Thiazolidine formation as a general and site-specific conjugation method for synthetic peptides and proteins.
A general and mild method for the conjugation of synthetic peptides and proteins through site-specific thiazolidine formation was developed. This method is based on the specific reaction of the 1,2-aminothiol of cysteine with an aldehyde under acidic conditions to form a stable thiazolidine product. The carbonyl precursors are derived from the 1,2-aminoalcohols of Ser or Thr or the vicinal cis-diols of glycoproteins, which can be selectively and rapidly converted to the aldehyde form by periodate oxidation. Since the position where the aldehyde is generated can be manipulated or predetermined, the thiazolidine formation is essentially site-specific. The potential of this method is demonstrated by the biotinylation of three synthetic peptides at the N-terminal Ser or Thr and at the carbohydrate sites of alpha 1-acid glycoprotein. 1-Biotinyl-6-cysteinyl-hexadiamide, a new, water-soluble, long-chained, 1,2-aminothiol derivate containing biotin, was prepared as a capture device. This reagent reacted rapidly with periodate-oxidized N-terminal Ser or Thr peptides and with glycoproteins under very mild conditions to form the thiazolidine conjugates. Based on our results, the thiazolidine conjugation method would be useful for the attachment of radiolabels, reporter groups, imaging agents, and cytotoxic drugs to peptides and proteins.


Significantly enhanced antibacterial activity of TiO2 nanofibers with hierarchical nanostructures and controlled crystallinity.
Recently, there has been increased interest in electrospun-titanium dioxide nanofibers (TiO2 NFs) as antibacterial agents owing to their advantages, such as simple and cost-effective fabrication processes, and high surface areas. However, the photocatalytic effects of TiO2 NFs are relatively low because of their low-ordered crystalline structure, and the antibacterial effect is only effective under UV illumination owing to their large band-gap energy. In this paper, we have demonstrated a significantly enhanced antibacterial activity of hierarchical anatase TiO2 NFs against Staphylococcus aureus in the presence of UV light. Furthermore, the uniform deposition of a large quantity of Ag nanoparticles on the surface of the TiO2 NFs ensured a significant enhancement of the antibacterial performance, even under dark conditions. These results were obtained by exploiting the enhanced photocatalytic effect achieved through control of the crystallinity, as well as the enhanced surface area of the nanomaterials.


Mast cell activation in sterile bladder and prostate inflammation.
Sterile inflammation of the bladder has often been associated with interstitial cystitis (IC), a urologic condition of unknown etiology, predominantly affecting young and middle-aged females, for which no effective therapy is known. Recent reports have indicated that IC is associated with an increased number of bladder mast cells. Here we report the case of a middle-aged man with chronic sterile hematuria, dysuria and lower abdominal pain associated with a high number of bladder and prostate mast cells. Following therapeutic transurethral resection of the trigone area, bladder neck and prostate, samples of bladder and prostate were examined with light and electron microscopy and contained many mast cells (about 150 cells/mm2) which were not degranulated. Nevertheless, mast cells contained many altered granules and urinary levels of histamine were elevated, implying secretion without exocytosis. These findings are discussed in the context of the pathophysiology of IC and possible therapeutic interventions.


Sensitization of tnf-induced apoptosis with polyamine synthesis inhibitors in different human and murine tumour cell lines.
Rat/mouse T cell hybridoma-derived PC60 R55/R75 cells were used as a model to study tumour necrosis factor (TNF)-induced apoptosis. The role of ornithine decarboxylase (ODC) activity and polyamines in this process was investigated. In PC60 R55/R75 cells, TNF-induced ODC activity was completely suppressed by externally added spermine (Spm). TNF decreased the intracellular levels of the three polyamines Spm, spermidine (Spd) and putrescine (Put). A reduction of the intracellular [Spm] with methylglyoxal bis(quanyl hydrasone) (MGBG), CGP48644a, or bis(ethyl)norspermine (BENSpm), clearly sensitized the cells towards the apoptotic effect of TNF. Conversely, an increase in intracellular [Spm] with DFMO or externally added Spm reduced cellular sensitivity. Similar results were obtained after TNF treatment of the human cell lines Kym 39A6 (rhabdomyosarcoma), HeLaH21 (cervix carcinoma) and U937 (histocytoma) and after alphaFas treatment of HeLaH21, U937 and CEM-CM3 (human T cell line). These results suggest that a decrease of intracellular Spm levels rather then ODC activity per se is involved in the sensitization towards apoptosis induced by TNF or alphaFas.


Radiation protection requirements for medical x-ray film.
Previous darkroom shielding requirements for medical x-ray film-assumed that the film should not be exposed to diagnostic x-ray radiation levels greater than 2 microGy (0.2 mR) for the life of the film. Modern medical x-ray films are much less sensitive to ionizing radiation, with most films showing at least an order of magnitude less sensitivity than previously assumed. Conversely, these same films when loaded in cassettes using modern intensifying screens exhibit an order of magnitude greater sensitivity when these cassettes are exposed to ionizing radiation. These data suggest that protection of modern medical x-ray film, stored in a darkroom, may require less shielding than previously assumed. Conversely, film loaded in a cassette will require greater shielding.


Inelastic neutron scattering and Raman spectroscopic investigation of L-alanine alaninium nitrate, a homologue of a ferroelectric material.
The 2 : 1 amino acid salt of L-alanine with nitric acid was crystallized and the vibrational spectrum measured at 25 K by incoherent inelastic neutron scattering (INS) spectroscopy. The spectrum was simulated using solid-state density functional theory based on a new 90 K structure determination. A feature observed at approximately 450 cm(-1) in the INS spectrum of L-alanine alaninium nitrate is noticeably absent in the calculation. Raman spectroscopy reveals spectral differences between the spectra at 77 and 293 K with a 450 cm(-1) feature appearing at low temperature. The nature of these spectral changes and the disagreement between the INS spectrum and its simulation are discussed in relation to an apparent structural change involving motion of a proton at low (<90 K) temperature.


Post consolidation therapy for adult patients with acute myeloid leukaemia.
One hundred and sixteen adult patients aged 14-73 with previously untreated acute myeloid leukaemia received induction and consolidation chemotherapy with daunorubicin, cytosine arabinoside and thioguanine. Two novel approaches to post consolidation therapy have been investigated. Patients aged 50 years or less who had no suitable matched allogeneic donor were considered for autologous bone marrow transplantation (BMT) using bone marrow which had been cultured in vitro for 14 d. Patients over the age of 50 years with normal bone marrow cellularity and peripheral blood count were treated with a single oral dose of busulphan 100 mg/m2 (without BMT rescue) 3 months following the completion of consolidation therapy. Eighty-seven patients (75%) achieved a complete remission. Of 70 patients who completed consolidation therapy, 40 were aged less than or equal to 50 years and 30 were greater than 50 years. Forty-three patients went on to receive post consolidation therapy in first CR (autologous BMT 12, allogeneic BMT 7, busulphan therapy 24). The event-free survival at 4 years was 47% for autologous BMT, 34% for allogeneic BMT and 45% for busulphan-treated patients. The survival for the older cohort of patients who received post consolidation therapy with single dose busulphan therapy was encouraging, and this agent should be considered for future post consolidation strategies.


Papillary intralymphatic angioendothelioma (PILA): a report of twelve cases of a distinctive vascular tumor with phenotypic features of lymphatic vessels.
Six childhood vascular tumors were designated as "malignant endovascular papillary angioendothelioma" by Dabska in 1969. Since then, a few reports of similar cases were published, often called "Dabska tumors." Twelve similar cases were identified in review of vascular tumors from the authors' institutions. There were five men and seven women, including seven adults. Patient ages ranged from 8 to 59 years (mean, 30 years). The tumors occurred in the dermis or subcutis of the buttocks or thigh (n = 6), thumb or hand (n = 3), abdomen (n = 2), and heel (n = 1). The tumor sizes ranged from 1 to more than 40 cm (mean, 7.0 cm). The unifying feature of all cases was distinctive intravascular growth of well-differentiated endothelial cells presenting as a matchstick columnar configuration, sometimes with a large production of matrix that was positive for collagen type IV. In half the cases, these intravascular proliferations had an associated actin-positive pericytic proliferation. There was minimal cytologic atypia and rare to absent mitotic activity. Two cases had an adjacent lymphangioma, and two additional cases had clusters of lymphatic vessels adjacent to the tumor. All but two of the cases showed varying degrees of stromal or intraluminal lymphocytes. Occasional epithelioid endothelial cells were seen, but no cases had features typical of epithelioid, spindle cell, or retiform hemangioendothelioma. Tumor cells were positive for vimentin, von Willebrand factor, CD31, and focally for CD34 and were negative for keratins, epithelial membrane antigen, S-100 protein, and desmin. Vascular endothelial cell growth factor receptor type 3, a recently introduced marker for lymphatic endothelia, was positive in all eight cases that were studied, supporting a lymphatic phenotype. Follow-up in 8 of the 12 cases showed no evidence of recurrences, metastases, or residual disease during follow-ups ranging from 1 to 17 years (mean, 9 years). Based on the proliferative borderline features and the lymphatic phenotype, we propose to designate these tumors as papillary intralymphatic angioendothelioma. Additional cases with extensive follow-up should be studied to rule out variants with malignant potential.


[Immune response and B hepatitis (author's transl)].
The different forms of chronic hepatitis are due to different individual immune responses after infection with hepatitis B virus. A report is given about specific and unspecific defense mechanisms coming into play after infection, about immunological and immunopathological reactions, and about the pathogenetic significance of these processes. At present unfortunately our knowledge in this particular field is rather limited; more detailed information is needed about humoral, cellular, immune complex related, and autoimmunological events, if one wishes to explain the different courses of hepatitis on these grounds.


A systematic review and meta-analysis of the efficacy of piracetam and piracetam-like compounds in experimental stroke.
Piracetam was a candidate neuroprotective drug for acute stroke ineffective in clinical trial. Here we use systematic review and meta-analysis to describe the evidence supporting a protective effect of piracetam and its derivatives in animal models of stroke. We present a systematic review of reports describing the use of piracetam and its derivatives in animal models of focal ischaemia, where the outcome was measured as an infarct size or neurological score (Der Simonian and Laird random effects meta-analysis). Only 2 studies, published 10 years after the first clinical trial of piracetam had been initiated, described its efficacy in animal models of stroke. A further 4 studies described the efficacy of related compounds. Piracetam and its derivatives improved the outcome by 30.2% (95% CI = 16.1-44.4). The median study quality was 4/10 (inter-quartile range = 4-6). Piracetam and its derivatives demonstrate neuroprotective efficacy in experimental stroke, but our findings raise concerns about the amount of available data, the quality of the studies and publication bias.


