Prostatic cancer treated by external irradiation at the Rotterdam Radiotherapy Institute.
Two-hundred-seventy-nine patients, mainly with prostatic cancer category T3NXM0 and T4NXM0 , have been treated by a full-course of external irradiation. Five- and 10-year survivals and relapse-free survivals are comparable to reports in literature. Complications in about 24% of all cases are acceptable but might be reduced in future by more sophisticated techniques. Important prognostic factors were the T-category of the primary, the histological grade according to WHO and according to Gleason, and to a lesser extent vascular invasion in the biopsy specimen and the diagnostic procedure: either transurethral resection or needle biopsy. Combinations of WHO-grade, Gleason-grade and T-category are possibly the best prognosticators . Persisting, positive transrectal cytology after the irradiation is probably an indicator of a slightly increased risk of metastasis. In spite of hormone therapy after evidence of metastasis, prognosis is poor and not significantly influenced by any pre-irradiation prognosticator.


Fine needle aspiration cytology in the diagnosis of mediastinal seminomas.
Fine needle aspiration cytology (FNAC) was employed to diagnose 117 cases of mediastinal tumours from January, 1985 till December, 1994. Six cases were diagnosed as mediastinal seminomas which are rare mediastinal malignant neoplasms. All patients had complete resolution of the mediastinal masses after external beam radiotherapy. Diagnosis of mediastinal masses by FNAC can spare the patients from more invasive diagnostic procedures and help the thoracic surgeons to plan immediate treatment.


Characterization of high affinity binding sites for charybdotoxin in synaptic plasma membranes from rat brain. Evidence for a direct association with an inactivating, voltage-dependent, potassium channel.
Charybdotoxin (ChTX), a potent peptidyl inhibitor of several types of K+ channels, binds to sites in vascular smooth muscle sarcolemma (Vázquez, J., Feigenbaum, P., Katz, G. M., King, V. F., Reuben, J. P., Roy-Contancin, L., Slaughter, R. S., Kaczorowski, G. J., and Garcia, M. L. (1989) J. Biol. Chem. 265, 20902-20909) which are functionally associated with a high conductance Ca2(+)-activated K+ channel (PK,Ca). 125I-ChTX also binds specifically and reversibly to a single class of sites in plasma membranes prepared from rat brain synaptosomes. These sites exhibit a Kd of 25-30 pM, as measured by either equilibrium or kinetic binding protocols and display a maximum density of about 0.3-0.5 pmol/mg of protein. Competition studies with native ChTX yield a Ki of 8 pM for the noniodinated toxin. The highest density of ChTX sites exists in vesicle fractions of plasma membrane origin. Binding of 125I-ChTX is modulated by metal ions that interact with K+ channels: Ba2+, Ca2+, and Cs+ cause inhibition of ChTX binding; Na+ and K+ stimulate binding at low concentration before producing complete inhibition as their concentration is increased. Stimulation of binding is due to an allosteric interaction that decreases Kd whereas inhibition results from an ionic strength effect. Tetraethylammonium ion has no effect on binding, but tetrabutylammonium ion blocks binding with a Ki of 2.5 mM. Different toxins (i.e. alpha-dendrotoxin, noxiustoxin) that inhibit an inactivating, voltage-dependent K+ channel (PK,V) block 125I-ChTX binding in brain. In marked contrast, iberiotoxin, a selective inhibitor of PK,Ca, has no effect on ChTX binding in this preparation. Inhibition of ChTX binding by alpha-dendrotoxin and noxiustoxin results from an allosteric interaction between separate binding sites for these agents and the ChTX receptor. Taken together, these results suggest that the ChTX sites present in brain are associated with PK,V rather than with PK,Ca. Therefore, 125I-ChTX is a useful probe for elucidating the biochemical properties of a number of different types of K+ channels.


