Fluorine-19 Magnetic Resonance Imaging and Positron Emission Tomography of Tumor-Associated Macrophages and Tumor Metabolism.
The presence of tumor-associated macrophages (TAMs) is significantly associated with poor prognosis of tumors. Currently, magnetic resonance imaging- (MRI-) based TAM imaging methods that use nanoparticles such as superparamagnetic iron oxide and perfluorocarbon nanoemulsions are available for quantitative monitoring of TAM burden in tumors. However, whether MRI-based measurements of TAMs can be used as prognostic markers has not been evaluated yet. In this study, we used positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) as a radioactive tracer and fluorine-19- (19F-) MRI for imaging mouse breast cancer models to determine any association between TAM infiltration and tumor metabolism. Perfluorocarbon nanoemulsions were intravenously administered to track and quantify TAM infiltration using a 7T MR scanner. To analyze glucose uptake in tumors, 18F-FDG-PET images were acquired immediately after 19F-MRI. Coregistered 18F-FDG-PET and 19F-MR images enabled comparison of spatial patterns of glucose uptake and TAM distribution in tumors. 19F-MR signal intensities from tumors exhibited a strong inverse correlation with 18F-FDG uptake while having a significant positive correlation with tumor growth from days 2 to 7. These results show that combination of 19F-MRI and 18F-FDG-PET can improve our understanding of the relationship between TAM and tumor microenvironment.


Room-Temperature Multiferroics and Thermal Conductivity of 0.85BiFe1-2xTixMgxO3-0.15CaTiO3 Epitaxial Thin Films (x = 0.1 and 0.2).
Thin films of 0.85BiFe1-2xTixMgxO3-0.15CaTiO3 (x = 0.1 and 0.2, abbreviated to C-1 and C-2, respectively) have been fabricated on (001) SrTiO3 substrate with and without a conductive La0.7Sr0.3MnO3 buffer layer. The X-ray θ-2θ and ϕ scans, atomic force microscopy, and cross-sectional transmission electron microscopy confirm the (001) epitaxial nature of the thin films with very high growth quality. Both the C-1 and C-2 thin films show well-shaped magnetization-magnetic field hysteresis at room temperature, with enhanced switchable magnetization values of 145.3 and 42.5 emu/cm3, respectively. The polarization-electric loops and piezoresponse force microscopy measurements confirm the room-temperature ferroelectric nature of both films. However, the C-1 films illustrate a relatively weak ferroelectric behavior and the poled states are easy to relax, whereas the C-2 films show a relatively better ferroelectric behavior with stable poled states. More interestingly, the room-temperature thermal conductivity of C-1 and C-2 films are measured to be 1.10 and 0.77 W/(m·K), respectively. These self-consistent multiferroic properties and thermal conductivities are discussed by considering the composition-dependent content and migration of Fe-induced electrons and/or charged point defects. This study not only provides multifunctional materials with excellent room-temperature magnetic, ferroelectric, and thermal conductivity properties but may also stimulate further work to develop BiFeO3-based materials with unusual multifunctional properties.


A theoretical model to address organizational human conflict and disruptive behavior in health care organizations.
This article proposes a theoretical model for leaders to use to address organizational human conflict and disruptive behavior in health care organizations. Leadership is needed to improve interpersonal relationships within the workforce. A workforce with a culture of internal conflict will be unable to achieve its full potential to delivery quality patient care.


Palliative Care in Kidney and Liver Diseases.
The role of palliative care is to recognize patients with advanced illnesses who are at risk for poor outcomes and to alleviate their pain and suffering. Patients with both kidney and liver disease are a very vulnerable population due to the unique pathophysiologic relationship these two organs share, which often leads to an abbreviated life expectancy and a significant symptom burden. These patients face many challenges in their care. This article discusses the importance of prognostication for early palliative care referrals as well as the management of the two most common complaints patients with kidney and liver disease face: pain and ascites.


Family leave policies, job share, and child care at U.S. schools and colleges of pharmacy.
A 10-question survey was mailed to the deans of 74 schools and colleges of pharmacy to characterize family leave policies, child care, and job share opportunities. Data were tabulated as percentage response received, and analyzed by geographic region and by public compared with private institutions. Sixty-four surveys were completed (response rate 86%). Forty-eight (75%) schools reported having a formal written family leave policy: 47 offered maternity leave, 31 parental leave, 27 caregiver leave, 24 paternal leave, and 24 adoptive or foster parent leave. The duration and compensation for family leave varied among schools. A statistical difference was found between the Northeast (100%) and South (55%) in having such a policy. On-site child care was available at 26 (41%) schools, including both infant and child care in 12 and additional sick child care in 2. Three (5%) schools reported faculty job share positions.


Childhood trauma and suicide risk in the population living in Zonguldak Province.
No previous study has investigated the association between early trauma and suicidal behavior in Zonguldak. The aim of this study was to investigate the incidence of childhood abuse and neglect in the general population living in Zonguldak province and the relationship between childhood trauma and suicidal ideations and attempts. The present study was carried out with 897 people in the general population, as assessed in a representative sample from Zonguldak province. The cluster sampling method was used. After obtaining written consent from the people who agreed to participate in the study, the Socio-demographic Information Form, Suicide Probability Scale, Childhood Trauma Questionnaire, Beck Depression Inventory, and Beck Anxiety Inventory were administered. The lifetime prevalence of suicidal ideations was 18.3% among those who experienced at least one type of early trauma, and it was 9.6% among those without a history of childhood trauma (P < 0.001). Only emotional abuse exhibited a significantly high odds ratio for lifetime suicidal ideations (odds ratio [OR] = 3.168, 95% confidence interval [CI] = 1.731-5.798) and attempts (OR = 3.467, 95% CI = 1.343-8.952). Emotional neglect showed a high odds ratio only for lifetime suicidal attempts (OR = 3.282, 95% CI = 1.287-8.371). There were significant correlations among the Beck Depression Inventory, Beck Anxiety Inventory, and Suicidal Probability Scale sub-scores and all six Childhood Trauma Questionnaire scores. Emotional abuse and neglect in childhood are significantly associated with lifetime suicidal ideations and attempts in the general population living in Zonguldak province. Therefore, clinicians should be aware of the importance of the childhood trauma in the patients with suicidal ideations and attempts.


Regulatory considerations for the approval of analgesic drugs for cattle in the United States.
Continuous life-cycle management of veterinary drugs by the Food and Drug Administration Center for Veterinary Medicine (CVM) ensures that safe and effective approved animal drugs are available for use in the United States. This article summarizes basic requirements for the approval of new animal drugs, with a specific focus on the approval of analgesic drugs for use in cattle. CVM encourages drug companies to use innovative approaches to demonstrate the effectiveness of analgesic drugs for cattle. There is an obvious need for continued research into the development of new animal drugs for the control of pain in cattle.


Hospitalizations for Kawasaki disease among children in the United States, 1988-1997.
To evaluate the epidemiologic pattern of Kawasaki disease (KD) in the United States over 10 years. The National Inpatient Sample, a stratified national sample of >900 hospitals in 22 states of the United States, was used. Data on hospital discharges from 1988-1997 were analyzed. Patients <18 years of age with a discharge diagnosis of KD were identified. There were 6442 patients with KD admitted to 651 hospitals. Median age at hospital admission was 2 years. Peak incidence by year of age was 1 year old. Children <2 years old accounted for 36.6% of all cases; <5 years old, 75.6%; and <10 years old, 95.6%. The age distribution seems to be wider than reported from Japan. The incidence for children <5 years old was 8.1 per 100 000 people in 1988, and increased to 18.5 in 1997. There were 3905 males (60.6%) and 2537 females (39.4%), for a male-to-female ratio of 1.54. The incidences were higher in winter and spring (December to May) and dropped to a nadir between July and September. No apparent change in seasonal pattern was noted over 10 years. The South census region showed a seasonal change 2 to 3 months ahead of other regions. The overall in-hospital mortality rate was 0.17%. The mortality rate in children > or =10 years (1.4%) was significantly higher in than children <10 years (0.11%). KD affects mainly children under 5 years of age, with a peak incidence in children 1 to 2 years of age. The incidence of KD was rising over the study period. There is a male predominance. Although KD occurs year-round, the lowest incidence is seen from July through September. Such seasonal variation did not change over the 10 years. Seasonal pattern may vary in different geographic regions. Mortality from KD is rare, although children > or =10 years are at higher risk.


Very-long-chain secondary alcohols and alkanediols in cuticular waxes of Pisum sativum leaves.
In cuticular waxes from leaves of Pisum sativum, 19 secondary alcohols, 10 primary/secondary alkanediols and three secondary/secondary alkanediols were identified by various chemical transformations with product assignment employing GC-MS. The homologous series of C29-C33 secondary alcohols (1.1 microg/cm2) was dominated by hentriacontanol isomers (94%). Only octacosanediols and trace amounts of hexacosanediols (< 1%) were detected in the primary/secondary alkanediol faction (0.7 microg/cm2). The secondary/secondary alkanediols (0.12 microg/cm2) contained a single homologue with chain length C31. All three compound classes showed characteristic isomer distributions with secondary functional groups predominantly located between C-14 and C-16. Based on the isomer compositions, the sequence of biosynthetic steps introducing the hydroxyl functions is discussed.


[Eight cases of calcific retropharyngeal tendinitis/retropharyngeal calcific tendinitis].
Calcific retropharyngeal tendinitis/retropharyngeal calcific tendinitis is an inflammation of the longus colli muscle caused by calcium hydroxyapatite crystal depositon in the longus colli muscle tendon. The three major symptoms are neck pain, limitations of neck movement, and swallowing pain. We treated 8 cases of calcific retropharyngeal tendinitis/ retropharyngeal calcific tendinitis. Each patient complained of neck pain, limitations of neck movement, and swallowing pain. The only local finding was the smooth swelling of the posterior pharyngeal wall. CT imaging showed calcification of the tendon of the longus colli muscle and a low density area in the retropharyngeal space without ring enhancement, suggesting a retropharyngeal abscess. MR imaging showed the smooth swelling of the retropharyngeal space and an increased signal intensity on T2-weighted MR imaging. Calcific retropharyngeal tendinitis heals spontaneously, and treatment is not usually required. However, the clinical outcomes are similar and can be confused with retropharyngeal abscess and pyogenic spondylitis, so antibiotics are administrated in many cases. In our report, 7 patients were hospitalized and were treated with the intravenous administration of antibiotics, while 1 patient who refused hospitalization was treated with an oral antibiotic. Steroids were administrated in 2 cases. The 7 patients who were hospitalized were cured within 6 to 10 days.