Comparison of the effectiveness of the treatment using standard methods and negative pressure wound therapy (NPWT) in patients treated with open abdomen technique.
Open abdomen technique is a surgical treatment in which the fascia and skin are left open in order to reduce the value of the intra-abdominal pressure. According to the World Society of the Abdominal Compartment Syndrome (WSACS) normal values of the intra-abdominal pressure are between 5 and 7 mm Hg. Intra-abdominal hypertension occurs when the pressure value is equal to or exceeds 12 mm Hg. The aim of the study was to compare the results of the open abdomen treatment using standard methods and negative pressure wound therapy. The study was in the form of a retrospective analysis of the documentation of the patients treated with open abdomen technique. The study included 37 patients treated in the Department of General and Endocrine Surgery and Gastroenterological Oncology and in the Department of Anesthesiology and Intensive Care of the Medical Sciences since 2009-2012. Patients were divided into two groups: group 1 (n = 20) was treated with standard surgical procedures (laparostomy, repeated peritoneal cavity lavage) and group 2 (n =17) was treated using negative pressure wound therapy (NPWT). The analysed clinical data included the period of hospitalization and clinical outcome (survival vs death), the occurrence of enteroatmospheric fistulae, cyclical determination of the quantitative C-reactive protein levels. The number of deaths during hospitalization in the group treated with NPWT was lower than in the group treated with standard methods (3 vs 9). The number of fistulae during hospitalization in the group treated with NPWT dropped as compared to the group treated using standard procedures (18% vs 70%). The decrease in the CRP levels was recorded in the group treated with NPWT and its increase - in the group treated with standard methods. The use of NPWT in patients requiring open abdomen treatment is reasonable due to the positive results with respect to survival rates and the decrease in the number of gastrointestinal fistulae. It is necessary to train the physicians in using this type of therapy in the form of workshops and in the clinical setting.


Pancreas transplants.
Cadaveric, whole pancreas transplantation has proved an effective therapy in the treatment of long-standing type 1 diabetes mellitus and is capable of achieving an insulin-independent eugyclaemic state. As a result, this procedure is being increasingly performed. However, the surgical procedure is complex and unfamiliar to many radiologists. Imaging with computed tomography (CT) and magnetic resonance imaging (MRI) gives excellent results and can be used confidently to diagnose vascular, enteric, and immune-mediated complications. We present a review of the normal post-transplantation appearance and the features of early and late complications.


Looking for some free energy? Call JEFREE (…).
In this communication, we present the Jarzynski's Equality FREe Energy (JEFREE) library, an efficient and easy-to-use C++ library targeted to the calculation of the free energy profile along a selected generalized coordinate of a system, within the framework of the nonequilibrium steered transformations as introduced by Jarzynski [Phys. Rev. E, 1997, 56, 5018]. JEFREE can be readily integrated into any code, since both C and FORTRAN wrappers have been developed, and easily customizable by a user thanks to the object-oriented programming paradigm offered by the C++ language. Also, JEFREE implements the novel idea of making a total "morphing" of the system energy landscape before initiating the proper steering stage. This proves to be an efficient mean to overtake the problematic sampling of the initial equilibrium state when the number of degrees of freedom is high and the landscape owns many local minima separated by large energy barriers. The calculation of the free energy profile for the rotation along torsion angles in alkyl chains is presented as an example of application of our tool.


Real-time method for NO(2) flow measurements.
Measurements of NO(2) flows are made without requiring prior experimental calibration of the flow meter. A tapered, variable area flow meter with a diameter ratio scale is used to make the real-time NO(2) flow measurements. The necessary parameters and calculations used to determine the viscosity and density of the flowing N(2)O(4)2NO(2) gas are presented. The limits of error associated with these parameters and errors associated with controlled flow measurement conditions are considered. Disregarding the scale reading error, which depends on the flow meter utilized, the limits of error are found to yield a measurement error less than 7%.


Nocturnal hyperglycaemia in type 2 diabetes with sleep apnoea syndrome.
We assessed glycaemic status in 26 overweight or obese people with type 2 diabetes suspected of having sleep apnoea syndrome (SAS). In people with SAS (n=13), nocturnal glycaemia was 38% higher, independent of body mass index (particularly during rapid eye movement sleep) compared with non-SAS subjects (p<0.008).


Use of 3D ultrasound as a new approach to assess obstetrical trauma to the pelvic floor.
To determine whether 3D ultrasound examination of pelvic floor anatomy after vaginal delivery allows detection of childbirth trauma. Pelvic floor anatomy was examined in 16 women during the puerperium with a 3D transrectal ultrasound probe. Images were acquired via the vaginal route for the assessment of anal morphology and the transrectal route to determine paravaginal fixation. Images of the anterior pelvic floor were calculated from the information stored in the volume block. Paravaginal defect is defined as a descent of the lateral vaginal wall below the suburethral vagina, whereas sphincter defects are characterised as thinning, or as gap formation of the anterior part of the internal anal sphincter. This new approach allowed the examination of a horizontal plane through the urethra and the periurethral tissue which is inaccessible with 2D ultrasound techniques. Morphology of the normal and traumatised anal sphincter could be demonstrated using reference planes perpendicular to the anal canal. Whereas in the past, defects of the vaginal attachment to the pelvic side wall could not be examined sonographically, 3D ultrasound can now be used to examine pelvic floor anatomy and to detect changes associated with trauma to the pelvic floor following vaginal delivery.


Suprasegmental and segmental timing models in Mandarin Chinese and American English.
This paper formalizes and tests two key assumptions of the concept of suprasegmental timing: segmental independence and suprasegmental mediation. Segmental independence holds that the duration of a suprasegmental unit such as a syllable or foot is only minimally dependent on its segments. Suprasegmental mediation states that the duration of a segment is determined by the duration of its suprasegmental unit and its identity, but not directly by the specific prosodic context responsible for suprasegmental unit duration. Both assumptions are made by various versions of the isochrony hypothesis [I. Lehiste, J. Phonetics 5, 253-263 (1977)], and by the syllable timing hypothesis [W. Campbell, Speech Commun. 9, 57-62 (1990)]. The validity of these assumptions was studied using the syllable as suprasegmental unit in American English and Mandarin Chinese. To avoid unnatural timing patterns that might be induced when reading carrier phrase material, meaningful, nonrepetitive sentences were used with a wide range of lengths. Segmental independence was tested by measuring how the average duration of a syllable in a fixed prosodic context depends on its segmental composition. A strong association was found; in many cases the increase in average syllabic duration when one segment was substituted for another (e.g., bin versus pin) was the same as the difference in average duration between the two segments (i.e., [b] versus [p]). Thus, the [i] and [n] were not compressed to make room for the longer [p], which is inconsistent with segmental independence. Syllabic mediation was tested by measuring which locations in a syllable are most strongly affected by various contextual factors, including phrasal position, within-word position, tone, and lexical stress. Systematic differences were found between these factors in terms of the intrasyllabic locus of maximal effect. These and earlier results obtained by van Son and van Santen [R. J. J. H van Son and J. P. H. van Santen, "Modeling the interaction between factors affecting consonant duration," Proceedings Eurospeech-97, 1997, pp. 319-322] showing a three-way interaction between consonantal identity (coronals vs labials), within-word position of the syllable, and stress of surrounding vowels, imply that segmental duration cannot be predicted by compressing or elongating segments to fit into a predetermined syllabic time interval. In conclusion, while there is little doubt that suprasegmental units play important predictive and explanatory roles as phonological units, the concept of suprasegmental timing is less promising.


Response patterns of the Spanish version of the 49-item short form of the Addiction Research Center Inventory after the use of sedatives, stimulants, and opioids.
This report examines the validity of the Spanish version of the 49-item short form of the Addiction Research Center Inventory (ARCI) for measuring subjective effects after the use of sedatives, stimulants, and opioids. Data from four clinical trials in which this questionnaire was used have been analyzed. The Spanish ARCI short form was found to be sensitive in measuring subjective effects after the administration of alcohol, triazolam, and flunitrazepam (sedatives), cocaine (stimulants), and morphine, pentazocine, and naloxone (opioids) and to distinguishing among them. The response patterns were similar to those previously reported for the same drugs with the English version of ARCI. It is concluded that Spanish version of the 49-item short form of ARCI is a valid instrument for assessing the subjective effects of psychoactive drugs in the Spanish-speaking population context.


Radical a-ions in electron capture dissociation: on the origin of species.
Radical a* ions appear in electron capture dissociation mass spectra sporadically, but sometimes with high intensity. Mechanistically, radical a ions are hypothesized to arise due to thermodynamically disadvantaged charge solvation on the backbone nitrogen (instead of carbonyl), which upon neutralization produces a hypervalent group instantly fragmenting into a radical b* and conventional y' ion. The former species is unstable and, after releasing a CO molecule, decays to an a* ion. Here we validate this scenario by direct observation of the complementarity of a* and y' ions by interrogation of an ECD MS/MS database of >10,000 doubly and >5,000 triply charged tryptic peptides. Intriguingly, the most abundant a*/y' pairs are found to come from the cleavage of the same backbone link as the most abundant c' and z* complementary ions. This result gives strong support to the "local" N-Cα bond cleavage mechanism, in which the dissociation occurs at the site of charge solvation. However, a second strong peak is observed in the c'/z* fragment distribution four residues away from the a*/y' cleavage, which supports the indirect N-Cα bond cleavage mechanism. The size distribution of a ions from doubly (but not triply!) charged precursors shows deficit of a3 ions, and possibly a6 ions.


Stability of the upper lumbar spine following progressive disruptions and the application of individual internal and external fixation devices.
Five fresh human cadavera were tested to determine range-of-motion measurements at the interspace of the first and second lumbar vertebrae after progressive disruption of the joint followed by internal and external stabilization. The disruption progressed from posterior to anterior, leaving the anterior longitudinal ligament and anterior part of the annulus fibrosus intact. Flexion-extension range of motion was most sensitive to progressive disruptions and was significant following disruption of the facets. The Taylor-Knight brace was effective for limiting lateral motion, fair for limiting flexion-extension, and not effective for rotation. The three-point hyperextension brace was fairly effective for flexion-extension only. The body cast was effective in limiting all motions. Wire loops partially cut through the spinous processes in all cases with extreme flexion. Harrington distraction rods were effective in limiting motion if under proper tension, but they dislodged in three of the five specimens. Data from this study show that flexion of the second lumbar vertebra on the first of 20 degrees or a lateral bend of 10 degrees seen on a routine roentgenogram without vertebral fracture indicates that all posterior ligaments and at least part of the annulus fibrosus must be disrupted. Because internal fixation failed on occasion, we strongly urge the use of external fixation and careful mobilization of the patient to prevent flexion and rotation if internal stabilization is used for disruptions of the upper lumbar spine. The body cast was the most effective in limiting motion of the external fixation devices tested.


