Tumor cell invasion inhibited by TIMP-2.
The 72-kd type IV collagenase is a member of the collagenase enzyme family that has been closely linked with the invasive phenotype of cancer cells. Previous studies have shown that both normal cells and highly invasive tumor cells produce the 72-kd type IV procollagenase enzyme in a complexed form consisting of the proenzyme and a novel tissue inhibitor of metalloproteinases, TIMP-2. The balance between activated enzyme and available inhibitor is thought to be a critical determinant of the matrix proteolysis associated with a variety of pathologic processes, including tumor cell invasion. In the present study, we demonstrate that alteration of the metalloproteinase-metalloproteinase-inhibitor balance in favor of excess inhibitor blocks human fibrosarcoma HT-1080 tumor cell invasion of a reconstituted basement membrane. The HT-1080 cell line produces both the 72-kd and the 92-kd type IV collagenases. Alteration of the type IV collagenase-inhibitor balance was achieved by addition of free TIMP-2 or antibodies to 72-kd type IV collagenase. Native, purified TIMP-2 was inhibitory in the range of 1-25 micrograms/mL. Addition of specific antiserum against the 72-kd type IV collagenase, which did not cross-react with the 92-kd type IV collagenase, inhibited HT-1080 cell invasion to the same extent. These results suggest that metalloproteinases, in particular the 72-kd type IV collagenase, are critical for tumor cell invasion of the reconstituted basement membrane. Our findings demonstrate that addition of the endogenous inhibitor TIMP-2 is able to block invasion. Thus, we recommend initiation of in vivo studies of the therapeutic potential of TIMP-2 to block tumor cell invasion and intravasation into the circulation.


COVID-19 vaccine booster hesitancy (VBH) of healthcare professionals and students in Poland: Cross-sectional survey-based study.
Since healthcare professionals (HCPs) play a critical role in shaping their local communities' attitudes toward vaccines, HCPs' beliefs and attitudes toward vaccination are of vital importance for primary prevention strategies. The present study was designed as a cross-sectional survey-based study utilizing a self-administered questionnaire to collect data about COVID-19 vaccine booster hesitancy (VBH) among Polish HCPs and students of medical universities (MUSs). Out of the 443 included participants, 76.3% were females, 52.6% were HCPs, 31.8% were previously infected by SARS-CoV-2, and 69.3% had already received COVID-19 vaccine booster doses (VBD). Overall, 74.5% of the participants were willing to receive COVID-19 VBD, while 7.9 and 17.6% exhibited their hesitance and rejection, respectively. The most commonly found promoter for acceptance was protection of one's health (95.2%), followed by protection of family's health (81.8%) and protection of community's health (63.3%). Inferential statistics did not show a significant association between COVID-19 VBH and demographic variables, e.g., age and gender; however, the participants who had been previously infected by SARS-CoV-2 were significantly more inclined to reject the VBD. Protection from severe infection, community transmission, good safety profile, and favorable risk-benefit ratio were the significant determinants of the COVID-19 VBD acceptance and uptake. Fear of post-vaccination side effects was one of the key barriers for accepting COVID-19 VBD, which is consistent with the pre-existing literature. Public health campaigns need to highlight the postulated benefits of vaccines and the expected harms of skipping VBD.


Sources of activator calcium in rabbit basilar artery.
The responses of segments of rabbit basilar and ear arteries to high K+ (K+, 45 mM), norepinephrine (NE, 10(-5) and 10(-7) M), and 5-hydroxytryptamine (5-HT, 10(-7) M) were tested before and after their incubation in calcium (Ca2+)-free Krebs solution for times varying from 2.5 to 60 min. The time course of evolution of the responses to K+ with Ca2+-free conditions in both vessels could be represented by a monoexponential curve. The rates of decline of the responses of amines in the ear artery were similar to K+ at first but then fell off at a slower rate. The decline in K+ contraction and the fast initial decline of the NE contraction may relate to the speed of removal of extracellular calcium, whereas the final slower NE decline reflects depletion of an intracellular pool. In the basilar artery, the NE and K+ response declined in a similar manner, whereas the 5-HT contraction showed a fast and a slow component of decline. These results for the maintained agonist response were confirmed using the Ca2+ influx antagonist, 3-methoxyverapamil (D 600). In addition, a D 600-insensitive phasic contraction was observed in both arteries. These results suggest that the steady-state NE contraction in the basilar artery is almost entirely dependent on loosely bound extracellular Ca2+. This is in contrast to the ear artery, where an additional tightly bound or intracellular Ca2+ pool is used. This source is present in the basilar artery but contributes only to a D 600-insensitive phasic component.


Multiphysics simulation of a compression-perfusion combined bioreactor to predict the mechanical microenvironment during bone metastatic breast cancer loading experiments.
Incurable breast cancer bone metastasis causes widespread bone loss, resulting in fragility, pain, increased fracture risk, and ultimately increased patient mortality. Increased mechanical signals in the skeleton are anabolic and protect against bone loss, and they may also do so during osteolytic bone metastasis. Skeletal mechanical signals include interdependent tissue deformations and interstitial fluid flow, but how metastatic tumor cells respond to each of these individual signals remains underinvestigated, a barrier to translation to the clinic. To delineate their respective roles, we report computed estimates of the internal mechanical field of a bone mimetic scaffold undergoing combinations of high and low compression and perfusion using multiphysics simulations. Simulations were conducted in advance of multimodal loading bioreactor experiments with bone metastatic breast cancer cells to ensure that mechanical stimuli occurring internally were physiological and anabolic. Our results show that mechanical stimuli throughout the scaffold were within the anabolic range of bone cells in all loading configurations, were homogenously distributed throughout, and that combined high magnitude compression and perfusion synergized to produce the largest wall shear stresses within the scaffold. These simulations, when combined with experiments, will shed light on how increased mechanical loading in the skeleton may confer anti-tumorigenic effects during metastasis.


Hypnosis in the treatment of trauma: a promising, but not fully supported, efficacious intervention.
Hypnotic techniques for the treatment of posttraumatic conditions were often used by the clinical pioneers of the end of the 19th century and by military therapists treating soldiers during the 20th century's conflagrations. More recently, hypnosis has also been used with survivors of sexual assault, accidents, and other traumas, and with various groups, including children and ethnic minorities. Nonetheless, there have been almost no systematic studies on the efficacy of hypnosis for posttraumatic disorders. This state of affairs is especially disappointing considering that: hypnosis can be easily integrated into therapies that are commonly used with traumatized clients; a number of PTSD individuals have shown high hypnotizability in various studies; hypnosis can be used for symptoms associated with PTSD; and hypnosis may help modulate and integrate memories of trauma. Hypnotic techniques may indeed be efficacious for posttraumatic conditions, but systematic group or single-case studies need to be conducted before reaching that conclusion.


Human serum antibodies to a major defined epitope of human herpesvirus 8 small viral capsid antigen.
The major antibody-reactive epitope of the small viral capsid antigen (sVCA) of human herpesvirus 8 (HHV-8) was defined by use of overlapping peptides. Strong IgG reactivity was found among approximately 50% of 44 human immunodeficiency virus-positive or -negative patients with Kaposi's sarcoma and 13 subjects who were seropositive by immunofluorescence assay (IFA) for the latent HHV-8 nuclear antigen. Only 1 of 106 subjects seronegative for both lytic and latent HHV-8 antigens and 10 of 81 subjects IFA-seropositive only for the lytic HHV-8 antigen had strong IgG reactivity to this epitope. Among 534 healthy Swedish women, only 1.3% were strongly seropositive. Comparison of the peptide-based and purified sVCA protein-based ELISAs found 55% sensitivity and 98% specificity. However, only 1 of 452 serum samples from healthy women was positive in both tests. In conclusion, the defined sVCA epitope was a specific, but not very sensitive, serologic marker of active HHV-8 infection. Such infection appears to be rare among Swedish women, even with sexual risk-taking behavior.


The impact of incorporating of a novice assistant into a laparoscopic team on operative outcomes in laparoscopic sigmoidectomy: a prospective study.
To evaluate whether the incorporation of a novice first assistant into a laparoscopic team affects operative outcomes after laparoscopic sigmoidectomy for sigmoid colon cancer. Sixty-five patients who underwent laparoscopic sigmoidectomy were prospectively enrolled in this study between March 2008 and October 2008. One surgeon with a novice first assistant during the study period carried out all operations. Outcomes of this population were compared with those of 50 patients (control group) that underwent laparoscopic sigmoidectomy between March 2007 and February 2008 by the same surgeon with an experienced first assistant. The 65 patients operated upon with the involvement of the novice (the patients group) were allocated to 2 groups by case number, that is, to an early group (case numbers 1 to 10) and to a late group (case numbers 11 to 65). Mean operative times were 233+/-50 minutes in the control group, 305+/-113 minutes in the early group, and 226+/-58 minutes in the late group (P=0.04). Multiple regression analysis showed that in the early group, body mass index and tumor diameter significantly contributed to operative time. The incidences of intraoperative and postoperative complications were not significantly different in the early, late, and control groups. The incorporation of a novice first assistant into a laparoscopic team was not found to affect operative outcomes adversely. However, in terms of operative time, novice assistants probably need experience of around 10 cases before they can be viewed as fully competent surgical team members during laparoscopic sigmoidectomy.


Labor conditions and the meanings of nursing work in Barcelona.
to analyze the relationship between the quantitative assessment of working conditions and the qualitative perception of one's own work experience. a sample of 1,760 nursing professionals from Barcelona answered a questionnaire assessing their working conditions and summarized their own current work experience in five key words. the textual corpus of the meanings of nursing work included 8043 lexical forms, which were categorized and codified. Respondents who rated their work conditions the highest expressed a vision of their work in terms of autonomy, achievement and well-being, while those who rated their work conditions the lowest talked mostly of exhaustion, depersonalization and negative climate. A correspondence analysis showed a close relationship between the quantitative assessments of working conditions and the verbal codes of the meaning of work. the meanings given to work were not only consistent with the numerical evaluations of the working conditions but also made them more understandable. The information obtained poses challenges for reflection and indicates ways to promote the positive aspects and prevent the negative conditions of nursing work.