Scalp recorded somatosensory evoked potentials in response to cauda equina stimulation in neurosurgical operations on the spinal cord.
Somatosensory evoked potentials were recorded from the scalp in response to cauda equina stimulation in a total of 30 patients who were treated neurosurgically for spinal space-occupying lesions. Reproducible potentials could be obtained intraoperatively in 26 patients (86.7%). Preoperatively all of the four remaining patients had severe neurological deficits and an incomplete para- or tetraparesis. On the basis of an acceptable amplitude reduction of up to 50% at the end of the operation, it was possible to make an accurate statement as to the expected postoperative neurological state in all of the 26 patients in whom potentials could be obtained intraoperatively. There were no false positive or false negative findings. Our results confirm the reliability and usefulness of this invasive stimulation and non-invasive recording technique when applied intraoperatively.


Precision Determination of the Small-x Gluon from Charm Production at LHCb.
The small-x gluon in global fits of parton distributions is affected by large uncertainties from the lack of direct experimental constraints. In this Letter, we provide a precision determination of the small-x gluon from the exploitation of forward charm production data provided by LHCb for three different center-of-mass (c.m.) energies: 5 TeV, 7 TeV, and 13 TeV. The LHCb measurements are included in the parton distribution function (PDF) fit by means of normalized distributions and cross-section ratios between data taken at different c.m. values, R_{13/7} and R_{13/5}. We demonstrate that forward charm production leads to a reduction of the PDF uncertainties of the gluon down to x≃10^{-6} by up to an order of magnitude, with implications for high-energy colliders, cosmic ray physics, and neutrino astronomy.


Electron transport in cytochromes P-450 by covalent switching.
The mechanism of electron transfer in cytochrome P-450cam is presented in terms of a covalent switching mechanism. We present a model of putidaredoxin built by homology, which helps explain protein-protein interactions. The mechanism is general enough to account for the genetic variations found in the superfamily of cytochromes P-450. The detail should assist in the design of novel P-450 inhibitors and may have wider implications. The sequence analysis supports our protein model, and highlights the role of cystein and aromatic residues in electron-transport mechanisms. Eukaryotic cytochromes P-450 appear to have evolved their own intramolecular tryptophan electron-transfer mediator, unlike prokaryotic P. putida P-450cam, which still relies upon the C-terminal tryptophan of its attendant electron-transport protein, putidaredoxin. On this basis our protein model is capable of rationalizing the transfer of electrons from NADH to the active site of P-450. At the electronic level the covalent switching that transfers pairs of electrons not only provides a plausible mechanism, but may also have ramifications in a wider context.


Prevalence and characteristics of catatonia on admission to an acute geriatric psychiatry ward.
This study aims to describe the prevalence of catatonia in a population of older acute psychiatric inpatients according to different diagnostic criteria. Secondary objectives are: to compare the catatonic symptom profile, prevalence, and severity, in respect to the underlying aetiology, and to evaluate the association between catatonic and somatic comorbidity. The study included 106 patients admitted to an acute geriatric psychiatry ward. Catatonia was assessed using the Bush Francis Catatonia Rating Scale (BFCRS). Catatonia was highly prevalent (n=42; 39.6%), even when using restrictive diagnostic criteria: Fink and Taylor (n=19; 17.9%) and DSM 5 (n=22; 20.8%). Depression was the most frequent psychiatric syndrome among catatonic patients (n=18; 42.8%). Catatonia was more frequent in depression (48.6%) and delirium (66.7%). Affective disorders showed a higher risk than psychotic disorders to develop catatonia (OR=2.68; 95% CI 1.09-6.61). This association was not statistically significant when controlling for dementia and geriatric syndromes. The most prevalent catatonic signs were excitement (64.3%), verbigeration (61.9%), negativism (59.5%), immobility/stupor (57.1%), and staring (52.4%). Catatonia in older psychiatric inpatients was highly prevalent. Depression was the most common psychiatric syndrome among catatonic patients, and catatonia was more frequent in depression and mania, as well as in delirium. Affective disorders were associated with a higher risk of developing catatonia compared to psychotic disorders. Somatic and cognitive comorbidity played a crucial aetiological role in catatonia in this series.


Benzylic C-H addition of aromatic amines to alkenes using a scandium catalyst.
An efficient and selective benzylic C(sp3)-H addition of o-CH3-substituted tertiary aromatic amines to alkenes has been achieved using an anilido-oxazoline ligand supported scandium catalyst, which provides an atom-economic method for the synthesis of a new family of alkylated tertiary anilines. A wide range of amine and alkene substrates are compatible with the catalyst system.


Expression of neurotensin receptors in human corneal keratocytes.
The purpose of the study was to investigate whether cultured human keratocytes express the neurotensin receptors (NTR1, NTR2, and NTR3), to determine the presence of neurotensin (NT) in keratocytes, and to assess the influence of NT on these cells. Human keratocytes were cultured in medium treated with various concentrations (10(-7)-10(-9) M) of JMV449 (a weakly degradable NT agonist). Cell proliferation and viability were analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay. Apoptosis was studied by nucleus labeling with a fluorescent dye and cold light fluorometry. NT, NTR1, NTR2, and NTR3 mRNA were detected in human keratocytes by means of reverse transcriptase-polymerase chain reaction (RT-PCR). NTR1 protein was detected by Western blot analysis. Functionality of NTR1 was assessed by intracellular calcium ([Ca2+]i) measurement with a dynamic imaging microscopy system. RT-PCR and Western blot analysis showed the expression of the NTR1 (mRNA and protein) and NTR3 mRNA in human corneal keratocytes. NT and NTR2 mRNA were undetectable. JMV449 induced a rapid and transient [Ca2+]i increase in human corneal keratocytes that was blocked by the specific antagonist SR48692. JMV449 significantly increased cell proliferation and viability after 72, 96, and 120 hours of culture, with a maximum effect at 10(-7) M (P < 0.005). Finally, JMV449 decreased keratocyte apoptosis, whatever the concentration used (P < 0.005). These results indicate that cultured human keratocytes express NTR1 and NTR3 and that NT may exert physiological effects on cornea such as regulation of keratocyte proliferation and apoptosis.


Theory and experiments for voltammetric and SECM investigations and application to ORR electrocatalysis at nanoelectrode ensembles of ultramicroelectrode dimensions.
Theoretical and experimental approaches to characterizing nanoelectrode (NE) ensembles of ultramicroelectrode dimensions (UME-NEEs) as a function of fraction of active area and random NE distribution are described. UME-NEEs were fabricated by addressing microregions of a gold-filled polycarbonate membrane through the UMEs of an underlying microfabricated addressable array. Results of Comsol Multiphysics 3D simulations based on randomly spaced NEs of 15 nm radius on a UME disk geometry of radii up to 5 μm are shown for steady-state voltammetry (SSV) and scanning electrochemical microscopy (SECM) experiments. Analytical equations were developed to describe the diffusion-limited steady-state current and steady-state voltammogram at an UME-NEE. These equations are shown to be in good agreement with the simulations and enabled evaluation of experimental SSVs. Comparison of experimental and simulated SECM approach curves, images, and tip voltammograms enabled the fraction of active area and distribution of NEs to be visualized and determined for individual UME-NEEs. Gold UME-NEEs are shown to be unique platforms for electrodeposition in forming nanoparticle electrodes (UME-NPEs). Electrocatalysis results for the oxygen reduction reaction (ORR) on Pt UME-NPEs in 0.1 M H2SO4 are also shown.


Serum IgG antibodies to gliadin in children with celiac disease as measured by an immunofluorescence method.
Antigliadin antibodies (AGAs) were studied in sera from 190 patients divided into five clinical groups. Group I included 28 sera from children with newly diagnosed celiac disease on a normal diet. Group II consisted of 43 sera from children with celiac disease who were fed a gluten-free diet (GFD). Group III included 25 sera from children with celiac disease who had been in remission but exposed to a gluten-containing diet (GCD). Group IV consisted of 46 sera from children with chronic diarrheal disorders other than celiac disease. Group V included 43 sera from healthy children. The observed p values proved that (a) mean titer levels of AGAs in Groups I and III were significantly higher than the mean values for all other groups (p less than 0.001), and (b) the mean titer level of AGAs in Group II was significantly higher than the mean values for Groups IV and V. A good correlation between the AGA titers and the morphology of the duodenal mucosa was found in children with celiac disease. The examination of IgG AGAs by the immunofluorescence technique used in our study appears to be a useful tool in the follow-up of individual patients to determine adherence to a GFD.


In Vitro Activities of LCB 01-0648, a Novel Oxazolidinone, against Gram-Positive Bacteria.
Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds. LCB01-0648 showed the most potent antimicrobial activities against clinically isolated Gram-positive bacteria. Against the methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates, LCB01-0648 showed the lowest MIC90s (0.5 mg/L) among the tested compounds. In addition, LCB01-0648 had the lowest minimum inhibitory concentrations (MICs) against the four linezolid-resistant S. aureus (LRSA) strains (range 2-4 mg/L). The results of the time-kill studies demonstrated that LCB01-0648 at a concentration 8× the (MIC) showed bactericidal activity against methicillin-susceptible Staphylococcus aureus MSSA or MRSA, but showed a bacteriostatic effect against LRSA. These results indicate that LCB01-0648 could be a good antibacterial candidate against multidrug-resistant (MDR) Gram-positive cocci.


Quantitative Cathodoluminescence Mapping: A CdMgSeTe Thin-Film Case Study.
Full-spectrum cathodoluminescence (CL) mapping provides a point-by-point spatial measurement of the apparent band gap of a semiconductor thin film. In most studies, analysis of the electrical film properties from CL is presented as color mapping images. We have developed a spectra data analysis algorithm to functionalize, analyze, and generate statistical measurements of the luminescence data to provide additional insights. This algorithm was coded in the R language program, and a set of CdMgSeTe films were studied as an application case study. CL maps were measured for samples with different luminescent responses. A quantitative measure of the heterogeneity of the films was generated by statistical analysis of luminescent intensity and wavelength, spectra type curves, frequency distributions of peak wavelength, and relative intensity maps. The final CL analysis facilitates the investigation of the CdMgSeTe films and has potential applications for many semiconductor films.