Vertical ZnO Nanotube Transistor on a Graphene Film for Flexible Inorganic Electronics.
The bottom-up integration of a 1D-2D hybrid semiconductor nanostructure into a vertical field-effect transistor (VFET) for use in flexible inorganic electronics is reported. Zinc oxide (ZnO) nanotubes on graphene film is used as an example. The VFET is fabricated by growing position- and dimension-controlled single crystal ZnO nanotubes vertically on a large graphene film. The graphene film, which acts as the substrate, provides a bottom electrical contact to the nanotubes. Due to the high quality of the single crystal ZnO nanotubes and the unique 1D device structure, the fabricated VFET exhibits excellent electrical characteristics. For example, it has a small subthreshold swing of 110 mV dec-1 , a high Imax /Imin ratio of 106 , and a transconductance of 170 nS µm-1 . The electrical characteristics of the nanotube VFETs are validated using 3D transport simulations. Furthermore, the nanotube VFETs fabricated on graphene films can be easily transferred onto flexible plastic substrates. The resulting components are reliable, exhibit high performance, and do not degrade significantly during testing.


Validation of genetic association in apelin-AGTRL1 system with hypertension in a larger Han Chinese population.
We have recently resequenced apelin and AGTRL1 genes to identify candidate polymorphisms in family-based association with hypertension and related phenotypes. In this study, we aimed to determine and replicate these polymorphisms via a larger, independent case-control study in Shanghai Han Chinese. Two polymorphisms [rs3761581 (A/C) and T-1860C] in apelin gene and two [rs7119375 (G/A), rs10501367 (G/A)] in AGTRL1 gene were genotyped using the TaqMan assay among 969 patients diagnosed with essential hypertension and 980 age and sex-matched controls. Data were analyzed using Haplo.stats program. In single-locus analysis, significant differences were observed in allele distribution of rs3761581 (P = 0.0156) in men and in rs7119375 (P = 0.0488) genotype distribution in women between patients and controls. Haplotype analysis indicated that haplotypes C-C-G-G (in order of T-1860C, rs3761581, rs7119375 and rs10501367) [adjusted odds ratio (ORadjusted) = 1.67, P = 0.0061] and T-A-A-A (ORadjusted = 1.62, P = 0.0008) conferred an increased risk for hypertension after adjustment for age, onset age, body mass index (BMI) and waist-to-hip ratio, whereas haplotype C-C-A-A (ORadjusted = 0.33, P = 0.0048) conferred a protective effect. In women, increased risk for hypertension was seen for haplotypes T-A-G-G (ORadjusted = 1.30, P = 0.0051), C-C-G-G (ORadjusted = 2.86, P < 0.0001), T-A-A-A (ORadjusted = 1.66, P = 0.0003) and C-C-A-A (ORadjusted = 2.65, P < 0.0001), whereas decreased risk was seen for haplotypes C-A-G-G (ORadjusted = 0.48, P < 0.0001) and T-C-G-G (ORadjusted = 0.40, P < 0.0001). Further haplotype-phenotype analyses indicated the robustness of these associations. For example, haplotype T-A-A-A was significantly associated with obesity index (BMI and waist-to-hip ratio) in both sexes and blood pressures in men (P-sim < 0.05). In this exploratory pilot case-control study, we found robust haplotype-based and haplotype-phenotype associations of four well characterized polymorphisms in apelin-AGTRL1 system with hypertension and related phenotypes.


Chronic plaque psoriasis.
Chronic plaque psoriasis, the most common form of psoriasis, is a papulosquamous disease defined by erythematous plaques with a silvery scale. The diagnosis usually is clinical, but occasionally a biopsy is necessary. Psoriasis affects 0.6 to 4.8 percent of the U.S. population, and about 30 percent of affected patients have a first-degree relative with the disease. Psoriasis is a T-cell-mediated autoimmune disease, but certain medications and infections are well-known risk factors. Management of psoriasis includes education about chronicity, realistic expectations, and use of medication. Steroids and vitamin D derivatives (e.g., calcipotriene) are the mainstays of topical therapy. Topical steroids and calcipotriene together may work better than either agent alone. Patients with psoriasis involving more than 20 percent of their skin or those not responding to topical therapy are candidates for light therapy; traditional systemic therapy; or systemic treatment with immunomodulatory drugs such as alefacept, efalizumab, and etanercept.


Mycobacterium bovis (BCG) vaccination. Progressive disease in a patient asymptomatically infected with the human immunodeficiency virus.
To report a case of progressive disease caused by Mycobacterium bovis after BCG vaccination in a patient asymptomatically infected with the human immunodeficiency virus (HIV). A 34-year-old white man about to commence employment as a developmental care worker had a BCG vaccination. Five months later, he had a positive result to a serological test for HIV antibody. Nine months after BCG vaccination, he presented with fever (38.7 degrees C), a large left axillary lymph node and a small left pleural effusion. The lymph node was biopsied and acid-fast bacilli observed in Ziehl-Neelsen stained smears. Culture grew Mycobacterium bovis (BCG). He was successfully treated with isoniazid, rifampicin and ethambutol for a period of nine months. BCG vaccination of asymptomatic HIV-positive patients is not recommended. The detection of those at risk for HIV infection before vaccination administration is essential. Self-exclusion based on information supplied to all potential recipients is likely to be the most effective method.


Correlation of carotid artery reactivity with cardiovascular risk factors and coronary artery vasodilator responses in asymptomatic, healthy volunteers.
Carotid artery reactivity (CAR%), involving carotid artery diameter responses to a cold pressor test (CPT), is a noninvasive measure of conduit artery function in humans. This study examined the impact of age and cardiovascular risk factors on the CAR% and the relationship between CAR% and coronary artery vasodilator responses to the CPT. Ultrasound was used to measure resting and peak carotid artery diameters during the CPT, with CAR% being calculated as the relative change from baseline (%). We compared CAR% between young (n = 50, 24 ± 3 years) and older participants (n = 44, 61 ± 8 years), and subsequently assessed relationships between CAR% and traditional cardiovascular risk factors in 50 participants (44 ± 21 years). Subsequently, we compared left anterior descending (LAD) artery velocity (using transthoracic Doppler) with carotid artery diameter (i.e. CAR%) during the CPT (n = 33, 37 ± 17 years). A significantly larger CAR% was found in young versus older healthy participants (4.1 ± 3.7 versus 1.8 ± 2.6, P < 0.001). Participants without cardiovascular risk factors demonstrated a higher CAR% than those with at least two risk factors (2.9 ± 2.9 versus 0.5 ± 2.9, P = 0.019). Carotid artery diameter and LAD velocity increased during CPT (P < 0.001). Carotid diameter and change in velocity correlated with LAD velocity (r = 0.486 and 0.402, P < 0.004 and 0.02, respectively). Older age and cardiovascular risk factors are related to lower CAR%, while CAR% shows good correlation with coronary artery responses to the CPT. Therefore, CAR% may represent a valuable technique to assess cardiovascular risk, while CAR% seems to reflect coronary artery vasodilator function.


Decrease in particle-induced osteolysis in obese (ob/ob) mice.
There may be variability in the susceptibility of different individuals to osteolysis from wear debris, and it is not clear whether some individuals may have a genetic predisposition for a more marked osteolytic response. The purpose of this study in mice was to determine whether genetically determined obesity can alter the response to particulate debris. Polyethylene particles were implanted onto the calvaria of seven wild-type mice and seven obese mice (ob/ob). Calvaria from unimplanted wild-type and obese mice served as controls. Calvaria were harvested after 7 days, stained with toluidine blue and for tartrate-specific alkaline phosphatase, and analyzed by histomorphometry. The osteoclast number per mm total bone perimeter was 8.000+/-3.464 in wild-type animals with particles and 2.857+/-1.676 in ob/ob animals with particles (p=0.002; Fisher's PLSD). Bone resorption was 1.895+/-0.713 mm/mm(2) in wild-type animals with particles and 1.265+/-0.494 mm/mm(2) in ob/ob animals with particles (p=0.0438; Fisher's PLSD). Particles induced a diminished osteolytic response in genetically determined obese mice, suggesting that obesity may have a protective role against particle-induced bone resorption-similar to obesity and osteoporosis. These important new findings may help to stimulate clinical studies which may define criteria to better identify patients at risk to develop particle-induced osteolysis.


T-box genes: what they do and how they do it.
Brachyury is the founder member of the T-box family of transcription factors, which is characterized by a DNA-binding domain of approximately 200 amino acids. Members of the T-box gene family play important roles in the development of both vertebrate and invertebrate embryos, including the control of gastrulation, development of the heart, and perhaps even the decision as to whether to form arm or leg. An understanding of how the T-box genes act requires analysis of how their expression is controlled, identification of their target genes, and an insight into how different family members exert different effects.


National study of emergency department visits for sepsis, 1992 to 2001.
Epidemiologic data on emergency department (ED) patients with sepsis are limited. Inpatient discharge records from 1979 to 2000 show that hospitalizations for sepsis are increasing. We examine the epidemiology of sepsis in US EDs and the hypothesis that sepsis visits are increasing. The National Hospital Ambulatory Medical Care Survey data (1992 to 2001) provided nationally representative estimates of frequency and disposition in adult ED visits for sepsis. Sepsis visits were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes; severe sepsis was defined as sepsis in conjunction with organ failure. Of 712 million adult visits during the 10-year period, approximately 2.8 million (0.40%, 95% confidence interval [CI] 0.33% to 0.46%) were related to sepsis. We found no significant increase in overall ED visits for sepsis from 1992 to 2001 (P for trend=.09). ED patients with sepsis were more likely to be elderly, non-Hispanic, and publicly insured and to arrive by ambulance compared with nonsepsis patients (all P<.01). The overall admission rate was 87% (95% CI 82% to 92%), with only 12% (95% CI 8% to 16%) of patients admitted to the ICU. The most frequent codiagnoses were pneumonia (13%), urinary tract infection (13%), and dehydration (11%). Severe sepsis accounted for 8% (95% CI 5% to 11%) of sepsis visits, for an annual incidence of 0.01%; 98% of patients with severe sepsis were admitted. In contrast to data from hospital discharges, ED visits for sepsis demonstrated no increase. Most ED visits for sepsis resulted in admission to non-critical care units.