Intramolecular vibrational energy redistribution in the highly excited fluoroform molecule: a quantum mechanical study using the multiconfiguration time-dependent Hartree algorithm.
The present paper is devoted to a detailed study of the intramolecular vibrational energy redistribution in fluoroform initiated by a local mode excitation of the CH stretch [nnu(CH) (n=1,...,4)]. All nine internal degrees of freedom are explicitly taken into account and the full quantum mechanical simulation is performed by means of the multiconfiguration time-dependent Hartree algorithm. The existence of different time scales considerably complicates the dynamics. The mode-to-mode energy transfer is analyzed by calculating the evolution of the partial energies of all vibrational modes. This study emphasizes the crucial role played by the two-dimensional FCH bending modes which act as an energy reservoir. The fast energy flow into these bending modes significantly hinders an energy flow from the CH chromophore. Finally, our results are compared with those obtained previously with the wave operator sorting algorithm approach.


The use of low-quality water on the transport and transformation of waste water in irrigation soils.
Waste water use for agricultural production in the semi-arid and arid climate areas is increasingly regarded as a solution for water shortage. Still today many questions remain unanswered about the mid- and long-term effect of irrigation by waste water on plant, soil and human health. In this paper the effect of the use of waste water on the soil hydraulic properties, the solute transport and transformation behaviour is being studied conducting steady state and non-steady state waste water application treatments on undisturbed soil columns and a field plot. Detailed spatial and temporal information on the propagation of water and solute is obtained using tensiometers, soil solute extraction and time domain reflectometry probes. The experimental data are processed using the HYDRUS-2D modeling tool. After calibration, the model is used in a predictive way as to simulate the mid- and long-term effects of the use of treated waste water as irrigation water.


Curcumin inhibits oral squamous cell carcinoma proliferation and invasion via EGFR signaling pathways.
Epidermal growth factor receptor (EGFR) is an effective molecular target of anti-cancer therapies. Curcumin is known to inhibit growth, invasion and metastasis by downregulating EGFR expression in some cancer cells. However, the mechanism underlying the effect of curcumin in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we investigated the efficacy of curcumin on proliferation and invasion in SCC-25 cell line. We also explored the effect of curcumin on the activition of EGFR and its downstream signaling molecules Akt, ERK1/2 and STAT3. Furthermore, we examined the inhibition effect of curcumin on EGF-induced EGFR phosphorylation and SCC-25 cells invasion. Our results showed that curcumin inhibited SCC-25 cells proliferation and induced G2/M phase arrest in a dose-dependent manner. Curcumin also inhibited SCC-25 cells invasion and downregulated MMP-2, MMP-9, uPA and uPAR expression. We further revealed that curcumin regulated the p-EGFR and EGFR downstream signaling molecules including Akt, ERK1/2 and STAT3. Finally, our data showed that crucumin reduced the EGF-induced phosphorylation of EGFR and suppressed EGF-triggered SCC-25 cells invasion. Taken together, our results suggest that curcumin reduced SCC-25 cells proliferation and invasion through inhibiting the phosphorylation of EGFR and EGFR downstream signaling molecules Akt, ERK1/2 and STAT3.


[China's contribution to research and development of antiparasitic products - Inspiration from Nobel Prize in Physiology or Medicine 2015].
Chinese scientist Tu You-you won the Nobel Prize in Physiology or Medicine 2015, due to her outstanding contribution to the discovery of antimalarial drug artemisinin. The discovery of artemisinin is a great breakthrough using modern pharmaceutical technology to excavate ancient Chinese traditional medicine resources, based on government's coordination mechanisms. This article analyzes the research and development status of the current global antiparasitic products, as well as China's needs and strengths in related areas. The authors propose that China should take the advantage of government financing and research capacity to strengthen the research and development of antiparasitic products, so as to contribute more to improving global health equity.


Chlamydia trachomatis genotypes and the Swedish new variant among urogenital Chlamydia trachomatis strains in Finland.
Our aims were to genotype Chlamydia trachomatis strains present in urogenital samples and to investigate the occurrence of the Swedish new variant of C. trachomatis in Finland. We genotyped 160 C. trachomatis positive samples with ompA real-time PCR and analyzed 495 samples for the new variant. The three most prevalent genotypes were E (40%), F (28%), and G (13%). Only two specimens containing bacteria with the variant plasmid were detected. It seems that in Finland the percentage of infections due to genotypes F and G has slightly increased during the last 20 years. Genotypes E and G appear to be more common, and genotypes J/Ja and I/Ia appear to be less common in Europe than in the USA. Although the genotype E was the most common genotype among C. trachomatis strains, the new variant was rarely found in Finland.


Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study.
Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.


Cu(II)-Catalyzed 6π-Photocyclization of Non-6π Substrates.
This research successfully achieved a Cu(II)-catalyzed 6π-photocyclization of non-6π substrates. The photoenolization converts ortho-alkylphenyl alkynl ketones into a triene-type intermediate which undergoes the subsequent 6π-photocyclization to give naphthol as the final product. Cu(II) catalyst facilitates both photoenolization and 6π-photocyclization. This research highlighted the tandem reaction strategy and the importance of metal catalysis in photochemistry.


Basal Autophagy Is Altered in Lagotto Romagnolo Dogs with an ATG4D Mutation.
A missense variant in the autophagy-related ATG4D-gene has been associated with a progressive degenerative neurological disease in Lagotto Romagnolo (LR) dogs. In addition to neural lesions, affected dogs show an extraneural histopathological phenotype characterized by severe cytoplasmic vacuolization, a finding not previously linked with disturbed autophagy in animals. Here we aimed at testing the hypothesis that autophagy is altered in the affected dogs, at reporting the histopathology of extraneural tissues and at excluding lysosomal storage diseases. Basal and starvation-induced autophagy were monitored by Western blotting and immunofluorescence of microtubule associated protein 1A/B light chain3 (LC3) in fibroblasts from 2 affected dogs. The extraneural findings of 9 euthanized LRs and skin biopsies from 4 living affected LRs were examined by light microscopy, electron microscopy, and immunohistochemistry (IHC), using antibodies against autophagosomal membranes (LC3), autophagic cargo (p62), and lysosomal membranes (LAMP2). Biochemical screening of urine and fibroblasts of 2 affected dogs was performed. Under basal conditions, the affected fibroblasts contained significantly more LC3-II and LC3-positive vesicles than did the controls. Morphologically, several cells, including serous secretory epithelium, endothelial cells, pericytes, plasma cells, and macrophages, contained cytoplasmic vacuoles with an ultrastructure resembling enlarged amphisomes, endosomes, or multivesicular bodies. IHC showed strong membranous LAMP2 positivity only in sweat glands. The results show that basal but not induced autophagy is altered in affected fibroblasts. The ultrastructure of affected cells is compatible with altered autophagic and endo-lysosomal vesicular traffic. The findings in this spontaneous disease provide insight into possible tissue-specific roles of basal autophagy.


Budd-Chiari syndrome caused by latent hepatic metastasis from a thymoma.
A 34-year-old woman visited our hospital because she had had abdominal bloating for 2 months. She had been diagnosed with invasive thymoma (WHO pathological type B2), for which she had undergone chemotherapy and total thymectomy 10 years previously. Six years previously, pleural dissemination was diagnosed and she had undergone right extra-pleural pneumonectomy. On presentation to our hospital, abdominal computed tomography and ultrasound scans revealed abundant ascites and a huge liver lesion, likely a metastasis from her thymoma, obstructing the inferior vena cava. The serum-ascites albumin gradient was high at 1.4 g/dL, which indicated portal hypertension. We diagnosed Budd-Chiari syndrome caused by liver metastasis from a previous thymoma. Steroid therapy resulted in shrinkage of her liver tumor and a marked decrease in her ascites. Although rare, Budd-Chiari syndrome caused by liver metastasis from a thymoma is a possible serious complication of advanced invasive thymoma.