Electrochemical chromatographic determinations of morphine antagonists in biological fluids, with applications.
The morphine antagonists naltrexone and naloxone were extracted from plasma and urine, separated on a chromatographic column, and assayed by electrochemical detection. Optimum oxidation potentials were 0.65 V for morphine and 0.75 V for naloxone and naltrexone. Assay sensitivities were 2-5 ng/mL for plasma and 10 ng/mL for urine. The assays were applied to determine red blood cell partition coefficients of 1.83 +/- 0.15 (SD) for naltrexone and 1.49 +/- 0.27 (SD) for naloxone in a concentration range of 10-3500 ng/mL. No significant time dependence for the partitioning could be observed. Plasma protein binding in the same concentration range, determined by ultracentrifugation, was 27.7% +/- 2.5% (SD) for naltrexone and 30.1% +/- 5.1% (SD) for naloxone. The degree of protein binding did not change in the presence of morphine for morphine-antagonist ratios between 1:10 and 10:1. No concentration dependencies of red blood cell partitioning or protein binding were observed.


British Columbia's One Nursing Regulator: A Critical Commentary on the Amalgamation Process.
Nursing organizations including regulatory colleges are undergoing transitions that fundamentally alter the face of Canadian nursing. As British Columbia regulatory and professional organizational transitions are held up as a potential model for the rest of Canada, we offer a critical commentary on a most recent transition to the One Nursing Regulator of all nursing role designations in the formation of the British Columbia College of Nursing Professionals in 2018. We draw attention to amalgamation processes - professional regulation and governance, the preservation of nursing history, allocation of nurses' fees and resources and the role distinctions and identities of registrant groups - Registered Nurses, Nurse Practitioners, Licensed Practical Nurses and Registered Psychiatric Nurses. We argue that nursing's collective engagement and nursing leadership in self-regulation and decision making related to professional practice is key to public safety and integral to the identity of Canadian nursing. In our critique we identify issues and raise questions for consideration in the coming years.


Minimal change nephrotic syndrome associated with non-Hodgkin lymphoid disorders: a retrospective study of 18 cases.
Few studies have examined the occurrence of minimal change nephrotic syndrome (MCNS) in patients with non-Hodgkin lymphoma (NHL). We report here a series of 18 patients with MCNS occurring among 13,992 new cases of NHL. We analyzed the clinical and pathologic characteristics of this association, along with the response of patients to treatment, to determine if this association relies on a particular disorder. The most frequent NHLs associated with MCNS were Waldenström macroglobulinemia (33.3%), marginal zone B-cell lymphoma (27.8%), and chronic lymphocytic leukemia (22.2%). Other lymphoproliferative disorders included multiple myeloma, mantle cell lymphoma, and peripheral T-cell lymphoma. In 4 patients MCNS occurred before NHL (mean delay, 15 mo), in 10 patients the disorders occurred simultaneously, and in 4 patients MCNS was diagnosed after NHL (mean delay, 25 mo). Circulating monoclonal immunoglobulins were present in 11 patients. A nontumoral interstitial infiltrate was present in renal biopsy specimens from 3 patients without significant renal impairment. Acute kidney injury resulting from tubular lesions or renal hypoperfusion was present in 6 patients. MCNS relapse occurred more frequently in patients treated exclusively by steroid therapy (77.8%) than in those receiving steroids associated with chemotherapy (25%). In conclusion, MCNS occurs preferentially in NHL originating from B cells and requires an aggressive therapeutic approach to reduce the risk of MCNS relapse.


Startup of electrophoresis in a suspension of colloidal spheres.
The transient electrophoretic response of a homogeneous suspension of spherical particles to the step application of an electric field is analyzed. The electric double layer encompassing each particle is assumed to be thin but finite, and the effect of dynamic electroosmosis within it is incorporated. The momentum equation for the fluid outside the double layers is solved through the use of a unit cell model. Closed-form formulas for the time-evolving electrophoretic and settling velocities of the particles in the Laplace transform are obtained in terms of the electrokinetic radius, relative mass density, and volume fraction of the particles. The time scale for the development of electrophoresis and sedimentation is significantly smaller for a suspension with a higher particle volume fraction or a smaller particle-to-fluid density ratio, and the electrophoretic mobility at any instant increases with an increase in the electrokinetic particle radius. The transient electrophoretic mobility is a decreasing function of the particle volume fraction if the particle-to-fluid density ratio is relatively small, but it may increase with an increase in the particle volume fraction if this density ratio is relatively large. The particle interaction effect in a suspension on the transient electrophoresis is much weaker than that on the transient sedimentation of the particles.


Anti-TNF combination therapy in inflammatory bowel disease: de novo or selective?
Anti-TNFs still remain the backbone of advanced therapies in inflammatory bowel diseases, but their efficacy is not universal and tends to diminish over time. As a consequence, there is the need for optimization of these treatments, and the use of combination therapy - i.e. an anti-TNF plus an immunosuppressant - is one of the main strategies. The rationale for this approach lies in the evidence that the immunosuppressant reduces the formation of antibodies directed against the anti-TNF, thus avoiding the reduction or elimination of circulating drug levels, and in the combination of the therapeutic effect of two drugs. Nowadays, two different combination therapies should be distinguished. In the "de novo" combination therapy, the anti-TNF is used in combination with an immunosuppressant from the beginning of the treatment, in order to prevent the formation of anti-drug antibodies. In the "selective" combination therapy, the immunosuppressant is added at a later time in patients who experience a loss of response during anti-TNF monotherapy due to the development of anti-drug antibodies. The purpose of this review is to summarize the available evidence on both de novo and selective combination therapy. In addition, we will express our point of view on the choice between these two different treatment modalities.


Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration.
Development of the skeleton is mediated through two distinct ossification mechanisms. Craniofacial bones are formed mainly through intramembranous ossification, a mechanism different from endochondral ossification required for development of the body skeleton. The skeletal structures are quite distinct between the two, thus they are likely to have their unique stem cell populations. The sutures serve as the growth center critical for healthy development of the craniofacial skeleton. Defects in suture morphogenesis cause its premature closure, resulting in development of craniosynostosis, a devastating disease affecting 1 in ~2,500 individuals. The suture mesenchyme has been postulated to act as the niche of skeletal stem cells essential for calvarial morphogenesis. However, very limited knowledge is available for suture biology and suture stem cells (SuSCs) have yet to be isolated. Here we report the first evidence for identification and isolation of a stem cell population residing in the suture midline. Genetic labeling of SuSCs shows their ability to self-renew and continually give rise to mature cell types over a 1-year monitoring period. They maintain their localization in the niches constantly produce skeletogenic descendants during calvarial development and homeostastic maintenance. Upon injury, SuSCs expand drastically surrounding the skeletogenic mesenchyme, migrate to the damaged site and contribute directly to skeletal repair in a cell autonomous fashion. The regeneration, pluripotency and frequency of SuSCs are also determined using limiting dilution transplantation. In vivo clonal expansion analysis demonstrates a single SuSC capable of generating bones. Furthermore, SuSC transplantation into injured calvaria facilitates the healing processes through direct engraftments. Our findings demonstrate SuSCs are bona fide skeletal stem cells ideally suited for cell-based craniofacial bone therapy as they possess abilities to engraft, differentiate.(Presented at the 1980th Meeting, April 16, 2019).


The Use of Ophthalmic Ultrasonography to Identify Retinal Injuries Associated With Abusive Head Trauma.
Abusive head trauma includes any nonaccidental injury inflicted to a child's head and body. It is often characterized by, but not limited to, the repetitive acceleration-deceleration forces with or without blunt head impact. It has a mortality rate of 30%, and 80% of survivors experience permanent neurologic damage. In this case series, we hypothesize that bedside ultrasonography can be useful in the identification of retinal injuries that are consistent with abusive head trauma. Ocular manifestations of abusive head trauma are identified by dilated ophthalmic examination showing retinal hemorrhages that are too numerous to count, multilayered, and extending to the periphery. Traumatic retinoschisis, splitting of the retinal layers with or without blood accumulating in the intervening space, is exclusive for abusive head trauma in infants without a history of significant cerebral crush injury. Direct visualization of intraocular structures is difficult when the eyelids are swollen shut or when dilatation must be delayed. We present a series of 11 patients with brain injuries who underwent ophthalmic point-of-care ultrasonography that revealed traumatic retinoschisis on average 60 hours earlier than direct ophthalmic visualization. Dilated ophthalmic examinations and autopsy reports confirmed retinoschisis and other forms of retinal hemorrhages that were too numerous to count, multilayered, and extending to the periphery in all 11 patients. One patient did not have a dilated ophthalmic examination; however, traumatic retinoschisis and retinal hemorrhages were confirmed on autopsy. Ocular point-of-care ultrasonography is a promising tool to investigate abusive head trauma through the identification of traumatic retinoschisis and retinal hemorrhages when pupillary dilatation and direct ophthalmic examination is delayed.


Pushing the boundaries in liver graft utilisation in transplantation: Case report of a donor with previous bile duct injury repair.
Liver transplantation is a recognised treatment for extensive bile duct injuries with secondary biliary cirrhosis or recurring sepsis. However, there have been no reports of successful liver transplantation from a donor who sustained a previous bile duct injury. Here we discuss the case of a liver transplant from a 51-year-old brain dead donor who had suffered a Strasberg E1 bile duct injury and had undergone a Roux-en-Y hepaticojejunostomy 24 years prior to donation. The liver was successfully recovered and transplanted into a 56-year-old male recipient with end stage liver disease consequent to alpha 1 antitrypsin deficiency. The graft continues to function well 36 months post-transplant, with normal liver function tests and imaging revealing a patent hepaticojejunostomy. The potential associated vascular injuries should be identified during bench preparation whilst the management of biliary reconstruction at the time of transplant should follow the principles of biliary reconstruction in cases with biliary injuries, extending the hilar opening into the left duct. This case highlights the successful utilisation of a post bile duct injury repair liver, employing an experienced procurement team and careful bench assessment and reconstruction.


Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is an autoimmune disorder mediated by Th1 immune responses. CTLA-4, expressed on the T cell surface, plays a negative role in regulating T cell activation. Single-nucleotide polymorphisms (SNPs) in CTLA4 have been implicated in susceptibility to several autoimmune disorders, including JIA. This study was undertaken to test 3 functional CTLA4 variants for association with JIA. Families of 531 children with JIA were genotyped for SNPs located in the promoter region (C-318T), exon 1 (A49G), and the 3'-untranslated region (CT60) of CTLA4 by polymerase chain reaction amplification and digestion. Family Based Association Testing (FBAT) was used to test CTLA4 SNPs and haplotypes for association with JIA. A second independent cohort of >300 children with JIA and >500 controls were genotyped for case-control analyses. Case-control analyses of the combined cohorts, as well as meta-analyses of published association studies of CTLA4 and JIA, were performed. There were no deviations of transmission of any of the CTLA4 variants to children with JIA, or JIA subtypes, determined by FBAT. No significant associations between CTLA4 C-318T or A49G SNPs and JIA were found in 650 JIA cases and 350 controls. Similarly, no significant associations with CT60 variants were found in >800 JIA cases and >500 controls. The meta-analysis also failed to confirm an association between JIA and CTLA4 variants. These results suggest that C-318T, A49G, CT60, and haplotypes tagged by these CTLA4 SNPs are not associated with JIA or major JIA subtypes.


Histone deacetylase inhibitors selectively suppress expression of HDAC7.
There are 18 histone deacetylases (HDAC) generally divided into four classes based on homology to yeast HDACs. HDACs have many protein substrates in addition to histones that are involved in regulation of gene expression, cell proliferation, and cell death. Inhibition of HDACs can cause accumulation of acetylated forms of these proteins, thus altering their function. HDAC inhibitors (HDACi), such as the hydroxamic acid-based vorinostat (suberoylanilide hydroxamic acid), inhibit the zinc-containing classes I, II, and IV, but not the NAD(+)-dependent class III, enzymes. HDACis are a group of novel anticancer agents. Vorinostat is the first HDACi approved for clinical use in the treatment of the cancer cutaneous T-cell lymphoma. Factors affecting expression of HDACs are not well understood. This study focuses on the effect of the HDACi vorinostat on the expression of class I and class II HDACs. We found that vorinostat selectively down-regulates HDAC7 with little or no effect on the expression of other class I or class II HDACs. Fourteen cell lines were examined, including normal, immortalized, genetically transformed, and human cancer-derived cell lines. Down-regulation of HDAC7 by vorinostat is more pronounced in transformed cells sensitive to inhibitor-induced cell death than in normal cells or cancer cells resistant to induced cell death. Modulation of HDAC7 levels by small interfering RNA-mediated knockdown or by HDAC7 overexpression is associated with growth arrest but without detectable changes in acetylation of histones or p21 gene expression. Selective down-regulation of HDAC7 protein may serve as a marker of response of tumors to HDACi.


The individualized rehabilitation interventions for dysphagia: a multidisciplinary case control study of acute stroke patients.
To examine the effects of the individualized rehabilitation programs on the recovery of swallowing during acute stroke. A total of 88 stroke patients with dysphagia (within 2 weeks of acute stroke) were enrolled and classified into the experimental and control groups (n=44). The control group was treated with conventional rehabilitation program, while a multidisciplinary rehabilitation team was established to offer physical, social and psychological support to dysphagic patient in experimental group. All patients were assessed for their swallowing function by the water swallow test before and after the treatment. After the treatment, the experimental group showed a significant improvement in the swallowing function than that of the control group (p < 0.05). Total effective rate improved significantly from 54.5% at control group to 88.6% at experimental group (p < 0.01), where 25 dysphagic patients were completely recovery after the individualized rehabilitation therapy. By contrast, only 12 patients were fully recovered from dysphagia when treatment with conventional rehabilitation training. The findings of present study showed evidence that the individualized rehabilitation interventions carried out by our multidisciplinary rehabilitation professionals provided effective therapeutic effects during the acute stroke dysphagia compared to the conventional rehabilitation interventions, which may shed light on a bright prospect of the individualized rehabilitation interventions in post-stroke dysphagic patients.


[Intraoperative radiotherapy of locally advanced and recurrent rectal cancer].
Intraoperative radiotherapy (IORT) offers a technique to increase radiation dose to the residual tumor or tumor bed while sparing neighboring radiosensitive organs. Beyond the mostly employed dedicated electron beam facilities, the afterloading--'flab'-technique was also used. In first prospective studies IORT was performed in patients with not completely resected locally advanced (T4) or recurrent tumors after complete external beam radiotherapy (50.4 Gy) as an additional boost dose, using small field sizes. This locally restricted dose escalation yielded higher local control and an increased prognosis. Nerves and ureters were dose limited. In our series IORT was performed for rectal carcinomas stages II and III. After an external beam radio- or radio-chemotherapy with 41.4 Gy, shrinking field boost irradiation was done intraoperatively with moderate doses and larger IORT field sizes. Compared to a historical control with high-dose external beam radiotherapy alone local control rate was increased. Radiogenic neuropathy or stenosis of the ureter was not observed. The impact on prognosis must awaited. Randomized studies are required to clearly describe the role of IORT in rectal carcinoma.


Physician practice volume and alternative surgical treatment for breast cancer in Florida.
To determine whether surgeon procedure volume is related to the selection of a surgical option (mastectomy versus breast-conserving surgery) for breast cancer treatment . STUDY SETTING/STUDY DESIGN: Secondary data sources were used to study surgical procedures performed for female breast cancer in Florida during the years 1997-98 in a retrospective population-based analysis. Surgical procedures for female breast cancer in Florida were identified during 1997 and 1998 (N = 28,380) by combining data from the Florida Acute Hospital and Short-term Psychiatric Inpatient Data Collection and the Ambulatory Outpatient Data Collection. A total of 1,320 physicians who provided breast surgical procedures in Florida during the two-year study period were identified. After controlling for selected patient and physician characteristics, the lowest volume surgeons were nearly twice as likely to perform mastectomies rather th an breast-conserving surgery compared with the highest volume group. Patients with Medicaid as an insurer were also nearly twice as likely to receive mastectomies. Patient demographic factors such as age, while statistically significant, were shown to be far less predictive of procedure choice. Forty-two percent of the physicians performed fewer than two surgeries on average per year. Patients treated by lower volume physicians have a greater likelihood of receiving mastectomies than do those patients treated by higher volume physicians.


The role of childhood trauma and PTSD in postpartum sleep disturbance.
Despite robust associations between postpartum sleep difficulties and maternal psychopathology, little attention has been paid to the role of childhood trauma and posttraumatic stress disorder (PTSD). In the present study, we examined sleep complaints in postpartum women with a history of childhood trauma compared to postpartum women who were not exposed to childhood trauma. Participants (N = 173) completed questionnaires by telephone at 4-months postpartum. After adjusting for nuisance variables, there were significantly higher rates of sleep disturbance (falling asleep and staying asleep) for women with a past history of neglect (OR = 4.84, p = .036 and 5.78, p = .006, respectively), physical abuse (OR = 9.20, p = .002 and 3.84, p = .044, respectively), and physical abuse with sexual abuse (OR = 5.95, p = .011 and 3.56, p = .045, respectively). Current PTSD was significantly associated with trouble staying asleep (OR = 4.21, p = .032) whereas recovery from PTSD was associated with trouble falling (OR = 4.19, p = .015) and staying asleep (OR = 3.69, p = .011). Our findings affirm the contribution of childhood trauma and PTSD to postpartum sleep.


Grape pomace improves performance, antioxidant status, fecal microbiota and meat quality of piglets.
In the present study, grape pomace (GP) was used as feed additive in the diet of weaned piglets in order to develop innovative feedstuffs and to investigate their potential beneficial effects on welfare, productivity and meat quality. For examining the antioxidant capacity of the experimental feeds, 24 piglets of 20 days old were assigned to two experimental groups receiving standard or experimental diet for 30 days. Blood and tissues collections were performed at four different time-points, 2, 20, 35 and 50 days post birth. The collected tissues were brain, heart, kidney, liver, lung, quadriceps muscle, pancreas, spleen and stomach. The following oxidative stress markers were assessed: reduced glutathione (GSH), catalase activity, total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), protein carbonyls (CARB) and H2O2 decomposition activity. The effect on bacterial growth was assessed by examining microbial populations in piglets' fecal microbiota. Furthermore, the average daily gain (ADG) was calculated and the fatty acid profile of quadriceps muscle was assessed. The results showed that piglets fed with the diet supplemented with GP, had significantly increased antioxidants mechanisms in almost all the tissues as shown by increases in GSH, H2O2 decomposition activity and TAC compared with control group. Piglets fed with the experimental diet exhibited decreased oxidative stress-induced damage to lipids and proteins as shown by decreases in TBARS and CARB in GP group compared with control. In addition, the experimental diet increased significantly ADG (by 23.65%) (P<0.05) and enhanced the growth of facultative probiotic bacteria (by up to 1.2 log colony forming units (CFU)/g) (P<0.05) and lactic acid bacteria (by up to 2.0 log CFU/g) (P<0.05) in GP group compared with the control group. GP supplementation inhibited the growth of pathogen populations such as Enterobacteriacae (by up to 1.8 log CFU/g) (P<0.05) and Campylobacter jejuni (by up to 1.0 log CFU/g) (P<0.05). Regarding fatty acid composition of meat, GP inclusion in piglets' diet increased significantly n-3 fatty acids (EPA; C20 : 5n-3, DHA; C22 : 6n-3, α-linolenic acid; C18 : 3n-3) and decreased significantly n-6/n-3 ratio compared with control (P<0.05). The results suggested that dietary GP supplementation may have a beneficial impact on piglets' welfare and may improve productivity as well as meat quality.


