Non-local crime density estimation incorporating housing information.
Given a discrete sample of event locations, we wish to produce a probability density that models the relative probability of events occurring in a spatial domain. Standard density estimation techniques do not incorporate priors informed by spatial data. Such methods can result in assigning significant positive probability to locations where events cannot realistically occur. In particular, when modelling residential burglaries, standard density estimation can predict residential burglaries occurring where there are no residences. Incorporating the spatial data can inform the valid region for the density. When modelling very few events, additional priors can help to correctly fill in the gaps. Learning and enforcing correlation between spatial data and event data can yield better estimates from fewer events. We propose a non-local version of maximum penalized likelihood estimation based on the H(1) Sobolev seminorm regularizer that computes non-local weights from spatial data to obtain more spatially accurate density estimates. We evaluate this method in application to a residential burglary dataset from San Fernando Valley with the non-local weights informed by housing data or a satellite image.


Development of a microelectronic chip array for high-throughput genotyping of Helicobacter species and screening for antimicrobial resistance.
A microelectronic array assay was developed to specifically genotype Helicobacter pylori versus Helicobacter heilmannii and to determine antimicrobial resistance. Helicobacter 16S rRNA and 23S rRNA genes were specifically generated with Helicobacter genus-specific primers, respectively. The single-nucleotide polymorphisms (SNPs) in 16S rRNA, 268T specific in the H. pylori sequence, and 263A specific in H. heilmannii were used as molecular markers for identification of H. pylori and H. heilmannii, respectively. A triple-base-pair resistant mutation, AGA965-967TTC in 16S rRNA, is known to be responsible for H. pylori tetracycline resistance and was detected to identify resistant strains. H. pylori macrolide resistance was determined by the identification of 3 defined mutations in the 23S rRNA gene using the same method. The assay could be directly used to detect H. pylori in feces. The assay performs multiple determinations, including identification of Helicobacter species and antibiotic resistances, on the same microelectronic platform and is highly amenable to the development of other DNA-based assays.


Diffusion-limited and advection-driven electrodeposition in a microfluidic channel.
Self-terminating electrochemical fabrication was used within a microfluidic channel to create a junction between two Au electrodes separated by a gap of 75 microm . During the electrochemical process of etching from the anode to deposition at the cathode, flow could be applied in the anode-to-cathode direction. Without applied flow, dendritic growth and dense branching morphologies were typically observed at the cathode. The addition of applied flow resulted in a densely packed gold structure that filled the channel. A computer simulation was developed to explore regimes where the diffusion, flow, and electric field between the electrodes individually dominated growth. The model provided good qualitative agreement relating flow to the experimental results. The model was also used to contrast the effects of open and closed boundaries and electric field strength, as factors related to tapering.


Numerical workflow of irreversible electroporation for deep-seated tumor.
The paper provides a numerical workflow, based on the 'real-life' clinical workflow of irreversible electroporation (IRE) performed for the treatment of deep-seated liver tumors. Thanks to a combination of numerical modeling, image registration algorithm and clinical data, our numerical workflow enables to provide the distribution of the electric field as effectively delivered by the clinical IRE procedure. As a proof of concept, we show on a specific clinical case of IRE ablation of liver tumor that clinical data could be advantageously combined to numerical simulations in a near future, in order to give to the interventional radiologists information on the effective IRE ablation. We also corroborate the simulated treated region with the post-treatment MRI performed 3 d after the treatment.


Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin.
The integrin alpha4beta7 binds to MAdCAM-1 and contributes to homing of lymphocytes to gut and other mucosal tissues. In humans, the alpha4beta7(hi) subset of circulating memory cells appears to have been primed in mucosal tissues. The factors that determine whether alpha4beta7(lo) naive cells become alpha4beta(hi) or alpha4beta7(-) cells upon differentiation are poorly understood but could include an influence of the activating antigen-presenting cell. To address this point, the induction of alpha4beta7 following activation of mouse cells with the APC-dependent stimulus soluble anti-CD3 has been examined. Almost all mouse T cells freshly isolated from mesenteric lymph nodes (MLN) and peripheral (PLN; axillary, brachial and inguinal) lymph nodes stained only weakly for alpha4beta7 but a subpopulation became alpha4beta7(hi) upon activation with anti-CD3 in a cell cycle- and accessory cell-dependent manner. A small proportion (approximately 1.5 %) of the starting cells gave rise to alpha4beta7(hi) cells after culture. A higher proportion of alpha4beta7(hi) cells were generated in MLN than PLN cultures. Peyer's patch cultures gave intermediate values. In crossover experiments, MLN dendritic cells (DC) induced higher proportions and numbers of alpha4beta7(hi) cells than PLN DC irrespective of the source of T cells. Therefore, in addition to their other immunoregulatory roles, DC have the potential to shape immune responses by influencing the homing of the lymphocytes they activate.


[Results of treating infections of the cervical mucosa with doxycycline polyphosphate in 53 infertile women].
Our study was carried out on 53 women who had been infertile for more than a year and who had cervical mucus infection. In 13 cases (group A) there was no other known associated factor to cause the infertility. In 26 cases (group B) there was an obvious associated factor and in a further 14 cases there was a latent associated factor. The physical characteristics as well as the bacteriological appearances of the mucus (which included a systematic search for aerobic bacteria and for chlamydia trachomatis (CT) and for ureaplasma urealyticum (UU) were studied both before and 6-8 weeks after treatment with doxycycline polyphosphate given in doses of 100 mg twice daily. Before treatment the bacteria most often found were escherichia coli (20 cases) and enterococci (18 cases). CT was only found once and UU six times, usually in association with other bacteria. In 75.5% of cases the treatment made the affecting organism go; and cut down or removed entirely the number of leucocytes in the mucus in 73.5% of cases. But the physical characteristics of the mucus were only improved in 43% of cases, and in 18 cases a new infective organism was found in the mucus after treatment. However, it was in too low a concentration to determine its pathogenicity. There were nine pregnancies within 4 months of the start of treatment, which means that 30% in group A and 19% in group B became pregnant. Infection of the cervical mucus therefore does really seem to be a factor in lowered fertility in certain women CT and UU seem to be rarely the responsible organisms. Doxycycline phosphophate in an efficient and well tolerated treatment in these infections.


Photooxidation-Driven Purely Organic Room-Temperature Phosphorescent Lysosome-Targeted Imaging.
The construction of host-guest-binding-induced phosphorescent supramolecular assemblies has become one of increasingly significant topics in biomaterial research. Herein, we demonstrate that the cucurbit[8]uril host can induce the anthracene-conjugated bromophenylpyridinium guest to form a linear supramolecular assembly, thus facilitating the enhancement of red fluorescence emission by the host-stabilized charge-transfer interactions. When the anthryl group is photo-oxidized to anthraquinone, the obtained linear nanoconstructs can be readily converted into the homoternary inclusion complex, accompanied by the emergence of strong green phosphorescence in aqueous solution. More intriguingly, dual organelle-targeted imaging abilities have been also distinctively achieved in nuclei and lysosomes after undergoing photochemical reaction upon UV irradiation. This photooxidation-driven purely organic room-temperature phosphorescence provides a convenient and feasible strategy for supramolecular organelle identification to track specific biospecies and physiological events in the living cells.


A comparison of the daily energy needs of the normal and dwarf broiler breeder hen.
Feeding trials were conducted to determine optimum daily calorie intake needs for broiler breeder hens of normal and dwarf (dw) genetic lines. Pullets were grown to 24 weeks of age with limited feed intake and placed on one of five series of energy intakes. Series 3 represented a composite of energy intakes suggested by major broiler breeders with Series 1 and 2 representing a slower rate of energy increase and Series 4 and 5 representing more rapid rates. It was found that energy intakes suggested by a composite of the recommendations by the major breeders resulted in performance equal or superior to that of other groups tested. Using prediction equations the maximum daily needs for energy for normal sized hens was 422 M.E. kcal./day, with 418 mg./day of lysine and 380 mg./day of methionine.


The number of operations required for completing breast reconstruction.
Breast reconstruction often requires multiple surgeries, which demands additional expense and time and is often contrary to the patient's expectation. The aim of this study was to review the number of operations that were needed for completion of breast reconstruction and to determine patient and clinical factors that influenced this number. We retrospectively reviewed the medical records of 254 cases of breast reconstructions (in 185 patients) that were performed between February 2005 and August 2009. We investigated the numbers of operations that were performed for individual case of breast reconstruction and analyzed the influence of variable factors. The purpose of the additional operations was also analyzed. The mean number of operations per breast was 2.37 (range, 1-9). The mean number of operations for mound creation was 2.24. Factors associated with an increased number of operation were use of an implant, contralateral symmetrization, complications, and nipple reconstruction. Considering the reconstruction method, either the use of a primary implant or the use of free abdominal tissue transfer demonstrated fewer surgeries than the use of an expander implant, and the number of operations using free transverse rectus abdominis musculocutaneous or deep inferior epigastric perforator flaps was less than the number of operations using pedicled transverse rectus abdominis musculocutaneous flaps. These data will aid in planning breast reconstruction surgery and will enable patients to be more informed regarding the likelihood of multiple surgeries.


Literature & medicine: humanities at the heart of health care: a hospital-based reading and discussion program developed by the maine humanities council.
Created by the Maine Humanities Council in 1997, Literature & Medicine: Humanities at the Heart of Health Care is a hospital-based humanities reading and discussion program for practicing health care professionals. To date, a total of 25 (65%) of Maine's hospitals have implemented the six-month program at least once, reaching over 900 participants. At the monthly meetings, participants discuss assigned readings-works of fiction, poetry, drama, and nonfiction that illuminate issues central to caring for people. Scholars selected to facilitate the discussion foster nonhierarchical, wide-ranging discussions of the texts. Participants connect the world of science with the world of lived experience and engage with humanistic perspectives and insights that help them do their work better. Literature & Medicine is unique in promoting statewide programs that involve a heterogeneous mix of veteran health care professionals. The program has been or will be implemented in seven other states, and organizers are exploring further expansion of the program through a national institute.


