 tailspike folds itself and associates prior to formation of the protrimer intermediate, and not after, as previously proposed. The C-terminal cysteines and triple β-helix domains apparently provide the staging for the correct auto-chaperone domain formation, needed for alignment of P22 tailspike native trimer.


Discriminant analyses of willingness to talk with a counselor and most difficult issues in the experience of unsheltered homeless men: self-actualization, loneliness, and depression.
Stepwise discriminant analyses of willingness to talk with a counselor (Wilks Lambda=.75, p<.001) and most difficult issues (Wilks Lambda=.81, p<.001) in 145 unsheltered homeless men's experience were examined using self-actualization constructs, loneliness, depression, and history-of-being-homeless variables. For example, homeless men with higher scores on loneliness, autonomy, courage, Jonah Complex, and self-acceptance were less willing to talk with a counselor. The variable, longer intervals of having a home after a first homeless episode, was associated with personal issues rather than with homeless issues. Selected participants' responses to the items, "what have you learned from your homeless experience that you could not have learned any other way" and "what would you like for me to know about your experience of homelessness," are posted to give perspective on a homeless person's internal frame of reference. This phenomenological approach indicated strengths as well as weaknesses of homeless men. Counseling programs should embrace all homeless persons including mentally well, nondrug-dependent homeless individuals.


[Reproducibility and validity of a new automatic method of specular microscopy analysis of corneal endothelium].
This prospective study was designed to test the reproducibility of a new automated technique for analyzing the corneal endothelium and to assess the validity of the technique by comparing it with a standard method. We used a contact specular microscope combined with a video camera (Tomey EM-1000) and a computer (IBM compatible PC, 486DX33) with suitable software (Tomey EM-1100, version 0.94). Video images of the corneal endothelium (area: 0.312 mm2) were passed directly into the computer input by means of a frame grabber and were automatically processed. The area to be analyzed could be varied by location and size (5580-135,150 microns2), depending on the quality of the image. Healthy corneas of 67 volunteers (age: 30.9 +/- 8.6 years) were examined. One examiner measured cell density three times in each of 42 eyes (retest-stability); three different examiners made one measurement in each of 25 eyes (objectivity). We evaluated the cell density determined by the computer after automated analysis and assessed the corrected cell density. This second result was obtained after the examiner had corrected the processed image by drawing in cell boundaries that the computer had not recognized or erasing cell boundaries the computer had sketched in by mistake. Additionally, a photograph of the corneal endothelium (specular microscope Bio Optics LSM 2000 A) was obtained from 40 volunteers to be used for manual cell counting applying a "fixed-frame" technique (validity). The corrected values showed a high retest-stability (reliability coefficient r = 0.943) and a high objectivity (r = 0.904). The values obtained by the automated method (2415 +/- 214 cells/mm2) did not differ significantly from those obtained by manual cell counting (2431 +/- 228 cells/mm2) (P = 0.898). The uncorrected values (2252 +/- 190 cells/mm2) were on average 7.2 +/- 2.6% lower than the corrected ones (177 +/- 69 cells/mm2). Retest-stability (r = 0.856) and objectivity (r = 0.737) of the uncorrected values were satisfactory. The uncorrected value was significantly lower than the value of manual cell counting (P < 0.001). The size of the analyzed area (range 12,750-84,708 microns2; average 31,438 +/- 10,655 microns2) had no significant effect on cell density (Spearman's correlation coefficient k = -0.150, P = 0.093). The automated method for analyzing the corneal endothelium quickly produces valid, reproducible results in normal corneas, provided that the correction mode of the software is applied.


Looking at families in nursing research: strategies for study design.
Pediatric nurses have identified the importance of studying children within the context of their families. There have been calls for attention to the family as the focus of study and unit of analysis in nursing research. One of the most important strategies for designing a study that keeps the focus on the family is the maintenance of study integrity. All the strategic choices made by the researcher when developing the research design need to reflect the theoretical premises on which the study is built. Throughout the study design, components of well-constructed family research will demonstrate consistency with the overall conceptual framework.


Fahr's Syndrome in the Setting of Abnormal Calcium-Phosphate Metabolism and Lupus Nephritis.
Fahr's syndrome is a rare neurodegenerative disorder characterized by bilateral calcifications of the basal ganglia and cerebral cortex. These deposits are made of calcium and phosphorus and are thought to be due to abnormalities in calcium-phosphate homeostasis. The clinical manifestation includes extrapyramidal symptoms (e.g., spastic paralysis), generalized or partial seizures, cognitive impairment, and neuropsychiatric symptoms. Here, we discuss a case of a young female with a medical history of systemic lupus erythematosus (SLE) and lupus nephritis who developed generalized seizures and was found to have extensive bilateral calcifications in the basal ganglia and cerebral cortex. Her laboratory workup showed disorganized calcium-phosphorus homeostasis.


Sinogram-affirmed iterative reconstruction of low-dose chest CT: effect on image quality and radiation dose.
OBJECTIVE. The purpose of this study is to compare sinogram-affirmed iterative reconstruction (SAFIRE) and filtered back projection (FBP) reconstruction of chest CT acquired with 65% radiation dose reduction. MATERIALS AND METHODS. In this prospective study involving 24 patients (11 women and 13 men; mean [± SD] age, 66 ± 10 years), two scan series were acquired using 100 and 40 Quality Reference mAs over a 10-cm scan length in the chest with a 128-MDCT scanner. The 40 Quality Reference mAs CT projection data were reconstructed with FBP and four settings of SAFIRE (S1, S2, S3, and S4). Six image datasets (FBP with 100 and 40 Quality Reference mAs, and S1, S2, S3, S4 with 40 Quality Reference mAs) were displayed on a DICOM-compliant 55-inch 2-megapixel monitor for blinded evaluation by two thoracic radiologists for number and location of lesions, lesion size, lesion margins, visibility of small structures and fissures, and diagnostic confidence. Objective noise and CT values were measured in thoracic aorta for each image series, and the noise power spectrum was assessed. Data were analyzed with analysis of variance and Wilcoxon signed rank tests. RESULTS. All 186 lesions were seen on 40 Quality Reference mAs SAFIRE images. Diagnostic confidence on SAFIRE images was higher than that for FBP images. Except for the minor blotchy appearance on SAFIRE settings S3 and S4, no significant artifacts were noted. Objective noise with 40 Quality Reference mAs S1 images (21.1 ± 6.1 SD of HU) was significantly lower than that for 40 Quality Reference mAs FBP images (28.5 ± 8.1 SD of HU) (p < 0.001). Noise power spectra were identical for SAFIRE and FBP with progressive noise reduction with higher iteration SAFIRE settings. CONCLUSION. Iterative reconstruction (SAFIRE) allows reducing the radiation exposure by approximately 65% without losing diagnostic information in chest CT.