Identification of rolling resistance as a shape parameter in sheared granular media.
Using contact dynamics simulations, we compare the effect of rolling resistance at the contacts in granular systems composed of disks with the effect of angularity in granular systems composed of regular polygonal particles. In simple shear conditions, we consider four aspects of the mechanical behavior of these systems in the steady state: shear strength, solid fraction, force and fabric anisotropies, and probability distribution of contact forces. Our main finding is that, based on the energy dissipation associated with relative rotation between two particles in contact, the effect of rolling resistance can explicitly be identified with that of the number of sides in a regular polygonal particle. This finding supports the use of rolling resistance as a shape parameter accounting for particle angularity and shows unambiguously that one of the main influencing factors behind the mechanical behavior of granular systems composed of noncircular particles is the partial hindrance of rotations as a result of angular particle shape.


HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition.
Despite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or therapy of colon cancer metastasis. CMT93 cells, a murine rectal cancer cell line with poor metastasising activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57BL/6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNA were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA. The genome-wide shRNA library screen identified Hnrnpll (heterogeneous nuclear ribonucleoprotein L-like) encoding a pre-mRNA splicing factor as a candidate metastasis suppressor gene. Knockdown of Hnrnpll enhanced matrigel invasion activity of colon cancer cells in vitro, as well as their metastatic ability in vivo. An RNA-immunoprecipitation analysis showed Hnrnpll-binding to Cd44 pre-mRNAs, and the level of Cd44 variable exon 6 (Cd44v6), a poor prognosis marker of colorectal cancer, was increased by knocking down Hnrnpll. A neutralising Cd44v6 antibody suppressed the matrigel invasion ability induced by Hnrnpll knockdown. HNRNPLL expression was downregulated when colon cancer cells were induced to undergo epithelial-mesenchymal transition (EMT). Immunohistochemistry of clinical samples indicated that colorectal cancer cells with low E-cadherin expression at the invasion front exhibited decreased HNRNPLL expression. HNRNPLL is a novel metastasis suppressor of colorectal cancer, and modulates alternative splicing of CD44 during EMT.


[The characteristics of the oral health promotion of patients with hematological diseases].
A total of 197 patients were subjected to planned sanitization of the oral cavity in St. Petersburg specialized dental hospital for short-term treatment. Critical values of blood parameters were determined for preventing the complications after planned sanitization. The probability of complications is lower if blood hemoglobin level is at least 100 g/liter, granulocyte count at least (1.5-2.0).10(9)/liter, platelet count at least 60.10(9)/liter, and erythrocyte content in patients with polycythaemia vera no more than (4.5-5.0).10(12)/liter. Preparation of patients to treatment carried out by a dentist together with a hematologist and total analgesia help eliminate stress reactions and effectively and timely correct the complications developing during treatment. This means that oral sanitization in patients with diseases of the blood system should be carried out at dental hospitals for short-term treatment.


Toxicity of dipyridyl compounds and related compounds.
Five dipyridyl isomers, 2,2'-, 2,3'-, 2,4'-, 3,3'-, and 4,4'-dipyridyl, are products resulting from the pyrolytic degradation of tobacco products and degradation of the herbicide paraquat, and therefore may be present in the environment. In this article, the toxicological properties of these dipyridyl isomers in humans and animals are reviewed. Epidemiological studies suggest that cancerous skin lesions in workers involved in the manufacturing of paraquat may be associated with exposure to dipyridyl compounds. Experimental animal studies suggest that dipyridyl isomers may have several toxicological effects. Three of the dipyridyl isomers (the 2,2', 2,4', and 4,4' isomers) appear to be inducers of some metabolic enzymes. The 2,2'-dipyridyl isomer, an iron chelator, appears to influence vasospasm in primate models of stroke. The cytotoxic effects of 2,2'-dipyridyl on several leukemia cell lines have been reported, and a potent teratogenic effect of 2,2'-dipyridyl has been observed in rats. Based on the results of paraquat studies in experimental animal models, it has been proposed that paraquat may have deleterious effects on dopaminergic neurons. These findings support the epidemiological evidence that paraquat exposure may be associated with the development of Parkinson's disease. Studies designed to determine an association between paraquat exposure and Parkinson's disease are complicated by the possibility that metabolic changes may influence the neurotoxicity of paraquat and/or its metabolites. Preliminary unpublished data in mice show that 300-mg/kg doses of 2,2'-dipyridyl are neurotoxic, and 300-mg/kg doses of 2,4'- and 4,4'-dipyridyls are lethal. These results are consistent with earlier studies in Sherman rats using high 2,2'- and 4,4'-dipyridyl doses. New studies are needed to further explore the toxicological properties of dipyridyls and their potential public health impact.


[Clinical differentiation and prognosis of acute hallucinatory conditions in schizophrenia].
Altogether 61 patients with schizophrenia manifesting for the first time by hallucinatory disorders, playing the leading part in the psychosis picture were examined. 3 typological varieties of acute hallucinatory conditions were described, their comparative characteristics were provided. It has been demonstrated that acute hallucinosis occurred during the disease in different clinical forms: so-called schizophrenic reactions in latent disease (variant I), phases and attacks within the framework of a well-defined attack-like (shift-like) and similar to a recurrent (variant and an attack-like progredient course, approximating to a continuous one (variant III). Problems of a comparative assessment of the further disease course manifesting by different conditions of acute hallucinosis and adequacy of the use of the elaborated typology thereof for prediction and choice of therapy are discussed.


Biology and behavior of Spathius agrili, a parasitoid of the emerald ash borer, Agrilus planipennis, in China.
Spathius agrili Yang (Hymenoptera: Braconidae) is a gregarious larval ectoparasitoid of the emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae) and is a recently described species. Both pest and parasitoid are native to China. In Tianjin City, China, S. agrili typically exhibited 3-4 generations per year, overwintering as a prepupa in a cocoon inside the host gallery. The multiple generations of S. agrili overlapped with its host, as did the emergence dates of the overwintering generation. From a single host, 1-18 S. agrili successfully developed to the adult stage (average 8.4), but in all cases the host was killed. The sex ratio (female: male) of the parasitoid adults emerging from field-collected cocoons was 2:1, whereas the sex ratio of parasitoids reared from field collected eggs and larvae was greater than 3:1. On average, adult females lived 29.1 d, and males lived 23.6 d when fed with 20% honey solution, significantly longer than without a nutritional supplement. Sexual reproduction is the normal mode of reproduction, but in the laboratory females did reproduce parthenogenetically, producing only males. The average fecundity was 23.3 eggs per female in the laboratory. S. agrili developed through five larval instars, and the larvae fed gregariously on the host hemolymph. The generation time from egg to adult wasp was 27-28 d at 22-26 degrees C. Natural parasitism rates were as high as 60%, and in October they reached over 90% in some stands. This study showed that S. agrili is a promising agent for biocontrol of A. planipennis.


Evaluation of simulation training in cardiothoracic surgery: the Senior Tour perspective.
The study objective was to introduce senior surgeons, referred to as members of the "Senior Tour," to simulation-based learning and evaluate ongoing simulation efforts in cardiothoracic surgery. Thirteen senior cardiothoracic surgeons participated in a 2½-day Senior Tour Meeting. Of 12 simulators, each participant focused on 6 cardiac (small vessel anastomosis, aortic cannulation, cardiopulmonary bypass, aortic valve replacement, mitral valve repair, and aortic root replacement) or 6 thoracic surgical simulators (hilar dissection, esophageal anastomosis, rigid bronchoscopy, video-assisted thoracoscopic surgery lobectomy, tracheal resection, and sleeve resection). The participants provided critical feedback regarding the realism and utility of the simulators, which served as the basis for a composite assessment of the simulators. All participants acknowledged that simulation may not provide a wholly immersive experience. For small vessel anastomosis, the portable chest model is less realistic compared with the porcine model, but is valuable in teaching anastomosis mechanics. The aortic cannulation model allows multiple cannulations and can serve as a thoracic aortic surgery model. The cardiopulmonary bypass simulator provides crisis management experience. The porcine aortic valve replacement, mitral valve annuloplasty, and aortic root models are realistic and permit standardized training. The hilar dissection model is subject to variability of porcine anatomy and fragility of the vascular structures. The realistic esophageal anastomosis simulator presents various approaches to esophageal anastomosis. The exercise associated with the rigid bronchoscopy model is brief, and adding additional procedures should be considered. The tracheal resection, sleeve resection, and video-assisted thoracoscopic surgery lobectomy models are highly realistic and simulate advanced maneuvers. By providing the necessary tools, such as task trainers and assessment instruments, the Senior Tour may be one means to enhance simulation-based learning in cardiothoracic surgery. The Senior Tour members can provide regular programmatic evaluation and critical analyses to ensure that proposed simulators are of educational value.


Studies of DNA 'Breathing' by Polarization-Sweep Single-Molecule Fluorescence Microscopy of Exciton-Coupled (iCy3)2 Dimer-Labeled DNA Fork Constructs.
Local fluctuations of the sugar-phosphate backbones and bases of DNA (often called DNA 'breathing') play a variety of critical roles in controlling the functional interactions of the DNA genome with the protein complexes that regulate it. Here, we present a single-molecule fluorescence method that we have used to measure and characterize such conformational fluctuations at and near biologically important positions in model DNA replication fork constructs labeled with exciton-coupled cyanine [(iCy3)2] dimer probes. Previous work has shown that the constructs that we tested here exhibit a broad range of spectral properties at the ensemble level, and these differences can be structurally and dynamically interpreted using our present methodology at the single-molecule level. The (iCy3)2 dimer has one symmetric (+) and one antisymmetric (-) exciton, with the respective transition dipole moments oriented perpendicular to one another. We excite single-molecule samples using a continuous-wave linearly polarized laser, with the polarization direction continuously rotated at the frequency of 1 MHz. The ensuing fluorescence signal is modulated as the laser polarization alternately excites the symmetric and antisymmetric excitons of the (iCy3)2 dimer probe. Phase-sensitive detection of the modulated signal provides information about the distribution of local conformations and the conformational interconversion dynamics of the (iCy3)2 probe. We find that at most construct positions that we examined, the (iCy3)2 dimer-labeled DNA fork constructs can adopt four topologically distinct conformational macrostates. These results suggest that in addition to observing DNA breathing at and near ss-dsDNA junctions, our new methodology should be useful to determine which of these pre-existing macrostates are recognized by, bind to, and are stabilized by various genome-regulatory proteins.