Prevalent Practices of Thyroid Diseases During Pregnancy Among Endocrinologists, Internists and General Practitioners.
Maternal thyroid disease in pregnancy is associated with adverse impact on both mother and fetus. Both the American thyroid association and the endocrine society have recently published guidelines for the management of thyroid disease in pregnancy. The objective of this survey was to assess and compare the current practices of various East-Asian physicians in the screening and management of thyroid disease in pregnancy. Completed survey questionnaires were collected from 112 physicians of six East-Asian countries. The survey was based on clinical case scenarios, asking questions about the clinical practices related to diagnosis and management of thyroid disease during pregnancy. Reponses from 76 endocrinologists and 33 internists and general practitioners (generalists) were analyzed. There were minor differences in treatment preferences for Graves' disease in pregnancy and tests to monitor antithyroid drugs between endocrinologists and generalists; the major difference being targeted free thyroxin, and also thyroxin, depicted in the upper end of normal range, by the majority of endocrinologist and within the normal range, by generalists. Compared to generalists, endocrinologists perform more targeted screening and are more familiar with its risk factors. Predominantly, endocrinologists increase levothyroxine dose in hypothyroid women, upon confirmation of pregnancy and also indicate full dose in a pregnant woman, diagnosed with overt hypothyroidism, and treat thyroid peroxidase antibody positive or negative pregnant women with thyroid stimulating hormone (2.5 - 5 mU/L), as compared to generalists. There is wide variation in the clinical practices of screening and management of thyroid disorders during pregnancy in East-Asia, with many clinicians, in particular general practitioners, not adhering to clinical practice guidelines, unfortunately.


[Local cold injuries; symptoms and therapy].
Etiology, pathophysiology, and clinical picture of local frost-injuries are described. By aid of literature, and by proper experiences in 49 patients, who had been treated at the University-Hospital of Innsbruck during the year of 1966 to 1973, therapy of local frost-injuries is discussed. Moreover the advantage of surgical therapy on the sympathicus over conservative treatment is pointed out.


Protective Gun Ownership as a Coping Mechanism.
Firearms are one of the central flashpoints in American life, and yet the motivations underlying their ownership have been generally understudied by psychologists. In this article, I review work from across the social sciences to model the psychological utility that people get from gun ownership. I propose the coping model of protective gun ownership and argue that those who own their weapon for protection are using their gun symbolically as an aid to manage psychological threats-to their safety, control, and sense of belongingness-that come from their belief that the world is a dangerous place and that society will not keep them safe. I discuss the ramifications of this coping strategy and present a research agenda for exploring this framework.


A National Needs Assessment to Identify Technical Procedures in Vascular Surgery for Simulation Based Training.
Practical skills training in vascular surgery is facing challenges because of an increased number of endovascular procedures and fewer open procedures, as well as a move away from the traditional principle of "learning by doing." This change has established simulation as a cornerstone in providing trainees with the necessary skills and competences. However, the development of simulation based programs often evolves based on available resources and equipment, reflecting convenience rather than a systematic educational plan. The objective of the present study was to perform a national needs assessment to identify the technical procedures that should be integrated in a simulation based curriculum. A national needs assessment using a Delphi process was initiated by engaging 33 predefined key persons in vascular surgery. Round 1 was a brainstorming phase to identify technical procedures that vascular surgeons should learn. Round 2 was a survey that used a needs assessment formula to explore the frequency of procedures, the number of surgeons performing each procedure, risk and/or discomfort, and feasibility for simulation based training. Round 3 involved elimination and ranking of procedures. The response rate for round 1 was 70%, with 36 procedures identified. Round 2 had a 76% response rate and resulted in a preliminary prioritised list after exploring the need for simulation based training. Round 3 had an 85% response rate; 17 procedures were eliminated, resulting in a final prioritised list of 19 technical procedures. A national needs assessment using a standardised Delphi method identified a list of procedures that are highly suitable and may provide the basis for future simulation based training programs for vascular surgeons in training.


A Novel Strategy for Detection and Enumeration of Circulating Rare Cell Populations in Metastatic Cancer Patients Using Automated Microfluidic Filtration and Multiplex Immunoassay.
Size selection via filtration offers an antigen-independent approach for the enrichment of rare cell populations in blood of cancer patients. We evaluated the performance of a novel approach for multiplex rare cell detection in blood samples from metastatic breast (n = 19) and lung cancer patients (n = 21), and healthy controls (n = 30) using an automated microfluidic filtration and multiplex immunoassay strategy. Captured cells were enumerated after sequential staining for specific markers to identify circulating tumor cells (CTCs), circulating mesenchymal cells (CMCs), putative circulating stem cells (CSCs), and circulating endothelial cells (CECs). Preclinical validation experiments using cancer cells spiked into healthy blood demonstrated high recovery rate (mean = 85%) and reproducibility of the assay. In clinical studies, CTCs and CMCs were detected in 35% and 58% of cancer patients, respectively, and were largely absent from healthy controls (3%, p = 0.001). Mean levels of CTCs were significantly higher in breast than in lung cancer patients (p = 0.03). Fifty-three percent (53%) of cancer patients harbored putative CSCs, while none were detectable in healthy controls (p<0.0001). In contrast, CECs were observed in both cancer and control groups. Direct comparison of CellSearch® vs. our microfluidic filter method revealed moderate correlation (R2 = 0.46, kappa = 0.47). Serial blood analysis in breast cancer patients demonstrated the feasibility of monitoring circulating rare cell populations over time. Simultaneous assessment of CTCs, CMCs, CSCs and CECs may provide new tools to study mechanisms of disease progression and treatment response/resistance.


Application of Inelastic Neutron Scattering to the Methanol-to-Gasoline Reaction Over a ZSM-5 Catalyst.
Inelastic neutron scattering (INS) is used to investigate a ZSM-5 catalyst that has been exposed to methanol vapour at elevated temperature. In-line mass spectrometric analysis of the catalyst exit stream confirms methanol-to-gasoline chemistry, whilst ex situ INS measurements detect hydrocarbon species formed in/on the catalyst during methanol conversion. These preliminary studies demonstrate the capability of INS to complement infrared spectroscopic characterisation of the hydrocarbon pool present in/on ZSM-5 during the MTG reaction.


Kappa and Hirschberg ratio measured with an automated video gaze tracker.
To develop a fast automated procedure to measure kappa and the Hirschberg ratio for immediate use in a video gaze tracker. Using the hardware platform of the PowerRefractor and a 200 mm lens, the pupil was imaged with a resolution of 57 pixels/mm, at a camera distance of 90 cm. Both the positions of the first Purkinje image and the edges of the pupil were located at 25 Hz sampling rate with subpixel resolution using video image processing software developed under Borland C++. Subjects fixated on a red spot on the left side of the monitor. If their fixation was stable (standard deviation <0.2 degrees in 25 subsequent measurements evaluated in 1 s), the fixation spot appeared automatically on the right side, and the procedure was repeated. Data on the angular position of the optical axis for both targets were stored and provided kappa and the Hirschberg ratio with a standard deviation of about 0.2 degrees or better. This enabled the system to track fixation with a resolution of about 0.2 degrees. (1) Kappa was +3.91+/-2.73 degrees (right eyes), -3.93+/-2.68 degrees (left eyes, mean +/- SD from 24 young adults). Kappa was highly correlated in both eyes (r = 0.8996), but there were significant asymmetries between both eyes in three subjects (delta up to 3 degrees). (2) The Hirschberg ratios were 12.93+/-1.23 degrees/mm = 22.56 delta/mm (right eyes) and 12.82+/-1.49 degrees/mm = 22.38 delta/mm (left eyes). They were also highly correlated in both eyes (r = 0.931). (3) Neither kappa nor the Hirschberg ratios were correlated to refractive errors (range +0.50 to -7.75 D, mean -1.73+/-2.29 D [spherical equivalents]). (1) The video gaze tracker measured fixation with an angular resolution high enough to display the eye position during reading of individual words on the computer screen. (2) The applicable Hirschberg ratio changed with the power of the spectacles of the subjects by about 3% per diopter. (3) In some subjects, there were significant differences in the geometry of both eyeballs, which may be important in the analysis of strabismus. (4) Consistent with the assumption of retinal stretching, the linear distance of the fovea from the optical axis appeared to increase in myopia.


The use of mid-infrared spectrometry to estimate the ration composition of lactating dairy cows.
The composition of cow milk is strongly affected by the feeding regimen. Because milk components are routinely determined using mid-infrared (MIR) spectrometry, MIR spectra could also be used to estimate an animal's ration composition. The objective of this study was to determine whether and how well amounts of dry matter intake and the proportions of concentrates, hay, grass silage, maize silage, and pasture in the total ration can be estimated using MIR spectra at an individual animal level. A total of 10,200 milk samples and sets of feed intake data were collected from 90 dairy cows at 2 experimental farms of the Agricultural Research and Education Centre in Raumberg-Gumpenstein, Austria. For each run of analysis, the data set was split into a calibration and a validation data set in a 40:60 ratio. Estimated ration compositions were calculated using a partial least squares regression and then compared with the respective observed ration compositions. In separate analyses, the factors milk yield and concentrate intake were included as additional predictors. To evaluate accuracy, the coefficient of determination (R2) and ratio to performance deviation were used. The highest R2 values (for kg of dry matter intake/for % of ration) for the individual feedstuffs were as follows: pasture, 0.63/0.66; grass silage, 0.32/0.43; concentrate intake, 0.39/0.34; maize silage, 0.32/0.33; and hay, 0.15/0.16. Estimation of groups of feedstuffs (forages, energy-dense feedstuffs) mostly resulted in R2 values >0.50. Including the parameters milk yield or concentrate intake improved R2 values by up to 0.21, with an average improvement of 0.04. The results of this study indicate that not all ration components may be estimated equally accurately. Even if some estimates are good on average, there may be strong deviations between estimated and observed values in individual data sets, and therefore individual estimates should not be overemphasized. Further research including pooled samples (e.g., bulk milk, farm samples) or variations in ration composition is called for.