Mass spectrometric study and modeling of the thermodynamic properties in the Gd2 O3 -ZrO2 -HfO2 system at high temperatures.
Materials based on the Gd2 O3 -ZrO2 -HfO2 system are promising for a wide range of high-temperature technological applications, such as for obtaining thermal barrier coatings in the aviation and space industry, as well as advanced materials in nuclear power applications. Experimental studies of the ceramics based on this system by the Knudsen effusion mass spectrometric method provides such valuable information as the vapor composition over the samples and enables derivation of the thermodynamic functions. Samples of ceramics in the Gd2 O3 -ZrO2 -HfO2 system were synthesized and analyzed by X-ray fluorescence and diffraction techniques. The vaporization processes and partial pressures of the vapor species over the samples were obtained by the high-temperature mass spectrometric method using the ion current comparison method. The derived thermodynamic functions were optimized within the Generalized Lattice Theory of Associated Solutions (GLTAS) approach. At the temperature of 2600 K, the GdO, ZrO, ZrO2 , HfO, and O vapor species were found over the samples, but only for the GdO and ZrO species were accurate experimental data on the partial pressures obtained. In all the ceramic samples, the Gd2 O3 activity was determined. On this experimental basis, modeling within the GLTAS approach was performed. It allowed the evaluation of the Gd2 O3 , ZrO2 , and HfO2 activities in the system under study and a rough approximation of the excess Gibbs energy as a function of composition to be obtained. At 2600 K the Gd2 O3 -ZrO2 -HfO2 system is characterized by negative deviations of its thermodynamic properties from the ideal behavior. Consistency of the obtained modeling results indicate reasonable uniformity of the energy parameters of the lattice model derived in calculations of the hafnia-containing oxide systems, which may be used in further modeling of multicomponent systems.


Multiple components of photodynamic therapy can phosphorylate Akt.
A growing number of clinically relevant molecular and cellular responses are observed following photodynamic therapy (PDT). PDT-mediated oxidative stress and PDT-induced tissue hypoxia can elicit the transcriptional and/or translational expression of genes associated with cellular stress, inflammation, angiogenesis, immuno-modulation, apoptosis and signal transduction. One of the signaling molecules activated by oxidative stress is Akt/protein kinase B. Phosphorylation of Akt/protein kinase B activates this signaling molecule and induces a survival response in effected cells and tissue. We hypothesized that PDT using Photofrin (PH) as the photosensitizer could also induce increased levels of Akt phosphorylation. Results from our initial set of experiments demonstrated that in vitro and in vivo PDT treatments induced Akt phosphorylation. Interestingly, incubation of mouse and human breast cancer cells with the porphyrin-based photosensitizer, PH, increased the expression of Akt phosphorylation in the absence of light. Exposure of the corresponding mouse and human-derived breast cancer tumors growing in mice to 630 nm light in the absence of PH administration also induced Akt phosphorylation. These results demonstrate that individual components of the PDT process, photosensitizer alone and light alone, as well as the complete PDT procedure can activate the Akt signaling pathway.


[Krakow Program for Secondary Prevention of Ischaemic Heart Disease. Part I. Genesis and objectives].
In recent years a number of studies concerning ischaemic heart disease prevention have been published. Evidence from clinical and epidemiological research has led to the formation of new guidelines, especially in the field of secondary prevention. Polish Cardiac Society also published recommendations on prevention of ischaemic heart disease. Relatively little is known about how well physicians in Poland follow the guidelines. No comprehensive studies concerning risk factories management after myocardial infarction or myocardial revascularization has been conducted in Poland. Patients with established coronary heart disease were deemed to be the top priority for prevention. However, little is known about quality of medical care in this high risk population. Therefore the Cracovian Program for Secondary Prevention of Ischaemic Heart Disease was planned. The aims of the Cracovian Program are: to monitor quality of clinical care (both in clinical and general practice) in the field of secondary prevention of ischaemic heart disease, and to assess factors influencing quality of medical care. The secondary aim of the survey is to improve integration of secondary prevention into clinical practice through meetings with physicians from Cracow cardiology departments and general practitioners, as well as to improve patient compliance and motivating them to change their lifestyle. In the first stage, which was carried out in 1997-98, an evaluation was conducted to access the realization of recommendations concerning secondary prevention. An assessment of integration of ischaemic heart disease prevention into clinical practice can now be performed. The genesis, aims and methods of the Cracovian Program for Secondary Prevention of Ischaemic Heart Disease are discussed in this paper. The quality of hospital, as well as postdischarge care in the field of secondary prevention is described in the next two publications.