The dyslipidemia of diabetes mellitus: giving triglycerides and high-density lipoprotein cholesterol a higher priority?
CVD is the primary cause of morbidity and mortality in patients who have diabetes mellitus. Most such patients have at least one lipid abnormality. Managing these complex lipid disorders is a crucial component of comprehensive diabetes mellitus care and limits the risk for cardiovascular morbidity and mortality. With the high prevalence of mixed lipid disorders, management must focus on all components of the lipid profile. Lowering LDL-C levels remains the first priority, but abnormalities in HDL-C and TG levels also should be treated aggressively. Statins, fibrates, and niacin, along with newer therapies such as ezetimibe, can improve significantly components of the lipid profile. Alone or in combination, these agents can treat the dyslipidemia of diabetes mellitus effectively and safely.


Differentiation of Benign from Malignant Adnexal Masses by Dynamic Contrast-Enhanced MRI (DCE-MRI): Quantitative and Semi-quantitative analysis at 3-Tesla MRI
Background: To evaluate the utility of the pharmacokinetic modeling derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiating benign from malignant adnexal masses. Methods: A total of 43 patients with 49 complex adnexal masses (27 benign, 3 borderline, and 19 malignant lesions) underwent preoperative DCE-MRI examinations on a 3 Tesla MRI. Using extended Tofts' model, quantitative analysis was performed in the solid components of all tumors. Three pharmacokinetic parameters were defined as volume transfer coefficient (Ktrans), the rate constant (Kep), and the plasma volume (Vp). Semi-quantitative analysis was also performed and the values of relative signal intensity (SI rel) wash-in-rate (WIR), the initial area under the curve (iAUC60), time-to-peak (TTP) and wash-out-rate (WOR) were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic characteristics of each DCE-MRI parameter in differentiating borderline/malignant tumors from benign lesions and to provide the optimal cutoff values for these variables. Results: SI rel had the highest diagnostic value (AUC=0.872; p<0.001; cut-off=121.4 associated with an overall accuracy=79.6%, sensitivity=95.5%, specificity=66.7%, NPV=94.8% and PPV=70.0%). Ktrans had the second highest AUC=0.836 (p<0.001; cut-off=0.034 associated with an overall accuracy=79.6%, sensitivity=86.4%, specificity=74.1%, NPV=87.0% and PPV=73.1%). The other factors found to be acceptable diagnostic parameters for borderline/malignant lesions included WIR (AUC=0.816; p<0.001), iAUC60 (AUC=0.808; p<0.001), Vp (AUC=0.795; p<0.001), SI max (AUC=0.737, p=0.005), SI peak (AUC=0.737; p=0.005) and Kep (AUC=0.681; p=0.031). Conclusion: Quantitative DCE-MRI is a relevant tool for differentiating benign from malignant adnexal masses. Among all the DCE parameters, SI rel and Ktrans are the most accurate discriminators.


Use of allogeneic platelet gel in the management of chemotherapy extravasation injuries: a case report.
The allogeneic platelet (PLT) gel offers to be a valid supportive measure in the management of chemotherapy extravasation injuries. We report a case of a 58-year-old patient with multiple myeloma enrolled for high-dose chemotherapy and autologous stem cell transplantation. As pretransplant therapy, the patient received induction therapy with bortezomib, adriblastina, and desametazone. A port was inserted in the vein on the back of the hand. After three cycles, the patient reported rapid development of redness, pain, and necrotic tissue in the left hand, and a diagnosis of extravasation was addressed. The patient presented a raw area on the back of the hand caused by cytotoxic/chemotherapeutic drug leakage because of the malposition of venous access devices. Skin ulcer was debrided, and the wound was reconstructed with a combination of local random rotational flap and abdomen skin graft. Two weeks later, a 20% skin flap necrosis was observed. In the context of wound healing, topical plasma-rich PLT gel is able to accelerate the regeneration and repair of tissue, so it was set out to assess PLT gel efficacy in this case. The PLT gel was applied topically once every 5 days, for a duration of 60 days on average. There were no adverse reactions observed during the topical therapy. Complete wound healing was observed after 12 PLT-rich plasma applications. No ulcer recurrence was noted in the patient during the follow-up period of 2-19 months.


Factors related to health-related quality of life in ankylosing spondylitis, overall and stratified by sex.
Ankylosing spondylitis (AS) begins early in life and often leads to reduced physical function, but less is known about the impacts it has on health-related quality of life (HRQoL). The aims of this study were to assess HRQoL using the Short Form-36 (SF-36) in a cohort of patients with AS compared with controls and to examine associations between SF-36 scores and spinal radiographic changes, physical function, disease activity and demographic data overall and stratified by sex. A cohort of patients with AS from Western Sweden were assessed using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with spinal radiographs, clinical examination and questionnaires, including the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Patient Global (BASG) and SF-36. Each patient's SF-36 results were compared with those of five age-matched and sex-matched persons (n = 1055) from the SF-36 Swedish normative population database. Associations between SF-36 physical component summary (PCS) and mental component summary (MCS) scores and disease-related and demographic factors were investigated using univariate and multivariable ogistic regression analyses with PCS and MCS below/above their respective median values as dependent variables. A total of 210 patients, age (median, IQR) 49.0 (21.2) years, symptom duration 24.0 (21.0) years, men 57.6% and HLAB27 87.1% were included. Patients with AS scored significantly lower (p < 0.001) compared to controls in all SF-36 domains and component summaries; PCS 42.4 (14.5) in AS versus 52.4 (11.8) in controls and MCS 47.9 (20.0) in AS versus 54.1 (10.1) in controls. Both men and women scored significantly lower in PCS compared with MCS. Multivariable logistic regression analyses revealed that living without a partner (OR 2.38, 95% CI 1.00-5.67), long symptom duration (year in decade OR 1.66, 95% CI 1.16-2.37), higher BASFI (OR 1.98, 95% CI 1.46-2.70) and ASDAS ≥ 2.1 (OR 3.32, 95% CI 1.45-7.62) were associated with worse PCS, while living without a partner (OR 3.04, 95% CI 1.34-6.91), fatigue (visual analogue scale for global fatigue greater than the median (OR 6.36, 95% CI 3.06-13.19) and ASDAS ≥ 2.1 (OR 2.97, 95% CI 1.41-6.25) with worse MCS. Some differences between sexes were observed in the results. The patients with AS had significantly lower HRQoL compared with controls. PCS was more affected compared to MCS in both sexes. Both disease-related and demographic factors were associated with HRQoL, partly overlapping for PCS and MCS. Factors associated with HRQoL showed some differences between sexes. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may potentially be improved. ClinicalTrials.gov, NCT00858819 . Registered on 9 March 2009. Last updated on 28 May 2015.


DHHC5 protein palmitoylates flotillin-2 and is rapidly degraded on induction of neuronal differentiation in cultured cells.
Post-translational palmitoylation of intracellular proteins is mediated by protein palmitoyltransferases belonging to the DHHC family, which share a common catalytic Asp-His-His-Cys (DHHC) motif. Several members have been implicated in neuronal development, neurotransmission, and synaptic plasticity. We previously observed that mice homozygous for a hypomorphic allele of the ZDHHC5 gene are impaired in context-dependent learning and memory. To identify potentially relevant protein substrates of DHHC5, we performed a quantitative proteomic analysis of stable isotope-labeled neuronal stem cell cultures from forebrains of normal and DHHC5-GT (gene-trapped) mice using the bioorthogonal palmitate analog 17-octadecynoic acid. We identified ∼300 17-octadecynoic acid-modified and hydroxylamine-sensitive proteins, of which a subset was decreased in abundance in DHHC5-GT cells. Palmitoylation and oligomerization of one of these proteins (flotillin-2) was abolished in DHHC5-GT neuronal stem cells. In COS-1 cells, overexpression of DHHC5 markedly stimulated the palmitoylation of flotillin-2, strongly suggesting a direct enzyme-substrate relationship. Serendipitously, we found that down-regulation of DHHC5 was triggered within minutes following growth factor withdrawal from normal neural stem cells, a maneuver that is used to induce neural differentiation in culture. The effect was reversible for up to 4 h, and degradation was partially prevented by inhibitors of ubiquitin-mediated proteolysis. These findings suggest that protein palmitoylation can be regulated through changes in DHHC PAT levels in response to differentiation signals.


Performances of automated digital imaging of Gram-stained slides with on-screen reading against manual microscopy.
The objective of this study was to evaluate the performances of the automated digital imaging of Gram-stained slides against manual microscopy. Four hundred forty-three identified Gram-stained slides were included in this study. When both methods agreed, we considered the results as correct, and no further examination was carried out. Whenever the methods gave discrepant results, we reviewed the digital images and the glass slides by manual microscopy to avoid incorrectly read smears. The final result was a consensus of multiple independent reader interpretations. Among the 443 slides analyzed in this study, 101 (22.8%) showed discrepant results between the compared methods. The rates of discrepant results according to the specimen types were 5.7% (9/157) for positive blood cultures, 42% (60/142) for respiratory tract specimens, and 22% (32/144) for sterile site specimens. After a subsequent review of the discrepant slides, the final rate of discrepancies dropped to 7.0% (31/443). The overall agreement between the compared methods and the culture results reached 78% (345/443) and 79% (349/443) for manual microscopy and automated digital imaging, respectively. According to culture results, the specificity for automated digital imaging and manual microscopy were 90.8% and 87.7% respectively. In contrast, sensitivity was 84.1% for the two compared methods. The discrepant results were mostly encountered with microorganism morphologies of rare occurrence. The results reported in this study emphasize that on-screen reading is challenging, since the recognition of morphologies on-screen can appear different as compared to routine manual microscopy. Monitoring of Gram stain errors, which is facilitated by automated digital imaging, remains crucial for the quality control of reported Gram stain results.