Morphological variation in cervical spinous processes: potential applications in the forensic identification of race from the skeleton.
Determination of race (ancestry) is an important step in the identification of individuals in forensic cases. Race is most commonly assessed using cranial traits. Few reliable postcranial indicators are known. In this study, the frequency of bifidity of cervical spinous processes at different vertebral levels was examined in a sample of 359 Americans of African (black) and European (white) descent. The sample was selected from the Hamann-Todd collection, a large modern anatomical collection of known sex and race. Spinous processes were classified as "bifid," "partially bifid," or "nonbifid" based on previously defined criteria. Sex and race were kept entirely unknown to the classifier (S.M.D.) during data collection. Data were analyzed using Chi-square and logistic regression analysis. At C2, most individuals (91%) had bifid spinous processes. At C7, nearly all (98%) had nonbifid spinous processes. Significant differences between race/sex subgroups were found at C3-C6. At each of these levels, whites showed a higher frequency of bifidity than blacks and males a higher frequency of bifidity than females. Differences between races were greater than differences within races. Logistic regression analysis revealed C3 and C4 to be the most useful levels for identifying race. Based on these levels, 76.05% of a validation subsample was correctly classified by race (80.25% for whites, 72.09% for blacks). Pending further study, morphology of the cervical spinous processes may provide an additional method for the determination of race in skeletal forensic cases.


Immune responses against Plasmodium falciparum asexual blood-stage antigens and disease susceptibility in Gabonese and Cameroonian children.
The frequency and level of cellular and humoral responses to seven synthetic peptides from asexual blood stages of Plasmodium falciparum were measured in two cohorts of children living in areas highly endemic for malaria in Gabon and Cameroon. A prospective longitudinal study was conducted for one year in these sites to examine the relationship between specific in vitro immune responses and susceptibility to clinical malaria. Clinical protection was related to high proliferative responses (merozoite surface antigen-1 [MSA-1] and MSA-2 peptides) as well as to elevated antibody levels (schizont extract, MSA-2, and rhoptry-associated protein-1 [RAP-1] peptides) in the village of Dienga, Gabon. Higher response rates of interferon-gamma but lower response rates of tumor necrosis factor-alpha to four and six peptides, respectively, were observed in Dienga than in Pouma that were independent of the older age of the Gabonese children. Age accounted only for the higher prevalence rate in Dienga of the antibody responders to the peptide from Pf155/ring-infected erythrocyte surface antigen (RESA). Our results support the inclusion of epitopes from MSA-1, MSA-2, RAP-1, and Pf155/RESA antigens in a subunit vaccine against malaria, but show that a longitudinal clinical, parasitologic, and immunologic study conducted according to identical criteria in two separate areas may lead to contrasting observations, demonstrating the geographic limitation of the interpretation of such results.


Battling Superbugs: How Phage Therapy Went From Obscure to Promising.
Until a dangerous bacterial infection left her husband near death 3 years ago, scientist Steffanie Strathdee had never heard of bacteriophage therapy. After it ultimately saved his life, however, she not only has become a staunch advocate of the therapy, but also now serves as co-director of the newly established Center for Innovative Phage Applications and Therapeutics (IPATH) at the University of California San Diego (UCSD) (Figure 1).


Stimulatory effect of hypercalcemia on pancreatic secretion is prevented by pretreatment with cholecystokinin and cholinergic agonists.
Recently, we demonstrated that hypercalcemia causes marked stimulation of feline exocrine pancreatic secretion, and that this effect is absent when a large dose of cholecystokinin (CCK) is infused prior to induction of hypercalcemia. To investigate this effect in more detail, anesthetized cats were given calcium i.v. after preadministration of CCK or urecholine (a cholinergic agonist) at specific doses, or of saline as a control. We found that the hypercalcemia-induced stimulation of pancreatic protein secretion was abolished after preadministration of CCK at large doses. After the prestimulus dose was decreased or the calcium dose was increased, however, the pancreatic secretory response to hypercalcemia was preserved. In contrast, the response to a submaximal dose of CCK was unchanged after prestimulation with a large dose of CCK. Similar results were obtained when urecholine instead of CCK was used as prestimulus. These findings indicate that loss of pancreatic responsiveness to hypercalcemia following prestimulation with CCK is dependent on doses of both prestimulus and calcium used, and that it is not specific for prestimulation with CCK but also inducible by cholinergic agonists. They further suggest that this phenomenon is not due to exhaustion of pancreatic secretory capacity, but may reflect decreased sensitivity to the hypercalcemic stimulus instead.


The stereoscopic (cyclopean) motion aftereffect is selective for spatial frequency and orientation of disparity modulation.
Across two experiments, this study investigated the spatial frequency tuning and orientation tuning (both in the disparity domain) of the stereoscopic (cyclopean) motion aftereffect. In Experiment 1, observers adapted to a moving stereoscopic grating of a given cyclopean spatial frequency and tested for the motion aftereffect with a static grating of the same or different spatial frequency. Robust motion aftereffects were induced only when the spatial frequency of the adapt and test stimuli was the same. In Experiment 2, observers adapted to a moving stereoscopic grating of a given cyclopean orientation and tested for the motion aftereffect with a static grating of the same or different orientation. Robust motion aftereffects were induced only when the orientation of the adapt and test stimuli was the same. Together, these results suggest that the stereoscopic motion aftereffect is tuned for cyclopean spatial frequency and orientation which, in turn, suggest that the stereoscopic motion aftereffect is mediated by low-level oriented spatial-frequency mechanisms.


Epithelial-mesenchymal transition: Initiation by cues from chronic inflammatory tumor microenvironment and termination by anti-inflammatory compounds and specialized pro-resolving lipids.
Epithelial mesenchymal transition (EMT) is a biological process that plays a critical role in cancer progression. Blocking the process of EMT can be an essential strategy in the development of anticancer drugs. In this paper, we briefly introduce recent research trends and issues of EMT, focusing on the relationship of EMT with the entire cycle of inflammation (from initiation to resolution of inflammation). Recent findings on the relationship between EMT and immune evasion are discussed. We will also explore the importance of controlling inflammation by anti-inflammatory compounds and specialized pro-resolving lipids to inhibit EMT process in cancer.


Low Bone Mineral Density in Elite Female Athletes With a History of Secondary Amenorrhea in Their Teens.
To determine whether secondary amenorrhea during teenage years influences bone mineral density (BMD) in female athletes in their 20s. Original research. Japan Institute of Sports Sciences. Two hundred ten elite female athletes older than 20 years were included in the study. Information on the participants' past (ie, during their teenage years) and current menstrual cycle, training time, history of stress fractures, and blood tests for hormones received was obtained. Bone mineral density of the lumbar spine was evaluated by dual-energy x-ray absorptiometry; low BMD was defined as a Z-score ≤-1. We investigated the correlation factors for low BMD in athletes in their 20s by univariable and multivariable logistic regression analysis. A total of 39 (18.6%) female athletes had low BMD. Secondary amenorrhea in their teens [odds ratio (OR), 7.11, 95% confidence interval (CI), 2.38-21.24; P < 0.001] and present body mass index (BMI) (OR, 0.56, 95% CI, 0.42-0.73; P < 0.001) were independent correlation factors for low BMD in the multivariable logistic regression analysis. The average Z-score for those with secondary amenorrhea in their teens and 20s, secondary amenorrhea in their 20s only, and regular menstruation was -1.56 ± 1.00, -0.45 ± 1.21, and 0.82 ± 1.11 g/cm, respectively. Secondary amenorrhea for at least 1 year during teenage years in female athletes and BMI at present was strongly associated with low BMD in their 20s.


Inhibitory Effects of Bacteriophage Preparations on Adenoviral Replication.
Bacteriophages (phages) are viruses of bacteria. Escherichia coli phage (T4) can potentially interfere with adsorption of HAdV-5 to cellular integrins by its KGD motif, while staphylococcal A5/80 phage does not possess this structure. The objective of this study was to investigate the effects of T4 and A5/80 phage preparations on type 5 human adenovirus (HAdV-5) DNA synthesis and the expression of HAdV-5 genes. Experiments were performed on the A549 cell line. HAdV-5 DNA synthesis was investigated with real-time PCR. Expression of HAdV-5 early (DBP) and late (hexon) genes was determined by quantitative real-time PCR in preincubation and coincubation experiments. While both phage preparations significantly reduced the expression of HAdV-5 genes, synthesis of HAdV-5 DNA was inhibited only by T4. Phage preparations show promise as novel antiviral agents. However, further studies are required to investigate their antiviral effects.


Imatinib mesylate as a novel treatment option for hypereosinophilic syndrome: two case reports and a comprehensive review of the literature.
Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Recent reports document the efficacy of imatinib mesylate in a large proportion of HES patients (65%). Rearrangements involving the platelet-derived growth factor receptor genes (PDGFRA and PDGFRB), both tyrosine kinase receptors, have been demonstrated to be pathogenetically linked to the dysregulated clonal overproduction of eosinophils. This refined hypothesis has been confirmed by the discovery of the novel FIP1L1-PDGFRA fusion gene, which is a gain-of-function gene on chromosome 4q12. Its product is an imatinib-sensitive tyrosine kinase, which can be found in a subset of patients with HES, particularly in those responding to treatment with imatinib mesylate. Here, we sum up recent knowledge of clinical features, pathophysiology and novel treatment aspects of HES by performing a comprehensive search of the available literature and report on 94 patients. We particularly address the issue of organ involvement and specific characteristics of the variable clinical pictures. In addition, two cases will be presented, which illustrate typical clinical scenarios and treatment outcome.


Heavy metal contents in whitefish (Coregonus lavaretus) along a pollution gradient in a subarctic watercourse.
Metallurgic industry is a source of serious environmental pollution related to the emission of heavy metals. Freshwater systems are focal points for pollution, acting as sinks for contaminants that may end up in fish and humans. The Pasvik watercourse in the border area between Finland, Norway and Russia is located in the vicinity of the Pechenganickel metallurgic enterprises, and the lower part of the watershed drains the Nikel smelters directly through Lake Kuetsjarvi. Heavy metal (Ni, Cu, Cd, Zn, Pb and Hg) concentrations in environment (water and sediments) and whitefish Coregonus lavaretus tissue (gills, liver, kidney and muscle) were contrasted between five lake localities situated along a spatial gradient of increasing distance (5-100 km) to the smelters. The heavy metal concentrations, in particular Ni, Cu and Cd, were highly elevated in Kuetsjarvi, but steeply declined with increasing distance to the smelters and were moderate or low in the other four localities. The study demonstrates that the majority of metal emissions and runoffs are deposited near the pollution source, and only moderate amounts of the heavy metal contaminants seem to be transported at further distances. Bioaccumulation of Hg occurred in all investigated tissues, and higher Hg concentrations in planktivorous versus benthivorous whitefish furthermore indicated that pelagic foraging is associated with higher levels of Hg biomagnification. Potential population ecology impacts of high heavy metal contaminations where mainly observed in whitefish in Kuetsjarvi, which showed depletions in growth rate, condition factor and size and age at maturation.