Infectious coryza: cross-protection studies, using seven strains of Haemophilus gallinarum.
Bacterins prepared from 7 strains of Haemophilus gallinarum were used to immunized chickens for cross-protection studies. Three distinct immunotypes were distinguished. Slight protection between immunotypes was evident for some strains. Airsacculitis could be prevented by use of these bacterins; however, prevention was related to immunotype specificity. Hyaluronic acid found in 2 strains rendered them inagglutinable in homologous antiserums. Treatment with hyaluronidase rendered them agglutinable.


Practice variation in the Dutch long-term care and the role of supply-sensitive care: Is access to the Dutch long-term care equitable?
Universal access and generous coverage are important goals of the Dutch long-term care (LTC) system. It is a legal requirement that everyone eligible for LTC should be able to receive it. Institutional care (IC) made up for 90% of Dutch LTC spending. To investigate whether access to IC is as equitable as the Dutch government aspires, we explored practice variation in entitlements to IC across Dutch regions. We used a unique dataset that included all individual applications for Dutch LTC in January 2010-December 2013 (N = 3,373,358). This dataset enabled an accurate identification of the need for care. We examined the local variation in the probability of being granted long-term IC and in the intensity of the care granted given that individuals have applied for LTC. We also investigated whether the variation observed was related to differences in the local availability of care facilities. Although our analyses indicated the presence of some practice variation, its magnitude was very small by national and international standards (up to 3%). Only a minor part of the practice variation could be accounted for by local supply differences in care facilities. Overall, we conclude that, unlike many other developed countries, the Dutch system ensured equitable access to long-term IC.


Non-invasive follow-up of a coronary artery pseudoaneurysm after percutaneous transluminal coronary rotational atherectomy (PTCRA).
Percutaneous transluminal coronary rotational atherectomy (PTCRA) is an established treatment forvery calcified and/or undilatable coronary lesions. In contrast to data from directional coronary atherectomy (DCA) procedures, coronary artery aneurysms (CAA) or pseudoaneurysms have not routinely been described as a complication after PTCRA. We present a case of a 74-year-old patient, with a major CAA, found on a routine control coronary angiogram 4 months after a PTCRA of LAD complicated by a coronary perforation. A conservative management guided by coronary CT angiography is proposed.


Bone Mineral Density and Fracture Risk Assessment to Optimize Prosthesis Selection in Total Hip Replacement.
The variability in patient outcome and propensity for surgical complications in total hip replacement (THR) necessitates the development of a comprehensive, quantitative methodology for prescribing the optimal type of prosthetic stem: cemented or cementless. The objective of the research presented herein was to describe a novel approach to this problem as a first step towards creating a patient-specific, presurgical application for determining the optimal prosthesis procedure. Finite element analysis (FEA) and bone mineral density (BMD) calculations were performed with ten voluntary primary THR patients to estimate the status of their operative femurs before surgery. A compilation model of the press-fitting procedure was generated to define a fracture risk index (FRI) from incurred forces on the periprosthetic femoral head. Comparing these values to patient age, sex, and gender elicited a high degree of variability between patients grouped by implant procedure, reinforcing the notion that age and gender alone are poor indicators for prescribing prosthesis type. Additionally, correlating FRI and BMD measurements indicated that at least two of the ten patients may have received nonideal implants. This investigation highlights the utility of our model as a foundation for presurgical software applications to assist orthopedic surgeons with selecting THR prostheses.


Real-Time Monitoring and Control of Nanoparticle Formation.
Methods capable of controlling synthesis at the level of an individual nanoparticle are a key step toward improved reproducibility and scalability in engineering complex nanomaterials. To address this, we combine the spatially patterned activation of the photoreductant sodium pyruvate with interferometric scattering microscopy to achieve fast, label-free monitoring and control of hundreds of gold nanoparticles in real time. Individual particle growth kinetics are well-described by a two-step nucleation-autocatalysis model but with a distribution of individual rate constants that change with reaction conditions.