Breast cancer in young women.
This eighth article in our series on breast disease focuses on breast cancer in young women. There are several challenges in the diagnosis of breast cancer in young women, and special consideration must be given to the woman's fertility and body image issues. The difficulty in distinguishing benign from malignant lesions on clinical and imaging assessment in this group stresses the importance of the triple test of clinical examination, mammography or ultrasound, and biopsy.


IRAK regulates macrophage foam cell formation by modulating genes involved in cholesterol uptake and efflux.
Interleukin-1 receptor-associated kinase-1 (IRAK1) is linked to the pathogenesis of atherosclerosis; however, its role in macrophage foam cell formation is not known. Therefore, the present study investigated the role of IRAK1 in lipid uptake, biosynthesis, and efflux in THP-1 derived macrophages and human monocyte-derived macrophages (HMDMs). Ox-LDL (40 μg/mL, 15 minutes-48 hours) treatment induced time-dependent increase in IRAK1, IRAK4, and Stat1 activation in THP-1 derived macrophages. IRAK1/4 inhibitor (INH) or IRAK1 siRNA significantly attenuated cholesterol accumulation, DiI-Ox-LDL binding, and uptake while cholesterol efflux to apoAI and HDL was enhanced in THP-1 derived macrophages and HMDMs. Ox-LDL treatment significantly increased the mRNA expression of CD36, LOX-1, SR-A, ABCA1, ABCG1, Caveolin-1, CYP27A1 while that of SR-BI was decreased. IRAK1/4 inhibition or IRAK1 knockdown, however, attenuated Ox-LDL-induced CD36 expression; augmented ABCA1 and ABCG1 expression while expression of others was unaffected in THP-1 derived macrophages and HMDMs. Moreover, IRAK1/4 inhibition had no significant effect on genes involved in lipid biosynthesis. In IRAK1/4 INH pre-treated THP-1 derived macrophages Ox-LDL-induced Stat1 phosphorylation and its binding to CD36 promoter was significantly attenuated while LXRα expression and its binding to the ABCA1/ABCG1 locus, NFATc2 activation and its binding to ABCA1 locus was enhanced. The present study thus demonstrates that IRAK regulates lipid accumulation by modulating CD36-mediated uptake and ABCA1-, ABCG1-dependent cholesterol efflux. Therefore, IRAK1 can be a potential target for preventing macrophage foam cell formation.


Comparative Proteomic Analysis of Posterior Silk Glands of Wild and Domesticated Silkworms Reveals Functional Evolution during Domestication.
The wild silkworm Bombyx mandarina was domesticated to produce silk in China approximately 5000 years ago. Silk production is greatly improved in the domesticated silkworm B. mori, but the molecular basis of the functional evolution of silk gland remains elusive. We performed shotgun proteomics with label-free quantification analysis and identified 1012 and 822 proteins from the posterior silk glands (PSGs) of wild silkworms on the third and fifth days of the fifth instar, respectively, with 128 of these differentially expressed. Bioinformatics analysis revealed that, with the development of the PSG, the up-regulated proteins were mainly involved in the ribosome pathway, similar to what we previously reported for B. mori. Additionally, we screened 50 proteins with differential expression between wild and domesticated silkworms that might be involved in domestication at the two stages. Interestingly, the up-regulated proteins in domesticated compared to wild silkworms were enriched in the ribosome pathway, which is closely related to cell size and translation capacity. Together, these results suggest that functional evolution of the PSG during domestication was driven by reinforcing the advantageous pathways to increase the synthesis efficiency of silk proteins in each cell and thereby improve silk yield.


A randomized trial of two types of nurse-assisted home care for patients with COPD.
Whereas pulmonary rehabilitation reduces symptoms and improves the quality of life of patients with COPD and is recommended in management guidelines, few patients have access to rehabilitation services. The purpose of this study was to investigate the effectiveness of increasing access to selected components of pulmonary rehabilitation by providing nurse-assisted home care that was composed of patient education, efforts to improve patient self-management skills, and enhanced follow-up. We conducted a 6-month, randomized, controlled trial. Primary care clinics associated with an urban academic health system. Patients were > or = 45 years of age with a physician diagnosis of COPD, and had a > or = 20-pack-year smoking history, had experienced at least one respiratory symptom during the past 12 months, and had airflow obstruction (ie, FEV1/FVC ratio, < 70%; FEV1, < 80%). Four nurses were trained in the use of the Global Initiative for Chronic Obstructive Lung Disease guidelines, and two of the four nurses received additional training in collaborative management. Patients were randomly assigned to usual care (UC), nurse-assisted medical management (MM), or nurse-assisted collaborative management (CM). The main outcome measures were of generic (Medical Outcome Study 36-item short form [SF-36], illness intrusiveness) and disease-specific (St. George's respiratory questionnaire [SGRQ]) quality of life and self-reported health-care utilization. Overall, 151 patients (UC group, 51 patients; MM group, 49 patients; and CM group, 51 patients) completed the study, their average age was 69 years, and 56.9% were women. The average change in the SF-36 general health domain for the MM group vs the UC group was 1.1 (95% confidence interval [CI], -7.9 to 11.2), and for the CM group vs the UC group the average change was 2.5 (95% CI, -7.0 to 12.3). The corresponding changes in SGRQ total domain were -2.9 (95% CI, -9.8 to 4.1) and -2.6 (95% CI, -9.5 to 4.3). There was no change in the number of self-reported emergency department visits or hospitalizations, but the utilization of these services was infrequent. The findings of our investigation and those from the published literature suggest that interventions to enhance patient education, self-management skills, and follow-up among patients with COPD do not result in clinically meaningful improvements in health status or self-reported health-care utilization. Moreover, future studies of disease management programs for patients with COPD need to evaluate interventions that address associated comorbidities, exercise, and social support.


Nuclear receptor hepatocyte nuclear factor 4alpha1 competes with oncoprotein c-Myc for control of the p21/WAF1 promoter.
The dichotomy between cellular differentiation and proliferation is a fundamental aspect of both normal development and tumor progression; however, the molecular basis of this opposition is not well understood. To address this issue, we investigated the mechanism by which the nuclear receptor hepatocyte nuclear factor 4alpha1 (HNF4alpha1) regulates the expression of the human cyclin-dependent kinase inhibitor gene p21/WAF1 (CDKN1A). We found that HNF4alpha1, a transcription factor that plays a central role in differentiation in the liver, pancreas, and intestine, activates the expression of p21 primarily by interacting with promoter-bound Sp1 at both the proximal promoter region and at newly identified sites in a distal region (-2.4 kb). Although HNF4alpha1 also binds two additional regions containing putative HNF4alpha binding sites, HNF4alpha1 mutants deficient in DNA binding activate the p21 promoter to the same extent as wild-type HNF4alpha1, indicating that direct DNA binding by HNF4alpha1 is not necessary for p21 activation. We also observed an in vitro and in vivo interaction between HNF4alpha1 and c-Myc as well as a competition between these two transcription factors for interaction with promoter-bound Sp1 and regulation of p21. Finally, we show that c-Myc competes with HNF4alpha1 for control of apolipoprotein C3 (APOC3), a gene associated with the differentiated hepatic phenotype. These results suggest a general model by which a differentiation factor (HNF4alpha1) and a proliferation factor (c-Myc) may compete for control of genes involved in cell proliferation and differentiation.