Liposome-Nanogel Structures for Future Pharmaceutical Applications: An Updated Review.
Nature uses combination of lipid bilayers and cross-linked macromolecular networks to achieve workability, multifunctionality, and dynamism in living cells of different types. Despite the concept of liposome-nanogel structures (lipobeads) is known for about 30 years, lipobead-based drug delivery systems are still largely experimental. The data available on nano- and giant lipobeads are reviewed to demonstrate technological achievability of lipobeads and to support the expectations that additional expenses on their production will be reimbursed by the potential advantages of their use. Indeed, lipobeads exhibit the properties attractive for the next generation of drug delivery systems: (i) retaining all the important benefits of polymeric and liposomal drug carriers, the hydrogel core brings mechanical stability and environmental responsiveness to the formulation in one construct, (ii) lipobeaddelivered combination therapy shows no toxicity on intravenously administered mice, accumulation of drug-loaded lipobeads both in the area surrounding tumor and within the tumor itself outside the vasculature, high therapeutic activity at the targeted site, and drastically increased survival, (iii) bipartite structure of lipobeads can provide a number of novel and unique options (e.g., consecutive multistep triggering and combined drug delivery systems). In addition, some ideas on the conceptually new drug delivery systems, new mechanisms of lipobead internalization into the cell and new schemes of drug release regulated by specific signaling are discussed.


[Accuracy of quantitative coronary angiography for different directions of the coronary artery].
We evaluated the effect of changes in the direction of the coronary artery in terms of the accuracy and precision of vessel diameter measurement in a quantitative coronary angiography system (QCA system). Vessel phantoms sized 0.3, 0.5, 1.0, 1.5, 2.0, and 2.5 mm in diameter were evaluated. The phantoms were aligned on an acrylic plate, and the angle to the television (TV) camera was altered. The deployed angles were 0 (perpendicular), 45, 90, and 135 degrees in clockwise order. The phantoms were imaged with matrices of 1024 x 1024 (1024(2)), 512 x 512 (512(2)), and 512 x 1024. Image size was 7 inches, and the frame rate was 15 frames per second. Minimal lumen diameters were measured on the ACA system. The results revealed that, in the 1024(2) matrix, overall accuracy for the 90-degree angle was significantly underestimated compared with the 0-degree angle (-0.14 vs. -0.014 mm; p=0.007). Accuracy for the 90-degree angle was better than that for the 0-degree angle when the vessel diameter was 1 mm or smaller (-0.02+/-0.16 vs. 0.10+/-0.22 mm). In addition, precision was better at the 90-degree angle than with the other angles in the 1024(2) matrix (overall precision=0.002 mm). In the 512(2) matrix, overall accuracy for the 90-degree angle was significantly underestimated compared with the 45-degree angle (-0.077 vs. 0.096 mm; p=0.02). In addition, accuracy for the 90-degree angle was better than that for the 45-degree angle below 1 mm (0.05+/-0.24 mm vs. 0.26+/-0.47 mm). In terms of overall accuracy, the 45-degree angle in the 512(2) matrix showed significant overestimation compared with that in the 1024(2) matrix (0.096 vs. -0.069 mm; p=0.015). There was no difference in accuracy in the 512 x 1024 matrix. Our results suggest that the direction of the vessel against the TV image affects accuracy of measurement in the QCA system.


TMPRSS3 modulates ovarian cancer cell proliferation, invasion and metastasis.
Overexpression of transmembrane protease, serine 3 (TMPRSS3) has been detected in ovarian cancer. However, the molecular mechanisms of TMPRSS3 in ovarian cancer remain unclear. In the present study, we found that TMPRSS3 was significantly expressed in ovarian cancer cells. Overexpression of TMPRSS3 promoted the proliferation, invasion and migration of A2780 cells. Conversely, knockdown of TMPRSS3 in HO8910 cells inhibited the proliferation, invasion and migration. Furthermore, TMPRSS3 affected the expression levels of E-cadherin, vimentin and Twist. In addition, TMPRSS3 induced activation of ERK1/2 in ovarian cancer cells, and the ERK1/2 pathway was required for the TMPRSS3-mediated proliferation, invasion and migration of ovarian cancer cells. Finally, knockdown of TMPRSS3 inhibited ovarian cancer HO8910 cell growth and metastasis in vivo. Collectively, the present study suggests that TMPRSS3 plays a crucial role in the development and progression of ovarian cancer. Therefore, TMPRSS3 represents a potential therapeutic target of ovarian cancer.


Conversion of food industrial wastes into bioplastics.
The usage of plastics in packaging and disposable products, and the generation of plastic waste, have been increasing drastically. Broader usage of biodegradable plastics in packaging and disposable products as a solution to environmental problems would heavily depend on further reduction of costs and the discovery of novel biodegradable plastics with improved properties. In the authors' laboratories, various carbohydrates in the growth media, including sucrose, lactic acid, butyric acid, valeric acid, and various combinations of butyric and valeric acids, were utilized as the carbon (c) sources for the production of bioplastics by Alcaligenes eutrophus. As the first step in pursuit of eventual usage of industrial food wastewater as nutrients for microorganisms to synthesize bioplastics, the authors investigated the usage of malt wastes from a beer brewery plant as the C sources for the production of bioplastics by microorganisms. Specific polymer production yield by A. Latus DSM 1124 increased to 70% polymer/cell (g/g) and 32 g/L cell dry wt, using malt wastes as the C source. The results of these experiments indicated that, with the use of different types of food wastes as the C source, different polyhydroxyalkanoate copolymers could be produced with distinct polymer properties.


The utility of an obesity-specific small for gestational age standard for pregnancies complicated by maternal obesity.
An obesity-specific standard for small for gestational age (SGA) pregnancies may help identify additional at risk pregnancies. This was a retrospective cohort study of all non-anomalous singleton neonates born in Texas from 2006-2011. Analysis was limited to births between 34 and 42 weeks gestation. Two SGA birth weight standards (birth weight ≤10th centile) were generated, one using the entire population (SGApop) and another using obese pregnancies (SGAcust). The outcomes of interest included: risks of stillbirth, neonatal death, 5-minute Apgar score below 7, NICU admission, and assisted ventilation >6 h. Using the population standard, the prevalence of SGA complicated by obesity was 8.1%, compared with 10.3% using the obesity-specific standard. 10,457 additional pregnancies were identified as SGA. Compared to obese AGA pregnancies, the aHR for stillbirth was 5.45 [4.28, 6.94] for SGApop, and 1.21 [0.54, 2.74] for SGAcust-pop. The risks for the following neonatal complications were slightly higher for SGAcust-pop group compared to AGA group: neonatal death aOR 1.40 [1.05, 1.87], low 5-minute Apgar 1.31 [1.09, 1.57], and NICU admission 1.13 [1.03, 1.25]. These risks were lower than SGApop. Using an obesity-specific SGA standard, a subgroup of pregnancies with marginally increased risk for neonatal complications was identified.


Hybrid Nanoreactors: Enabling an Off-the-Shelf Strategy for Concurrently Enhanced Chemo-immunotherapy.
Immunosuppressive tumors generally exhibit poor response to immune checkpoint blockade based cancer immunotherapy. Rationally designed hybrid nanoreactors are now presented that have integrated functions as Fenton catalysts and glutathione depletion agents for amplifying the immunogenic cell death and activating immune cells. A simple physical mixture of nanoreactors and chemodrugs in combination with immune checkpoint blockades show synergistically and concurrently enhanced chemo-immunotherapy efficacy, inhibiting the growth of both treated primary immunosuppressive tumors and untreated distant tumors. The off-the-shelf strategy uses tumor antigens generated in situ and avoids cargo loading, and is thus a substantial advance in personalized nanomedicine for clinical translation.


[The effect of standardised sodium hypochlorite solution on bacteria pathogenic for the urinary tract (author's transl)].
Stable sodium hypochlorite solution shows excellent disinfectant properties, even in higher dilution. Parallel to clinical tests in vitro experiments were made to show the changes of morphology of bacteria pathogenic for the urinary tract by scanning microscope. Two hours after incubation of the bacteria with sodium hypochlorite solution containing 40 mg available chlorine/1 severe damages of the bacterial morphology up to complete destruction were evident in all cases. Gram-negative rod-shaped bacilli were more, gram-positive cocci were less damaged.


Effect of cryoprotectants and their concentration on in vitro development of vitrified-warmed immature oocytes in buffalo (Bubalus bubalis).
Experiments were conducted to study the effect of cryoprotectants, dimethyl sulfoxide (DMSO), ethylene glycol (EG), 1,2-propanediol (PROH), and glycerol at different concentrations (3.5, 4, 5, 6, and 7 M each with 0.5 M sucrose and 0.4% BSA in DPBS) on survival, in vitro maturation, in vitro fertilization, and post-fertilization development of vitrified-thawed immature buffalo oocytes. The COCs were harvested from the ovaries by aspirating the visible follicles. The recovery of post-thaw morphologically normal oocytes was lower in 3.5 and 4 M DMSO, EG, and PROH compared to 5, 6, and 7 M. In all the concentrations of glycerol, an overall lower numbers of oocytes recovered were normal compared to other cryoprotectants. Less number of oocytes reached metaphase-II (M-II) stage from the oocytes cryopreserved in any of the concentrations of DMSO, EG, PROH, and glycerol compared to fresh oocytes. Among the vitrified groups, highest maturation was obtained in 7 M solutions of all the cryoprotectants. The cleavage rates of oocytes vitrified in different concentrations of DMSO, EG, PROH, and glycerol were lower than that of the fresh oocytes. The cleavage rates were higher in oocytes cryopreserved in 6 and 7 M DMSO, EG, PROH, and glycerol compared with oocytes cryopreserved in other concentrations. However, the percentage of morula and blastocyst formation from the cleaved embryos did not vary in fresh oocytes and vitrified oocytes. In conclusion, this report describes the first successful production of buffalo blastocysts from immature oocytes cryopreserved by vitrification.