The 8 dimensions of quality.
Healthcare providers can better develop strategies for achieving and maintaining high-quality care by reviewing quality of care laws and metrics in relation to eight dimensions of quality: Reporting. Documentation. Quantity or access to care. Patient satisfaction. Provider reputation. Clinical processes. Utilization review. Medical necessity determinations.


Management of persistent vaginitis.
With vaginitis remaining a common condition that leads women to seek care, it is not surprising that some women develop chronic vulvovaginal problems that are difficult to diagnose and treat. With a differential diagnosis that encompasses vulvar disorders and infectious and noninfectious causes of vaginitis, accurate diagnosis is the cornerstone of choosing effective therapy. Evaluation should include a symptom-specific history, careful vulvar and vaginal examination, and office-based tests (vaginal pH, amine test, saline and 10% potassium hydroxide microscopy). Ancillary tests, especially yeast culture with speciation, are frequently crucial to obtaining a correct diagnosis. A heavy but normal physiologic discharge can be determined by excluding other causes. With vulvovaginal candidiasis, differentiating between Candida albicans and non-albicans Candida infection has important treatment ramifications. Most patients with C albicans infections can be successfully treated with maintenance antifungal therapy, usually with fluconazole. Although many non-albicans Candida, particularly Candida glabrata, may at times be innocent bystanders, vaginal boric acid therapy is an effective first choice for many true non-albicans Candida infections. Recurrent bacterial vaginosis, a difficult therapeutic challenge, can often be controlled with maintenance therapy. Multiple options, especially high-dose tinidazole, have been used for metronidazole-resistant trichomoniasis. With the aging of the U.S. population, atrophic vaginitis and desquamative inflammatory vaginitis, both associated with hypoestrogenism, are encountered frequently in women with persistent vaginitis.


Brownian motion exhibiting absolute negative mobility.
We consider a single Brownian particle in a spatially symmetric, periodic system far from thermal equilibrium. This setup can be readily realized experimentally. Upon application of an external static force F, the average particle velocity is negative for F>0 and positive for F<0 (absolute negative mobility).


Pigmented medulloepithelioma: report of a case and review of the literature.
A 9-year-old male child had a IV ventricular medulloepithelioma of classical histology, showing tubulopapillary and undifferentiated areas. The unusual feature, however, was the presence of melanin pigmentation in the cells, which was further confirmed by electron microscopy. So far 28 cases of medulloepithelioma have been reported in the English literature. However, none of them showed melanin pigmentation. To the best of our knowledge this is the first case of pigmented medulloepithelioma in the English literature.


A comparative in vitro study on fluoride release and water sorption of different flowable esthetic restorative materials.
The objective of the study was to evaluate fluoride release and water sorption of three flowable esthetic restorative materials: a giomer, a fluoride-releasing resin composite, and a nonfluoridated resin composite. Ten samples from a giomer, a fluoride releasing nano-hybrid, and a nonfluoridated nano-hybrid composite were prepared and immersed in deionized water. Fluoride measurements were done using an ion-specific electrode attached to a microprocessor-based fluoride meter after 1 day, 1 week, and 4 weeks. Another thirty samples were made and placed in desiccators. Water sorption was calculated by weighing the specimens before and after water immersion for 1 day, 1 week, and 4 weeks. Data analysis was done using two-way ANOVA, paired t-test (P < 0.05), and Pearson's correlation coefficient to calculate correlations between fluoride release and water sorption. The highest fluoride release was from giomer after 1 day, it was statistically significant from all other groups. Both nano-hybrid composites after 1 day showed significantly lower water sorption which was different than all the other groups. Pearson's correlation showed no significant correlations between fluoride release and water sorption. Fluoride release is material and time dependent, while water sorption is material dependent.