Paramecium aurelia revisited.
The species Paramecium aurelia sensu latu, containing 15 sexually isolated subspecies (syngens), is the classic example of a sibling species complex in the ciliates. Using DNA sequence comparison, it is now possible to see whether this example parallels other studied sibling species complexes. We sequenced the internal transcribed spacer (ITS) region of the nuclear ribosomal cistron for 13 of the syngens plus two other Paramecium species and several Tetrahymena spp. Using available spirotrich sequences of the internal transcribed spacer 2 (ITS2), we established the RNA transcript folding pattern for ciliates. Ciliates exhibit the two highly conserved helices in their RNA transcript folding pattern in common with other eukaryotes, despite their unusual nuclear behavior and their presumed low copy number of micronuclear ribosomal repeats. Consequently, the set of 111-116 ITS2 nucleotide positions that are relatively conserved in evolution can be derived and used for comparative analysis. Mating behavior (i.e. gamete agglutination and fusion) is the character showing greatest correlation with the degree of ITS2 evolution in the P. aurelia complex, as also found in other eukaryotes. The degree of change in the ITS2 relatively conserved sequences found among the sibling species of P. aurelia is the same degree as found among the sibling species of the Drosophila melanogaster-mauritania-sechellia-simulans-yakuba species complex. The relatively conserved subregion of ITS2, determined from transcript secondary structure, is a tool for identifying the level of the biological species in the absence of knowledge of sexual compatibility in both micro- and macro-eukaryote species complexes.


Humans differ from other hominids in lacking an activating NK cell receptor that recognizes the C1 epitope of MHC class I.
Modulation of human NK cell function by killer cell Ig-like receptors (KIR) and MHC class I is dominated by the bipartite interactions of inhibitory lineage III KIR with the C1 and C2 epitopes of HLA-C. In comparison, the ligand specificities and functional contributions of the activating lineage III KIR remain poorly understood. Using a robust, sensitive assay of KIR binding and a representative panel of 95 HLA class I targets, we show that KIR2DS1 binds C2 with ~50% the avidity of KIR2DL1, whereas KIR2DS2, KIR2DS3, and KIR2DS5 have no detectable avidity for C1, C2, or any other HLA class I epitope. In contrast, the chimpanzee has activating C1- and C2-specific lineage III KIR with strong avidity, comparable to those of their paired inhibitory receptors. One variant of chimpanzee Pt-KIR3DS2, the activating C2-specific receptor, has the same avidity for C2 as does inhibitory Pt-KIR3DL4, and a second variant has ~73% the avidity. Chimpanzee Pt-KIR3DS6, the activating C1-specific receptor, has avidity for C1 that is ~70% that of inhibitory Pt-KIR2DL6. In both humans and chimpanzees we observe an evolutionary trend toward reducing the avidity of the activating C1- and C2-specific receptors through selective acquisition of attenuating substitutions. However, the extent of attenuation has been extreme in humans, as exemplified by KIR2DS2, an activating C1-specific receptor that has lost all detectable avidity for HLA class I. Supporting such elimination of activating C1-specific receptors as a uniquely human phenomenon is the presence of a high-avidity activating C1-specific receptor (Gg-KIR2DSa) in gorilla.


Can the C-reactive protein-to-plasma albumin ratio be an alternative scoring to show mortality and morbidity in patients with colorectal cancer?
This study aims to demonstrate the sensitivity and specificity of C-reactive protein to plasma albumin (CRP/ALB) ratio in predicting morbidity and mortality in patients operated for colorectal cancer followed up in the intensive care unit by comparing it with current scoring systems. The data of patients who underwent surgery for colorectal cancer and hospitalized in the intensive care unit between 2015-2018 with available data were retrospectively analyzed in this study. The CRP/ALB ratio, the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) prepared for both gastrointestinal and colorectal surgery, and the Association of Coloproctology of Great Britain and Ireland (ACPGBI-CRC) scoring system prepared for colorectal patients, were compared to determine their success in predicting mortality and morbidity. A total of 119 patients were included in this study. Mortality was observed in nine patients and morbidity was observed in 38 patients. When compared with P-POSSUM, which is the only scoring system showing morbidity, the CRP/ALB ratio was found to have a high prediction accuracy. The C reactive protein to plasma albumin ratio values was found to have lower power than P-POSSUM, CR-POSSUM and ACPGBI-CRC. Although scoring systems are useful in predicting morbidity and mortality in colorectal patients, they are difficult to use in practice since they include many parameters. that the findings obtained in this study suggest that the CRP/ALB ratio, which can be calculated without any additional cost, may help the clinician predict mortality and especially morbidity.


How do individuals with Asperger syndrome respond to nonliteral language and inappropriate requests in computer-mediated communication?
Computer-mediated communication in individuals with Asperger syndrome, Tourette syndrome and normal controls was explored with a program called Bubble Dialogue (Gray, Creighton, McMahon, and Cunninghamn (1991)) in which the users type text into speech bubbles. Two scenarios, based on Happé (1994) were adapted to investigate understanding of figure of speech and sarcasm, and a third, developed by ourselves, looked at responses to inappropriate requests (lending money and disclosing home address on a first meeting). Dialogue transcripts were assessed by 62 raters who were blind to the clinical diagnoses. Hierarchical linear modelling revealed that rated understanding of a figure of speech was predicted mainly by verbal ability and executive ability, as well as by clinical diagnosis, whereas handling inappropriate requests was predicted by age, verbal ability, executive ability and diagnosis. Notably, the Tourette comparison group showed better understanding than the Asperger group in interpreting a figure of speech and handling inappropriate requests, and differences between these groups were possibly attributable to individual differences in executive ability. In contrast, understanding sarcasm was predicted by age but not by either verbal ability, executive ability or clinical diagnosis. Evidently, there is a complicated relation between Asperger syndrome, verbal ability and executive abilities with respect to communicative performance.


[Direct venous thrombolysis and venous angioplasty in the upper extremity].
Venous thromboses of stenoses in the upper extremity are often the result of a compression syndrome of the shoulder girdle, the Paget-von Schroetter syndrome, vascular surgery, space-occupying lesions in the mediastinum or the result of catheterisation. Direct venous thrombolysis and venous angioplasty were performed successfully in six patients.


Forearm instability.
Forearm instability results from trauma, which disrupts the radial head, the interosseous membrane, and the triangular fibrocartilage complex. Inadequate treatment of injuries to these forearm stabilizers may result in the complex problem of chronic longitudinal forearm instability. Delayed recognition and/or treatment of injuries producing forearm dissociation has led to poor patient outcomes, which makes timely recognition of the injury pattern imperative. This article discusses relevant aspects of forearm anatomy and current concepts in the diagnosis and treatment options for this complex injury pattern.


Antibody to nuclear material eluted from isolated spleen vessels in systemic lupus erythematosus.
Splenic blood vessels were isolated from surrounding cells by treatment with trypsin and the use of ultrasound. This procedure retained vascular-bound immunoglobulins which were recovered by acid elution of vessels isolated from a patient with systemic lupus erythematosus. These eluted immunoglobulins reacted with material from cell nuclei as demonstrated by immunofluorescence.


A calorimetric study on diflunisal release from poly(lactide-co-glycolide) microspheres by monitoring the drug effect on dipalmitoylphosphatidylcholine liposomes: temperature and drug loading influence.
Diflunisal release from poly-Lactide-co-Glycolide (50:50, 34,000 MW) microspheres loaded with two different amounts of drug (2.5 +/- 0.5% and 10 +/- 0.5% w/w) was monitored by following the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine unilamellar vesicles at different temperatures. The effects of the drug released from the microspheres on the thermotropic behavior of lipid aqueous dispersion containing different molar ratios of drug was detected by differential scanning calorimetry and was compared with the effects exerted by the free Diflunisal. Diflunisal affects mainly the temperature (Tm) of the transition characteristic of phospholipid vesicles as model biomembrane, causing a shift toward lower values. This shift was modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Afterward, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and differently Diflunisal-loaded microspheres as well as free powdered Diflunisal after incubation for increasing times at three different temperatures (25, 37, and 50 degrees C). The Tm shifts of the lipid bilayer, caused by the drug released from polymeric system as well as by the free drug during incubation periods, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres as well as by the temperature acting on drug solubility and membrane disorder. This drug release model, monitored by the calorimetric technique shows that a) the poly-Lactide-co-Glycolide microspheres are a good delivery system able to sustain the drug release; b) the differential scanning calorimetry technique applied on the drug interaction with biomembranes constitutes a good tool to follow the drug release; 3) this model, representing an innovative alternative in vitro model, should be used to determine the different kinetics involved in the drug transfer from a drug delivery system to a membrane as uptake site.


Stable angina pectoris: recent advances in predicting prognosis and treatment.
Substantial progress has been made in the ability to predict individuals at the highest risk of acute myocardial infarction and occlusive cerebrovascular events, as well as in the ability to reduce these risks by vigorous reductions in serum cholesterol and LDL cholesterol concentrations. The development of stents has been a clear advance in the interventional treatment of coronary heart disease in that stents provide an effective acute treatment for significant coronary narrowings in symptomatic patients and reduce the risk of restenosis lesions subsequently. Heparin-coated stents appear to provide additive protection against the risk of thrombosis and the future development of restenosis lesions. Preliminary studies done on human carotid atherosclerotic plaque suggest that unstable plaque might be detected in the future by their temperature heterogeneity, which helps identify plaques with relatively thin fibrous caps, marked inflammation, and adjacent lipid pools.