Chiari malformation type III treated with primary closure.
Chiari malformations represent various clinical and anatomic processes that entail varying degrees of involvement of the rhombencephalon (hindbrain). The type III Chiari malformation is distinctly rare. Chiari described only one case of his type III deformity, which is indicative of its rarity. We report a case of Chiari malformation type III, a female child who presented to us at the age of 1 month with a swelling at the back of the neck since birth. MRI revealed a Chiari type III malformation with a high cervical meningoencephalocele along with herniation of cerebellar tissue through the bony defect in the posterior elements of the C2 vertebra. At surgery, the meningoencephalocele was excised along with the gliotic cerebellar tissue, and a posterior fossa decompression along with augmentation duraplasty was done. The postoperative period was uneventful. The case and relevant literature is reviewed.


Does acupuncture help patients with spasticity? A narrative review.
Spasticity is a motor disorder encountered after upper motor neuron lesions. It adversely affects quality of life in most patients and causes long-term burden of care and has significant financial implications. The effect of conventional therapies for spasticity including physical therapy, surgery, and pharmacotherapy are not always satisfying because of the short-term effects or side effects in some patients. Acupuncture is a part of traditional medicine originating from China. It has been used to resolve functional recovery problems after central nervous system injury for many years in Asian countries and is increasingly popular in western countries. Some researches suggest that acupuncture has therapeutic potential to help improve limb movement function and decrease the severity of spasticity. This review synthesizes studies involving stroke, brain injury, spinal cord injury, cerebral palsy, and multiple sclerosis to give an overall picture of the effect and potential mechanisms of acupuncture on spasticity occurring after upper motor neuron lesions. Moderate-quality evidence suggests that electroacupuncture combined with conventional routine care (pharmacological/rehabilitation) could reduce spasticity and improve motor function and activities in daily living after stroke. However, there is not enough evidence to conclude that acupuncture (including electroacupuncture) could reduce spasticity with other central nervous system diseases.


Clinical observation on treatment of Tourette syndrome in Chinese children by clonidine adhesive patch.
To evaluate the therapeutic effectiveness and safety of clonidine adhesive patch in treating Tourette syndrome (TS). From July 2010 to July 2014,a total of 261 children, who met the Chinese Classification of Mental Disorders (third edition) diagnostic criteria for TS, aged 5-12 years, were referred to the department of Pediatrics, Shaanxi Provincial People's Hospital. The patients were divided randomly into a treatment group (clonidine adhesive patch, n = 128) and a control group (haloperidol, n = 116), 17cases dropped out. The clinical effectiveness was assessed by the Yale Global Tic Severity Scale (YGTSS) at the end of fourth week. The short-term effectiveness and adverse reaction to the treatment were assessed at the end of treatment. The YGTSS score in both groups decreased after 4 weeks of treatment, but the clonidine adhesive patch group showed a higher reduction in the overall tic symptom scores (40.05 ± 3.44%) than that of the control group (17.88 ± 4.40%; P < 0.05). In the clonidine adhesive patch group, the effectiveness was 81.3% (effective in 104 patients), while it was 66.4% in the control group (effective in 77 patients). The overall effectiveness rate showed no statistical significance between the two groups (p > 0.05). There were no severe adverse events in both groups, but mild side effects (decrease of blood pressure and dizziness) were observed in 3 patients in the clonidine adhesive patch group. 2 had mild cervical muscle tension and 4 had mild drowsiness and fatigue in the control group. In the treatment of TS in children and adolescents, the clonidine adhesive patch is superior to the standard treatment with haloperidol with a safer and better-tolerated profile.


Laser disc decompression. The importance of proper patient selection.
The value of adherence to selection criteria for laser disc decompression (LDD) was evaluated. A total of 204 patients who underwent LDDs were identified. Follow-up information could be obtained for 164 (80.8%) patients. Results were compared based on the selection criteria. Laser disc decompression is a relatively new procedure. Few reports concerning outcome of LDD exist; and none deal specifically with patient selection. This study compared the results of LDD performed among patients who met appropriate selection criteria with those who did not. Also, the value of discography in patient selection for LDD was investigated. Two independent reviewers extracted data from patient charts. From this information, each patient was assigned to one of three groups: 1) those who met all selection criteria for LDD (leg pain, positive physical examination finding such motor, sensory, or reflex deficits, and/or straight leg raise, contained disc herniation confirmed by discography); 2) those who did not meet the selection criteria (had a normal physical examination, the presence of stenosis, spondylolisthesis, extruded disc fragment, leakage of discographic dye from the outer annulus, multiple prior lumbar surgeries); or 3) those who could not be assigned to either of the first two groups for reasons such as discography not being performed or inadequate physical examination data recorded in the chart. At 1 year follow-up, each patient was sent a questionnaire assessing outcome. Successful outcome was defined to be no subsequent lumbar surgery, the patient felt that LDD had helped, and if the patient was working before symptom onset, he was able to work at the time of follow-up. Among the 41 patients who met all selection criteria, the success rate was 70.7% (29/41); among patients who did not meet all the criteria, the success rate was only 28.6% (12/42); significantly less than in the first group (P < 0.005). Among patients who could not be assigned definitively to either of the first two groups, the success rate was 55.6% (45/81). Also, the success rate among patients with discographic confirmation of a contained disc herniation was significantly greater than among those who either did not have discography performed or extravasation of contrast was noted (70.7% vs. 44.4%, P < 0.035). These results emphasize the importance of strict adherence to appropriate selection criteria to obtain satisfactory results from LDD.


[Practical considerations and questions in the treatment of chronic lymphocytic leukemia].
Understanding the pathogenesis and refine the treatment of chronic lymphocytic leukemia have been tremendously improved in the past decade. Treatment outcome and estimated prognosis have become more accurate due to the advanced molecular biological techniques and the classical prognostic markers. Incorporation of fludarabine and rituximab into the standard protocols fundamentally improved treatment outcome in chronic lymphocytic leukemia. Chemoimmunotherapy has improved not only the remission rates but had a significant impact on overall survival, as well. Eliminating residual leukemia and achieving complete hematological remissions at such high rates establish potential background for cure. Still, a great deal of dispute has been emerged regarding everyday clinical practice. Authors present their institutional experiences and review the literature.


The state of the clinical trials system today.
This article describes the components, process, and regulatory requirements of the clinical trials system as well as the changes that have resulted from increased attention to patient safety. Also discussed are the economic and scientific pressures on pharmaceutical and medical device companies to run efficient clinical trials with rapid enrollment of subjects. The complexity of the clinical trials system and the demand for efficient trials that protect patients has led to the need for special training of physicians who conduct clinical trials. This year the first board examination for certified physician investigators will be offered through the Physician Investigator Certification Program of the American Academy of Pharmaceutical Physicians.


Aurora-A kinase inhibitor scaffolds and binding modes.
Aurora kinases (A-C) belong to the serine/threonine protein kinase family. In recent years, the constitutive or elevated expression of Aurora kinases has been found in cancer cells and oncogene transfected cells. In this review, we summarize the common binding modes of Aurora-A kinase inhibitors, the hot spot residues in the binding sites and the privileged inhibitor structures. Our review of the reported chemical scaffolds of Aurora-A kinase inhibitors and their binding modes could provide a useful framework from which new design strategies for inhibitors might be assessed or developed.


A model of collaborative agency and common ground.
As more healthcare delivery is provided via collaborative means there is a need to understand how to design information and communication technologies (ICTs) to support collaboration. Existing research has largely focused on individual aspects of ICT usage and not how they can support the coordination of collaborative activities. In order to understand how we can design ICTs to support collaboration we need to understand how agents, technologies, information and processes integrate while providing collaborative care delivery. Co-agency and common ground have both provided insight about the integration of different entities as part of collaboration practices. However there is still a lack of understanding about how to coordinate the integration of agents, processes and technologies to support collaboration. This paper combines co-agency and common ground to develop a model of collaborative agency and specific categories of common ground to facilitate its coordination.


Regional differences in glutathione accumulation pathways in the rat cornea: Mapping of amino acid transporters involved in glutathione synthesis.
In this study we have sought to complete the identification and localisation of uptake pathways involved in accumulating precursor amino acids involved in GSH synthesis in the rat cornea. To do this, we performed reverse transcription PCR (RT-PCR) to identify the Excitatory Amino Acid Transporters (EAAT 1-5) responsible for glutamate uptake, and glycine transporters (GLYT 1-2) at the transcript level. Western blotting was used to verify protein expression, while immunolabelling of sagittal sections was used to localise transporters to the different layers of the cornea. Immunolabelling of en face sections was used to examine the subcellular distribution of proteins in the corneal endothelium. Our findings revealed EAAT 1-5 and GLYT 1-2 to be expressed at the transcript and protein level in the rat cornea. Immunohistochemistry revealed all amino acid transporters to be localised to the epithelium. In the majority of cases, labelling was restricted to the epithelium, and labelling absent from the stroma or endothelium. However, EAAT 4 and GLYT 2 labelling was detected in the stroma with EAAT 4 labelling also present in the endothelium. Overall, the identification of amino acid transporters strongly supports the existence of an intracellular GSH synthesis pathway in the rat corneal epithelium. This suggests that regional differences in GSH accumulation pathways exist, with direct uptake of GSH and intracellular synthesis of GSH restricted to the endothelial and epithelial cell layers, respectively. This information is important in the design of targeted strategies to enhance GSH levels in specific layers of the cornea to prevent against oxidative damage, corneal swelling and loss of corneal transparency.


Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women.
Because it has been reported that vitamin D, given to mother or infant, can prevent type I diabetes in children, that diabetes is more common in adults with low serum vitamin D and that insulin secretion and action are related to vitamin D levels in healthy young adults we examined the relationship between serum vitamin D metabolites and fasting serum glucose in patients attending our outpatient clinics. Retrospective examination of convenience sample of postmenopausal women attending our osteoporosis clinics. A total of 753 postmenopausal women attending a university hospital outpatient clinic and not on any treatment known to affect glucose metabolism. Body weight and height, serum 25-hydroxyvitamin D [25(OH)D], serum 1,25-dihydroxyvitamin D [1,25(OH)2D], serum PTH and fasting serum glucose. On simple correlation fasting serum glucose was a positive function of age (P < 0.05), weight (P < 0.001) and body mass index (BMI) (P < 0.001) and a negative function of serum 25(OH)D (P < 0.001), but it was not significantly related to either serum 1,25(OH)2D, PTH or creatinine. When fasting serum glucose was regressed simultaneously on age, BMI and 25(OH)D, glucose was still an inverse function of 25(OH)D (P = 0.006). Fasting serum glucose increased as 25(OH)D levels fell throughout the range of serum 25(OH)D measured but the greatest increase was observed in those with 25(OH)D below 40 nmol/l.