Intentional motor phantom limb syndrome.
To investigate the clinical and anatomic correlates of a previously unreported form of chronic supernumerary phantom limb, which developed only in association with motor intent directed at a hemiplegic-anesthetic upper limb. We explored the phenomenology of the phantom illusion in the light of motor control models. Hemodynamic correlates of supernumerary phantom limb were studied with an fMRI sensorimotor paradigm consisting of finger-thumb opposition movements. The kinesthetic-proprioceptive illusion of a third arm was triggered by any attempt to move the paretic limb, by bimanual actions, and by motor imagery involving the nonfunctional limb. The responsible lesion destroyed the posterior part of the posterior limb of the internal capsule on the opposite side, damaging corticospinal and thalamocortical tracts. Comparison between fMRI signals performed during virtual movement of the phantom hand vs imaginary movement of the paretic hand showed increased activation in thalamus and caudate nucleus in the first condition. A preserved sense of agency provided by intact premotor processes translating intention into action may lead to the vivid feeling of movement in a paralyzed limb, similar to kinesthetic illusions in amputees. The interruption of thalamic afferences may explain the persistence and stability of the phantom by preventing any correction of the mismatch between expected and effective movement. The increased blood oxygen level-dependent (BOLD) signal in the basal ganglia-thalamus-cortex pathway during movement of the supernumerary hand may reflect an abnormal closed-loop functioning of the thalamocortical system underlying the phantom phenomenon.


Development of classification criteria for hand osteoarthritis: comparative analyses of persons with and without hand osteoarthritis.
Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA. In a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC). Strong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies. Differences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups.


Sleep complaints are associated with increased suicide risk independently of psychiatric disorders: results from a national 3-year prospective study.
Prior research suggests that sleep disturbances are associated with increased risk of suicide. However, sleep disturbances are associated with a wide range of psychiatric disorders, and it is unknown whether this association is independent of psychopathology. In a large nationally representative prospective survey, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we used structural equation modeling to examine the shared and specific effects of three sleep complaints (i.e., trouble falling asleep, early morning awakening, and hypersomnia) on the 3-year occurrence of attempting suicide. Because psychiatric disorders increase the risk of suicide attempt almost exclusively through a general psychopathology factor representing their shared effect, covariates included that factor, prior history of suicide attempt, and a wide range of sociodemographic and clinical characteristics. The 3-year prevalence rate of suicide attempt was 0.6% (n = 241). Compared with participants who did not attempt suicide between the two waves, those who did reported significantly more frequently having trouble falling asleep (44.6% vs. 16.6%), early morning awakening (38.9% vs. 12.7%), and hypersomnia (35.0% vs. 10.7%). Following adjustments, effects of sleep complaints on this risk were significant and exerted almost exclusively through a general sleep complaints factor representing the shared effect across all sleep complaints. There were no residual associations of any individual sleep complaint with attempting suicide above that association. Sleep complaints are associated with an increased risk of attempting suicide independently of psychopathology, and should be included in suicide risk assessments as these symptoms may provide targets for reducing the risks of suicidal behaviors.


Pleiotropic effects of Ubp6 loss on drug sensitivities and yeast prion are due to depletion of the free ubiquitin pool.
Mutation of the mouse Usp14 gene, encoding the homolog of yeast deubiquitinating enzyme Ubp6, causes ataxia. Here we show that deletion of the UBP6 gene in Saccharomyces cerevisiae causes sensitivity to a broad range of toxic compounds and antagonizes phenotypic expression and de novo induction of the yeast prion [PSI+], a functionally defective self-perpetuating isoform of the translation termination factor Sup35. Conversely, overexpression of ubiquitin (Ub) increases phenotypic expression and induction of [PSI+] in the wild type cells and suppresses all tested ubp6Delta defects, indicating that they are primarily due to depletion of cellular Ub levels. Several lines of evidence suggest that Ubp6 functions on the proteasome. First, Ub levels in the ubp6Delta cells can be partly restored by proteasome inhibitors, suggesting that deletion of Ubp6 decreases Ub levels by increasing proteasome-dependent degradation of Ub. Second, fluorescence microscopy analysis shows that Ubp6-GFP fusion protein is localized to the nucleus of yeast cell, as are most proteasomes. Third, the N-terminal Ub-like domain, although it is not required for nuclear localization of Ubp6, targets Ubp6 to the proteasome and cannot be functionally replaced by Ub. The human ortholog of Ubp6, USP14, probably plays a similar role in higher eukaryotes, since it fully compensates for ubp6Delta defects and binds to the yeast proteasome. These data link the Ub system to prion expression and propagation and have broad implications for other neuronal inclusion body diseases.