Vitamin-mineral supplement fails to improve IQ of mentally retarded young adults.
Twenty mentally retarded persons participated in a study to determine the effect of large doses of vitamin-mineral supplements on IQ, educability, electrophysiological responsiveness, and pyridoxine metabolism. Using a double-blind matched group experimental design, we administered supplements and placebos for 6 months. Pre- and postmeasurements showed no significant effects on any of the measured variables.


Transcriptome profiling of Staphylococci-infected cow mammary gland parenchyma.
Genome-wide gene expression profiling allows for identification of genes involved in the defense response of the host against pathogens. As presented here, transcriptomic analysis and bioinformatics tools were applied in order to identify genes expressed in the mammary gland parenchyma of cows naturally infected with coagulase-positive and coagulase-negative Staphylococci. In cows infected with coagulase-positive Staphylococci, being in 1st or 2nd lactation, 1700 differentially expressed genes (DEGs) were identified. However, examination of the 3rd or 4th lactations revealed 2200 DEGs. Gene ontology functional classification showed the molecular functions of the DEGs overrepresented the activity of cytokines, chemokines, and their receptors. In cows infected with coagulase-negative Staphylococci, in the 1st or 2nd lactations 418 DEGs, while in the 3rd or 4th lactations, 1200 DEGs were identified that involved in molecular functions such as protein, calcium ion and lipid binding, chemokine activity, and protein homodimerization. Gene network analysis showed DEGs associated with inflammation, cell migration, and immune response to infection, development of cells and tissues, and humoral responses to infections caused by both types of Staphylococci. A coagulase-positive Staphylococci infection caused a markedly stronger host response than that of coagulase-negative, resulting in vastly increased DEGs. A significant increase in the expression of the FOS, TNF, and genes encoding the major histocompatibility complex proteins (MHC) was observed. It suggests these genes play a key role in the synchronization of the immune response of the cow's parenchyma against mastitis-causing bacteria. Moreover, the following genes that belong to several physiological pathways (KEGG pathways) were selected for further studies as candidate genes of mammary gland immune response for use in Marker Assisted Selection (MAS): chemokine signaling pathway (CCL2, CXCL5, HCK, CCR1), cell adhesion molecules (CAMs) pathway (BOLA-DQA2, BOLA-DQA1, F11R, ITGAL, CD86), antigen processing and presentation pathway (CD8A, PDIA3, LGMN, IFI30, HSPA1A), and NOD-like receptor signaling pathway (TNF, IL8, IL18, NFKBIA).


Kaurenoic acid activates TGF-β signaling.
Kaurenoic acid (ent-kaur-16-en-19-oic acid: KA) is a key constituent found in the roots of Aralia continentalis Kitagawa (Araliaceae) that has been used for treating rheumatism in traditional Asian medicine. Although KA was reported to suppress inflammation by activating Nrf2, the anti-inflammatory function of KA is less characterized. Given the complex nature of the inflammatory response and the critical role of TGF-β in resolving inflammation, we hypothesized that KA suppresses inflammatory response by activating TGF-β signaling. Murine macrophage RAW 264.7, human lung epithelial cell MRC-5, and a TGFβRII defective cell HCT116 were treated with various amounts of KA. KA was also administered to mouse lung via intratracheal (i.t.) route. Phosphorylated Smad2 and Smad3 were analyzed by western blot. TGFβ-dependent gene expression was determined by immunoblotting of α-SMA and luciferase assay. KA induced the phosphorylation of Smad2 and Smad3, key activator molecules in TGF-β signaling. EW7197, an inhibitor for activin receptor-like kinase 5/TGF-β receptor I (TGFβR1) suppressed KA-mediated phosphorylation of Smad2. Similarly, KA failed to phosphorylate Smad2 in HCT116, suggesting that KA acts through the prototypic TGFβR. KA treatment increased the transcriptional activity driven by a Smad-binding element in a luciferase reporter assay and induced the α-smooth muscle actin (α-SMA). Similarly, i.t. KA induced the phosphorylation of Smad2 and increased the expression ofα-SMA in mouse lungs. KA activated TGF-β signaling, suggesting that TGFβ signaling is associated with KA suppressing inflammation.


Structure and Electrical-Transport Relations in Ba(Zr,Pr)O3-δ Perovskites.
Members of the perovskite solid solution BaZr1-xPrxO3-δ (0.2 ≤ x ≤ 0.8) with potential high-temperature electrochemical applications were synthesized via mechanical activation and high-temperature annealing at 1250 °C. Structural properties were examined by Rietveld analysis of neutron powder diffraction and Raman spectroscopy at room temperature, indicating rhombohedral symmetry (space group R3̅c) for members x = 0.2 and 0.4 and orthorhombic symmetry (Imma) for x = 0.6 and 0.8. The sequence of phase transitions for the complete solid solution from BaZrO3 to BaPrO3 is Pm3̅m → R3̅c → Imma → Pnma. The structural data indicate that Pr principally exists as Pr4+ on the B site and that oxygen content increases with higher Pr content. Electrical-conductivity measurements in the temperature range of 250-900 °C in dry and humidified (pH2O ≈ 0.03 atm) N2 and O2 atmospheres revealed an increase of total conductivity by over 2 orders of magnitude in dry conditions from x = 0.2 to x = 0.8 (σ ≈ 0.08 S cm-1 at 920 °C in dry O2 for x = 0.8). The conductivity for Pr contents x > 0.2 is attributable to positively charged electronic carriers, whereas for x = 0.2 transport in dry conditions is n-type. The change in conduction mechanism with composition is proposed to arise from the compensation regime for minor amounts of BaO loss changing from predominantly partitioning of Pr on the A site to vacancy formation with increasing Pr content. Conductivity is lower in wet conditions for x > 0.2 indicating that the positive defects are, to a large extent, charge compensated by less mobile protonic species. In contrast, the transport mechanism of the Zr-rich composition (x = 0.2), with much lower electronic conductivity, is essentially independent of moisture content.