Adult ADHD vs. bipolar disorder in the DSM-5 era: a challenging differentiation for clinicians.
Patients with adult attention-deficit/ hyperactivity disorder (ADHD) and bipolar disorder can present with similar symptoms, including increased energy, distractibility, disorganization, impulsivity, hyperactivity, and rapid speech. Determining whether the patient has either, or possibly both, of these syndromes can be a complex task. This review attempts to clarify where these disorders overlap, both symptomatically and epidemiologically, and where they diverge, to help clinicians increase the accuracy of their diagnoses. Changes to diagnostic criteria from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (from DSM-IV-TR to DSM-5) are discussed, as is the evidence base for pharmacological treatments. Studies and sources were identified using computerized searches. Adult ADHD and bipolar disorder have multiple overlapping symptoms, but there are differences in prevalence (ADHD affects 4.4% of adults in the United States versus 1.4% for bipolar disorder), onset of symptoms (usually before age 7 years in ADHD versus after age 12 years in bipolar disorder), disease course (chronic in ADHD versus cyclical in bipolar disorder), mood symptoms (absent in ADHD but always present in bipolar disorder), and psychotic symptoms (absent in ADHD but sometimes present in bipolar disorder). Approximately 20% of adult patients with ADHD also have bipolar disorder, while 10%-20% of patients with bipolar disorder have adult ADHD. Comorbidity of bipolar disorder and ADHD is associated with an earlier age of onset and a more chronic and disabling course of bipolar disorder, as well as more psychiatric comorbidity. Distinguishing between adult ADHD and bipolar disorder requires careful attention to phenomenology and awareness of epidemiology, with a focus on childhood history, lifetime course of symptoms, and the possibility of comorbidity.


One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea.
An efficient and odourless procedure for a one-pot synthesis of thioesters by the reaction of benzoic anhydrides, thiourea and various organic halides (primary, allylic, and benzylic) or structurally diverse, electron-deficient alkenes (ketones, esters, and nitriles) in the presence of Et3N has been developed. In this method, thiobenzoic acids were in situ generated from the reaction of thiourea with benzoic anhydrides, which were subjected to conjugate addition with electron-deficient alkenes or a nucleophilic displacement reaction with alkyl halides.


Predictors of Food Sensitization in Children and Adults Across Europe.
The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences. To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures. Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non-cross-reactive) FS. Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS. Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed.


Gastropexy for prevention of gastric dilatation-volvulus in dogs: history and techniques.
Gastric dilatation-volvulus (GDV) is a common and catastrophic disease of large and giant-breed dogs. Treatment of GDV includes medical stabilization followed by prompt surgical repositioning of the stomach in its normal anatomic position. To prevent reoccurrence, gastropexy is used to securely adhere the stomach to the body wall. Effective gastropexy decreases the recurrence of GDV from as high as 80% to less than 5%. The purpose of this article is to describe the history, indications, and techniques for gastropexy. Gastropexy was first reported in veterinary medicine in 1971 for the management of gastric reflux, and later in 1979 for treating and preventing the recurrence of GDV. Gastropexy is indicated in all dogs that undergo surgical correction of GDV. Additionally, prophylactic gastropexy should be strongly considered at the time of surgery in dogs undergoing splenectomy for splenic torsion and potentially other splenic pathology, and in dogs of at-risk breeds, such as Great Danes, that are undergoing exploratory celiotomy for any reason owing to evidence for increased risk of GDV in these patients. Although there are numerous techniques described, gastropexy is always performed on the right side of the abdomen, near the last rib. Ensuring an anatomically correct gastropexy location is vital to prevent postoperative complications such as partial pyloric outflow obstruction. Gastropexy can be performed as part of an open surgical approach to the abdomen or using a minimally invasive technique. When combined with surgical correction of GDV, gastropexy is almost always performed as an open procedure. The stomach is repositioned, the abdomen explored, and then a permanent gastropexy is performed. Techniques used for open gastropexy include incisional, belt-loop, circumcostal, and incorporating gastropexy, as well as gastrocolopexy. Each of these has been described later. Incisional gastropexy is currently the most commonly performed method of surgical gastropexy in dogs; it is quick, relatively easy, safe, and effective. Minimally invasive techniques for gastropexy are often used when gastropexy is performed as an elective, isolated procedure. Minimally invasive techniques include the grid approach, endoscopically guided miniapproach, and laparoscopic gastropexy. Laparoscopic gastropexy is the least invasive alternative; however, it requires special equipment and significant surgical expertise to perform. The authors consider it a veterinarian's responsibility to educate the owners of at-risk large and giant dog breeds about prophylactic gastropexy given such a favorable risk-benefit profile.


Lateral Medullary Infarction with or without Extra-Lateral Medullary Lesions: What Is the Difference?
Lateral medullary infarction (LMI) is not an uncommon disease. Although lesions are usually restricted to the lateral medullary area, some patients have additional infarcts in other parts of the brain. The clinical features and prognosis of isolated LMI (pure LMI, LMIpr) have been investigated. However, it remains unclear whether clinical characteristics, prognosis and factors associated with prognosis differ between patients with LMIpr and those with additional lesions (LMI plus, LMIpl). Patients with LMI identified by MRI were enrolled. The demographic and clinical characteristics, in-hospital outcome (intensive care unit [ICU] admission, pneumonia and modified Rankin scale [mRS] at discharge), and long-term residual symptoms (vertigo/dizziness, sensory disturbances, dysphagia) and outcomes (occurrence of stroke, acute coronary syndrome [ACS], death, and mRS at follow-up) were compared between LMIpr and LMIpl patients. Factors associated with poor functional outcome (mRS 2-6) at the follow-up were analyzed. Among 248 LMI patients, 161 (64.9%) had LMIpr and 87 (35.1%) had LMIpl. During admission, patients with LMIpl more frequently experienced ICU care, pneumonia and had a higher discharge mRS (3 vs. 2; p < 0.001) than LMIpr patients. The occurrence of stroke, ACS, frequency of death and functional outcome was not different during follow-up. However, residual neurologic symptoms such as dizziness (p = 0.002), dysphagia (p = 0.04) and sensory symptoms (p < 0.001) were more frequent in LMIpr than in LMIpl patients. In LMIpr patients, the rostral location of LMI was associated with poor functional outcome (p = 0.041), whereas in LMIpl patients, the presence of medial posterior-inferior cerebellar artery lesion was associated with good functional outcome (p = 0.030). Although the short-term outcome is poorer in LMIpl than LMIpr patients, long-term residual symptoms are more common in LMIpr patients. The location of the LMI and extra-medullary lesion affects the long-term functional outcome of LMIpr and LMIpl patients respectively.


Influence of side chain configuration on anti-inflammatory analgesic and anti-pyretic properties of 4-biphenylyl alkanoic acids.
A study on the influence of the number of carbon atoms in the side chain as well as side chain configuration on some pharmacologic properties of 4-biphenylyl alkanoic acids is presented. Unlike the chemical structure dependent anti-inflammatory properties, mild analgesic and anti-pyretic properties were neither dependent upon number of carbon atoms nor side chain configuration.


A combined helium atom scattering and density-functional theory study of the Nb(100) surface oxide reconstruction: Phonon band structures and vibrational dynamics.
Helium atom scattering and density-functional theory (DFT) are used to characterize the phonon band structure of the (3 × 1)-O surface reconstruction of Nb(100). Innovative DFT calculations comparing surface phonons of bare Nb(100) to those of the oxide surface show increased resonances for the oxide, especially at higher energies. Calculated dispersion curves align well with experimental results and yield atomic displacements to characterize polarizations. Inelastic helium time-of-flight measurements show phonons with mixed longitudinal and shear-vertical displacements along both the ⟨1̄00⟩, Γ̄X̄ and ⟨11̄0⟩, Γ̄M̄ symmetry axes over the entire first surface Brillouin zone. Force constants calculated for bulk Nb, Nb(100), and the (3 × 1)-O Nb(100) reconstruction indicate much stronger responses from the oxide surface, particularly for the top few layers of niobium and oxygen atoms. Many of the strengthened bonds at the surface create the characteristic ladder structure, which passivates and stabilizes the surface. These results represent, to our knowledge, the first phonon dispersion data for the oxide surface and the first ab initio calculation of the oxide's surface phonons. This study supplies critical information for the further development of advanced materials for superconducting radiofrequency cavities.


Behavioral model for Homalodisca vitripennis (Hemiptera: Cicadellidae): optimization of host plant utilization and management implications.
The glassy-winged sharpshooter, Homalodisca vitripennis (Germar), (Hemiptera: Cicadellidae), is a xylophagous leafhopper native to the southeastern United States and northern Mexico, with recent introductions into California, Arizona, French Polynesia, and Hawaii. It is a primary vector of the xylem-limited bacterium, Xylella fastidiosa Wells et al., the causative agent of Pierce's disease of grape, citrus variegated chlorosis, phony peach, and numerous leaf scorch diseases. H. vitripennis uses several hundred species of host plants for feeding, development, and reproduction. Variation in host utilization allows H. vitripennis to respond to diurnal and seasonal changes in its nutrient-poor food source, xylem fluid, as well as changing nutritional requirements of each leafhopper developmental stage. Here we provide a conceptual model that integrates behavior, life history strategies, and their associated risks with the nutritional requirements of adult and nymphal stages of H. vitripennis. The model is a useful heuristic tool that explains patterns of host plant use, describes insect behavior and ecology, suggests new associations among the ecological components, and most importantly, identifies and supports the development of suppression strategies for X. fastidiosa aimed at reducing vector populations through habitat manipulation.