[Acquiring laparoscopic skill for colorectal surgery: based on the experience of a colorectal surgeon].
Laparoscopic colorectal surgery is a skill-dependent procedure. The present study aims to analyze the learning curve of a properly trained surgeon, with basic laparoscopic techniques, to become skillful in performing laparoscopic colorectal operations. A series of non-selective, consecutive 189 cases of laparoscopic colorectal surgery were accomplished, from December 2009 to February 2012, by one surgeon with years of skilled technique in laparoscopic cholecystectomy, rich experience in assisting laparoscopic colorectal surgery, and experience of approximately 180 procedures of gastric and colorectal surgery annually. 170 out of 189 procedures were radical operations for colorectal neoplasma, including right colectomies in 28 cases, left colectomies in 5 cases, sigmoidectomies in 28 cases, high Dixon procedures in 45 cases, low Dixon (total mesorectal excision, TME) procedures in 41 cases and Miles procedure in 23 cases. 19 other patients underwent combined procedures for multi-primary tumors or inflammatory enteritis. All these procedures were analyzed according to time span (the earlier half and later half) in respect to length of surgery, intraoperative blood loss, number of lymph nodes retrieved, intraoperative events and postoperative complications. For radical right colectomy, the D2 dissection conducted in the earlier phase (n = 8) had the similar length of surgery, more blood loss and less LN retrieval, compared with the D3 dissection conducted in recent phase (n = 20). The earlier performed high Dixon procedures (n = 22) consumed longer time than the later procedures (n = 23) consumed, but with similar blood loss and LN retrieval. Low Dixon (TME) procedures showed significant differences in length of surgery and blood loss relative to time span. Recently performed simoidectomy and Miles procedures showed a trend of shorter time consumed compared with earlier performed procedures. Conversion ratio to open surgery was 1.05%. Adverse effects occurred in 8 cases of surgeries, including intestinal injury (3/189), insufficient distal margin (2/189), intraoperative bleeding (2/189) and vaginal injury (1/76). There was no operative death. Chief complications included urinary retention 5.82%, ileus 4.76%, anastomotic leak 4.24%, perineal infection 23.08% (6/26), wound dehiscence 2.65%, gastrointestinal bleeding 1.59%, peritoneal infection 1.06%. Surgery for distal rectum tended to have more complications, such as urinary retention, anastomotic leak and perineal infection. The later performed low Dixon procedures produced insignificantly fewer anastomotic leaks than those in the earlier phase. For a trained surgeon with basic laparoscopic techniques, there are at least 15 - 25 cases of different procedures needed for him/her to become skilled to perform laparoscopic surgery. The learning curve should also depend on the annual number of colorectal surgeries.


Novel putative drugs and key initiating genes for neurodegenerative disease determined using network-based genetic integrative analysis.
Understanding the genetic causes of neurodegenerative disease (ND) can be useful for their prevention and treatment. Among the genetic variations responsible for ND, heritable germline variants have been discovered in genome-wide association studies (GWAS), and nonheritable somatic mutations have been discovered in sequencing projects. Distinguishing the important initiating genes in ND and comparing the importance of heritable and nonheritable genetic variants for treating ND are important challenges. In this study, we analysed GWAS results, somatic mutations and drug targets of ND from large databanks by performing directed network-based analysis considering a randomised network hypothesis testing procedure. A disease-associated biological network was created in the context of the functional interactome, and the nonrandom topological characteristics of directed-edge classes were interpreted. Hierarchical network analysis indicated that drug targets tend to lie upstream of somatic mutations and germline variants. Furthermore, using directed path length information and biological explanations, we provide information on the most important genes in these created node classes and their associated drugs. Finally, we identified nine germline variants overlapping with drug targets for ND, seven somatic mutations close to drug targets from the hierarchical network analysis and six crucial genes in controlling other genes from the network analysis. Based on these findings, some drugs have been proposed for treating ND via drug repurposing. Our results provide new insights into the therapeutic actionability of GWAS results and somatic mutations for ND. The interesting properties of each node class and the existing relationships between them can broaden our knowledge of ND.


C-reactive protein gene rs1205 polymorphism is not associated with the risk of colorectal cancer.
The relationship between C-reactive protein (CRP) gene rs1205 polymorphism and the risk of colorectal cancer (CRC) has been investigated previously. However, the results were conflicting. In the present study, we assessed whether CRP gene rs1205 polymorphism was associated with the risk of CRC by meta-analysis. We searched in PubMed, Embase, and the CNKI databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Seven original studies involving 4,181 cases and 10,601 controls analyzed the association between CRP gene rs1205 polymorphism and CRC risk. No significant association was found between CRP gene rs1205 polymorphism and CRC risk in this meta-analysis. Sensitivity analysis did not draw different findings. Stratification analyses of ethnicity, type of cancer, and genotype method also did not obtain any association between CRP gene rs1205 polymorphism and CRC risk. In conclusion, this meta-analysis indicates that CRP gene rs1205 polymorphism was not associated with the risk of CRC.


Different stress modalities result in distinct steroid hormone responses by male rats.
Since both paradoxical sleep deprivation (PSD) and stress alter male reproductive function, the purpose of the present study was to examine the influence of PSD and other stressors (restraint, electrical footshock, cold and forced swimming, N = 10 per group) on steroid hormones in adult Wistar male rats. Rats were submitted to chronic stress for four days. The stressors (footshock, cold and forced swimming) were applied twice a day, for periods of 1 h at 9:00 and 16:00 h. Restrained animals were maintained in plastic cylinders for 22 h/day whereas PSD was continuous. Hormone determination was measured by chemiluminescent enzyme immunoassay (testosterone), competitive immunoassay (progesterone) and by radioimmunoassay (corticosterone, estradiol, estrone). The findings indicate that PSD (13.7 ng/dl), footshock (31.7 ng/dl) and cold (35.2 ng/dl) led to lower testosterone levels compared to the swimming (370.4 ng/dl) and control (371.4 ng/dl) groups. However, progesterone levels were elevated in the footshock (4.5 ng/ml) and PSD (5.4 ng/ml) groups compared to control (1.6 ng/ml), swimming (1.1 ng/ml), cold (2.3 ng/ml), and restrained (1.2 ng/ml) animals. Estrone and estradiol levels were reduced in the PSD, footshock and restraint groups compared to the control, swimming and cold groups. A significant increase in corticosterone levels was found only in the PSD (299.8 ng/ml) and footshock (169.6 ng/ml) groups. These changes may be thought to be the full steroidal response to stress of significant intensity. Thus, the data suggest that different stress modalities result in distinct steroid hormone responses, with PSD and footshock being the most similar.


The masculine principle in lesbian families: a Jungian understanding.
Using the concepts of individuation and masculine and feminine principles from Jungian psychology, the author explores the use of the masculine principle in parenting male children in families without an embodied father. The role of lesbian parents' own relationship with the masculine within themselves, features of the initiation process, and the function that team sports can play in a boy child's development are presented and examined. Lesbian parenting of sons is explored from both personal and professional perspectives.


Decoding P300 Variability Using Convolutional Neural Networks.
Deep convolutional neural networks (CNN) have previously been shown to be useful tools for signal decoding and analysis in a variety of complex domains, such as image processing and speech recognition. By learning from large amounts of data, the representations encoded by these deep networks are often invariant to moderate changes in the underlying feature spaces. Recently, we proposed a CNN architecture that could be applied to electroencephalogram (EEG) decoding and analysis. In this article, we train our CNN model using data from prior experiments in order to later decode the P300 evoked response from an unseen, hold-out experiment. We analyze the CNN output as a function of the underlying variability in the P300 response and demonstrate that the CNN output is sensitive to the experiment-induced changes in the neural response. We then assess the utility of our approach as a means of improving the overall signal-to-noise ratio in the EEG record. Finally, we show an example of how CNN-based decoding can be applied to the analysis of complex data.


Levodopa improves time-based prospective memory in Parkinson's disease.
The present study was aimed at investigating the effect of acute levodopa administration on the performance of a group of individuals with Parkinson's disease (PD) on a time-based prospective memory task. Twenty PD patients and 15 healthy controls were administered a task that required executing three actions after 10 min had elapsed in three consecutive trials. Scores were computed for correct recall of the intention to perform the actions and for correct execution of the actions. PD participants were evaluated after a 12-hr drug wash-out in two conditions: (1) after levodopa administration ("on"); (2) without drug administration ("off"). In the "on" condition, PD patients were significantly more accurate in retrieving the intention to perform the actions than in the "off" condition and their performance was actually comparable to that of healthy controls. The increased accuracy in complying with the prospective memory task following levodopa medication supports the idea that dopamine depletion plays a role in the prospective memory deficits observed in PD patients.


Parathyroid surgery in chronic renal failure: subtotal parathyroidectomy or autotransplantation?
In the period 1970-1983, 27 patients with end stage renal failure underwent neck exploration for hyperparathyroidism. In 1977 the operative policy changed from subtotal parathyroidectomy to total parathyroidectomy and autotransplantation. Eight patients underwent subtotal parathyroidectomy while fifteen patients underwent total parathyroidectomy and autotransplantation. All were cured of their symptoms and hypercalcaemia was resolved. There was no significant difference in the requirement for postoperative calcium and vitamin D supplements between the two groups. Recurrent hypercalcaemia developed in one patient who had undergone total parathyroidectomy and autotransplantation. Resolution followed removal of approximately half the transplant. There were four deviations from the operative policy.


Low-dose alemtuzumab vs. standard policy for prevention of graft-versus-host disease in unrelated and related allogeneic stem cell transplantation-a matched pair analysis.
Antibody-mediated in vivo T cell depletion is common prior to unrelated (URD) or mismatched allogeneic stem cell transplantation (alloSCT) and optional in HLA-identical sibling (FAM) alloSCT. While anti-thymocyte globulin (ATG) is the current standard, alemtuzumab is an alternative. The optimal dose of alemtuzumab has not been defined. This retrospective analysis compares low-dose alemtuzumab with ATG in URD alloSCT and with no antibody in FAM alloSCT. Twenty-eight patients treated with alemtuzumab (10 mg; HLA mismatch, 20 mg) were matched to 28 patients who have either received ATG (URD) or no antibody (noAB) according to disease, disease stage, age, transplant type and risk state. Both groups were compared for engraftment, outcome, disease-free (DFS) and overall survival (OS), graft-versus-host disease (GvHD), freedom from GvHD (ffGvHD) and transplant-related mortality (TRM). No significant differences were found between the groups for leukocyte engraftment, GvHD, ffGvHD, TRM, DFS and OS. There was a trend for reduction of cGvHD by alemtuzumab (p = 0.05). A transplant-type stratified subanalysis consolidated equivalency of alemtuzumab and ATG in URD-SCT and indicates possible superiority of low-dose alemtuzumab compared to noAB in FAM-SCT. Low-dose alemtuzumab, as part of conditioning regimen prior to alloSCT, is safe and comparable to standard ATG. Prospective trials, particularly comparing alemtuzumab vs. noAB in FAM alloSCT, should be conducted.