Alkaloids from Lepidium meyenii (Maca), structural revision of macaridine and UPLC-MS/MS feature-based molecular networking.
Lepidium meyenii Walp., known as Peruvian ginseng, is widely used in ethnomedicine. To date, L. meyenii is cultivated worldwide at high-altitude and is commonly used as a food supplement. However, its medicinal value is still controversial and its mechanism of action remains unknown, due to limited knowledge about the phytochemical constituents of this plant species. In this study, a multidisciplinary approach comprising conventional NMR- and HRMS-based structure elucidation, quantum mechanical calculation of NMR chemical shifts and UPLC-MS/MS feature-based molecular networking was applied to analyse the phytochemical profile of L. meyenii. In the current work, three previously undescribed imidazole alkaloids were identified using extensive spectroscopic techniques (HRMS, NMR), for which the names lepidiline E, F and G were adopted. In addition, two amidine alkaloids were reported, representing an undescribed class of alkaloids in L. meyenii, and 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, a well-known β-carboline alkaloid, was also isolated from L. meyenii for the first time. Molecular networks of imidazole, amidine and β-carboline alkaloids in L. meyenii were constructed by the Global Natural Products Social Molecular Networking (GNPS) web platform, resulting in the tentative identification of three undescribed analogues. In addition, the structure of a previously reported compound named 'macaridine' was revised as macapyrrolin C based on density functional theory (DFT) calculations and comprehensive comparison of NMR data.


Survival Nomograms after Curative Neoadjuvant Chemotherapy and Radical Surgery for Stage IB2-IIIB Cervical Cancer.
The purpose of this study was to develop nomograms for predicting the probability of overall survival (OS) and progression-free survival (PFS) in locally advanced cervical cancer treated with neoadjuvant chemotherapy and radical surgery. Nomograms to predict the 5-year OS rates and the 2-year PFS rates were constructed. Calibration plots were constructed, and concordance indices were calculated. Evaluated variableswere body mass index, age, tumor size, tumor histology, grading, lymphovascular space invasion, positive parametria, and positive lymph nodes. In total 245 patients with locally advanced cervical cancer who underwent neoadjuvant chemotherapy and radical surgery were included for the construction of the nomogram. The 5-year OS and PFS were 72.6% and 66%, respectively. Tumor size, grading, and parametria status affected the rate of OS, whereas tumor size and positive parametria were the main independent PFS prognostic factors. We constructed a nomogram based on clinicopathological features in order to predict 2-year PFS and 5-year OS in locally advanced cervical cancer primarily treated with neoadjuvant chemotherapy followed by radical surgery. This tool might be particularly helpful for assisting in the follow-up of cervical cancer patients who have not undergone concurrent chemoradiotherapy.


Relationship between the number of occlusal contacts and masticatory muscle activity in healthy young adults.
The electromyographic (EMG) potentials of left and right masseter and temporalis anterior muscles were recorded in 23 healthy young adults during: 1. a 3-second maximum voluntary clench (MVC) on cotton rolls positioned on the posterior teeth (standardized recording); and 2. a 3-second MVC in intercuspal position. EMG potentials recorded in intercuspal position were standardized as a percentage of the mean potentials of the standardized recording, and the EMG muscle activity was calculated. The number of occlusal contacts in intercuspal position was assessed by using eight microm thick shim stocks. Two groups of subjects with either 1. Less than ten occlusal contacts (11 subjects with "few contacts"); or 2. At least ten occlusal contacts (12 subjects with "many contacts") were selected. The MVC muscle activity in the "few contacts" group was significantly lower than that recorded in the "many contacts" group (p<0.005). In conclusion, the number of occlusal contacts and masticatory muscular function are significantly related, at least in young adults with a sound stomatognathic apparatus.


Papillotomy and functional disorders of the sphincter of Oddi.
The term "functional" as applied to disorders of the sphincter of Oddi is indefinite since it encompasses a spectrum of disorders from histopathologic fibrosis of the sphincter to sphincteric dysfunction without evident pathologic transformation. Although there are several approaches to the diagnosis of sphincter of Oddi dysfunction, the diagnosis still depends on the exclusion of other causes of obstruction. Reports of surgical sphincteroplasty in patients with this diagnosis suggest that the outcome is unpredictable. Operative mortality ranges from 0.6% to 6.0% and morbidity from 3.3% to 18%. Operative sphincteroplasty appears to have no adverse sequelae long-term, although there are few reports of extended follow-up. In our experience, about 10% of patients undergoing endoscopic sphincterotomy for calculi have recurrent biliary problems during extended follow-up, but most problems were not formidable. In large series of patients undergoing endoscopic sphincterotomy, papillary stenosis is the indication for the procedure in about 5% of cases. With this indication, immediate complications occur with greater frequency compared to endoscopic sphincterotomy for choledocholithiasis. The validity of every proposed test for sphincter dysfunction and/or stenosis has been challenged, and the diagnosis must still be considered imprecise. This fundamental problem makes it difficult to interpret the results of endoscopic sphincterotomy. It also necessitates a cautious approach to management of this disorder by endoscopic sphincterotomy. Other methods of sphincter manipulation such as endoscopic balloon dilation have not been studied extensively. Although endoscopic sphincterotomy has been performed in a few patients with idiopathic recurrent pancreatitis, the procedure must be considered experimental in this group of patients.


Mutational analysis of ABCG2: role of the GXXXG motif.
ABCG2 (BCRP/MXR/ABCP) is a half-transporter associated with multidrug resistance that presumably homodimerizes for function. It has a conserved GXXXG motif in its first transmembrane segment, a motif that has been linked with dimerization in other proteins, e.g., glycophorin A. We substituted either or both glycines of this GXXXG motif with leucines to evaluate the impact on drug transport, ATP hydrolysis, cross-linking, and susceptibility to degradation. All mutants also carried the R482G gain-of-function mutation, and all migrated to the cell surface. The mutations resulted in lost transport for rhodamine 123 and impaired mitoxantrone, pheophorbide a, and BODIPY-prazosin transport, particularly in the double leucine mutant (G406L/G410L). Basal ATPase activity of the G406L/G410L mutant was comparable to the empty vector transfected cells with no substrate induction. Despite impaired function, the mutants retained susceptibility to cross-linking using either disuccinimidyl suberate (DSS) or the reducible dithiobis(succinimidyl propionate) (DSP) and demonstrated a high molecular weight complex under nonreducing conditions. Mutations to alanine at the same positions yielded fully functional transporters. Finally, we exposed cells to mitoxantrone to promote folding and processing of the mutant proteins, which in the leucine mutants resulted in increased amounts detected on immunoblot and by immunofluorescence. These studies support a hypothesis that the GXXXG motif promotes proper packing of the transmembrane segments in the functional ABCG2 homodimer, although it does not solely arbitrate dimerization.