Independent activity of the homologous small regulatory RNAs AbcR1 and AbcR2 in the legume symbiont Sinorhizobium meliloti.
The legume symbiont Sinorhizobium meliloti expresses a plethora of small noncoding RNAs (sRNAs) whose function is mostly unknown. Here, we have functionally characterized two tandemly encoded S. meliloti Rm1021 sRNAs that are similar in sequence and structure. Homologous sRNAs (designated AbcR1 and AbcR2) have been shown to regulate several ABC transporters in the related α-proteobacteria Agrobacterium tumefaciens and Brucella abortus. In Rm1021, AbcR1 and AbcR2 exhibit divergent unlinked regulation and are stabilized by the RNA chaperone Hfq. AbcR1 is transcribed in actively dividing bacteria, either in culture, rhizosphere or within the invasion zone of mature alfalfa nodules. Conversely, AbcR2 expression is induced upon entry into stationary phase and under abiotic stress. Only deletion of AbcR1 resulted into a discrete growth delay in rich medium, but both are dispensable for symbiosis. Periplasmic proteome profiling revealed down-regulation of the branched-chain amino acid binding protein LivK by AbcR1, but not by AbcR2. A double-plasmid reporter assay confirmed the predicted specific targeting of the 5'-untranslated region of the livK mRNA by AbcR1 in vivo. Our findings provide evidences of independent regulatory functions of these sRNAs, probably to fine-tune nutrient uptake in free-living and undifferentiated symbiotic rhizobia.


Cognition and the Default Mode Network in Children with Sickle Cell Disease: A Resting State Functional MRI Study.
Cerebrovascular complications are frequent events in children with sickle cell disease, yet routinely used techniques such as Transcranial Doppler (TCD), Magnetic Resonance (MRI) and Angiography (MRA), insufficiently explain the cause of poor cognitive performances. Forty children with SS-Sβ° (mean age 8 years) underwent neurocognitive evaluation and comprehensive brain imaging assessment with TCD, MRI, MRA, Resting State (RS) Functional MRI with evaluation of the Default Mode Network (DMN). Sixteen healthy age-matched controls underwent MRI, MRA and RS functional MRI.Children with SCD display increased brain connectivity in the DMN even in the absence of alterations in standard imaging techniques. Patients with low neurocognitive scores presented higher brain connectivity compared to children without cognitive impairment or controls, suggesting an initial compensatory mechanism to maintain performances. In our cohort steady state haemoglobin level was not related to increased brain connectivity, but SatO2<97% was. Our findings provide novel evidence that SCD is characterized by a selective disruption of connectivity among relevant regions of the brain, potentially leading to reduced cognition and altered functional brain dynamics. RS functional MRI could be used as a useful tool to evaluate cognition and cerebral damage in SCD in longitudinal trials.


Parity-violation energy of biomolecules-IV: protein secondary structure.
The parity-violation energy difference between enantiomeric forms of the same amino acid sequence, from the amyloid β-peptide involved in Alzheimer's disease, in both α-helix and β-sheet configurations, is investigated with ab-initio techniques. To this end, we develop an extension of the N2 computational scheme that selectively includes neighboring amino acids to preserve the relevant H-bonds. In agreement with previous speculations, it is found that the helical α structure is associated with larger parity-violation energy differences than the corresponding β form. Implications for the evolution of biological homochirality are discussed as well as the relative importance of various effects in determining the parity-violation energy.


Parathyroid hormone-related protein prevents high-fat-diet-induced obesity, hepatic steatosis and insulin resistance in mice.
Obesity, closely related to systematic metabolic disorders, has become a major public health problem in recent decades. Here, we aimed to study the function of Parathyroid hormone-related protein (PTHrP) on high fat diet (HFD) induced murine obesity. Male C57BL/6J mice were transduced with adeno-associated virus vector encoding PTHrP (AAV-PTHrP) or adeno-associated virus control vector (AAV-Vehicle), following with HFD for 8 weeks. In addition, mice without transduction were fed on normal diet or HFD, respectively. Histological, metabolic and biochemical changes were detected. At the endpoint of experiment, body weight of mice treated with AAV-PTHrP did not increase as much as mice with AAV-Vehicle, but similar as mice with normal diet. Food efficiency ratio and weight of interscapular brown adipose tissue and epididymal white adipose tissue in mice overexpressed PTHrP were also lower than mice transducted with AAV-Vehicle. Besides, administration of AAV-PTHrP inhibited HFD-induced adipocyte hypertrophy. Protein level of PKA signaling pathway and thermogenic gene in adipose tissue exhibited a significant raise in HFD + AAV-PTHrP group, whereas transcription of inflammatory gene were decreased. Additionally, PTHrP overexpression ameliorated HFD-induced dyslipidemia, hepatic steatosis and insulin sensitivity. In HFD-induced murine obesity model, PTHrP is crucial to maintain metabolic homeostasis. PTHrP drives white adipose tissue browning and inhibits whitening of brown adipose tissue. Most importantly, PTHrP prevented HFD-induced obesity, hepatic steatosis and insulin resistance.


[Diffuse sclerosing osteomyelitis of the mandible and SAPHO syndrome].
Diffuse sclerosing osteomyelitis of the mandible (DSOM) and SAPHO (synovitis, acne, palmo-plantar pustulosis and psoriasis, hyperosteosis, osteitis) syndrome are not commonly associated. SAPHO has not been described to date in the stomatology and maxillo-facial surgery literature in French. Were report here a homogeneous series of 12 patients with DSOM. All patients had mandibular osteitis. Five patients with multifocal osteitis wre considered to present SAPHO syndrome because of the associated skin lesions. One patient with a unique focus of mandibular osteitis and palmo-plantar pustulosis probably had early-stage SAPHO syndrome. The diagnosis in the other cases was diffuse sclerosis osteitis of the mandible. We compared our series with those reported in the literature, emphasizing diagnostic and therapeutic difficulties. Diffuse sclerosing osteomyelitis of the mandible should be distinguished from microbial osteitis. Early diagnosis is required to avoid successive and unnecessary dental avulsions. There is a possible link between DSOM and SAPHO and all patients should have a complete work-up including whole-body scintigraphy to search for other foci. A biopsy is indicated to rule out malignancy. Nonsteroidal antiinflammatory drugs can improve patient comfort in this particularly long syndrome. Although the efficacy is demonstrated, surgery and antibiotics can only delay relapse for a few months.


Effectiveness and Drug Survival of TNF Inhibitors in the Treatment of Ankylosing Spondylitis: A Prospective Cohort Study.
The aim of this research was to describe the effectiveness and drug survival of tumor necrosis factor (TNF) inhibitors in the treatment of ankylosing spondylitis (AS) and to analyze the effect of concomitant treatment with conventional disease-modifying antirheumatic drugs. Patients with AS identified from the National Register for Biologic Treatment in Finland starting their first TNF inhibitor treatment between July 2004 and December 2011 were included. Treatment response was measured as an improvement of 50% (or 20 mm) after 6 months of treatment onset compared to the baseline Bath AS Disease Activity Index (BASDAI) score. Treatment response and 2-year drug survival were modeled with logistic regression and time-dependent Cox proportional hazard models, respectively. The study comprised 543 patients, of whom 123 also commenced a second TNF inhibitor during the followup. Treatment was discontinued within 24 months by 25% and 28% of the users of the first and the second TNF inhibitors, respectively. BASDAI response at 6 months was achieved by 52% and 25% of the users of the first and the second TNF inhibitors, respectively. Etanercept (ETN; HR 0.42, 95% CI 0.29-0.62) and adalimumab (ADA; HR 0.48, 95% CI 0.30-0.77) were associated with better drug survival in comparison to infliximab (IFX). Also, concurrent use of sulfasalazine (SSZ; HR 0.70, 95% CI 0.49-0.99) decreased the hazard for treatment discontinuation. TNF inhibitors are equipotent in the treatment of AS; however, ETN and ADA were found superior to IFX in drug survival. The use of SSZ improves treatment continuation.


Management of an immature, partially necrotic permanent molar by pulp revascularization: Two-year follow-up.
Root canal treatment of immature teeth is considered a great challenge for both the dentist and the patient. The thinness of the root canals walls and the lack of an apical barrier leads to unpredictable treatment results. Revascularization is a novel promising treatment option in the field of regenerative endodontics for management of immature necrotic permanent teeth. This case presents a successful treatment of an 8-year-old patient with a partially necrotic, immature permanent mandibular right first molar pulp by revascularization. The revascularization procedure was performed in two appointments using nitrous oxide sedation to reduce the child's anxiety during treatment. Following root canal disinfection with NaOCl, a triple antibiotic paste (ciprofloxacin, metronidazole, and minocycline) was applied into the canal. One week later, induction of bleeding, application of MTA, and tooth restoration using a stainless steel crown were performed. At the subsequent follow-up appointments (3, 9, and 16 months) the tooth was asymptomatic. After 2 years a radiographic assessment revealed complete periapical healing and apical closure, as well as increase in root length and dentin thickness. This case supports the evidence of revascularization as a biological treatment option for the management of necrotic young permanent teeth.


Reactive oxygen species and autophagy modulation in non-marine drugs and marine drugs.
It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine drugs and marine drugs reported to be involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. In this review, we describe the strategy of oxidative stress-based therapy and connect the ROS modulating effect to the regulation of apoptosis and autophagy. Finally, we focus on exploring the function and mechanism of cancer therapy by the autophagy modulators including inhibitors and inducers from non-marine drugs and marine drugs.


Statistical physics of Bose-Einstein-condensed light in a dye microcavity.
We theoretically analyze the temperature behavior of paraxial light in thermal equilibrium with a dye-filled optical microcavity. At low temperatures the photon gas undergoes Bose-Einstein condensation, and the photon number in the cavity ground state becomes macroscopic with respect to the total photon number. Owing to a grand-canonical excitation exchange between the photon gas and the dye molecule reservoir, a regime with unusually large fluctuations of the condensate number is predicted for this system that is not observed in present atomic physics Bose-Einstein condensation experiments.