Finite-time stabilization and H∞ control of Port-controlled Hamiltonian systems with disturbances and saturation.
The finite-time stabilization and finite-time H∞ control problems of Port-controlled Hamiltonian (PCH) systems with disturbances and input saturation (IS) are studied in this paper. First, by designing an appropriate output feedback, a strictly dissipative PCH system is obtained and finite-time stabilization result for nominal system is given. Second, with the help of the Hamilton function method and truncation inequality technique, a novel output feedback controller is developed to make the PCH system finite-time stable when IS occurs. Further, a finite-time H∞ controller is designed to attenuate disturbances for PCH systems with IS, and sufficient conditions are presented. Finally, a numerical example and a circuit example are given to reveal the feasibility of the obtained theoretical results.


Spices as a source of lead exposure: a market-basket survey in Sri Lanka.
We performed a laboratory analysis of spices sold in Sri Lanka for lead content. Samples of curry powder, chili powder and turmeric powder from seven provinces, collected using the market basket survey method, underwent atomic absorption spectrometry. Blanks and standards were utilised for instrument calibration and measurement accuracy. The results were validated in two different laboratories. All samples were found to have lead levels below the US Food and Drug Administration's action level of 0.5 μg/g. Spices sold in Sri Lanka contain lead concentrations that are low and within the stipulated safety standards.


Ultralow power artificial synapses using nanotextured magnetic Josephson junctions.
Neuromorphic computing promises to markedly improve the efficiency of certain computational tasks, such as perception and decision-making. Although software and specialized hardware implementations of neural networks have made tremendous accomplishments, both implementations are still many orders of magnitude less energy efficient than the human brain. We demonstrate a new form of artificial synapse based on dynamically reconfigurable superconducting Josephson junctions with magnetic nanoclusters in the barrier. The spiking energy per pulse varies with the magnetic configuration, but in our demonstration devices, the spiking energy is always less than 1 aJ. This compares very favorably with the roughly 10 fJ per synaptic event in the human brain. Each artificial synapse is composed of a Si barrier containing Mn nanoclusters with superconducting Nb electrodes. The critical current of each synapse junction, which is analogous to the synaptic weight, can be tuned using input voltage spikes that change the spin alignment of Mn nanoclusters. We demonstrate synaptic weight training with electrical pulses as small as 3 aJ. Further, the Josephson plasma frequencies of the devices, which determine the dynamical time scales, all exceed 100 GHz. These new artificial synapses provide a significant step toward a neuromorphic platform that is faster, more energy-efficient, and thus can attain far greater complexity than has been demonstrated with other technologies.


Thalidomide in low doses is effective for the treatment of resistant or relapsed multiple myeloma and for plasma cell leukaemia.
Thalidomide is an effective treatment for relapsed multiple myeloma (MM), but is associated with a significant side effect profile at higher doses. In a recent study, only half of the enrolled patients were able to tolerate the maximum dose of 800 mg/day [Singhal, S., et al. (1999) "Antitumor activity of thalidomide in refractory multiple myeloma", New Engl. J. Med. 341, 1565-1571]. Moreover, the dose-response relationship has not been defined. We report our use of low dose thalidomide in a small cohort of 12 patients-eight with relapsed or refractory MM and four with plasma cell leukaemia (PCL). Five of the 12 (42%) patients had a partial response, showing a median fall in their PP/BJP of 80% (63-90%) at a median dose of 175 mg (100-300 mg) with negligible side effects. Three of four patients with PCL showed an impressive response to treatment with thalidomide as a single agent. No patient who failed to show any evidence of response at low dose (<150 mg/day) responded to higher doses. In this study, thalidomide induces a similar rate of response at a lower and better tolerated dose than previously reported and produced "best ever" responses in patients with resistant PCL.


Ongoing electroencephalographic signal study of simple arithmetic using linear and non-linear measures.
This study examined patterns of variation in the ongoing electroencephalogram during performance of three visual tasks. One task required exact arithmetic calculations on Arabic numerals. A second task involved pseudoword processing as a control for the verbal (phonological) component that is, by definition, part of arithmetic tasks. A third task primarily required visual/graphemic processing, which is also involved in the other two tasks. Spectral power in the alpha range was lowest during the pseudoword task, followed by power during the arithmetic task, and finally by power in the visual task, indicating more prominent desynchronization during engagement in the analysis of word-like printed material. Finally, linear (power in the gamma range) and non-linear measures (correlation dimension) provided evidence of predominant right hemisphere engagement during the arithmetic task.


Patents on Endophytic Fungi Related to Secondary Metabolites and Biotransformation Applications.
Endophytic fungi are an important group of microorganisms and one of the least studied. They enhance their host's resistance against abiotic stress, disease, insects, pathogens and mammalian herbivores by producing secondary metabolites with a wide spectrum of biological activity. Therefore, they could be an alternative source of secondary metabolites for applications in medicine, pharmacy and agriculture. In this review, we analyzed patents related to the production of secondary metabolites and biotransformation processes through endophytic fungi and their fields of application. We examined 245 patents (224 related to secondary metabolite production and 21 for biotransformation). The most patented fungi in the development of these applications belong to the Aspergillus, Fusarium, Trichoderma, Penicillium, and Phomopsis genera and cover uses in the biomedicine, agriculture, food, and biotechnology industries.


Loss of progesterone receptor links to high proliferation and increases from primary to metastatic endometrial cancer lesions.
In endometrial cancer loss of progesterone receptor (PR, gene name PGR) is associated with aggressive disease and altered response to hormonal treatment. The aim of this study was to investigate changes in PR expression level with disease progression, and explore whether differences in gene expression according to PR status can be linked to processes involved in cancer development elucidating new therapeutic opportunities. 686 primary endometrial cancers and 171 metastatic lesions were investigated for PR expression in relation to clinical and histopathological data. Protein levels were investigated by immunohistochemistry and reverse phase protein array, and mRNA levels by DNA oligonucleotide microarray. PR protein level was significantly associated with PGR mRNA expression (P<0.001) and patient survival (P<0.001). Loss of PR increased with disease progression, with 23% of the primary tumours and 76% of metastases demonstrating PR loss. Using a cell cycle progression signature score, PR loss was associated with increased proliferation for both oestrogen receptor (ER) positive and negative tumours. Through a Connectivity Map search, CDK inhibitors and other drugs with anti-proliferative effects were suggested in particular for treatment of patients with loss of PR. Loss of PR in endometrial cancer is associated with increased proliferation, poor survival, and increases from primary to metastatic lesions. Based on expression profiles, CDK inhibitors may have activity in PR negative tumours, supporting further testing in clinical trials for patients with systemic endometrial cancer dependent on PR status.


In vitro cultures of human pancreatic stem cells: gene and protein expression of designated markers varies with passage.
Adult stem cells may possess great plasticity, but the cellular mechanisms regulating their fate are not fully understood. Prior to application of stem cell populations in regenerative medicine, major challenges remain to be overcome. Fundamental questions about in vitro growth and spontaneous differentiation of adult stem cell populations must be resolved. In this study, we comprehensively characterized a stem cell population derived from human pancreatic tissue by analyzing mRNA and protein expression in consecutive passages. We examined transcription and protein expression levels of markers related to stem cells or differentiated cells, respectively, as well as the growth rate of a primary human pancreatic stem cell population. In particular, the course of spontaneous mRNA and protein expression of the genes for alpha-smooth muscle actin (alpha-SMA), neurofilaments (NF), cytokeratin 18 (CK18) and nestin was examined during 11 passages by means of RT-PCR and immunocytochemistry. The cell population showed exponential growth over 10 of the 11 examined passages. Both the spontaneous expression of stem cell-related mRNA and protein as well as the characteristics of spontaneous differentiation were variable. Changes in mRNA and protein expression showed no direct correlation. These results demonstrate the unpredictable behaviour of spontaneously differentiating stem cells, being influenced by numerous, barely traceable extrinsic factors. Characterization studies of stem cell populations therefore require improved analysis techniques together with strictly controlled cell cultivation conditions to improve global gene and protein expression analyses.


Transient hypoparathyroidism induced by synthetic human parathyroid hormone-(1-34) treatment.
Daily injections of low doses of a synthetic fragment of human PTH [hPTH-(1-34) have increased iliac trabecular bone volume when used in the treatment of osteoporosis. In approximately 50 patients no major side-effects had occurred. However, during daily sc 100-micrograms injections of the peptide, one patient repeatedly developed parathyroid hypofunction which resolved each time treatment was stopped. Specific immunoglobulin G (IgG) antibodies binding [125I]hPTH-(1-34) were identified in the patient's serum, and positive immunohistochemical reactions were obtained when bovine parathyroid sections were exposed to the patient's IgG. After adsorption with PTH, the patient's IgG, free of anti-PTH antibodies, reacted with renal cell membranes, as demonstrated by indirect immunofluorescence and blocked renal PTH-dependent adenylate-cyclase activation in vitro. These results support the hypothesis that anti-PTH receptor as well as anti-PTH antibodies were generated during hPTH-(1-34) treatment, which led to the development of hypoparathyroidism when their titers were high.


CTHRC1 overexpression predicts poor survival and enhances epithelial-mesenchymal transition in colorectal cancer.
Collagen triple helix repeat containing (CTHRC1), which was identified as a cancer-related factor, is a promigratory protein involved in multiple processes, including vascular remodeling, antifibrosis, metabolism, bone formation, and cancer. In this study, we aimed to investigate the clinical significance and possible role of CTHRC1 in the process of epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC). Here, we revealed that CTHRC1 mRNA and protein levels are both upregulated in CRC tissues compared with those of paired noncancerous tissues. Moreover, the overexpression of CTHRC1 correlated with poor prognosis in patients with CRC (especially colon cancer). Furthermore, we showed that CTHRC1 induced EMT and promoted cell motility in CRC cells. Importantly, we demonstrated that CTHRC1 promoted EMT by activating transforming growth factor-β (TGF-β) signaling, revealing a possible effective therapeutic treatment for patients with CRC.