[Effect of suppression of apnea on arterial pressure and plasma catecholamines in normotensive patients with sleep apnea].
The association of high blood pressure (HBP) and the sleep apnea syndrome (SPS) and the beneficial effect of SAS treatment on HBP are well known. The direct effect of the continuous nocturnal administration of positive air pressure (CPAP) on blood pressure is not, however, well known. The aim of this study was to evaluate the blood pressure (BP), plasma catecholamines (PC) and urinary derivatives of catecholamines (UDC) in 17 normotensive subjects (4 females; age 49 +/- 11 years) with SAS, prior to and after correction of apnea with CPAP. Twenty-four hour outpatient registry of blood pressure (OPRBP) and after nocturnal polysomnography were performed both basal and during CPAP administration for two nights. Urine was collected over these 24 hour period for measurement of UDC. At 7 hours a blood sample was collected for measurement of PC. SAS was corrected by CPAP in all the patients with a reduction in mean BP (24 h: 87 +/- 6 vs 84 +/- 6 mmHg, p < 0.05, diurnal, 90 +/- 6 vs 87 +/- 6 mmHg, p < 0.05, nocturnal, 84 +/- 6 vs 82 +/- 7 mmHg, NS) and the percentage of diastolic BP > 90 mmHg (24 h: 10 +/- 7 mmHg vs 6.5 +/- 6 mmHg, p < 0.01, diurnal, 15 +/- 10 vs 10 +/- 10 mmHg, p < 0.05, nocturnal 5.2 vs 5 vs 3 +/- 4 mmHg, p < 0.05). The plasma catecholamines tended to reduce, although not significantly, without changes of urinary metabolites. There is a significant decrease in blood pressure with the administration of continuous positive air pressure even in normotensive patients. An early correction of sleep apnea syndrome may reduce the high prevalence of hypertension associated with this syndrome.


Probability and Flux Densities in the Center-of-Mass Frame.
For an arbitrary nonstationary wave function of a nonrelativistic closed many-body system consisting of arbitrary interacting particles, the general expressions for the time-dependent one-particle probability and flux densities in the center-of-mass frame without applying Born-Oppenheimer approximation are obtained. Even the wave function for the translation is additionally introduced; it disappears in the center-of-mass frame automatically. It is shown that for the rotational ground state the time-dependent probability and flux densities of an arbitrary particle in the center-of-mass frame are isotropic. It means that the angular dependence is absent but these densities depend on radius and time. More importantly, it is shown that the angular components of the time-dependent flux density vanish. With these statements, one can calculate the radial component of the radius- and time-dependent electronic flux density within the Born-Oppenheimer approximation via the continuity equation. Application of this theory to the pulsating or exploding "quantum bubble" of the vibrating or dissociating Na2 molecule in the rotational ground state, respectively, is found elsewhere in this issue.


Precancerous lesions of oral mucosa.
Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque-like, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary. The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used.


Comparative assessment of the ligand and metal ion binding properties of integrins alpha9beta1 and alpha4beta1.
Integrins alpha9beta1 and alpha4beta1 form a distinct structural class, but while alpha4beta1 has been subjected to extensive study, alpha9beta1 remains poorly characterized. We have used the small molecule N-(benzenesulfonyl)-(L)-prolyl-(L)-O-(1-pyrrolidinylcarbonyl)tyrosine (3) to investigate the biochemical properties of alpha9beta1 and directly compare these properties with those of alpha4beta1. Compound 3 has a high affinity for both integrins with K(D) values of < or =3 and 180 pM for alpha9beta1 in 1 mM Mn2+ (activating) and 1 mM Ca2+ and 1 mM Mg2+ (nonactivating) conditions and < or =5 and 730 pM for alpha4beta1 under the corresponding conditions. Ca2+ treatment promoted the binding of 3 to both integrins (EC50 = 30 microM Ca2+ in both cases). Compound 3 binding to both integrins was also stimulated by the addition of the activating monoclonal antibody TS2/16. These findings indicate that the mechanisms by which metal ions and TS2/16 regulate ligand binding to alpha9beta1 and alpha4beta1 are similar. The binding of 3 to both integrins induced the mAb 9EG7 LIBS epitope, a property consistent with occupancy of the receptor's ligand binding site by 3. But whereas EGTA treatment inhibited the binding of 9EG7 to alpha4beta1, it stimulated the binding of 9EG7 to alpha9beta1. The 9EG7 and TS2/16 effects point to contributions of the beta1-chains on binding. Cross-linking data revealed that the integrin alpha-chains are also involved in binding the small molecule, as stable linkages were observed on both the alpha9 chain of alpha9beta1 and the alpha4 chain of alpha4beta1. Extensive structure-activity analyses with natural and synthetic ligands indicate distinct features of the ligand binding pockets. Most notable was the estimated >1000-fold difference in the affinity of the integrins for VCAM-1, which binds alpha4beta1with an apparent K(D) of 10 nM and alpha9beta1 with an apparent K(D) of >10 microM. Differences were also seen in the binding of alpha9beta1 and alpha4beta1 to osteopontin. Compound 3 competed effectively for the binding of VCAM-1 and osteopontin to both integrins. While these studies show many similarities in the biochemical properties of alpha9beta1 and alpha4beta1, they identify important differences in their structure and function that can be exploited in the design of selective alpha9beta1 and alpha4beta1 inhibitors.


Rio1 mediates ATP-dependent final maturation of 40S ribosomal subunits.
During the last step in 40S ribosome subunit biogenesis, the PIN-domain endonuclease Nob1 cleaves the 20S pre-rRNA at site D, to form the mature 18S rRNAs. Here we report that cleavage occurs in particles that have largely been stripped of previously characterized pre-40S components, but retain the endonuclease Nob1, its binding partner Pno1 (Dim2) and the atypical ATPase Rio1. Within the Rio1-associated pre-40S particles, in vitro pre-rRNA cleavage was strongly stimulated by ATP and required nucleotide binding by Rio1. In vivo binding sites for Rio1, Pno1 and Nob1 were mapped by UV cross-linking in actively growing cells. Nob1 and Pno1 bind overlapping regions within the internal transcribed spacer 1, and both bind directly over cleavage site D. Binding sites for Rio1 were within the core of the 18S rRNA, overlapping tRNA interaction sites and distinct from the related kinase Rio2. Site D cleavage occurs within pre-40S-60S complexes and Rio1-associated particles efficiently assemble into these complexes, whereas Pno1 appeared to be depleted relative to Nob1. We speculate that Rio1-mediated dissociation of Pno1 from cleavage site D is the trigger for final 18S rRNA maturation.