Sleep disturbance in clients attending a specialist addiction clinic.
Sleep problems are common among clients attending alcohol and drug services, yet the specific components of sleep disturbed by primary drug of concern (PDOC), and their relationships to affective disorder symptoms are unclear. We examined sleep problems in clients (n = 32) attending a specialist addiction clinic. Global sleep quality was rated poor by >90% of participants (particularly disturbances, latency and efficiency components), with significant associations (p < .05) between poor sleep quality and depression (r = .517), anxiety (r = .571) and stress (r = .503). Sleep quality was significantly poorer among those with a nonalcohol PDOC compared with alcohol as PDOC, t(22) = 3.09, p = .005. Poor sleep is almost ubiquitous among clients attending alcohol and drug services. However, components of sleep quality disturbed differ in terms of PDOC, highlighting the need for individualised sleep interventions.


Rhinovirus and coronavirus infection-associated hospitalizations among older adults.
Rhinoviruses and coronaviruses are recognized as the major causes of the common cold syndrome. The role of these viruses in more serious respiratory illnesses resulting in hospitalization is less well defined. During a winter when influenza A infection was prevalent, 100 elderly adults hospitalized because of cardiopulmonary illnesses were evaluated for rhinovirus and coronavirus infection. Patients who tested negative for influenza or respiratory syncytial virus had nasal swab samples tested for rhinovirus, coronavirus OC43, and coronavirus 229E by reverse-transcription polymerase chain reaction and for coronaviruses by serologic testing. Twelve percent of patients had rhinovirus or coronavirus identified (rhinovirus, 4 patients; coronavirus 229E, 4 patients; coronavirus OC43, 3 patients; and mixed rhinovirus/coronavirus 229E infection, 1 patient). All patients had significant underlying diseases. Although all patients recovered, the mean length of stay was 8 days; 4 persons had pneumonia, and 1 required ventilator support. These data suggest that rhinoviruses and coronaviruses may be associated with serious respiratory illnesses in frail older adults.


Postprandial Reactive Hypoglycemia.
Reactive hypoglycemia (RH) is the condition of postprandially hypoglycemia occurring 2-5 hours after food intake. RH is clinically seen in three different forms as follows: idiopathic RH (at 180 min), alimentary (within 120 min), and late RH (at 240-300 min). When the first-phase insulin response decreases, firstly, blood glucose starts to rise after the meal. This leads to late but excessive secretion of the second-phase insulin secretion. Thus, late reactive hypoglycemia occurs. Elevated insulin levels also cause down-regulation of the insulin post-receptor on the muscle and fat cells, thus decreasing insulin sensitivity. The cause of the increase in insulin sensitivity in IRH at 3 h is not completely clear. However, there is a decrease in insulin sensitivity in late reactive hypoglycaemia at 4 or 5 hours. Thus, patients with hypoglycemia at 4 or 5 h who have a family history of diabetes and obesity may be more susceptible to diabetes than patients with hypoglycemia at 3 h. We believe that some cases with normal glucose tolerance in OGTT should be considered as prediabetes at <55 or 60 mg/dl after 4-5 hours after OGTT. Metformin and AGI therapy may be recommended if there is late RH with IFG. Also Metformin, AGİ, TZD, DPP-IVInhibitors, GLP1RA therapy may be recommended if there is late RH with IGT. As a result, postprandial RH (<55 or 60 mg/dl), especially after 4 hours may predict diabetes. Therefore, people with RH along with weight gain and with diabetes history in the family will benefit from a lifestyle modification as well as the appropriate antidiabetic approach in the prevention of diabetes.


Seasonal diagnosis of echocardiographically demonstrated endocarditis.
Many cardiac and infectious diseases have a seasonal incidence. It is not known whether similar variations exist for endocarditis. As echocardiography plays a key role in diagnosing endocarditis, patients referred for echocardiography with suspected endocarditis from 1993 through 2001 were identified. The modified Duke criteria were used in establishing endocarditis. The echocardiography date was arbitrarily used to determine season: fall/winter (October to March) and spring/summer (April to September). For the 1,279 patients referred for echocardiography to rule out endocarditis, there was no seasonal difference between the total number of referred fall/winter and spring/summer patients (645 patients vs 634 patients, respectively). However, endocarditis was found in 41 fall/winter patients (6.4%) and 19 spring/summer patients (3.0%) patients (odds ratio, 2.20; 95% confidence interval, 1.26 to 3.83; p = 0.004). This seasonal disparity was present in 7 of the 9 years studied. No clinical factors could account for this seasonal disparity. As with many other cardiac diseases, a significant fall/winter predominance for endocarditis was found.


Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review.
Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore, vegetarians have reduced creatine stores and may benefit from supplementation. to determine the effects of creatine supplementation on vegetarians. PubMed and SPORTDiscus. Eligibility criteria: Randomized controlled trials (parallel group, cross-over studies) or prospective studies. Vegetarians. Creatine supplementation. Study appraisal and synthesis: A total of 64 records were identified, and eleven full-text articles (covering nine studies) were included in this systematic review. Creatine supplementation in vegetarians increased total creatine, creatine, and phosphocreatine concentrations in vastus lateralis and gastrocnemius muscle, plasma, and red blood cells, often to levels greater than omnivores. Creatine supplementation had no effect on brain levels of phosphocreatine. Creatine supplementation increased lean tissue mass, type II fiber area, insulin-like growth factor-1, muscular strength, muscular endurance, Wingate mean power output, and brain function (memory and intelligence) in vegetarian participants. Studies were mixed on whether creatine supplementation improved exercise performance in vegetarians to a greater extent compared to omnivores. Studies that were reviewed had moderate-high risk of bias. Overall, it appears vegetarian athletes are likely to benefit from creatine supplementation.


Phialophora richardsiae infection in humans.
Phialophora richardsiae infection in humans is rare. The first human isolate was recovered from a patient with a phaeomycotic cyst in 1968. Since 1975 seven other cases have appeared in the world literature, and an additional case is reported here. The mean age of these nine patients was 61.4 years. Two patients had diabetes mellitus, one had diabetes mellitus and disseminated adrenocortical carcinoma, and one had a myeloproliferative disorder. The mode of acquisition was presumed to be inoculation with contaminated plant material, but a history consistent with an inoculation injury was obtained in only four patients and a retained splinter was found in the lesion of only one patient. Infection with P. richardsiae was not associated with systemic symptoms or signs. Six patients presented with a single subcutaneous cystic granulomatous lesion. One patient had chronic dacryocystitis. More extensive or invasive disease occurred in two patients, both with an ultimately fatal underlying neoplastic process. A specific etiologic diagnosis was made by culture of purulent material obtained by excisional biopsy in six patients, incision and drainage in one patient, aspiration in one, and spontaneous drainage in one. Subcutaneous nodules were cured with surgical excision. There is insufficient information concerning antifungal therapy to recommend its use.


Nanoscale silicon field emitter arrays with self-aligned extractor and focus gates.
Out-of-plane focusing is essential for electron beam collimation in gated field emission sources. The focus electrode redirects electrons emitted by the tip with a wide angle towards the central axis, resulting a small focal spot at the anode. Here, we demonstrate for the first time, very high density (108 emitters/cm2) arrays of double-gated field emission electron sources with self-aligned apertures and integrated nanowire current limiters. Release of the emitters after fabrication required the combination of a highly selective dry-etch and an isotropic wet-etch to avoid the loss of the insulator between the two gates. The aperture diameters are ∼360 nm and ∼570 nm for the extractor gate and focus gate, respectively. The turn-on voltage was low (15-20) V and anode currents of 400 nA were measured at 25 V. We compared devices with different extractor gate thicknesses resulting from planarization non-uniformity, and demonstrate the influence of the focus gate on anode current. The focal spot size was measured, using a low energy phosphor screen, to be around 700 µm for a 500 µm device when the [Formula: see text] ratio was 0.35.


Characterization of the PP2A alpha gene mutation in okadaic acid-resistant variants of CHO-K1 cells.
Okadaic acid (OA)-resistant variants of Chinese hamster ovary cells, clones CHO/OAR6-6 and CHO/OAR2-3, were isolated from a CHO-K1 culture. These variant cells were 17- to 26-fold more resistant to OA than the parental cells. The phosphorylase phosphatase activity of the variant cell extracts was 2- to 4-fold more resistant to OA than that of the parental cells in the presence of inhibitor 2, a specific inhibitor of type 1 protein serine/threonine phosphatase (PP1). Nucleotide sequencing of PP2A alpha (an isotype of PP2A catalytic subunit) cDNA demonstrated that both variants have a T-->G transversion at the first base of codon 269 (805 nt), which results in substitution of glycine for cysteine. We expressed in COS-1 cells a mutant PP2A alpha tagged with the influenza hemagglutinin epitope. The recombinant mutant PP2A alpha protein immunoprecipitated with an anti-influenza hemagglutinin antibody was more resistant than the wild type to OA, their IC50 values being 0.65 nM and 0.15 nM, and their IC80 values being 4.0 nM and 0.45 nM, respectively. The cysteine at residue 269 present only in highly OA-sensitive protein serine/threonine phosphatase catalytic subunit isozymes, PP2A alpha, PP2A beta, and PPX, is suggested to be involved in the binding of OA. CHO/OAR6-6 and CHO/OAR2-3 cells also overexpressed the P-glycoprotein, and the efflux of OA was more rapid. It is suggested that the PP2A alpha mutation in cooperation with a high level of P-glycoprotein makes the CHO-K1 variants highly resistant to OA.