Physicochemical Parameters as a Tool for the Assessment of Origin of Honey.
Honey is a complex mixture of various substances, and its composition depends on both botanical and geographical origin, as well as anthropogenic factors. The accurate identification of honey origin guarantees the satisfaction of consumers' needs and has an impact on the honey market value. Physicochemical parameters, some of which are used in routine analysis of honey quality, could be useful for the assessment of its origin. In this review, special attention is paid to those studies that assessed the sugar and mineral composition of honey, whether they were investigated in terms of botanical or geographical origin, or for the characterization of honey type. The oligosaccharides present in honey and the electrical conductivity of honey correlate strongly with its botanical origin. Mineral content could be indicative for distinguishing honeys according to their botanical and geographical origins because it depends on both the soil composition and the floral type of melliferous plants. This review provides insight into the results obtained by various studies from approximately the last 10 years concerning the sugar profile and the mineral and trace element content of different types of honey. An attempt was made to statistically analyze the results regarding mineral and trace element content in order to identify indicators that could distinguish honey by origin.


The topography of agoraphobia.
Findings from empirical research and clinical practice are comprehensively integrated into a topography of the agoraphobic syndrome. The following topics are discussed successively: the agoraphobic syndrome (core mechanism and life pattern), the pathogenesis (causal mechanism, antecedents, and predispositions), the different kinds of anxiety from which agoraphobes can suffer, and the broad-spectrum therapeutic implications.


Stereotypes Influence Destination Memory In Normal Aging.
Background/Study Context: A substantial body of literature suggests that stereotypes can play a determining role in making judgments about the source of information. This study investigated this issue for destination memory or remembering to whom information has been previously told. Younger adults and older adults told six medical and six mechanical facts to a picture depicting a physician, and also told six different medical and six different mechanical facts to a picture depicting a mechanic. On a subsequent recognition task, participants had to decide to whom each fact had been previously told. Analysis showed better destination memory for destination-consistent facts than for inconsistent facts, a stereotypical tendency that was more apparent in older adults than in younger adults. Difficulties in attributing facts to their fact-inconsistent destination were reliably correlated with executive functions in younger adults and older adults. Executive functions are likely to be required to monitor discrepancies between facts and their inconsistent destination, whereas no such monitoring is required when statements are consistent with their destination.


Heliox administration during high-frequency jet ventilation augments carbon dioxide clearance.
We report the combined use of heliox and high-frequency jet ventilation to augment carbon dioxide clearance, with a focus on the important technical considerations. Our case is a 5-month old infant with acute respiratory failure associated with gas trapping, hypercarbia, respiratory acidosis, and air leak. Despite maximal conventional ventilation, bronchodilator therapy, corticosteroids, and sedation, the infant continued to demonstrate worsening gas exchange necessitating an escalation of support to high-frequency oscillatory ventilation. After the development of an air leak and continued difficulties with carbon dioxide clearance, the patient was transitioned to high-frequency jet ventilation. Persistent hypercarbia resulted in the addition of heliox to facilitate ventilation. Improvements in gas exchange occurred rapidly. The combination of heliox and high frequency jet ventilation resulted in improved carbon dioxide clearance, respiratory stabilization, and the ability to wean ventilator settings.


Effects of silicone expanders and implants on echocardiographic image quality after breast reconstruction.
Use of silicone expanders and implants is the most common breast reconstruction technique after mastectomy. Postmastectomy patients often need echocardiographic monitoring of potential cardiotoxicity induced by cancer chemotherapy. The impairment of the echocardiographic acoustic window caused by silicone implants for breast augmentation has been reported. This study investigates whether the echocardiographic image quality was impaired in women reconstructed with silicone expanders and implants. The records of 44 consecutive women who underwent echocardiographic follow-up after breast reconstruction with expanders and implants at the authors' institution from January of 2000 to August of 2012 were reviewed. The population was divided into a study group (left or bilateral breast expanders/implants, n=30) and a control group (right breast expanders/implants, n=14). The impact of breast expanders/implants on echocardiographic image quality was tested (analysis of covariance model). Patients with a breast expander/implant (left or bilateral and right breast expanders/implants) were included. The mean volume of the breast devices was 353.2±125.5 cc. The quality of the echocardiographic images was good or sufficient in the control group; in the study group, it was judged as adequate in only 50 percent of cases (15 patients) and inadequate in the remaining 15 patients (p<0.001). At multivariable analysis, a persistent relationship between device position (left versus right) and image quality (p=0.001) was shown, independent from other factors. Silicone expanders and implants in postmastectomy left breast reconstruction considerably reduce the image quality of echocardiography. This may have important clinical implications, given the need for periodic echocardiographic surveillance before and during chemotherapy. Therapeutic, III.


Alcohol consumption and risk of renal cell carcinoma: a prospective study of Swedish women.
Previous literature, although not consistent, suggests that moderate alcohol consumption might be associated with decreased risk of renal cell carcinoma (RCC) in women. Thus, we examined the association between alcohol intake and the incidence of RCC by analyzing data from the Swedish Mammography Cohort, a population-based prospective cohort of 59,237 women, aged 40-76 years, who, at baseline in 1987-1990, were cancer free and had completed a food-frequency questionnaire including questions about alcohol consumption. Through June 30, 2004, 132 incident cases of RCC were diagnosed. We used the Cox proportional hazards model to estimate age and body mass index (BMI) adjusted rate ratios (RRs) and their 95% confidence intervals (CIs). Women who consumed >4.3 grams per day of alcohol (ethanol) had nonsignificantly lower risk of RCC than did women who consumed <2.5 g/d (RR = 0.71, 95% CI 0.42-1.19); among women > or = 55 years of age at entry into the cohort, corresponding risk estimates were RR = 0.33, 95% CI 0.10-1.05, p for trend = 0.04 and among women with BMI >25 kg/m2, RR = 0.30, 95% CI 0.09-0.97, p for trend = 0.04. Consistent with these findings, women who drank 1 or more servings of total alcoholic beverages per week had lower RCC risk than did women who drank less (RR = 0.62, 95% CI 0.41-0.94); the corresponding estimate for women > or = 55 years of age was RR = 0.44, 95% CI 0.22-0.88. Results from our prospective cohort study of middle-aged and elderly women indicate that moderate alcohol consumption may be associated with decreased risk of RCC.


Updated MS²PIP web server delivers fast and accurate MS² peak intensity prediction for multiple fragmentation methods, instruments and labeling techniques.
MS²PIP is a data-driven tool that accurately predicts peak intensities for a given peptide's fragmentation mass spectrum. Since the release of the MS²PIP web server in 2015, we have brought significant updates to both the tool and the web server. In addition to the original models for CID and HCD fragmentation, we have added specialized models for the TripleTOF 5600+ mass spectrometer, for TMT-labeled peptides, for iTRAQ-labeled peptides, and for iTRAQ-labeled phosphopeptides. Because the fragmentation pattern is heavily altered in each of these cases, these additional models greatly improve the prediction accuracy for their corresponding data types. We have also substantially reduced the computational resources required to run MS²PIP, and have completely rebuilt the web server, which now allows predictions of up to 100 000 peptide sequences in a single request. The MS²PIP web server is freely available at https://iomics.ugent.be/ms2pip/.


Characterization and Correction of Low Frequency Artifacts in Segmental Bioimpedance Measurements.
Bioimpedance analysis can be used for remote monitoring of volume status for various conditions such as congestive heart failure. The measurement is typically performed with four electrodes, two of them driving an alternating current through the tissue and the other two sensing the resulting voltage. Issues with the measurement setup such as stray capacitance or electrode mismatch can cause artifacts that impact Cole parameters used for volume estimation. While previous research has focused on mitigating high frequency artifacts, little research has been done to understand the cause and impact of low frequency artifacts, nor how to mitigate the impact of these artifacts. These artifacts are most prevalent in wearable segmental bioimpedance systems, especially using textile electrodes, so future research in this area is needed for these systems to be viable. The present study uses simulations to identify the potential sources of low frequency artifacts, and explores techniques to minimize the impact of these artifacts on Cole parameters. Theoretical analysis and simulations show that the mismatch of the voltage electrodes causes artifacts at low frequency. These artifacts are highly dependent on the impedance of the negative current injecting electrode. Averaging measurements of the mismatch of both voltage electrodes and limiting high frequency measurements to 200 kHz can reduce errors due to these artifacts from over 137% to less than 3%. The results of this study suggest the impact of low frequency artifacts can be significantly reduced, enabling future development of wearable bioimpedance systems.Clinical relevance- Reducing the impact of low frequency artifacts on Cole parameter estimation enables wearable segmental bioimpedance systems that can be used for remote monitoring of volume status in home environments.


Automatic detection of erthemato-squamous diseases using adaptive neuro- fuzzy inference systems.
A new approach based on adaptive neuro-fuzzy inference system (ANFIS) was presented for detection of erythemato-squamous diseases. The domain contained records of patients with known diagnosis. Given a training set of such records, the ANFIS classifiers learned how to differentiate a new case in the domain. The six ANFIS classifiers were used to detect the six erythemato-squamous diseases when 34 features defining six disease indications were used as inputs. To improve diagnostic accuracy, the seventh ANFIS classifier (combining ANFIS) was trained using the outputs of the six ANFIS classifiers as input data. The proposed ANFIS model combined the neural network adaptive capabilities and the fuzzy logic qualitative approach. Some conclusions concerning the impacts of features on the detection of erythemato-squamous diseases were obtained through analysis of the ANFIS. The performances of the ANFIS model were evaluated in terms of training performances and classification accuracies and the results confirmed that the proposed ANFIS model has some potential in detecting the erythemato-squamous diseases. The ANFIS model achieved accuracy rates which were higher than that of the stand-alone neural network model.