Statistical Aspects of Partial Edentulism in a Sample of Adults in Craiova, Romania.
The purpose of the study was to analyze the prevalence of different forms of partial edentulism and the description of the various parameters associated with this disease. Materials and Methods. The study was conducted on a total of 204 subjects who presented themselves at the Clinic of Dental Prosthetics and Oral Rehabilitation Clinic of the Faculty of Dentistry Craiova between October 2015 and June 2016. Results. Of the 204 subjects diagnosed with partial edentulism, 51.47% belonged to the age group of 20-29 years, 52.46% were female and 82.84% came from the urban environment. The most frequent cause of the edentulism was dental caries and their complications. The present study has shown that the partial edentulism forms encountered, especially those of the Kennedy III class, had an increased frequency among the young population, especially in the maxillary arch.


Synthesis and biological activity of luteinizing hormone-releasing hormone and related peptides.
Syntheses of the decapeptide luteinizing hormone-releasing hormone, less thanGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 are described. The basic properties of arginine can provide a simple repetitive isolation procedure for arginine-containing peptides. The biological activities of the decapeptide, of a range of fragments and modified fragments, and of two analogs with alteration in the series at position 4 were measured by in vitro incubation with sheep pituitary slices, measuring the liberated LH by bioassay. None of the compounds of shortened sequence were active, with the exception of less thanGlu-His-Trp which showed 1% of the decapeptide in one of four experiments. Neither [Ser(But)4]-LH-RH-nor [Leu4]-LH-RH showed significant activity indicating (despite the known activity of [Ala4]-LH-RH) the importance of this part of the structure for full biological activity.


Nano-Sized Secondary Organic Aerosol of Diesel Engine Exhaust Origin Impairs Olfactory-Based Spatial Learning Performance in Preweaning Mice.
The aims of our present study were to establish a novel olfactory-based spatial learning test and to examine the effects of exposure to nano-sized diesel exhaust-origin secondary organic aerosol (SOA), a model environmental pollutant, on the learning performance in preweaning mice. Pregnant BALB/c mice were exposed to clean air, diesel exhaust (DE), or DE-origin SOA (DE-SOA) from gestational day 14 to postnatal day (PND) 10 in exposure chambers. On PND 11, the preweaning mice were examined by the olfactory-based spatial learning test. After completion of the spatial learning test, the hippocampus from each mouse was removed and examined for the expressions of neurological and immunological markers using real-time RT-PCR. In the test phase of the study, the mice exposed to DE or DE-SOA took a longer time to reach the target as compared to the control mice. The expression levels of neurological markers such as the N-methyl-d-aspartate (NMDA) receptor subunits NR1 and NR2B, and of immunological markers such as TNF-α, COX2, and Iba1 were significantly increased in the hippocampi of the DE-SOA-exposed preweaning mice as compared to the control mice. Our results indicate that DE-SOA exposure in utero and in the neonatal period may affect the olfactory-based spatial learning behavior in preweaning mice by modulating the expressions of memory function-related pathway genes and inflammatory markers in the hippocampus.


Three-dimensional turbulent relative dispersion by the Gledzer-Ohkitani-Yamada shell model.
We study pair dispersion in a three-dimensional incompressible high Reynolds number turbulent flow generated by Fourier transforming the dynamics of the Gledzer-Ohkitani-Yamada (GOY) shell model into real space. We show that GOY shell model can successfully reproduce both the Batchelor and the Richardson-Obukhov regimes of turbulent relative dispersion. We also study how the crossover time scales with the initial separations of a particle pair and compare it to the prediction by Batchelor.


Influence of infection during pregnancy on fetal development.
Infection by bacteria, viruses, and parasites may lead to fetal death, organ injury, or limited sequelae depending on the pathogen. Here, we consider the role of infection during pregnancy in fetal development including placental development and function, which can lead to fetal growth restriction. The classical group of teratogenic pathogens is referred to as 'TORCH' (Toxoplasma gondii, others like Treponema pallidum, rubella virus, cytomegalovirus, and herpes simplex virus) but should include a much broader group of pathogens including Parvovirus B19, Varicella zoster virus, and Plasmodium falciparum to name a few. In this review, we describe the influence of different infections in utero on fetal development and the short- and long-term outcomes for the neonate. In some cases, the mechanisms used by these pathogens to disrupt fetal development are well known. Bacterial infection of the developing fetal lungs and brain begins with an inflammatory cascade resulting in cytokine injury and oxidative stress. For some pathogens like P. falciparum, the mechanisms involve oxidative stress and apoptosis to disrupt placental and fetal growth. An in utero infection may also affect the long-term health of the infant; in many cases, a viral infection in utero increases the risk of developing type 1 diabetes in childhood. Understanding the varied mechanisms employed by these pathogens may enable therapies to attenuate changes in fetal development, decrease preterm birth, and improve survival.


A Seven-Year Study of Phenolic Concentrations of the Dioecious Salix myrsinifolia.
In boreal woody plants, concentrations of defensive phenolic compounds are expected to be at a high level during the juvenile phase and decrease in maturity, although there is variation between plant species. Females of dioecious species, like most of the Salicaceae, are expected to invest their resources in defense and reproduction, while males are expected to be more growth-oriented. We studied age- and sex-dependent changes in leaf and stem phenolics, and in height and diameter growth in a dioecious Salix myrsinifolia plants over a seven-year time period. In addition, we registered flowering as well as rust damage in the leaves. From the first year and throughout ontogenetic development from juvenile to adult phases, there was no significant change in the concentrations of any of the studied compounds in the leaves of S. myrsinifolia. In the stems, the concentrations of six out of 43 identified compounds decreased slightly with age, which may be partly explained by dilution caused by the increment in stem diameter with age. The fairly steady chemistry level over seven years, accompanied by moderate genotypic phenolic variation, indicates important roles of chemical defenses against herbivory for this early-successional species.


Use of neuroendocrine serum markers in the follow-up of patients with cancer of the prostate.
Neuroendocrine (NE) differentiation of prostatic adenocarcinomas has received increasing attention in recent years as a result of possible implications on prognosis and therapy. The incidence of NE cells in tumors has been reported from 10% up to 100%. Several studies have shown chromogranin A (CgA) to be the most reliable serum marker of NE differentiation. We have followed 22 patients with prostatic adenocarcinoma over a 2-year period. The patients underwent a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. The prostatic tissue specimens were stained immunohistochemically using antibodies against CgA, chromogranin B (CgB), neuron-specific enolase (NSE), thyroid-stimulating hormone (TSH), serotonin, and somatostatin. In addition, each specimen was stained with hematoxylin & eosin (H & E), and saffran for tumor grading. Blood samples were taken preoperatively and after 1, 3, 6, and 24 months. The serum values of CgA, CgB, pancreastatin (Pst), NSE, and prostate-specific antigen (PSA) were determined from each sample. Carcinomas with groups of CgA-positive cells had higher serum levels of CgA compared to carcinomas with no or only scattered CgA-positive NE cells. During the 2-year period, there were no statistical significant variations in serum levels of CgA, NSE, Pst, and PSA. However, there was a significant increase in serum levels of CgB during the same period, P = 0.002, possibly due to an increase in number of NE cells in tumor or to a relative increase in production of CgB in the NE cells.