The development of a Cannabis Knowledge Assessment Tool (CKAT).
Misconceptions about the health risks of cannabis remain prevalent, indicating the need to improve public health messaging and determine the effectiveness of educational programming. Our objective was to develop a standardized questionnaire to measure knowledge about cannabis in the context of cannabis legalization. A Cannabis Knowledge Assessment Tool (CKAT) was created using the Delphi method. A purposive sample of healthcare professionals, policymakers, academics, patients, and students served as the content and development experts. Principal component analysis from the codes identified from open-ended feedback guided the item development. Upon completion, the CKAT was administered as a pre- and post-test in four schools (7th and 9th Grade) in Canada. The data were analysed to determine whether knowledge scores changed after participating in a cannabis education program. Twenty-four experts initially participated in the Delphi process and 18 (75% retention) continued throughout. Principal component analysis identified 3 domains: 1) effects of cannabis on the individual, 2) general information about cannabis, and 3) cannabis harm reduction. The final questionnaire consisted of 16 multiple-true-false questions (64 items) and received a Flesch-Kincaid Grade Level of 6.3, and a SMOG index score of 7.6. The CKAT was completed by 132 students; seventy-three 7th grade and fifty-nine 9th grade students. The baseline mean CKAT score was 46.2 (SD:5.5), which increased to 50.7 (SD:4.6) after the cannabis educational program (p<0.05). A novel tool to measure knowledge of cannabis was developed and piloted in 7th grade and 9th grade students. Future studies are required to test usability and validity of the CKAT in other contexts.


Toxicological significance of liver hypertrophy produced by inducers of drug-metabolizing enzymes.
Changes in enzyme activity due to induction by chemicals is an important property that can determine the type of response seen in tissues exposed to environmental chemicals. Two major types of response, acute irreversible liver cell injury or death (necrosis) and long-term cancer induction, are discussed in terms of their modulation by enzyme induction. Most commonly, enzyme induction leads to a more severe toxic response by the liver, and to more cell death. However, inducers may have a protective effect, especially in carcinogenesis, when they most frequently protect against cancer induction if used early in the process. There is a discrepancy between this observation and the increase in mutagenic activity of liver preparations observed after induction. However, when enzyme induction occurs at a later stage, after initiation, it often accelerates or promotes cancer induction. Also, new cell populations constantly observed during liver carcinogenesis are composed of very hypertrophic hepatocytes containing a large amount of smooth endoplasmic reticulum. This is associated with a radical change in enzyme activities in the reticulum, which may account in part for the characteristic resistance exhibited by initiated cells to hepatotoxins and carcinogens. The resistance is considered to be an important property that may play a key role in the development of cancer under some circumstances.


Predicting the partitioning behavior of various highly fluorinated compounds.
Due to their high degree of fluorination, highly fluorinated compounds (HFCs) have unique substance properties that differ from many other organic contaminants. To predict the environmental behavior of HFCs, models that predict both absorptive and adsorptive partitioning are needed; however, the accuracy of existing models has not heretofore been thoroughly investigated for these compounds. This report has two parts: first we show that a well-established polyparameter linear free energy relationship used to predict experimental adsorption constants underestimates values for HFCs by several orders of magnitude. We found a mechanistic explanation for the model's inaccuracy and adjusted it accordingly. In the second part of this report, we evaluate various models that predict saturated subcooled liquid vapor pressure (pL*), air-water partition constant (Kaw), and the octanol-water partition constant (Kow) based on molecular structure. These parameters are typically required for general environmental fate and transport models. Here, we found that SPARC and COSMOtherm make predictions usually within 1 order of magnitude of the experimental value, while the commonly used EPI SUITE and ClogP perform more inaccurately. The least accurate predictions occurred with ClogP for the fluorotelomer alcohols, where the estimated values were off by 2 to almost 5 orders of magnitude.


Microfluidic organotypic device to test intestinal mucosal barrier permeability ex vivo.
To protect the body from external pathogens, the intestines have sophisticated epithelial and mucosal barriers. Disruptions to barrier integrity are associated with a variety of disorders such as irritable bowel disease, Crohn's disease, and celiac disease. One critical component of all barriers are collagens in the extracellular matrix. While the importance of the intestinal barrier is established, current models lack the ability to represent the complex biology that occurs at these barriers. For the current study a microfluidic device model was modified to determine the effectiveness of collagen breakdown to cause barrier disruption. Bacterial collagenase was added for 48 h to the luminal channel of a dual flow microfluidic device to examine changes in intestinal barrier integrity. Tissues exhibited dose-dependent alterations in immunoreactive collagen-1 and claudin-1, and coincident disruption of the epithelial monolayer barrier as indicated by goblet cell morphologies. This ex vivo model system offers promise for further studies exploring factors that affect gut barrier integrity and potential downstream consequences that cannot be studied in current models.


The Camden & Islington Research Database: Using electronic mental health records for research.
Electronic health records (EHRs) are widely used in mental health services. Case registers using EHRs from secondary mental healthcare have the potential to deliver large-scale projects evaluating mental health outcomes in real-world clinical populations. We describe the Camden and Islington NHS Foundation Trust (C&I) Research Database which uses the Clinical Record Interactive Search (CRIS) tool to extract and de-identify routinely collected clinical information from a large UK provider of secondary mental healthcare, and demonstrate its capabilities to answer a clinical research question regarding time to diagnosis and treatment of bipolar disorder. The C&I Research Database contains records from 108,168 mental health patients, of which 23,538 were receiving active care. The characteristics of the patient population are compared to those of the catchment area, of London, and of England as a whole. The median time to diagnosis of bipolar disorder was 76 days (interquartile range: 17-391) and median time to treatment was 37 days (interquartile range: 5-194). Compulsory admission under the UK Mental Health Act was associated with shorter intervals to diagnosis and treatment. Prior diagnoses of other psychiatric disorders were associated with longer intervals to diagnosis, though prior diagnoses of schizophrenia and related disorders were associated with decreased time to treatment. The CRIS tool, developed by the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC), functioned very well at C&I. It is reassuring that data from different organizations deliver similar results, and that applications developed in one Trust can then be successfully deployed in another. The information can be retrieved in a quicker and more efficient fashion than more traditional methods of health research. The findings support the secondary use of EHRs for large-scale mental health research in naturalistic samples and settings investigated across large, diverse geographical areas.


Bioactive constituents from Chinese natural medicines. XXVI. Chemical structures and hepatoprotective effects of constituents from roots of Rhodiola sachalinensis.
The methanolic extract from the roots of Rhodiola sachalinensis was found to show a protective effect on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes. From the methanolic extract, five new glycosides, two monoterpene glycosides, two flavonol bisdesmosides, and a cyanogenic glycoside, were isolated together with 34 known compounds. The structures of new constituents were elucidated on the basis of chemical and physicochemical evidence. In addition, the principal constituents, sachalosides III and IV, rhodiosin, and trans-caffeic acid, displayed hepatoprotective effects.


Ebola in West Africa.
Ebola viral disease (EVD) is a severe and life-threatening disease. The current Ebola outbreak in West Africa entered its second year and is unprecedented because it is the largest one in history, involved urban centers and affected a large number of health care workers. It quickly escalated from medical into a humanitarian, social, economic, and security crisis. The primary pillars to prevent EVD are: early diagnosis, isolation of patients, contact tracing and monitoring, safe burials, infection prevention and control and social mobilization. The implementation of all these components was challenged in the field. Key lessons from this Ebola outbreak are that countries with weak health care systems can't withstand the major outbreaks; preparedness to treat the first confirmed cases is a national emergency; all control measures must be coordinated together and community engagement is the great factor to combat this disease.


A simple screening test for hearing impairment in elderly patients.
This study investigated the reliability of simple bedside free-field voice testing in the detection of hearing impairment in patients admitted to a geriatric unit. Sixty-two consecutive admissions were assessed at four graduated levels of loudness by geriatrician and otolaryngologist independently. Pure tone audiometry was then performed blind. Voice testing by both observers was concordant in 88% of all ears and in 100% of ears able to hear a whispered voice (WV) at 2 ft (approximately 0.6 m). The WV at 2 ft was the most discriminant test with a sensitivity of 100%, a specificity of 84% and a predictive value of 92% for hearing impairment likely to benefit from provision of a hearing aid. Free-field voice testing appears a simple, reliable and reproducible test for detecting hearing impairment in elderly patients.


Multiparametric magnetic resonance imaging to characterize cabotegravir long-acting formulation depot kinetics in healthy adult volunteers.
Cabotegravir long-acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection. Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic-guided injection targeting the gluteal muscles. MRI was performed to determine injection-site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue and combined IM/SC compartments, and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3 and 8. Linear regression analysis examined correlations between MRI-derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (Cmax ) and partial area under the concentration-time curve (AUC) through Weeks 4 and 8. Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n = 2), combined IM/SC compartments (n = 4), SC compartment (n = 1) and retroperitoneal cavity (n = 1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, Cmax and partial AUC through Weeks 4 and 8. MRI clearly delineated cabotegravir LA injection-site location and depot kinetics in healthy adults. Although injection-site variability was observed, drug depot surface area correlated with both plasma Cmax and partial AUC independently of anatomical distribution.


Food for thought: Will adolescent girls with eating disorders self-monitor in a CBT group?
This study of a Cognitive Behavior Therapy group examined the process of self-monitoring by adolescent females with eating disorders in group treatment. Five females, aged 17-18 with Anorexia Nervosa (n = 2) and Bulimia Nervosa (n = 3), participated in an 8-week treatment group. Self-monitoring occurred on 50% of the days and was highest during the first 3 weeks of treatment. Commitment to monitoring was related to the girls' self-reported readiness to change. Girls with Anorexia self-monitored as frequently as those with Bulimia. The clinical usefulness of self-monitoring with adolescents is discussed.


A child with sclerocornea, short limbs, short stature, and distinct facial appearance.
We describe a boy with sclerocornea, short limbs, short stature and a distinct facial appearance. The resemblance to other reports of affected sibs suggests that this is a newly recognised, autosomal recessive syndrome.