Effects of winter manure application in Ohio on the quality of surface runoff.
Winter application of manure poses environmental risks. Seven continuous corn, instrumented watersheds (approximately 1 ha each) at the USDA-ARS North Appalachian Experimental Watershed research station near Coshocton, Ohio were used to evaluate the environmental impacts of winter manure application when using some of the Ohio Natural Resources Conservation Service recommendations. For 3 yr on frozen, sometimes snow-covered, ground in January or February, two watersheds received turkey litter, two received liquid swine manure, and three were control plots that received N fertilizer at planting (not manure). Manure was applied at an N rate for corn; the target level was 180 kg N ha(-1) with a 30-m setback from the application area to the bottom of each watershed. Four grassed plots (61 x 12 m) were used for beef slurry application (9.1 Mg ha(-1) wet weight); two plots had 61 x 12 m grassed filter areas below them, and two plots had 30 x 12 m filter areas. There were two control plots. Nutrient concentrations were sometimes high, especially in runoff soon after application. However, most events with high concentrations occurred with low flow volumes; therefore, transport was minimal. Applying manure at the N rate for crop needs resulted in excess application of P. Elevated P losses contributed to a greater potential of detrimental environmental impacts with P than with N. Filter strips reduced nutrient concentrations and transport, but the data were too limited to compare the effectiveness of the 30- and 61-m filter strips. Winter application of manure is not ideal, but by following prescribed guidelines, detrimental environmental impacts can be reduced.


CD73 expression and clinical significance in human metastatic melanoma.
CD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target. CD73 expression was detected in TC in 54% of melanoma metastases, involving < 50% TC in the majority of the cases, with variable intensity. CD73 expression was significantly associated with a lower Breslow's depth of the primary lesion and was more frequent in patients having received prior non-surgical therapies. In an adjusted analysis, CD73 expression in TC (H-score > 37.5 or intensity > 1) significantly correlated to decreased overall survival (OS) from biopsy. Of the samples containing TIMC, 35% presented CD73+ TIMC. Highly infiltrated tumors were more likely to contain CD73+ TIMC. CD73 expression in TIMC (percentage ≥1%) significantly correlated with improved OS from biopsy. Immunohistochemistry detected CD73 expression in more than half of metastatic melanomas. While CD73 expression in TC significantly correlated with decreased OS, CD73 expression in TIMC significantly associated with improved OS. These results encourage the study of anti-CD73 therapies for metastatic melanoma patients. CD73 expression was assessed by immunohistochemistry in metastatic melanomas from 114 patients. Immunostainings were evaluated in tumor cells (TC) (percentage, intensity (1-3) and H-score) and in tumor-infiltrating mononuclear cells (TIMC) (percentage).


Identification of sapovirus GV.2, astrovirus VA3 and novel anelloviruses in serum from patients with acute hepatitis of unknown aetiology.
Hepatitis is a general term meaning inflammation of the liver, which can be caused by a variety of viruses. However, a substantial number of cases remain with unknown aetiology. We analysed the serum of patients with clinical signs of hepatitis using a metagenomics approach to characterize their viral species composition. Four pools of patients with hepatitis without identified aetiological agents were evaluated. Additionally, one pool of patients with hepatitis E (HEV) and pools of healthy volunteers were included as controls. A high diversity of anelloviruses, including novel sequences, was found in pools from patients with hepatitis of unknown aetiology. Moreover, viruses recently associated with gastroenteritis as sapovirus GV.2 and astrovirus VA3 were also detected only in those pools. Besides, most of the HEV genome was recovered from the HEV pool. Finally, GB virus C and human endogenous retrovirus were found in the HEV and healthy pools. Our study provides an overview of the virome in serum from hepatitis patients suggesting a potential role of these viruses not previously described in cases of hepatitis. However, further epidemiologic studies are necessary to confirm their contribution to the development of hepatitis.


A Dengue Vaccine: Will It be Accepted and Is It Feasible? Lessons from Barranquilla, Colombia, and Merida, Venezuela.
With one vaccine on the market and others in clinical trials, policy makers in dengue endemic regions face the decision of whether to introduce a dengue vaccine in their communities. The World Health Organization (WHO) recommends that individualized assessments be conducted before any vaccine introduction to evaluate disease burden and the strength of current vaccination programs. This study seeks to aid in that decision-making process by examining the acceptability and feasibility of dengue vaccine introduction in Barranquilla, Colombia, and Merida, Venezuela. Surveys were administered February-June of 2018 for three groups: patients (n = 351), health professionals (n = 197), and government officials (n = 26). In Barranquilla, most respondents reported dengue to be a moderate-severe problem, that a dengue vaccine would be useful in their communities, and that their current vaccination programs could handle the addition of a new vaccine. In Venezuela, respondents were less likely to view dengue as a major concern and listed multiple barriers to not just dengue vaccine introduction, but to providing current vaccines as well. Further work is needed in Colombia to more objectively assess the country's readiness as a whole for a future dengue vaccine. As political and social unrest continues in Venezuela, however, future initiatives should focus on trust and capacity building. This study can serve as a framework for future assessments of the acceptability and feasibility of a dengue vaccine in both targeted areas and on larger scales.


System for laboratory proficiency testing in bacteriology: organisation and impact on microbiology laboratories in health care facilities funded by the Ontario Government.
The Ministry of Health requires that all medical laboratories in the Province of Ontario participate in a laboratory proficiency testing program (LPTP). In bacteriology compliance has been excellent. Eighty-six laboratories, for various reasons over the period under review, have surrendered their licence or, because of poor performance on LPTP test surveys, have had their licence withdrawn by the Ministry. The highest percentage of withdrawals occurred in small hospitals in isolated areas. In April 1979 there were 249 participating laboratories. Participants' results are first analysed by computer, and, subsequently, approximately 20% of participants' reports are reviewed by the Committee. Various Committee actions ensue: correspondence with the laboratory director regarding errors; an offer of a visit; and possibly a report via a senior LPTP committee to the Ministry that a laboratory is non-proficient and, in LPTP's terms of reference, non-remediable. Subsequent Ministry action might be the withdrawal of a laboratory's licence. However, this last recourse only occurs when educational efforts have proved ineffectual. Overall, performance in LPTP bacteriology surveys has improved over the period 1975-8, with 68% of 263 laboratories achieving a score of 70% or higher and 26% of 263 laboratories scoring less than 60%.


High-resolution prediction of leaf onset date in Japan in the 21st century under the IPCC A1B scenario.
Reports indicate that leaf onset (leaf flush) of deciduous trees in cool-temperate ecosystems is occurring earlier in the spring in response to global warming. In this study, we created two types of phenology models, one driven only by warmth (spring warming [SW] model) and another driven by both warmth and winter chilling (parallel chill [PC] model), to predict such phenomena in the Japanese Islands at high spatial resolution (500 m). We calibrated these models using leaf onset dates derived from satellite data (Terra/MODIS) and in situ temperature data derived from a dense network of ground stations Automated Meteorological Data Acquisition System. We ran the model using future climate predictions created by the Japanese Meteorological Agency's MRI-AGCM3.1S model. In comparison to the first decade of the 2000s, our results predict that the date of leaf onset in the 2030s will advance by an average of 12 days under the SW model and 7 days under the PC model throughout the study area. The date of onset in the 2090s will advance by 26 days under the SW model and by 15 days under the PC model. The greatest impact will occur on Hokkaido (the northernmost island) and in the central mountains.


AKAP12 regulates vascular integrity in zebrafish.
The integrity of blood vessels controls vascular permeability and extravasation of blood cells, across the endothelium. Thus, the impairment of endothelial integrity leads to hemorrhage, edema, and inflammatory infiltration. However, the molecular mechanism underlying vascular integrity has not been fully understood. Here, we demonstrate an essential role for A-kinase anchoring protein 12 (AKAP12) in the maintenance of endothelial integrity during vascular development. Zebrafish embryos depleted of akap12 (akap12 morphants) exhibited severe hemorrhages. In vivo time-lapse analyses suggested that disorganized interendothelial cell-cell adhesions in akap12 morphants might be the cause of hemorrhage. To clarify the molecular mechanism by which the cell-cell adhesions are impaired, we examined the cell-cell adhesion molecules and their regulators using cultured endothelial cells. The expression of PAK2, an actin cytoskeletal regulator, and AF6, a connector of intercellular adhesion molecules and actin cytoskeleton, was reduced in AKAP12-depleted cells. Depletion of either PAK2 or AF6 phenocopied AKAP12-depleted cells, suggesting the reduction of PAK2 and AF6 results in the loosening of intercellular junctions. Consistent with this, overexpression of PAK2 and AF6 rescued the abnormal hemorrhage in akap12 morphants. We conclude that AKAP12 is essential for integrity of endothelium by maintaining the expression of PAK2 and AF6 during vascular development.


Pre-existing adenovirus immunity modifies a complex mixed Th1 and Th2 cytokine response to an Ad5/HIV-1 vaccine candidate in humans.
The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732). Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36) or Ad5-seropositive (titer >200; n = 34). Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes). At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008), and significantly more IP-10 (p = 0.0009), IL-2 (p = 0.006) and IL-10 (p = 0.05) in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these results suggest that vector-specific humoral responses may reduce vaccine-induced T-cell responses by previously undetected mechanisms.


Sensory Processing Difficulties in Youths With Disruptive Mood Dysregulation Disorder.
Difficulty modulating sensory information has been described in children with developmental disorders. However, the relation of sensory processing difficulties (SPD) to emotional regulation problems remains poorly understood. The aim of this study is to determine the rate and patterns of SPD in youth with disruptive mood dysregulation disorder (DMDD). Participants were DMDD patients aged 6-16 years presenting at a university hospital in outpatient or inpatient facilities (n = 30). For each participant, the parent-reported Sensory Profile, the Affective Lability Scale, the Beck Depression Inventory-Second Edition, the Child Behavior Checklist/4-18, and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version were completed. The scores of the Sensory Profile of the DMDD youths were compared to those obtained in a clinical control group and to the manual scores for same-age typically developing youths. SPD were reported in 53% of the subjects in the DMDD group compared to 33% in the clinical control group (p = 0.405). Youths with DMDD showed a significant difference on almost all items of the Sensory Profile compared to typically developing youth. The Sensory Profile was found to discriminate best between the participants with DMDD and those in the clinical control group with regard to the category "Behavioral outcomes of sensory processing" and the factor "Fine motor/perceptual behavior." All types of sensory processing patterns were reported in the DMDD youths: sensation avoiding (40%), low registration (27%), sensory sensitivity (20%), and sensation seeking (10%). As a group, youths with DMDD have significantly more SPD when compared to typical youths. Therefore, SPD could be an important factor to consider in youths with DMDD when providing comprehensive assessment and therapeutic interventions.