Fungal melanins and their interactions with metals.
Fungal melanins are dark brown or black pigments located in cell walls. They also exist as extracellular polymers. Melanized fungi possess increased virulence and resistance to microbial attack as well as enhanced survival while under environmental stress. Melanins contain various functional groups which provide an array of multiple nonequivalent binding sites for metal ions. Pigmented Cladosporium cladosporoides was shown to biosorb 2.5- to four-fold more Ni, Cu, Zn, Cd, and Pb than albino Penicillium digitatum and at four- to six-fold higher rates. Metal desorption was significantly lower for extracellular melanin than from pigmented or albino biomass which indicated the strength of the melanin-metal bond. At equilibrium, tributyltin chloride (TBTC) concentrations of 2.5 mM, pigmented and albino Aureobasidium pullulans absorbed approximately 0.9 and 0.7 mumol TBTC mg -1 dry wt, respectively, whereas purified extracellular melanin exhibited uptake levels of approximately 22 mumol TBTC mg-1 dry wt at an equilibrium concentration of only 0.4 mM. Addition of melanin to the growth medium reduced the toxic effect of CuSO4 and TBTC due to melanin metal binding and sequestration.


Role of the L-arginine/nitric oxide pathway in ischaemic/reoxygenation injury of the human myocardium.
The role of the L-arginine/nitric oxide (NO) pathway in myocardial ischaemic/reperfusion injury remains controversial in experimental animal models. The aim of the present studies was to investigate the role of this pathway in the human myocardium. Myocardial specimens from right atrial appendages of patients undergoing elective coronary bypass graft surgery were incubated in crystalloid buffer at 37 degrees C and subjected to 120 min of simulated ischaemia followed by 120 min of reoxygenation. Tested drugs were added 15 min before ischaemia, and maintained during ischaemia and throughout reoxygenation. Ischaemia resulted in severe myocardial damage, as assessed by the leakage of lactate dehydrogenase (LDH) into the incubation medium and by the capacity of the tissue to reduce 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan product. L-Arginine (10 mM), a precursor of NO, significantly decreased LDH leakage (from 9.0+/-0.6 to 5.3+/-0.3 units/g wet wt; P<0.05), but had no effect on MTT reduction or oxygen consumption. D-Arginine (10 mM), N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5 mM), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (at 1, 100, 500 and 1000 microM), an NO donor, had no significant effects on the measured indices, and L-NAME did not reverse the protection afforded by L-arginine against LDH leakage. In addition, the formation of nitrotyrosine was not influenced by ischaemia/reoxygenation alone or by the agents investigated. In conclusion, these data suggest that L-arginine affords modest protection against ischaemic/reoxygenation injury of the human myocardium, an action that is NO-independent, and that NO metabolism does not play a significant role in this model.


[Alteration of inositol 1,4,5-trisphosphate receptor binding after 6-hour hemispheric ischemia in the gerbil brain].
Inositol 1,4,5-trisphosphate (IP3) has recently been known to play vital roles as one of the second messengers to control intracellular metabolism of calcium ion. Therefore, alterations of IP3 receptor binding and local cerebral blood flow (1CBF) were evaluated at 6 hours after occlusion of the right common carotid artery in the gerbil brain. The autoradiographic method developed in our laboratory enabled us to measure both parameters in the same brain. Animals attaining more than 5 in their ischemic scores, which were assessed at 1 hour after the occlusion, were utilized. LCBF was measured by the 14C-iodoantipyrine method at the end of the experiment. After frozen brains were cut into serial slices on a cryostat, the IP3 receptor binding was evaluated in vitro by using 3H-inositol 1,4,5-trisphosphate as the ligand. LCBF fell below 10 ml/100 g/min in most of the cerebral regions on the occluded side. In contrast a significant reduction in IP3 binding was noted only in the hippocampus CA1 on the occluded side. The IP3 binding tended to decrease when the values of 1CBF were reduced below 20 ml/100 g/min in this region. These findings suggest that the selective alteration of IP3 receptor binding in the hippocampus CA1 may be closely associated with the selective vulnerability of this region to ischemia.


Alpha calcium/calmodulin dependent protein kinase II in learning-dependent plasticity of mouse somatosensory cortex.
Calcium/calmodulin dependent protein kinase II (CaMKII), and more specifically its alpha subunit, is widely believed to be fundamental for hippocampal synaptic plasticity. In the cerebral cortex, deprivation-evoked plasticity was shown to depend on alphaCaMKII autophosphorylation abilities. Here we analyzed how learning-induced functional reorganization of cortical representations affected alphaCaMKII in adult Swiss mice. Mice were subjected to short-lasting sensory training in which stimulation of whiskers was paired with tail shock. The pairing results in enlargement of functional representation of vibrissae activated during the training. alphaCaMKII protein and its autophosphorylation level were determined by Western-blotting in somatosensory cortex crude synaptosomal fraction (P2) and postsynaptic protein-enriched, Triton X-100 insoluble fraction (TIF). The first training session resulted in an increase in alphaCaMKII autophosphorylation at autonomy site observed in TIF. A similar increase was also observed after the first session of just whiskers stimulation, which alone does not induce rearrangement of cortical representations. These data indicate that increased autophosphorylation of postsynaptic alphaCaMKII is not a correlate of induction phase of plasticity related reorganization of cortical representation of vibrissae. The increase observed in both experimental groups was transient and did not persist in the maintenance phase of the plastic change. Furthermore, we found that the training caused a delayed upregulation of alphaCaMKII protein level in crude synaptosomal fraction, but not in TIF, and the upregulation was not accompanied by an increase in autophosphorylation level of the kinase. The result indicates alphaCaMKII involvement in the late phase of plastic change and suggests the participation of a presynaptic pool of kinase rather than postsynaptic at this point.


[Sports activities after osteotomies around the knee].
In the current literature, the rate of return to sports following high tibial osteotomy is high. Patients are largely able to carry out the type of exercise done before the onset of symptoms and are satisfied with the clinical outcome. In general, however, a differentiated view of the sporting ability should be made, and the different requirements of the sport should be considered. A classification according to functional and biomechanical movement analysis seems to advisable. In addition, the recommendations of the treating physician seem to have a high impact on the postoperative level of the sports activities of the patients. A realistic assessment (by both the patient and the treating physician) that considers the sport, its requirements and the level of performance is necessary.


Thermomechanical behavior of the cornea.
Shrinkage of corneal collagen is used during thermokeratoplasty, a method to remodel the corneal curvature. The goal of our investigations was to determine the optimal temperature range for maximal shrinkage of the collagen fibers with minimal damage. By means of a commercially available stress-strain-measuring device including a paraffin oil bath at temperatures varying from 35 degrees to 120 degrees C, strips of pig cornea measuring 5 mm in width and 9 mm in length were investigated in the stress range of sigma = (0.5-12.5) x10(4) N/m2 by stress-strain, stress-relaxation, and creep measurements. The biomechanical properties of the cornea remained unchanged in the temperature range of 30-50 degrees C. Starting at 60 degrees C, shrinkage occurred that increased up to a temperature of 90 degrees C. The maximal rate of shrinkage of 57 +/- 12% was determined at temperatures of 75 degrees and 80 degrees C. At above 100 degrees C the shrinkage effect decreased because of the destruction of intermolecular bonds between the collagen fibers. The stress-strain curves generated for shrunken corneas were flatter than those generated for native corneas, which means that Young's modulus is significantly reduced. For the achievement of optimal shrinkage during thermokeratoplasty, temperatures of 70-85 degrees C should be reached in the tissue to be coagulated. Higher temperatures are capable of causing a shrinkage effect but also induce the destruction of tissue.


Positioning invasive versus noninvasive urodynamics in the assessment of bladder outlet obstruction.
To provide evidence of promising tests to noninvasively diagnose bladder outlet obstruction (BOO) in men with benign prostatic hyperplasia. Pressure-flow studies are usually performed to prove BOO prior to prostatectomy. However, pressure-flow studies are invasive, expensive, time consuming, and potentially harmful to the patient due to unwarranted side-effects. In the last decade, attempts were made to diagnose BOO noninvasively. Ultrasound-derived measurements such as bladder or detrusor wall thickness or intravesical prostatic protrusion and urodynamic-derived measurements such as isovolumetric bladder pressure by the condom catheter or penile cuff tests show promising results. Likelihood ratios of all tests were calculated for this study and indicated a good ability to detect BOO. Noninvasive measurements of bladder/detrusor wall thickness, intravesical prostatic protrusion, or isovolumetric bladder pressure might replace invasive pressure-flow studies in the future if only information about BOO is needed. These tests are applicable for the majority of patients with lower urinary tract symptoms and suspected BOO. However, urodynamic investigations are still indicated in patients requiring detailed information about the bladder filling and voiding phases and to assess the precise cause of lower urinary tract symptoms.


Residual venous obstruction in patients with a single episode of deep vein thrombosis and in patients with recurrent deep vein thrombosis.
Residual venous obstruction (RVO) in patients with previous deep vein thrombosis (DVT) of the lower limbs has been suggested as an independent risk factor for recurrent venous thromboembolism (VTE). RVO could be a marker of a persistent prothrombotic state. We have compared the rate of RVO in patients with DVT and a personal history of at least one previous episode of VTE to the rate of RVO among patients with a first episode of DVT. All patients underwent compression ultrasonography (CUS) of the lower limbs 1 year after index DVT. RVO was arbitrarily defined as a thrombus occupying, at maximal compressibility, more than 20% of the vein area in the absence of compression. 50 consecutive patients with recurrent DVT and 50 age and sex-matched patients with a single episode of DVT were enrolled. The index event was idiopathic in 62% of patients with recurrent DVT and in 60% of patients with a single episode. In 74% of patients with recurrent DVT the index event occurred in either the contralateral leg or in a different segment of the ipsilateral leg. RVO was detected in 50% of patients with a single episode of DVT and in 88% of patients with recurrent DVT (p<0.00001). The prevalence of RVO is significantly higher in patients with recurrent DVT than in patients with a single episode. This finding supports the importance of RVO as a potential marker of a persistent prothrombotic state.


Infantile onset spinocerebellar ataxia represents an allelic disease distinct from other hereditary ataxias.
Hereditary ataxias are a heterogeneous group of progressive neurodegenerative disorders characterized by symptoms and signs originating mainly in the CNS. A new representative of this disease group is infantile onset spinocerebellar ataxia, an autosomal recessively inherited syndrome so far reported only in the genetically isolated Finnish population. The etiology of hereditary ataxias still remains unknown, but the gene loci behind many of them have been mapped to different chromosomal regions. We have carried out linkage analyses with markers on the regions of the previously identified ataxia loci to determine whether the infantile onset spinocerebellar ataxia syndrome represents the same allelic disease as any of the previously identified hereditary ataxias. Here we report that the infantile onset spinocerebellar ataxias syndrome does not segregate with any of the markers closely linked to the other hereditary ataxias. Consequently, it represents a genetically distinct disease, the gene locus of which still has to be identified.