Separation and labeling of specific subpopulations of Botryllus blood cells.
Blood cells of the colonial tunicate Botryllus were separated by density gradient centrifugation in Percoll. Unseparated blood cells were used to immunize mice for development of hybridoma cell lines producing anti-Botryllus monoclonal antibodies. These antibodies identify specific subpopulations of blood cells, indicating possible divisions of these cells into defined subgroups sharing particular differentiation antigens. Additional studies utilizing fluorescein- conjugated lectins also revealed differential binding to density- and monoclonal antibody-defined blood cell fractions. These methods allow separation of the different Botryllus blood cell types for functional studies.


The Supreme Court's decision in McCulloch v Forth Valley Health Board: Does it condone healthcare injustice?
The UK Supreme Court's recent judgement in McCulloch v Forth Valley Health Board clarifies the standard for the identification of 'reasonable' alternative medical treatments. The required standard is that of a reasonable doctor: treatments that would be accepted as proper by a responsible body of medical opinion. Accordingly, the assessment of consent involves a two-stage test: first, a 'reasonable doctor' test for identifying alternative treatments; followed by a 'reasonable person in the patient's position' test for identifying the material risks of these reasonable alternative treatments. The separation of consent into two stages is consistent with not only a certain conception of freedom but also a nuanced construct of respect for autonomy that has a normative base. Furthermore, reliance on a reasonable doctor in the first stage is in keeping with a sociological account of medical professionalism, which posits that only doctors, and none others, can determine what is a proper treatment. Yet, reliance on a reasonable doctor permits a plurality of standards for reasonableness, because differences in opinion among doctors are pervasive. The reasons for some differences might be acceptable as unavoidable imperfections in medical decision-making to a reasonable person. But reasons for other differences might be objectionable; and the resultant inequalities in medical treatments would be considered unfair. One solution is to make the plurality of reasonable alternatives available to the patient, but this would introduce practical uncertainty and it is rejected by the Court. The Court's approach may be pragmatic; however, it seems to allow avoidable injustice in healthcare.


Large-Scale Purification of r28M: A Bispecific scFv Antibody Targeting Human Melanoma Produced in Transgenic Cattle.
30 years ago, the potential of bispecific antibodies to engage cytotoxic T cells for the lysis of cancer cells was discovered. Today a variety of bispecific antibodies against diverse cell surface structures have been developed, the majority of them produced in mammalian cell culture systems. Beside the r28M, described here, no such bispecific antibody is known to be expressed by transgenic livestock, although various biologicals for medical needs are already harvested-mostly from the milk-of these transgenics. In this study we investigated the large-scale purification and biological activity of the bispecific antibody r28M, expressed in the blood of transgenic cattle. This tandem single-chain variable fragment antibody is designed to target human CD28 and the melanoma/glioblastoma-associated cell surface chondroitin sulfate proteoglycan 4 (CSPG4). With the described optimized purification protocol an average yield of 30 mg enriched r28M fraction out of 2 liters bovine plasma could be obtained. Separation of this enriched fraction by size exclusion chromatography into monomers, dimers and aggregates and further testing regarding the biological activity revealed the monomer fraction as being the most appropriate one to continue working with. The detailed characterization of the antibody's activity confirmed its high specificity to induce the killing of CSPG4 positive cells. In addition, first insights into tumor cell death pathways mediated by r28M-activated peripheral blood mononuclear cells were gained. In consideration of possible applications in vivo we also tested the effect of the addition of different excipients to r28M. Summing up, we managed to purify monomeric r28M from bovine plasma in a large-scale preparation and could prove that its biological activity is unaffected and still highly specific and thus, might be applicable for the treatment of melanoma.


Minimally invasive transforaminal lumbar interbody fusion with ipsilateral pedicle screw and contralateral facet screw fixation.
The purpose of this study was to introduce a minimally invasive transforaminal lumbar interbody fusion (TLIF) technique that involves ipsilateral pedicle screw (PS) and contralateral facet screw (FS) fixation. Eight men and 15 women (mean age 59.5 years, range 48-68) underwent the aforementioned TLIF procedure for degenerative spondylolisthesis and uni- or bilateral radiculopathy. Twenty-two patients underwent one-level fusion and one patient two-level fusion (L4-S1). In all cases the various procedures were undertaken via one small incision. There were no intraoperative complications. The mean estimated blood loss (EBL) was 310 ml, and the mean operative time was 150 minutes in cases of one-level fusion. The follow-up period ranged from 13 to 28 months (mean 19 months). The mean Numeric Rating Scale score reflected improvement-reductions from 7.5 (back pain) and 7.4 (leg pain) to 2.3 and 0.7, respectively (p < 0.0001). The mean Oswestry Disability Index (ODI) scores also reflected improved status (ODI of 33.1 before the surgery to 7.6 after the surgery; p < 0.0001). Examination indicated that 22 of 24 fusion sites exhibited osseous union. At the last follow-up examination, satisfactory outcomes were observed in 21 out of 23 patients. The TLIF with ipsilateral PS and contralateral FS fixation has the advantages over the conventional TLIF of reduced EBL and diminished soft-tissue injury.


Cigarette smoke-induced proteostasis imbalance in obstructive lung diseases.
The airway and alveolar surface is exposed daily to 8,000 L of air containing oxygen, particles, bacteria, allergens and pollutants, all of which have the potential to induce oxidative stress within cells. If one is also a cigarette smoker, then the exposure to reactive oxidants increases exponentially. More than any other tissue, the lung is at risk of undergoing oxidative changes in protein expression, structure and function. The oxidant burden of chronic cigarette smoke exposure can overwhelm the lung cells' capacity to maintain proteostasis, a process of regulated protein synthesis, folding and turnover. Somewhat surprisingly, most chronic cigarette smokers do not develop chronic obstructive pulmonary disease (COPD), likely because cells initiate a highly effective unfolded protein response (UPR) in the presence of oxidant-derived endoplasmic reticulum (ER) stress that allows cells to survive. The UPR initiates several signaling pathways that decrease protein translation, limit cell cycle progression, increase protein degradation and chaperone-mediated protein folding, and activate the transcription factor Nrf2 that induces antioxidant gene expression. Each of these actions decreases ER stress in a process of "healthy proteostasis". If these responses are insufficient, apoptosis ensues. In this article, we review the mechanisms of healthy and dysfunctional proteostasis related to cigarette smoke exposure and COPD.


Assessment of in vivo effects of the prestige fuel oil spill on the mediterranean mussel immune system.
A laboratory experiment was carried out to study immune function alteration of the mussel Mytilus galloprovincialis when exposed to the Prestige oil spilled in November 2002 on the northwestern Spanish coast. Mussels were maintained for 4 months in tanks with flowing seawater and with 1, 2, and 0 kg (controls) Prestige fuel oil. Polycyclic aromatic hydrocarbon concentrations, which were determined in gills and digestive glands, were higher in digestive glands. The methylphenantrene and dibenzothiophene profiles confirmed the real exposure of mussels to the fuel oil. Immune data analysis revealed that no differences between fuel-treated and control animals were found in the cellular immune parameters measured (hemocyte viability, phagocytic activity, nitric oxide production, and chemiluminescence emission). In addition, histologic observations did not reveal tissue lesions in any of the samples, probably because of the short time of fuel-oil exposure. In contrast, significant differences were found in serum protein concentration and lysozyme activity between the fuel-treated mussels and controls. However, these humoral immune parameters were dependant on numerous environmental and physiologic factors, so it was difficult to ascertain the real effect of the fuel oil on their variability. Because hemocytes are the primary line of defense of bivalve mollusks, the results obtained in the present study suggest that the mussel immune system was not significantly affected by exposure to the Prestige fuel oil.


Operative treatment of III grade open fractures of the tibial diaphysis.
Open fractures, especially III grade open fractures of the tibial diaphysis, according to the Gustilo classification still remains a serious therapeutic problem. The aim of the study was to evaluate the clinical results after operative treatment of III grade open fractures of diaphysis of the tibia and to promote a new method of fracture fixation. 48 patients with open fractures of the tibial diaphysis, classified as type III A and B, according to the Gustilo classification, were operatively treated. Patients were divided into two groups depending on the manner of fracture fixation. Patients in group A (30 pts.) were treated with an external fixator and those in group B (18 pts.) with unreamed intramedullary nails. The time of the union of the fracture, problems with the union (malunion and nonunion), infection, different complications and the functional outcome were examined. Late complications and their treatment were not the object of the study. The follow-up period was at least 12 months. The results of the study showed a mean time of union of 38.4 weeks in patients in group A, and 32.8 for those in group B. Malunion was noticed in 5 (16.6%) in group A and 2 (11.1%) in group B, nonunion in 4 (13.35) in group A and in 2 (11.1%) patients in group B. Superficial infection developed in 7 (23.3%) and deep in 6 (20%) of the patients in group A and in group B in 4 (22.2%) and 2 (11.1%) of the patients. Results from the functional examination showed 26.6% excellent and the same percent of fair results in group A. In group B there were 55.5% excellent and 11.1% fair results. Different types of complications were noticed in the patients from both groups. The final results of the examination showed a shorter time of union, a lower percentage of complications and a better functional outcome in the patients in group B. Unreamed intramedullary interlocking nailing of open fractures of the diaphysis of the tibia (grade III A and B according Gustilo classification) is a relatively safe method of operative treatment with fewer complications compared with external fixation.


Plasminogen activation by staphylokinase enhances local spreading of S. aureus in skin infections.
Staphylococcus aureus (S. aureus) is a frequent cause of skin and soft tissue infections. A unique feature of S. aureus is the combined presence of coagulases that trigger fibrin formation and of the plasminogen activator staphylokinase (SAK). Whereas the importance of fibrin generation for S. aureus virulence has been established, the role of SAK remains unclear. We studied the role of plasminogen activation by SAK in a skin infection model in mice and evaluated the impact of alpha-2-antiplasmin (α2AP) deficiency on the spreading and proteolytic activity of S. aureus skin infections. The species-selectivity of SAK was overcome by adenoviral expression of human plasminogen. Bacterial spread and density was assessed non-invasively by imaging the bioluminescence of S. aureus Xen36. SAK-mediated plasmin activity increased the local invasiveness of S. aureus, leading to larger lesions with skin disruption as well as decreased bacterial clearance by the host. Even though fibrin and bacterial surfaces protected SAK-mediated plasmin activity from inhibition by α2AP, the deficiency of α2AP resulted in increased bacterial spreading. SAK-mediated plasmin also induced secondary activation of gelatinases, shown both in vitro and in lesions from the in vivo model. SAK contributes to the phenotype of S. aureus skin infections by enhancing bacterial spreading as a result of fibrinolytic and proteolytic activation.