[The ship's log of Ellerbeek: common sense and serendipity in the treatment of scurvy].
In accordance with the usual practice, chief surgeon Joan Ellerbeek recorded his observations during his voyage with the East Indiaman Mars to the Cape of Good Hope in 1776 in a logbook for the Dutch East India Company. During the voyage he was confronted with an increasing number of scurvy patients. Intuitive insight and serendipity led him to try using the seaweed ('Gramen Marinum') which had grown on the ship as an anti-scurvy agent, in the empirical and medical tradition of his time. The results were spectacular. Not only James Lind should therefore be credited with the solution of the problem of scurvy. Many before and after him, including Ellerbeek, also made a contribution.


The Impact of Heat Load on Cattle.
Heat stress and cold stress have a negative influence on cattle welfare and productivity. There have been some studies investigating the influence of cold stress on cattle, however the emphasis within this review is the influence of heat stress on cattle. The impact of hot weather on cattle is of increasing importance due to the changing global environment. Heat stress is a worldwide phenomenon that is associated with reduced animal productivity and welfare, particularly during the summer months. Animal responses to their thermal environment are extremely varied, however, it is clear that the thermal environment influences the health, productivity, and welfare of cattle. Whilst knowledge continues to be developed, managing livestock to reduce the negative impact of hot climatic conditions remains somewhat challenging. This review provides an overview of the impact of heat stress on production and reproduction in bovines.


Cell death in acromegalic cardiomyopathy.
Prolonged untreated acromegaly leads to a nonspecific myopathy characterized by ventricular dysfunction and failure. However, the mechanisms responsible for the alterations of cardiac pump function remain to be defined. Because cell death is implicated in most cardiac disease processes, the possibility has been raised that myocyte apoptosis may occur in the acromegalic heart, contributing to the deterioration of ventricular hemodynamics. Ten acromegalic patients with diastolic dysfunction and 4 also with systolic dysfunction were subjected to electrocardiography, Holter monitoring, 2-dimensional echocardiography, cardiac catheterization, and biventricular and coronary angiography before surgical removal of a growth hormone-secreting pituitary adenoma. Endomyocardial biopsies were obtained and analyzed quantitatively in terms of tissue scarring and myocyte and nonmyocyte apoptosis. Myocardial samples from papillary muscles of patients who underwent valve replacement for mitral stenosis were used for comparison. The presence of apoptosis in myocytes and interstitial cells was determined by confocal microscopy with the use of 2 histochemical methods, consisting of terminal deoxynucleotidyl transferase (TdT) assay and Taq probe in situ ligation. Acromegaly was characterized by a 495-fold and 305-fold increase in apoptosis of myocytes and nonmyocytes, respectively. The magnitude of myocyte apoptosis correlated with the extent of impairment in ejection fraction and the duration of the disease. A similar correlation was found with the magnitude of collagen accumulation, indicative of previous myocyte necrosis. Myocyte death was independent from the hormonal levels of growth hormone and insulin-like growth factor-1. Apoptosis of interstitial cells did not correlate with ejection fraction. Myocyte cell death, apoptotic and necrotic in nature, may be critical for the development of ventricular dysfunction and its progression to cardiac failure with acromegaly.


[Evaluation of clinical, laboratorial and ultrasonographic predicting factors of malignancy in thyroid nodules].
To evaluate the risk of malignancy in thyroid nodules through clinical, laboratory, ultrasonographic and cytological aspects. 741 nodules of 407 patients. The cytology was benign (60,5%), indeterminate (23,3%), malignant (8,3%) or nondiagnostic (7,6%). The prevalence of cancer in indeterminate citology was 18,5% (16% in follicular lesions, 44% in suspicious). The diagnosis of malignancy was 17,2% (n = 70). The frequency of cancer in women (15,2%) was lower than in men (27,9%). There was an inverse relation between age and cancer risk. There was no statistical significance in the prevalence of cancer according to number, size of nodules or TSH levels. Hypoechogenicity and microcalcifications on ultrasound were risk factors. The risk of malignancy was higher in men, hypoechoic nodules, with microcalcifications and was inversely related to age. The TSH level was not an independent factor predictive of malignancy.


Developmental and family environment predictors of diagnostic decision-making in children with autism spectrum disorder and comorbid disorders.
Clinical psychologists are observing an increasing number of children with comorbid disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, depressive disorders and others. Due to the importance of higher efficacy of implementing early therapeutic interventions, factors determining the age of first diagnostic intervention and the age of diagnosis are particularly significant aspects when considering this topic. An in-depth analysis of the documentation of 112 patients of one of the psychological and pedagogical counselling centres was conducted to identify family and developmental factors that contribute to the diagnostic decision-making process in children with comorbid disorders. These children were 2-17 years old and diagnosed with co-occur-rence of ASD and other disorders. The results indicate that children with comorbid disorders are reported for diagnostic intervention at the age of 4 years old and 3 months old (M = 4.24, SD = 2.29) and the mean age of receiving an ASD diagnosis is 7 years old and 3 months old (M = 7.28, SD = 3.25). Predictors of the age of diagnostic intervention and ASD diagnosis were also identified. Somatic diseases and potentially speech disorders were related to the earlier age of diagnostic intervention, whereas learning difficulties were related to the later age of diagnostic intervention. Moreover, it has been found that children with comorbid externalizing disorders have an earlier age of diagnostic intervention than children without disrupting behaviours. However, this circumstance does not affect the age of ASD diagnosis. It is important to raise parents' awareness of detecting early markers of disorders as intervention and diagnosis are implemented too late. In such circumstances, therapeutic interventions under-taken may have limited effectiveness.


Action of RNase II and polynucleotide phosphorylase against RNAs containing stem-loops of defined structure.
The 3'-->5' exoribonucleases, RNase II and polynucleotide phosphorylase (PNPase), play an essential role in degrading fragments of mRNA generated by prior cleavages by endonucleases. We have assessed the ability of small RNA substrates containing defined stem-loop structures and variable 3' extensions to impede the exonucleolytic activity of these enzymes. We find that stem-loops containing five G-C base pairs do not block either enzyme; in contrast, more stable stem-loops of 7, 9, or 11 bp block the processive action of both enzymes. Under conditions where enzyme activity is limiting, both enzymes stall and dissociate from their substrates six to nine residues, on average, from the base of a stable stem-loop structure. Our data provide a clear mechanistic explanation for the previous observation that RNase II and PNPase behave as functionally redundant.


Postural cardiovascular reflexes: comparison of responses of forearm and calf resistance vessels.
Simultaneous measurements were made of changes in vascular resistance in the forearm and calf in response to moving from supine to sitting or to head-down tilt. The subjects were healthy male volunteers, 21-63 yr. Blood flows were measured by venous occlusion plethysmography using mercury-in-Silastic strain-gauges. The gauges were maintained at the same level relative to the heart during the postural changes. Arterial blood pressure was measured by auscultation; heart rate was counted from the plethysmograms. Changing from supine to sitting caused a decrease in forearm blood flow from 4.13 +/- 0.14 to 2.16 +/- 0.19 ml.100 ml-1.min-1. Corresponding calf flows were 4.21 +/- 0.32 and 4.40 +/- 0.59 ml.100 ml-1.min-1. There was no change in mean arterial blood pressure, and heart rate increased by 8.0 +/- 1.5 beats/min. Arrest of the circulation of both legs with occlusion cuffs on the thighs before sitting, to prevent pooling of blood in them, reduced the degree of forearm vasoconstriction. Neck suction (40 Torr) during sitting, to oppose the decrease in transmural pressure at the carotid sinuses, inhibited the vasoconstriction. During a 30 degrees head-down tilt, there was a dilatation of forearm but not of calf resistance vessels. A Valsalva maneuver caused a similar constriction of both vascular beds. Thus, when changes in vascular resistance in forearm and calf are compared, the major reflex adjustments to changes in posture take place in the forearm.


Intralesional immunotherapy for non-genital warts: A systematic review and meta-analysis.
Background Intralesional immunotherapy has been reported to be effective for warts and to show good safety profiles, but this has not yet been systematically studied. Aims To determine the efficacy and safety of intralesional immunotherapy for treating non-genital warts. Methods We comprehensively searched the MEDLINE, Embase, Web of Science and Cochrane Library databases from the times of their inception to January 3, 2020. The primary outcome was the rate of complete response of all lesions. The distant complete response rate of warts located in an anatomically different body part and the recurrence rate were also analyzed. Results A total of 54 prospective studies was ultimately included. The immunotherapeutic agents used were Mycobacterium w vaccine, measles, mumps and rubella vaccine, purified protein derivative, Candida antigen, interferon, bacillus Calmette-Guérin vaccine and others. The pooled rate of complete response among all patients with non-genital warts treated using intralesional immunotherapy was 60.6% (95% confidence interval 54.8-66.5%). The pooled recurrence rate was 2.0% (95% confidence interval, 1.1-2.9%). All reported adverse events were mild and transient. Limitations The heterogeneity among studies Conclusion Intralesional immunotherapy is suggested for use in patients with multiple warts, given its promising results, good safety profile and low recurrence rate.


A statistical approach to sensorimotor strategies: conjugate cross-correlations.
A simple method, based on cross-correlation functions (CCFs) between two time series of kinematic or physiological measurements, is proposed for the analysis of multisegmental movements. Special emphasis is placed on measuring accelerations. When the movements of two body segments are coordinated but consistently time lagged, their CCF displays a peak at the corresponding time abscissa. The reproducible positions of the peaks reflect biomechanical or physiological constraints. Several significantly large peaks can be observed in a CCF. It is possible to identify coordinated movements involving more than two segments by applying simple rules of compatibility between the time lags and between the signs of the correlation peaks. With the method proposed, it is possible to determine the signs of relative variation and the time lags of the successive statistically correlated segmental movements. This is particularly useful in the case of both continuous and periodic sensorimotor control, where classical poststimulus methods cannot be applied. Unlike the classical poststimulus methods, this method does not require a time origin, and it is not necessary to monitor the muscles or even to specify exactly which ones are involved. The method is also applicable to experiments involving a time origin (e.g., and applied perturbation), although in this case it is less accurate than the averaging technique. Individual postural strategies can be identified, which suggests some interesting potential applications of the method to clinical studies.