West Nile virions aligned along myelin lamellae in organotypic spinal cord cultures.
Organotypic spinal cord cultures infected with West Nile Virus (WNV) exhibited a remarkable arrangement of virions among lamellae of the myelin sheath. Virions were first observed in neurons and only at day 4 after infection appeared within the myelin lamellae. Virions were observed only in the central myelin, aligned along the interperiod lines and therefore attached to the outer side of the oligodendrocyte membrane. In spite of this peculiar location of the virions, their presence was not associated with severe damage to the axon or to the myelin sheath. The causes of the formation of this viral pattern, its morphological features, and the role which it might have in viral infection in vivo are considered.


Identification of 12 animal species meat by T-RFLP on the 12S rRNA gene.
The verification of authenticity of meat products is relevant for economical, religious or public health concerning reasons. A molecular approach using terminal restriction fragment length polymorphism (T-RFLP) was developed to distinguish 12 common economically important meat species. The partial 12S rRNA gene was amplified with double-fluorescently labeled primers. The amplified fragments were digested with two endonucleases and only the terminal restriction fragment containing labeled primer was detected on capillary electrophoresis system ABI3100. AluI and Tru9I generated differently-sized terminal fragments in different species. Pig and buffalo can be separated by 3'-terminal fragment of AluI digestion. Horse, turkey, goat, sheep, deer, and cattle can be further separated by 5'-terminal fragment of Tru9I digestion. Dog and chicken, sturgeon and salmon can finally be separated by 5'-terminal fragment of AluI digestion and 3'-terminal fragment of Tru9I digestion. Our results demonstrated the potential feasibility and applicability of T-RFLP method for rapid and accurate identification of animal species.


Effects of muscle fatigue and temperature on electromechanical delay.
The effect of repeated maximal isometric knee extensions on electromechanical delay (EMD) and associated muscle temperature changes were investigated on seven college aged subjects. The exercise produced a significant reduction in muscle contraction force, rate of force development and muscle conduction velocity, whilst the muscle temperature increased by 2.1 degrees C. The EMD increased from a pre-exercise value of 38.4 (SEM 3.4) ms to 55.7 (SEM 3.4) ms post-exercise. In an attempt to evaluate the effect of muscle temperature on EMD, hot and ice-water bags were placed on the quadriceps muscle to alter muscle temperature. The EMD in isometric maximal knee extension was measured at 38, 36, 34, 32 and 30 degrees C. The results showed that the EMD elongated at muscle temperatures either lower or higher than 36 degrees C. It was speculated that the increased muscle temperature might contribute to 20-25% of the EMD elongation found during the fatiguing intermittent exercise. The information of the effects of muscle temperature on EMD could be useful when evaluating the effects of strenuous exercise, in which a substantial muscle temperature change might occur, on the time delay between myoelectrical activity and force generation.


Stem cells from human hair follicles: first mechanical isolation for immediate autologous clinical use in androgenetic alopecia and hair loss.
Hair follicles are known to contain a well-characterized niche for adult stem cells: the bulge, which contains epithelial and melanocytic stem cells. Stem cells in the hair bulge, a clearly demarcated structure within the lower permanent portion of hair follicles, can generate the interfollicular epidermis, hair follicle structures, and sebaceous glands. The bulge epithelial stem cells can also reconstitute in an artificial in vivo system to a new hair follicle. In this study, we have developed a new method to isolate human adult stem cells by mechanical centrifugation of punch biopsy from human hair follicles without culture condition. Here, we used human follicle stem cells (HFSCs), to improve the hair density in 11 patients (38 to 61 years old) affected by AGA in stage 3-5 as determined by the Norwood-Hamilton classification scale. The primary outcomes were microscopic identification and counting of HFSCs. The secondary outcomes were clinical preliminary results and safety and feasibility in HFSCs-treated scalp. Each scalp tissue suspension contained about 3,728.5±664.5 cells. The percentage of hair follicle-derived mesenchymal stem cells CD44+ [from dermal papilla (DP)] was about 5%+0.7% whereas the percentage of hair follicle epithelial stem cells CD200+ (from the bulge) was about 2.6%+0.3%. In total, 23 weeks after the last treatment with HFSCs mean hair count and hair density increases over baseline values. In particular, a 29%±5% increase in hair density for the treated area and less than a 1% increase in hair density for the placebo area. We have shown that the isolated cells are capable to improve the hair density in patients affected by androgenetic alopecia (AGA). These cells appear to be located in the bulge area of human.


Pain-Related Drug Use Among Older Adults With Activity Limiting Pain Who Received Home Care Services.
Pain is a common problem for patients receiving home care, often limiting mobility and contributing to functional decline. Pharmacological pain management is common, but all drugs bring some risk of side effects and adverse reactions. The opioid epidemic has brought into question analgesic prescribing patterns across all care settings. This study, which used data collected between 2012 and 2014, examines the pain medications used by older adults with activity-limiting pain receiving home care physical therapy in a large metropolitan home care agency. Eighty-five percent of subjects took at least one analgesic medication on admission to home care, and of these, 51.3% were using an opioid, 33.1% used acetaminophen, and 23.2% used nonsteroidal anti-inflammatory drugs (NSAIDs). At the 60-day follow-up, the most common medication classes taken by participants included acetaminophen (38%), opioids (35.9%), and NSAIDs (31.6%). We found racial/ethnic differences in analgesic use at baseline but not at follow-up. At baseline, analgesic use differed by pain type, but there were no differences at follow-up. The high use of medications to control pain by patients receiving home care, particularly opioid use, underscores the importance of providers being alert to potential adverse drug reactions.


Deaths from influenza A, subtype H1N1, during the 1979 Auckland epidemic.
We report seven cases of influenza-associated deaths in persons under twenty-two years of age, five of whom were previously fit and well, during an influenza A epidemic affecting Auckland city during the second quarter of 1979. Despite intensive care in three of the patients, all followed a similar course of fatal hypoxaemia. The failure of appropriate therapy in those patients with staphylococcal superinfection was a further feature. Influenza A-subtype H1N1 was isolated from throat swabs and/or post-mortem lung in five of the cases. This subtype has not been responsible for epidemic influenza or influenzal outbreaks in New Zealand since the early 1950s. The isolates were most similar to the A/Brazil/11/78 strain which has not previously been isolated in New Zealand. The susceptibility of young people is attributed to lack of previous antigenic exposure in those born since the mid-1950s.


Knowledge, attitude, and practice of urban Gujarati type 2 diabetics: Prevalence and impact on disease control.
Type 2 diabetes is the modern epidemic wherein patient care needs multiple approaches, education, and self-awareness being one of them. There are some knowledge, attitude, and practice (KAP) studies from India but very few relating it with disease control. We tried to study KAP of treated type 2 diabetics and its correlation with glycemic control. Cross-sectional KAP study. We formulated KAP questionnaires in the form of KAP - 10 points for each and total 30. We recruited 200 type 2 diabetics (96 males, 104 females) treated by MD physicians with known current glycemic status. They were asked KAP questionnaires one to one by a direct interview in local language and results were associated with various factors and glycemic control. KAP score on was average 19 out of 30 in type 2 diabetics having mean age 58 years, mean duration 9 years. KAP score was unaffected by gender, occupation, duration of disease but significantly affected by current age, and education level. Only 40% patients had good glycemic control who scored better KAP than poor glycemic. There was positive correlation between KAP score and glycemic control, with significance for only glycosylated hemoglobin and not fasting blood sugar, postprandial blood sugar. Physician treated type 2 diabetics of our region had moderate KAP score, affected by age, education which suggested to affect glycemic control. Lacunae in knowledge regarding incurability of disease, attitudes toward complication, self-care, and good practices like walking, enriching knowledge need improvement so as an optimum glycemic control.


Functional monolithic materials for boronate-affinity chromatography via Schrock catalyst-triggered ring-opening metathesis polymerization.
Monolithic polymeric materials are prepared via ring-opening metathesis copolymerization of norborn-2-ene with 1,4,4a,5,8,8a-hexahydro-1,4,5,8-exo,endo-dimethanonaphthalene in the presence of macro- and microporogens, that is, of n-hexane and 1,2-dichloroethane, using the Schrock catalyst Mo(N-2,6-(2-Pr)(2) -C(6) H(3) )(CHCMe(2) Ph)(OCMe(3) )(2) . Functionalization of the monolithic materials is accomplished by either terminating the living metal alkylidenes with various functional aldehydes or by post-synthesis grafting with norborn-5-en-2-ylmethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate. Finally, boronate-grafted monolithic columns (100 × 3 mm i.d.) are successfully applied to the affinity chromatographic separation of cis-diol-based biomolecules.


In the proper context: Neuropeptide regulation of behavioral transitions during food searching.
Neuromodulation enables transient restructuring of anatomically fixed neural circuits, generating alternate outputs and distinct states that allow for flexible organismal responses to changing conditions. We recently identified a requirement for the neuropeptide-like protein NLP-12, a Caenorhabditis elegans homolog of mammalian Cholecystokinin (CCK), in the control of behavioral responses to altered food availability. We showed that deletion of nlp-12 impairs turning during local food searching while nlp-12 overexpression is sufficient to induce deep body bends and enhance turning. nlp-12 is solely expressed in the DVA interneuron that is located postsynaptic to the dopaminergic PDE neurons and presynaptic to premotor and motor neurons, well-positioned for modulating sensorimotor tasks. Interestingly, DVA was previously implicated in a NLP-12 mediated proprioceptive feedback loop during C. elegans locomotion. Here, we discuss the modulatory effects of NLP-12 with an emphasis on the potential for circuit level integration with olfactory information about food availability. In addition, we propose potential mechanisms by which DVA may integrate distinct forms of sensory information to regulate NLP-12 signaling and mediate context-dependent modulation of the motor circuit.


Natural Snake Venom Inhibitors and their Pharmaceutical Uses: Challenges and Possibilities.
Nowadays, treatment with specific antivenins is considered the only cure for snakebites accidents. However, access to antivenom obstructs the successful implementation of the World Health Organization international guidelines. In the last few years, natural organic compounds, peptides, and proteins with the ability to inhibit snake toxins and obtained from different sources such as plant extracts and animal blood have been proposed as antivenoms. In this work, we will focus on the inhibitors of the main venom toxins, phospholipases A2 and metalloproteinases, and their application as novel antivenoms.