Professional assessment of optimal nursing care intensity level. A new method for resource allocation as an alternative to classical time studies.
In the article a new method is presented for allocation of staff resources, 'Professional Assessment of Optimal Nursing Care Intensity Level' (PAONCIL). This method is presented as an alternative to classical time study, which has traditionally been considered to belong to systems for patient classification. By means of this method the optimal nursing care intensity level for individual wards can be established. The study comprised 8 wards, and the nurses working in these wards provided a total of 8,458 professional assessments of optimal nursing care intensity levels. The material was analysed by means of simple linear regression analysis. The nursing care intensity scores per nurse in a single ward were used as independent variables and the average PAONCIL score for the same calendar day was used as a dependent variable. The average determination coefficient for different wards were 0.37; the PAONCIL instrument thus explained 37% of the nursing care intensity/nurse variation. This corresponded to a linear correlation of 0.60. In five out of six wards for adults the optimal nursing care intensity/nurse scores were close to each other, ranging from 3.0 to 3.6. The advantage of the PAONCIL method is that it can be easily implemented in a ward, can be used time and again, is advantageous and is based on quality aspects. The PAONCIL method has been developed on the basis of a caring science perspective and can be seen as an administrative method for the nurse manager, with whose help 'good care' can become possible.


Microbial ecology of nitrifying bacteria in wastewater treatment process examined by fluorescence in situ hybridization.
The microbial ecology of nitrifying bacteria in various types of wastewater treatment processes and the dynamic response of the microbial ecology in biofilms were investigated using fluorescence in situ hybridization (FISH) with 16S rRNA-targeted oligonucleotide probes. Nitrifying bacteria were found to exhibit various organizational forms under different conditions of substrate composition and concentration. Ammonia-oxidizing bacteria were dominant in ammonia-rich inorganic wastewater, while heterotrophic bacteria and ammonia-oxidizing bacteria were localized at different positions in the biofilm in organic wastewater. The dynamics of the microbial ecology in the biofilm with regard to the spatial distribution of ammonia-oxidizing bacteria and heterotrophic bacteria caused by a gradual change in substrate composition was successfully monitored by FISH analysis.


[The effect of metal ions on the lipolytic activity of Mycobacterium rubrum and Actinomyces streptomycini].
Hydrolysis of olive oil by intact cells of Mycobacterium rubrum 403 and "acetone" preparations of Actinomyces streptomycini 116 was found to be inhibited by the following ions: Ca2+, Mg2+, Mn2+, Ba2+, Co2+, Cd2+, Cu2+, Zn2+, Fe2+, Fe3+, Ni2+. Olive oil is hydrolyzed by the growing culture of Act. streptomycini 116 only in the presence of bivalent metal ions. The biosynthesis of lipase by Mycobatcerium rubrum 403 and Act. streptomycini 116 is increased twofold by magnesium ions. The biosynthesis of lipase by Act. stroptomycini 116 is stimulated also by calcium ions.


Innovations and Future Directions in Head and Neck Microsurgical Reconstruction.
Head and neck reconstructive microsurgery is constantly innovating because of a combination of multidisciplinary advances. This article examines recent innovations that have affected the field as well as presenting research leading to future advancement. Innovations include the use of virtual surgical planning and three-dimensional printing in craniofacial reconstruction, advances in intraoperative navigation and imaging, as well as postoperative monitoring, development of minimally invasive reconstructive microsurgery techniques, integration of regenerative medicine and stem cell biology with reconstruction, and the dramatic advancement of face transplant.


Dynamics of replication foci and nuclear matrix during S phase in Allium cepa L. cells.
The sequential organisation of replication foci during S phase in onion ( Allium cepa) and their relationship to the nuclear matrix were investigated. To discern their structural features and temporal firing sequence, immunodetection of 5-bromo-2'-deoxyuridine (BrdU) was carried out after in vivo feeding in synchronised cells released from a 14-h-long hydroxyurea block. Replication foci consisted of small replication granules, called replisomes, which clustered together. Analysis of synchronous binucleate cells that maintained in their two nuclei the specular symmetry of distribution of sister chromosomes in anaphase, showed that replication starts in small replication foci at the telomeric pole (pattern I), though the telomeres themselves formed large foci that were late-replicating. The rDNA replication foci (pattern II) also become replicated in early S phase. Replication of large foci, including the heterochromatin (IV), occurred in late S phase and finished at the centromeric nuclear pole (pattern V). Labelling of proliferating cell nuclear antigen (PCNA) in nuclear matrices, prepared from S-phase nuclei after extensive DNase digestion, demonstrated that replication foci were always stably anchored to the nuclear matrix. Thus, association with the nucleoskeleton is not exclusively mediated by the replicating or nascent DNA. The overlapping of patterns I, II and III in the nuclear matrix, in contrast to the results of BrdU localisation in nuclei, suggests that PCNA becomes associated with the nuclear matrix before the replication foci are operative, and remains bound during replication.


Biodiversity thresholds in invertebrate communities: The responses of dung beetle subgroups to forest loss.
Extinction thresholds have been predicted to be critical values of habitat loss in which an abrupt reduction in populations occurs through the interaction between reduced habitat and increased isolation in the landscape. In communities, extinction thresholds are referred to as 'biodiversity thresholds'. The biodiversity threshold values documented so far occur between 30% and 50% of habitat cover in landscapes. However, the assessment of biodiversity thresholds has mainly focused on vertebrate and plant communities. Here, we evaluated the occurrence of biodiversity thresholds in dung beetle communities by sampling ten 3,600 ha Atlantic Forest landscapes with forest cover ranging from 5% to 55%. We analysed the response patterns (abundance, gamma and mean alpha diversity) of community subgroups with different levels of forest dependency (forest species, generalist species, and open-area species) using model selection, comparing null, linear, bell-shaped and logistic models. The response of the community of forest species equally fits both linear and logistic models predicting a biodiversity threshold at 25% forest cover. Generalist species showed peak abundance at 20% forest cover although this result reflects a very poor generalist assembly. Open-area specialists did not respond to the amount of forest. The two most plausible models for forest species suggest two different biodiversity management options. Since the biodiversity threshold model represents a more dramatic scenario for the loss of biodiversity in Atlantic forest landscapes, we suggest, based on precautionary principle, that our results should strength guidelines that consider minimum values of forest cover in management strategies to avoid abrupt biodiversity loss and impacts on ecosystem services.


A hominoid-specific nuclear insertion of the mitochondrial D-loop: implications for reconstructing ancestral mitochondrial sequences.
A nuclear integration of a mitochondrial control region sequence on human chromosome 9 has been isolated. PCR analyses with primers specific for the respective insertion-flanking nuclear regions showed that the insertion took place on the lineage leading to Hominoidea (gibbon, orangutan, gorilla, chimpanzee, and human) after the Old World monkey-Hominoidea split. The sequences of the control region integrations were determined for humans, chimpanzees, gorillas, orangutans, and siamangs. These sequences were then used to construct phylogenetic trees with different methods, relating them with several hominoid, Old Work monkey, and New World monkey mitochondrial control region sequences. Applying maximum-likelihood, neighbor-joining, and parsimony algorithms, the insertion clade was attached to the branch leading to the hominoid mitochondrial sequences as expected from the PCR-determined presence/absence of this integration. An unexpected long branch leading to the internal node that connects all insertion sequences was observed for the different phylogeny reconstruction procedures. This finding is not totally compatible with the lower evolutionary rate in the nucleus than in the mitochondrial compartment. We determined the unambiguous substitutions on the branch leading to the most recent common ancestor (MRCA) of the mitochondrial inserts according to the parsimony criterium. We propose that they are unlikely to have been caused by damage of the transposing nucleic acid and that they are probably due to a change in the evolutionary mode after the transposition.


AuDis: an automatic CRF-enhanced disease normalization in biomedical text.
Diseases play central roles in many areas of biomedical research and healthcare. Consequently, aggregating the disease knowledge and treatment research reports becomes an extremely critical issue, especially in rapid-growth knowledge bases (e.g. PubMed). We therefore developed a system, AuDis, for disease mention recognition and normalization in biomedical texts. Our system utilizes an order two conditional random fields model. To optimize the results, we customize several post-processing steps, including abbreviation resolution, consistency improvement and stopwords filtering. As the official evaluation on the CDR task in BioCreative V, AuDis obtained the best performance (86.46% of F-score) among 40 runs (16 unique teams) on disease normalization of the DNER sub task. These results suggest that AuDis is a high-performance recognition system for disease recognition and normalization from biomedical literature.Database URL: http://ikmlab.csie.ncku.edu.tw/CDR2015/AuDis.html.