Emergency Non-occlusive High Capacity Bypass Surgery for Ruptured Giant Internal Carotid Artery Aneurysms.
Managing ruptured giant internal carotid artery (ICA) aneurysms in an emergency situation is very challenging. By reporting two cases, we discuss the role of the Excimer Laser-assisted Non-occlusive Anastomosis (ELANA) technique as an armamentarium for cerebrovascular surgeons dealing with giant ICA aneurysms presenting with subarachnoid hemorrhage (SAH). The management of two consecutive patients treated with ELANA bypass during a 6-month period (June- December 2013) for ruptured giant ICA aneurysms in an emergency setting is presented. The two patients presented with SAH and newly diagnosed giant ICA aneurysms (both Fisher 3; WFNS scores 2 and 4, respectively). Both patients received an emergent high-capacity extra- to intracranial (EC-IC) bypass with interposition of a saphenous vein graft between the external carotid artery (ECA) and the ICA-termination. The intracranial anastomosis was performed by the use of the non-occlusive ELANA technique. The aneurysms were successfully trapped, and there were no major complications and no major persistent morbidity in either patient. A good clinical outcome was obtained with a modified Rankin scale of 2 at the last follow-up in both patients. Emergency ELANA bypass surgery is a useful instrument for managing patients with giant ICA aneurysms presenting with SAH. In experienced hands, the technique does not seem to carry increased risk and may expand the surgical options due to its non-occlusive nature.


Prismatic imaging polarimeter calibration for the infrared spectral region.
The calibration of a complete Stokes birefringent prismatic imaging polarimeter (BPIP) in the MWIR is demonstrated. The BPIP technique, originally developed by K. Oka, is implemented with a set of four Yttrium Vanadate (YVO(4)) crystal prisms. A mathematical model for the polarimeter is presented in which diattenuation due to Fresnel effects and dichroism in the crystal are included. An improved polarimetric calibration technique is introduced to remove the diattenuation effects, along with the relative radiometric calibration required for the BPIP operating with a thermal background and large detector offsets. Data demonstrating emission polarization are presented from various blackbodies, which are compared to data from our Fourier transform infrared spectropolarimeter.


Influence of Ozone Treatment on Ultrafiltration Performance and Nutrient Flow in a Membrane Based Nutrient Recovery Process from Anaerobic Digestate.
: Membrane filtration of biological suspensions is frequently limited by fouling. This mechanism is well understood for ultrafiltration of activated sludge in membrane bioreactors. A rather young application of ultrafiltration is the recovery of nutrients from anaerobic digestates, e.g., from agricultural biogas plants. A process chain of solid/liquid separation, ultrafiltration, and reverse osmoses separates the digestate into different products: an organic N-P-fertilizer (solid digestate), a recirculate (UF retentate), a liquid N-K-fertilizer (RO retentate) and water. Despite the preceding particle removal, high crossflow velocities are required in the ultrafiltration step to overcome fouling. This leads to high operation costs of the ultrafiltration step and often limits the economical application of the complete process chain. In this study, under-stoichiometric ozone treatment of the ultrafiltration feed stream is investigated. Ozone treatment reduced the biopolymer concentration and apparent viscosity of different digestate centrates. Permeabilities of centrate treated with ozone were higher than without ozone treatment. In a laboratory test rig and in a pilot plant operated at the site of two full scale biogas plants, ultrafiltration flux could be improved by 50%-80% by ozonation. Nutrient concentrations in the fertilizer products were not affected by ozone treatment.


Transcriptional regulation of human CYP3A4 basal expression by CCAAT enhancer-binding protein alpha and hepatocyte nuclear factor-3 gamma.
Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more than 50% of currently used therapeutic drugs, yet the mechanisms that control CYP3A4 basal expression in liver are poorly understood. Several putative binding sites for CCAAT/enhancer-binding protein (C/EBP) and hepatic nuclear factor 3 (HNF-3) were found by computer analysis in CYP3A4 promoter. The use of reporter gene assays, electrophoretic mobility shift assays, and site-directed mutagenesis revealed that one proximal and two distal C/EBP alpha binding sites are essential sites for the trans-activation of CYP3A4 promoter. No trans-activation was found in similar reporter gene experiments with a HNF-3 gamma expression vector. The relevance of these findings was further explored in the more complex DNA/chromatin structure within endogenous CYP3A4 gene. Using appropriate adenoviral expression vectors, we found that both hepatic and nonhepatic cells overexpressing C/EBP alpha had increased CYP3A4 mRNA levels, but no effect was observed when HNF-3 gamma was overexpressed. In contrast, overexpression of HNF-3 gamma simultaneously with C/EBP alpha resulted in a greater activation of the CYP3A4 gene. This cooperative effect was hepatic-specific and also occurred in CYP3A5 and CYP3A7 genes. To investigate the mechanism for HNF-3 gamma action, we studied its binding to CYP3A4 promoter and the effect of the deacetylase inhibitor trichostatin A. HNF-3 gamma was able to bind CYP3A4 promoter at a distal position, near the most distal C/EBP alpha binding site. Trichostatin A increased C/EBP alpha effect but abolished HNF-3 gamma cooperative action. These findings revealed that C/EBP alpha and HNF-3 gamma cooperatively regulate CYP3A4 expression in hepatic cells by a mechanism that probably involves chromatin remodeling.


Clinical and histological evaluation of an analogue of palmitoylethanolamide, PLR 120 (comicronized Palmidrol INN) in cats with eosinophilic granuloma and eosinophilic plaque: a pilot study.
Fifteen cats with eosinophilic granuloma or eosinophilic plaque were given PLR 120 at the dosage of 10 mg kg-1 twice daily for one month. PLR-120 down-modulates mast cell degranulation via a receptor-mediated mechanism. No other drugs were permitted and cats were kept free of parasites throughout the study. A clinical evaluation and skin biopsies were performed before and after the treatment. Clinical improvement was assessed at 15 and 30 days. Mast cell numbers were counted and their granular content was assessed by densitometric analysis on toluidine blue-stained sections before and after the treatment. Ten of 15 (67%) cats showed clinical improvement of signs and lesions. There was no significant difference between mast cell numbers in skin biopsies taken before and after the trial, whereas the number of granules was significantly increased (P < 0.009). This pilot study suggests that PLR-120 might be a useful drug for the treatment of eosinophilic granuloma and eosinophilic plaque.


Induction of c-fos expression following stimulation of pulmonary neuroendocrine cell proliferation by alterations in CO2/O-2 concentration.
Pulmonary neuroendocrine (PNE) cells were harvested and cultivated from peripheral lung tissue of 15 day old fetal hamsters under selective growth conditions, including a 10% CO2 atmosphere. Following 24 h of serum starvation under 10% CO2, PNE cells placed in a 5% CO2 atmosphere failed to proliferate over the next 24 h, while cells kept at 10% CO2 showed a 2.7-fold increase in cell number. Addition of nicotine to the cell culture medium resulted in an additional concentration-dependent increase in cell number under a 10% CO2 atmosphere, while nicotine did not stimulate the proliferation of cells maintained at 5% CO2. The nicotinic receptor antagonist hexamethonium completely blocked the stimulatory effect of nicotine on cell growth. As a first step towards determining the molecular mechanisms regulating the mitogenic stimulation of PNE cells by alterations in CO2/O-2 and nicotine, cells that had been serum starved under a 10% CO2 atmosphere for 24 h were removed from the incubator and either left untreated or treated with 1 mu M nicotine under ambient air. The cells were then returned to either a 5% or 10% CO2 atmosphere. Removal of the cells from a 10% CO2 environment and subsequent reintroduction to a high CO2 concentration resulted in a 3- to 4-fold increase in c-Sos RNA expression within 15-30 min upon return to the cell culture incubator. c-fos RNA levels their decreased back to control values by 1 h. Reintroduction into a 5% CO2 atmosphere, which failed to stimulate cell growth in the proliferation assay, caused only a 2-fold increase in the levels of c-fos transcripts. The CO2-mediated increases in c-Sos transcripts were observed both in the presence and absence of nicotine, suggesting that the effects of nicotine were mediated through a fos-independent pathway. Neither the alterations in CO2/O-2 concentration or treatment with nicotine altered the levels of c-myc or c-jun gene transcripts. Nicotine thus acts indirectly but synergistically with high CO2 concentrations to stimulate PNE cell proliferation.


Clinical relevance of melatonin in ovarian and placental physiology: a review.
Within the last decade, the synthesis of melatonin in and its functions at the level of the peripheral reproductive organs has come into better focus. Melatonin is produced at several reproductive organ sites, e.g., the oocyte, ovarian follicular cells and the placental cytotrophoblasts. Moreover, these cells also contain membrane receptors for this indoleamine. In addition, via the free radical scavenging activity of melatonin and its metabolites, oxidative stress is reduced in all reproductive organ cells ensuring their optimal function. Enhancement of oocyte maturation and preservation of oocyte quality may be major functions of melatonin. Oocyte damage reduces successful fertilization and the development of a healthy fetus. The findings that melatonin protects the oocyte from toxic oxygen species have implications for improving the outcome of in vitro fertilization-embryo transfer procedures, as already shown in two published reports. Some actions of melatonin in the placenta may be context specific. Thus, melatonin is believed to function in the maintenance of optimal placental homeostasis by deferring apoptosis of villous cytotrophoblasts, while protecting syncytiotrophoblasts from oxidative damage. Melatonin reduces oxidative damage in the placenta and may improve hemodynamics and nutrient transfer at the placental-uterine interface. The use of melatonin to treat preeclampsia should also be considered.