Anti-cyclooxygenase effects of lipid extracts from the New Zealand green-lipped mussel, Perna canaliculus.
Total lipid extracts of P. canaliculus (a bivalve marine mollusc native to New Zealand, commonly called the green-lipped mussel) and Mytilus edulis (commonly called the common blue mussel) moderately inhibited ovine COX-1 and COX-2 pure enzymes in vitro. The inhibition was increased after the mussel extracts were saponified by KOH hydrolysis. Protease- and protease-lipase-hydrolysed lipid extracts of P. canaliculus exhibited similarly strong COX inhibition as the KOH-hydrolysed extract. Lyprinol(R) (a commercial extract from P. canaliculus) also exhibited strong inhibition of both COX isoforms, an effect that was increased 10-fold upon subsequent hydrolysis. In contrast, fish oil was not as anti-COX active as Lyprinol. The Lyprinol free fatty acid fraction, and to a lesser extent the Lyprinol triglyceride fraction, were the only lipid classes of Lyprinol to exhibit strong inhibition of the COX isoforms. The purified PUFA extracts were all bioactive, potently inhibiting COX-1 and COX-2. Incubation of Lyprinol in the absence of exogenous arachidonic acid (AA) showed the appearance of alternate prostaglandin metabolites, confirming Lyprinol PUFA as a competitive substrate inhibitor of AA metabolism.


Ectoparasite load in the crested porcupine Hystrix cristata Linnaeus, 1758 in Central Italy.
The crested porcupine Hystrix cristata is a large body-sized rodent, occurring in Europe only in the Italian Peninsula, where it may have been introduced in early Medieval times. Its parasite fauna is currently poorly known and limited to few anecdotal observations. We have analyzed the ectoparasite load of 165 crested porcupines from Tuscany and Latium (Central Italy). Both captured and road-killed individuals were checked for fleas and ticks. Overall, only 39 porcupines were infested by four species of ticks and five of fleas. Abundance of ectoparasites was higher in areas with higher habitat richness, with respect to densely wooded areas. The most frequent species was the flea Pulex irritans (25%), whose prevalence peaked in winter probably because of optimal abiotic conditions in the porcupine's den. The remaining species of both hard ticks (Rhipicephalus bursa, Pholeoixodes hexagonus, and Ixodes ventalloi) and fleas (Paraceras melis, Ctenocephalides canis, Dasypsyllus gallinulae, and Hystrichopsylla talpae), all with prevalence lower than 5%, could be due to den sharing with other vertebrates, mainly carnivores such as, e.g., red foxes and badgers. The second most prevalent species was the generalist tick Ixodes ricinus (21%). An adult male-biased parasitism for ticks has been detected, suggesting a possible role of testosterone related immune-depressive effect. The low richness in dominant ectoparasite species, built up by locally acquired generalist taxa, provides support to the allochthonous origin of this rodent in Italy.


Treating calcific aortic stenosis: an evolving science.
Calcific aortic stenosis is a common valvular disease, but its pathophysiology remains undetermined and important considerations exist for treatment. Pathophysiology, treatment by the advanced practice nurse, and literature review are discussed in the context of a case study.


Bottom-up synthesis of MoS2 nanospheres for photothermal treatment of tumors.
Photothermal therapy (PTT) is providing new opportunities for killing cancer cells. In this work, we introduce a new nanomedicine based on spherical MoS2 nanoparticles for PTT treatment of tumors, prepared using "green" bottom-up technology. To increase water solubility and avoid rapid clearance by the reticuloendothelial system, polyethylene glycol (PEG) was used to coat them. These MoS2-PEG nanospheres with an appropriate size (∼100 nm) exhibit high photothermal conversion efficiency (26.7%). In vitro cellular studies revealed that the MoS2-PEG nanospheres showed negligible cytotoxicity. Additionally, through combining the MoS2-PEG nanosphere samples with NIR irradiation at 808 nm, excellent in vitro tumor cell killing efficacy was achieved. In the 4T1 tumor model, the MoS2-PEG nanospheres exhibited good antitumor efficiency in vivo, displaying complete tumor inhibition over 16 days after treatment. Therefore, MoS2-PEG nanospheres played an important role in tumor destruction, and this concept for developing spherical MoS2-based nanomedicines can serve as a platform technology for the next generation of in vivo PTT agents.


Conservation of primary structure in the hisI gene of the archaebacterium, Methanococcus vannielii, the eubacterium Escherichia coli, and the eucaryote Saccharomyces cerevisiae.
A 2.7 kilobase pair (Kb) fragment of DNA, which complements mutations in the hisI locus of Escherichia coli, has been cloned and sequenced from the genome of the methanogenic archaebacterium Methanococcus vannielii. The cloned DNA directs the synthesis of three polypeptides, with molecular weights of 71,000, 29,000 and 15,600 in minicells of E. coli. Subcloning and mutagenesis demonstrates that hisI complementation results from the activity of the 15,600 molecular weight polypeptide. The primary structure of this archaebacterial gene and its gene product have been compared with the functionally equivalent gene and protein from the eubacterium E. coli (hisI) (Chiariotti et al. 1986) and from the eucaryote Saccharomyces cerevisiae (his4A) (Donahue et al. 1982). The DNA sequences of the archaebacterial and eubacterial genes are 40% homologous, the archaebacterial and eucaryotic DNA sequences are 47% homologous and, as previously reported (Bruni et al. 1986) the eubacterial and eucaryotic DNA sequences are 45% homologous. In E. coli the hisI locus is part of a bifunctional gene (hisI/E) within the single his operon. In S. cerevisiae the his4A locus is part of a multifunctional gene (his4) which encodes a protein with at least four enzymatic activities. The his genes of S. cerevisiae do not form an operon and are not physically linked. The M. vannielii hisI gene does not appear to be part of a multifunctional DNA sequence and, although it does appear to be within an operon, the open reading frames (ORFs) 5' and 3' to the M. vannielii hisI gene are not related to any published his sequences.(ABSTRACT TRUNCATED AT 250 WORDS)


Structure-activity relationships for abiotic thiol reactivity and aquatic toxicity of halo-substituted carbonyl compounds.
Using abiotic thiol reactivity (EC50) and Tetrahymena pyriformis toxicity (IGC50) data for a group of halo-substituted ketones, esters and amides (i.e. SN2 electrophiles) and related compounds a series of structure-activity relationships are illustrated. Only the alpha-halo-carbonyl-containing compounds are observed to be thiol reactive with the order I > Br > Cl > F. Further comparisons disclose alpha-halo-carbonyl compounds to be more reactive than non-alpha-halo-carbonyl compounds; in addition, the reactivity is reduced when the number of C atoms between the carbonyl and halogen is greater than one. Comparing reactivity among alpha-halo-carbonyl-containing compounds with different beta-alkyl groups shows the greater the size of the beta-alkyl group the lesser the reactivity. A comparison of reactivity data for 2-bromoacetyl-containing compounds of differing dimensions reveals little difference in reactivity. Regression analysis demonstrates a linear relationship between toxicity and thiol reactivity: log (IGC(50)(-1)) = 0.848 log (EC(50)(-1)) + 1.40; n=19, s=0.250, r2=0.926, r2(pred)=0.905, F=199, Pr > F=0.0001.


Occurrence of Yersinia enterocolitica in Poultry Products.
In a study on isolation of Yersinia enterocolitica from poultry products, usefulness of the following enrichment media was evaluated: phosphate-buffered saline solution with and without addition of 1% sorbitol plus 0.15% bile salts, modified Rappaport medium and selenite broth. Plating was performed on MacConkey agar directly from the incubated broths and after treatment of the enrichment broths with a potassium hydroxide solution. Seventy-three of 108 (68%) samples of poultry products contained Y. enterocolitica . Y. enterocolitica was isolated most frequently after enrichment in phosphate-buffered saline solution with sorbitol and bile salts. Nearly all Y. enterocolitica strains were found after KOH-treatment. Serotyping showed that the isolated strains mainly belonged to the category of the non-pathogenic, so called "environmental" strains.


Microwave-assisted solid-phase synthesis of 5-carboxamido-N-acetyltryptamine derivatives.
[reaction: see text] The synthesis of the indole skeleton of new melatoninergic analogues was realized using solid-phase methodology in association with microwave irradiation. This combination speeds up the solid-phase drug discovery process in rigorously established conditions.


Microbial transformations of steroids--I. Rare transformations of progesterone by Apiocrea chrysosperma.
When Apiocrea chrysosperma is incubated with progesterone for 7 days in a peptone, yeast-extract medium, eight major metabolites are produced. Each compound has been purified and its structure determined by high-field 1D and 2D 1H nuclear magnetic resonance (NMR) spectroscopy. A clear synthetic pattern is recognisable. The products have been formed by multiple transformation reactions, usually double hydroxylations. Seven compounds are tertiary alcohols in which the hydroxyl group is located on the underside of the progesterone skeleton at either the axial 9 alpha- or the axial 14 alpha-site. One compound has hydroxyl groups at both these sites. Five metabolites are also secondary progesterone alcohols, the hydroxyl groups being at the 6 beta-, 15 alpha- or 15 beta-sites. Two compounds are monohydroxy metabolites; one is dehydrogenated in ring B and the other has lost the pregnane side-chain. The structures of the eight metabolites are 6 beta, 9 alpha-dihydroxyprogesterone; 6 beta, 14 alpha-dihydroxyprogesterone; 9 alpha, 14 alpha-dihydroxyprogesterone; 9 alpha, 15 beta-dihydroxyprogesterone, 14 alpha, 15 alpha-dihydroxyprogesterone; 14 alpha, 15 beta-dihydroxyprogesterone; 14 alpha-hydroxypregna-4,6-diene-3,20-dione and 15 alpha-hydroxyandrostene-3,17-dione. All compounds, except the last one, are biologically rare because they are not products of mammalian progesterone or androstenedione metabolism. They would be difficult to synthesise chemically. We believe that the compounds, 9 alpha, 15 beta-dihydroxyprogesterone; 14 alpha, 15 alpha-dihydroxyprogesterone and 14 alpha-hydroxypregn-4,6-diene-3,20-dione, have not been reported previously as microbial transformation products of progesterone.