Effect of alloxan-diabetes on the metabolism of rabbit colon smooth muscle.
The metabolism of colon smooth muscle from normal and alloxan-diabetic rabbits was studied in vitro. Glucose uptake, incorporation of glucose minus14-C into glycogen and incorporation of leucine minus-14C into protein were determined. These three parameters were all depressed in diabetic smooth muscle incubated in a medium containing 5.6 mM glucose. Raising the glucose concentration in the medium to 22.2 mM almost doubled the glucose uptake both in diabetic and normal smooth muscle and at this glucose concentration no significant difference in this parameter was found. Insulin (0.1 U/ml) added in vitro stimulated glucose uptake, incorporation of glucose minus14-C into glycogen and incorporation of leucine minus14-C into protein in diabetic colon smooth muscle. Insulin stimulated glucose uptake to the same degree in normal and diabetic colon smooth muscle, while its effect on glucose minus14-C and leucine minus14-C incorporation tended to be somewhat more pronounced in diabetic colon muscle.


Daboia (Vipera) palaestinae envenomation in horses: Clinical and hematological signs, risk factors for mortality and construction of a novel severity scoring system.
Daboia palaestinae is the most common venomous snake in Israel and an important cause of envenomations in humans and animals. Although specific antivenom is produced from horses, little documentation exists regarding the characteristics of envenomed horses. This survey was constructed to describe the clinical, hematological and biochemical characteristics of D. palaestinae envenomation in horses, to identify risk factors for fatality and to construct a prognostic snakebite severity scale (SSS) to be used by veterinarians in the field. Data regarding 123 equine snakebite cases were collected over four years. Clinical signs most frequently described were local swelling (100%), tachycardia (67%), increased respiratory effort (62%), bite marks (44%) and reduced appetite (50%). Blood samples were collected at initial presentation from 23 of these horses. Hematological and biochemical abnormalities described in the majority of the sampled cases included leukocytosis (52%), neutrophilia (78%), increased creatine phosphokinase (77%), hypoproteinemia (50%), decreased total carbon dioxide (54%), and hyperphosphatemia (54%). The overall case fatality rate was 20.3% (25/123 horses). Risk factors associated with increased mortality (P < 0.05) were body weight below 200 kg, hind limb envenomation, severity of local swelling, mental status, respiratory effort, bleeding disorders, dehydration, basophilia, monocytosis, bilirubinemia, hypocalcemia and hyperphosphatemia. These risk factors were used to construct an SSS adapted for the assessment of envenomed horses in the field, consisting of seven dichotomous parameters. A cutoff value of 1.5 predicted mortality with 95% sensitivity and 68% specificity. In the future, this tool could assist clinicians with case management and communication with owners.


Comparing pregnant women's nutritional knowledge to their actual dietary intake.
The purpose of this study was to describe differences between low-and middle-income pregnant women's general nutritional knowledge, usual dietary intake and weight gain. A descriptive design employing a questionnaire with a convenience sample of women (N = 109) from both childbirth education classes and a free prenatal clinic. Women with a low prepregnant body mass index (BMI) gained less weight, and women with high BMI tended to gain more weight than recommended. Most women had inadequate general nutritional knowledge, and their dietary intake did not meet all the nutritional requirements of pregnancy. Women attending the free prenatal clinic had more accurate knowledge of the recommended number of servings for some food groups (fruits and vegetables, meats and dairy) than women in childbirth education classes. No differences were noted between the groups in total weight gain. Further research is needed to evaluate pregnant women's nutritional knowledge and actual dietary practices, to develop effective strategies designed to promote adequate nutritional intake in pregnant women, and to help women remain within the Institute of Medicine (IOM) weight gain recommendations. Consistent individualized nutritional assessment and counseling during pregnancy could provide a foundation for continued healthy eating habits during the postpartum period and possibly throughout the woman's life.


Calibration of the Schiøtz tonometer for the normal canine eye.
The Schiøtz tonometer with 5.5-, 7.5-, and 10-g weights was calibrated for the normal canine eye, using a transducer with open and closed reservoir systems. The line of best fit for the observations was determined, and the equation of this line was utilized to derive a calibration table for the conversion of tonometer scale readings to mm of Hg intraocular pressure.


[Biomaterials based on collagen].
The review deals with collagen which is an essential natural polymer for preparing of biomaterials used in different fields of medicine. Besides discussing the structure of the basic polymer, the antigenicity of collagen materials as well as the bioactive properties of the collagen implants are described. The substantial part of the paper is oriented to the bioengineering processes of the preparation of the collagen matrix and composite structures. For these the physical and chemical modification of collagen are used. The processes of the modification are shown to be important in the fixing of the structure, improving the mechanical properties and influencing and directing the resorption of collagen materials in organism. Two types of materials are subdued to a detailed discussion. One which is combined with glycosoaminoglycanes and serves as the temporary skin cover and the second type, the structure of which, in the combination with hydroxylapatite imitates bone. (Tab. 4, Ref. 22.)


An industry update: the latest developments in therapeutic delivery.
The present industry update covers the period 1-31 January 2017, with information sourced from company press releases, regulatory and patent agencies as well as the scientific literature. With a new year come new resolutions, annual operation plans but also reports and outlooks for the years(s) to come. A number of the latter have been published in January forecasting various spaces in drug delivery (Market and Research). Also a number of financing deals were closed being fresh into the year such as Ossianix and Ocular Therapeutix and contract manufacturers will show their offerings at the 2017 MD&M West Medtech event (Lubrizol, Trelleborg). The US FDA released some new (draft) guidelines for combination products to regulate standards and disputes in this increasingly important field. Recent advances in artificial pancreas technology demonstrates that while the age of nanotechnology and gene therapy (Bluebird Bio) has arrived, implantable, closed-loop delivery systems (Medtronic) are just to pass successfully the clinic and come in reach of patients.