Embryonic divergence of oligodendrocyte and astrocyte lineages in developing rat cerebrum.
Oligodendrocyte and astrocyte lineages were traced in rat forebrain sections using single- and double-label immunoperoxidase and indirect immunofluorescent techniques. Antibodies were directed against antigenic markers, the expressions of which overlapped in time: GD3 ganglioside in immature neuroectodermal cells; vimentin in radial glia; glial fibrillary acidic protein (GFAP) in astrocytes; and carbonic anhydrase (CA) and galactocerebroside (GC) in oligodendrocytes. A histochemical stain for iron was also used as a marker of oligodendrocytes. Small cells of the subventricular zone (SVZ) were stained with anti-GD3 but not with the other antibodies. By 16 d of gestation (E16), the SVZ generated large, round cells and thick, process-bearing cells that were GD3+/CA+/iron+. These cells then appeared in the cingulum and, with time, increased in numbers and extended thick processes as they filled the subcortical white matter. These cells eventually lost their reactivity to anti-GD3 but became GC+/CA+ with processes extending to myelin sheaths. At E15 radial glia were stained with the anti-vimentin antibody but were negative for GFAP. At birth, only the vimentin+ radial glia midline between the 2 ventricles were GFAP+, but with time more vimentin+ cells became GFAP+. By 7 d of postnatal age all the vimentin+ cells were GFAP+ and had converged predominately on the cingulum. With time these cells condensed and took on characteristic shapes of astrocytes. The embryonic separation of the oligodendrocyte and the astrocyte lineage is supported by four pieces of evidence: (1) GD3+ cells were double labeled with anti-CA, and then went on to become GC+; (2) vimentin+ and GFAP+ cells were not also GD3+; (3) ultrastructural localization of anti-GD3 was confined to cells with characteristics consistent with developing oligodendrocytes; and (4) the shapes of GD3+, CA+, GC+, or iron+ cells did not resemble those of the vimentin+ or GFAP+ cells.


Impact of age and co-morbidities in patients with newly diagnosed glioblastoma: a pooled data analysis of three prospective mono-institutional phase II studies.
To analyse the impact of age and co-morbidities on compliance and outcomes in GBM patients enrolled in three prospective phase II trials. GBM patients (≥ 18 years) were treated with radiotherapy (60 Gy) or enrolled in a Fractionated Stereotactic Conformal-Radiotherapy Phase II trial (69.4 Gy). Concomitant and adjuvant chemotherapy with Temozolomide (TMZ) was administered. Charlson Index Co-morbidity (CCI) was used to assess co-morbidity. Toxicity was evaluated according to RTOG score. Survival analysis was performed by the Kaplan-Maier. Influence of age and co-morbidity was evaluated using log-rank test. From 2001 to 2008, 146 patients were enrolled: 56 (38.4 %) aged over 65 and 90 under 65. CCI ≥ 1 was observed in 41 % of elderly and 22 % of young group. Patients' compliance was 97.9 % for radio-chemotherapy. Acute toxicity was mild with no difference between the groups. Global median progression-free survival (PFS) and overall survival (OS) were 12 and 18 months, respectively. Age, surgery and radiation dose correlated with survival (p = 0.01, p = 0.04 and p = 0.03). CCI ≤ 2 did not show any influence on OS. Our data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while CCI ≤ 2 did not correlated with OS.


Trends in recombinant protein use in animal production.
Recombinant technologies have made possible the production of a broad catalogue of proteins of interest, including those used for animal production. The most widely studied proteins for the animal sector are those with an important role in reproduction, feed efficiency, and health. Nowadays, mammalian cells and fungi are the preferred choice for recombinant production of hormones for reproductive purposes and fibrolytic enzymes to enhance animal performance, respectively. However, the development of low-cost products is a priority, particularly in livestock. The study of cell factories such as yeast and bacteria has notably increased in the last decades to make the new developed reproductive hormones and fibrolytic enzymes a real alternative to the marketed ones. Important efforts have also been invested to developing new recombinant strategies for prevention and therapy, including passive immunization and modulation of the immune system. This offers the possibility to reduce the use of antibiotics by controlling physiological processes and improve the efficacy of preventing infections. Thus, nowadays different recombinant fibrolytic enzymes, hormones, and therapeutic molecules with optimized properties have been successfully produced through cost-effective processes using microbial cell factories. However, despite the important achievements for reducing protein production expenses, alternative strategies to further reduce these costs are still required. In this context, it is necessary to make a giant leap towards the use of novel strategies, such as nanotechnology, that combined with recombinant technology would make recombinant molecules affordable for animal industry.


Nursing workload in the emergency department: a methodological proposal.
This study aimed to propose a methodology for identifying the nursing workload in the Emergency Department (ED). this is methodological research, undertaken in a public general hospital in the municipality of São Paulo, Brazil, in the areas: triage, shock room, emergency room, suturing room, and medication/procedures for adult and pediatric patients rooms, using different strategies and instruments. Due to the characteristics of the data collection, distinct samples were obtained in each of the areas. The average daily workload, in hours, corresponded to: triage 48; shock room 30.9; emergency 170.6; observation of adult patients 293.6; observation of pediatric patients 108.7; medication/procedures in adult patients 175.5; medication/procedures in pediatric patients 60.4; and suturing 7.9. The instruments used for data collection were shown to be appropriate and made it possible to construct a methodological proposal for identification of workload of nursing professionals in E.D. in a general public hospital.


The Relationship Between Housing Status and Substance Use and Sexual Risk Behaviors Among People Currently Seeking or Receiving Services in Substance Use Disorder Treatment Programs.
Although HIV risk behaviors such as substance use and condomless sex are prevalent among people currently seeking or receiving services at substance use disorder (SUD) treatment programs, associations with housing status in this population have not been well studied. We examined the associations between housing status, substance use and HIV-related sexual risk behaviors among 1281 participants from 12 US community-based SUD programs. In addition, substance use was examined as a potential mediator of the relationship between housing status and sexual risk behaviors. We conducted Chi-square, univariate and multivariate logistic regression models on data from the National Drug Abuse Treatment Clinical Trials Network HIV Rapid Testing and Counseling study. Path analysis was used to test the mediation and indirect effects. Unstable housing was significantly associated with having multiple concurrent condomless sex partners, condomless sex with non-primary partners, and partners of unknown HIV serostatus. Homelessness was significantly associated with condomless vaginal sex and condomless sex with any substance use. The path between unstable housing and sexual risk behaviors was mediated by problematic drug use, particularly by cocaine, opioids, and marijuana use. Because housing status impacts HIV risk behaviors for individuals in SUD treatment programs, both housing status and substance use behaviors should be assessed upon program entry in order to identify and mitigate risk behaviors.


Comparison of central corneal thickness measurements by ultrasound pachymeter, optical coherence tomography and corneal topography.
To compare central corneal thickness (CCT) measured by standard ultrasound pachymeter with optical coherence tomography (OCT) and corneal topography A cross-sectional study of central corneal thickness measurement by ultrasound pachymeter, OCT and corneal topography in 30 eyes of 30 healthy volunteers was done by a single examiner at Thammasat University Hospital between October 2010 and January 2011. The results were compared using ANOVA for repeated measures and Pearson correlation. Mean central corneal thickness by ultrasound pachymeter OCT and corneal topography were 552.1 +/- 33.6 microm, 554.5 +/- 33.0 microm and 552.8 +/- 39.0 microm respectively. There were no statistically significant differences in the measurement results among the three modalities (p = 0.718). There was a significant linear correlation between OCT and ultrasound pachymeter (Pearson correlation = 0.985, p < 0.001), corneal topography and ultrasound pachymeter (Pearson correlation = 0.965, p < 0.001) and corneal topography and OCT (Pearson correlation = 0.965, p < 0.001). Mean central corneal thickness among ultrasonic pachymeter, OCT and corneal topography were comparable and had significant linear correlations. In clinical practice, these three modalities could be interchangeable.


Body fluid proteomics: Prospects for biomarker discovery.
Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e., the tissue interstitial fluid, TIF). A major challenge of clinical chemistry is to quantitatively map these perturbed protein profiles - the so-called "signatures of disease" - using modern proteomic technologies. This information can be utilized to design protein biomarkers for the early detection of disease, monitoring disease progression and efficacy of drug action. Here, we discuss the use of body fluids in the context of prospective biomarker discovery, and the marked 1000-1500-fold dilution of body fluid proteins, during their passage from TIF to the circulatory system. Further, we discuss proteomics strategies aimed at depleting major serum proteins, especially albumin, in order to focus on low-abundance protein/peptides in plasma. A major limitation of depletion strategies is the removal of low-molecular weight protein/peptides which specifically bind major plasma proteins. We present a prototype model, using albumin, for understanding the multifaceted nature of biomarker research, highlighting the involvement of albumin in Alzheimer's disease. This model underscores the need for a system-level understanding for biomarker research and personalized medicine.


The relationship between the Leicester cough questionnaire, eosinophilic airway inflammation and asthma patient related outcomes in severe adult asthma.
Severe asthma is characterised by a variety of symptoms, which include chronic cough, however the mechanisms responsible for cough reflex hypersensitivity in asthma remain poorly elucidated. Current asthma patient-related outcome instruments such as the six-point Juniper Asthma Control Score (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) were not primarily designed to capture cough and its related morbidity in asthma. The Leicester Cough Questionnaire (LCQ) is a patient-related outcome instrument designed to capture the health-related quality of life associated with cough. To date the LCQ has not been evaluated in a severe asthma population. We evaluated 262 extensively characterised adult patients with severe asthma attending the Leicester Severe Asthma Service. All patients had a clinician diagnosis of asthma and objective physiological evidence and met the ATS/ERS criterion for servere asthma. In all patients we evaluated a) the LCQ distribution and b) the relationships between the LCQ and ACQ-6, AQLQ, airway inflammation in sputum. The LCQ demonstrated the following properties; mean: 15.0, standard deviation: 4.54, median: 15.48, and range: 11.6-19.2. We found a moderate correlation between LCQ and ACQ-6 (r = - 0.605, p < 0.0001) and a LCQ and AQLQ (r = 0.710, p < 0.0001). There was no relationship between LCQ and log10 sputum percentage eosinophils (%). A proportion of patients with severe asthma have a significant degree of cough-related morbidity that appears independent of eosinophilic airway inflammation and is not captured fully by existing asthma patient-reported outcome instruments. Our preliminary findings suggest that further research is now required to validate the LCQ and its responsiveness in severe asthma populations to capture cough-related morbidity and response to specific interventions.