Primary retroperitoneal paraganglioma mimicking a ureteral tumor: a case report and literature review.
Paragangliomas (PGLs) arise from chromaffin cells of the extra-adrenal sites along the sympathetic and/or the parasympathetic chain. Majority of the PGLs occur in the abdomen. When retroperitoneal PGLs produce symptoms of compression or invasion of adjacent organs, they could be misdiagnosed as a tumor of adjacent organs. Here, we report a rare case of ureteral obstruction caused by an extra-adrenal retroperitoneal PGL that mimicked a ureteral tumor. A 46-year-old female presented with a 2-year history of hypertension. Routine laboratory tests were unremarkable. The computed tomography (CT) scan showed a hypervascular mass located in the left mid-ureteral section. Ureteropyelography revealed left ureteral obstruction at the level of L4 to L5 vertebrae and hydroureteronephrosis. Cystoscopy confirmed left ureteral obstruction. Based on the clinical and imaging findings, a left ureteral tumor was suspected preoperatively. The tumor was completely resected, and the involved segment of the ureter was removed. No significant enlarged lymph nodes were seen in the pelvic cavity and retroperitoneum. A histopathological examination of the tumor confirmed retroperitoneal PGL partly infiltrating the ureter. The patient's blood pressure returned to the normal range postoperatively. Our case demonstrates the importance of considering extra-adrenal PGL in the differential diagnosis of retroperitoneal tumors.


Study of IgE-dependent sulphidoleukotriene cellular releasability.
Cellular releasability of mediators, as termed by Lichtenstein and Conroy (1), can be triggered by interaction with allergens, anti-IgE antibodies or other agonists. Genetic factors can also influence the cell releasability. We studied 104 subjects, including 92 atopic patients (62 sensitive to D. pteronyssinus and 54 sensitive to Lolium perenne) and 12 healthy controls. Sulphidoleukotriene (sLT) production was measured after allergen and anti-IgE stimulus with CAST-ELISA, and histamine release using a fluorometric method. We found a significant sLT production after anti-IgE stimulation, higher than in basal conditions with medium alone. The sLT production was also significantly higher in sensitive patients than in healthy controls. We found 14.5% of healthy and atopic subjects to be non-responders to anti-IgE stimulus. We also found a positive and significant correlation between sLT production and histamine release. Moreover, we observed a significant positive correlation between IgE-dependent and antigen-specific sLT release. We also noticed a decrease in sLT production and a decrease in histamine release with aging. Male patients had a sLT production significantly higher than female patients. With respect to clinical diagnosis, the group of patients with rhinitis had the highest mediator production. Finally, pollinic patients studied during the spring had a higher sLT production to anti-IgE than those studied out of this season. We conclude that quantification of sLT production after anti-IgE stimulation is a useful method to study cell releasability of mediators and that such releasability is higher in atopic patients than in healthy donors. We must emphasize the usefulness in allergy diagnosis of relying not only on the use of methods demonstrating the existence of sensitization to an allergen, but also of techniques able to quantify the ability to respond to that allergen. In this way we would be able to evaluate the clinical and immunological evolution of patients and to follow up the efficacy of their treatment.


Do dogs sense hypoglycaemia?
To summarize the current knowledge on the phenomenon of dogs, both trained and untrained, sensing hypoglycaemia and alerting their owners to it. Electronic databases were searched for all types of articles reporting on untrained or trained 'diabetes alert' dogs. Articles published up until December 2014 in the English or German language were included. Several case reports and observational studies provide evidence that animals can perform at a level above that attributable to chance, and may reliably detect low diurnal as well as nocturnal hypoglycaemic episodes. Behavioural changes in untrained dogs were reported during 38-100% of hypoglycaemic events experienced by their owners. The sensitivity and specificity of the performance of trained diabetes alert dogs sensing hypoglycaemia ranged from 22 to 100% and 71 to 90%, respectively. Additionally, 75-81% of patients with diabetes who owned a trained dog reported a subsequent improvement in their quality of life. Nevertheless, the available data are limited and heterogeneous because they rely on low patient numbers and survey-based studies prone to recall bias. Further research is needed to confirm the preliminary data on the reliability and mechanism underlying the dogs' abilities to detect hypoglycaemia, and its impact on patient outcomes.


Sorption equilibrium of a wide spectrum of organic vapors in Leonardite humic acid: modeling of experimental data.
In a recent publication we presented experimental Leonardite humic acid/air partition coefficients for 188 polar and nonpolar organic compounds measured with one consistent method. In this paper these experimental data are evaluated with various model predictions. For the PcKocWIN model some major shortcomings become apparent. The octanol-based Karickhoff-model exhibits a good performance for the nonpolar compounds but not for the polar ones. A good description of the whole data set is achieved with a polyparameter linear free energy relationship (pp-LFER) that explicitly accounts for the nonpolar (van der Waals and cavity formation) and polar (electron donor/acceptor) interactions between the sorbate molecule and the sorbent phase. With this pp-LFER model, most of the humic acid/air partition coefficients could be predicted within a factor of 2. The pp-LFER model also successfully predicts organic-C/water partition coefficients (K(ioc)) collected from the literature when it is combined with a pp-LFER for air/water partition coefficients. This supports our earlier conclusion that the thermodynamic cycle is applicable in the humic acid/water/air system. Based on our experimental data, we present a pp-LFER-model for humic acid/air and humic acid/water partitioning at any ambient temperatures.


[Management of postoperative pancreatic fistula resistant to octreotide therapy].
Pancreatic fistula is a rare postoperative complication, usually occurring after pancreatic surgery. Majority of them heal spontaneously, some patients require somatostatin/octreotide treatment. The authors have presented 11 patients with postoperative pancreatic fistula, in whom octreotide therapy in dose of 0.1 mg t.i.d./10 days has been ineffective. The causes of pancreatic fistula have been as follows: necrosectomy of the infected pancreatic necrosis--5 patients, distal pancreatic resection--2 patients, insulinoma enucleation--2 patients, gastrectomy with partial pancreatectomy--2 patients. In 9 patients endoscopic stenting of the main pancreatic duct has been performed. In remained 2 patients after Roux-en-Y gastrectomy the endoscopic access to Vater papilla has been impossible and the patients have received one intramuscular injection of long acting somatostatin analogue. In 8 of 9 patients with pancreatic stenting and in two patients after gastrectomy the fistula has been closed within the period of 6-17 days. In one patient after the necrosectomy the prosthesis implacement has been ineffective. This patient has been successfully treated with two additional injections of long acting somatostatin analogue (one injection/14 days). Authors have concluded that endoscopic pancreatic stenting has been an effective method of treatment of the postoperative pancreatic fistula, resistant to octreotide therapy. In some cases, additional administration of long acting somatostatin analogue has been necessary.


Happy ending of life-threatening upper GI bleeding.
Strongyloides stercoralis is an intestinal nematode in humans, and estimated about tens of millions of people are infected worldwide. This parasite is endemic in tropical or temperate and subtropical climates like Bangladesh. The authors report a 33-year-old man who presented with recurrent life-threatening upper gastrointestinal bleeding from gastric infection by S stercoralis.