An approach for estimating workplace exposure to o-toluidine, aniline, and nitrobenzene.
A comprehensive approach to estimating worker exposure to o-toluidine, aniline, and nitrobenzene using a combination of surface wipe, dermal badge, and air samples is described. Desorption of each sample was accomplished with ethanol followed by analyses using capillary gas chromatography with flame ionization detection. Analyte recovery was maximized when the gauze wipes and dermal badges were immediately desorbed in ethanol after sample collection. Sample collection of the airborne analytes was improved over previous solid sorbent samples by using a sampling train consisting of an acid-treated glass fiber filter in series with a large capacity silica gel tube (520/260 mg). The greatest recoveries of aniline and o-toluidine were from the acid-treated glass fiber filters and nitrobenzene from the large capacity silica gel sorbent tubes. The limit of detection for each analyte (1 micrograms) was approximately 10 times more sensitive than reported in previous National Institute for Occupational Safety and Health methods. Analyte recoveries for air samples were greatest under conditions of moderate relative humidity (53%), moderate sample volumes (< 50 L), and low flow rates (0.2 L/min). The overall relative standard deviation of the analytical method was 4.3%.


Clearing the air: A study of cannabis-related presentations to urban Alberta emergency departments following legalization.
Non-medical cannabis recently became legal for adults in Canada. Legalization provides opportunity to investigate the public health effects of national cannabis legalization on presentations to emergency departments (EDs). Our study aimed to explore association between cannabis-related ED presentations, poison control and telemedicine calls, and cannabis legalization. Data were collected from the National Ambulatory Care Reporting System from October 1, 2013, to July 31, 2019, for 14 urban Alberta EDs, from Alberta poison control, and from HealthLink, a public telehealth service covering all of Alberta. Visitation data were obtained to compare pre- and post-legalization periods. An interrupted time-series analysis accounting for existing trends was completed, in addition to the incidence rate ratio (IRR) and relative risk calculation (to evaluate changes in co-diagnoses). Although only 3 of every 1,000 ED visits within the time period were attributed to cannabis, the number of cannabis-related ED presentations increased post-legalization by 3.1 (range -11.5 to 12.6) visits per ED per month (IRR 1.45, 95% confidence interval [CI]; 1.39, 1.51; absolute level change: 43.5 visits per month, 95% CI; 26.5, 60.4). Cannabis-related calls to poison control also increased (IRR 1.87, 95% CI; 1.55, 2.37; absolute level change: 4.0 calls per month, 95% CI; 0.1, 7.9). Lastly, we observed increases in cannabis-related hyperemesis, unintentional ingestion, and individuals leaving the ED pre-treatment. We also observed a decrease in co-ingestant use. Overall, Canadian cannabis legalization was associated with small increases in urban Alberta cannabis-related ED visits and calls to a poison control centre.


Are all patients with psoriasis at increased risk for coronary artery disease?
Associations have been recently recognized between psoriasis and an increased incidence of atherosclerotic diseases. However, there are scarce data on the prevalence of coronary lesions in patients with psoriasis. The aim of this study was to identify the calcified and non-calcified atherosclerotic coronary lesions in patients with psoriasis compared to controls. Forty patients with psoriasis and 42 control subjects matched for age, sex, and cardiovascular risk profile were included in this case-control study. Coronary lesions were evaluated by a 128-slice dual source multidetector computed tomography scanner. Coronary calcification scoring was calculated according to the Agatston score. The prevalence of atherosclerotic coronary lesions (psoriasis: 15%, controls: 16.7%; P = 0.83) and the mean coronary calcification scoring (psoriasis: 9.9 ± 35.2 Agatston unit, controls 2.8 ± 12.0 Agatston unit; P = 0.81) did not show a significant difference between the two groups. Multivariate analysis identified age ≥48 years and fasting blood glucose ≥99.0 mg/dl as independent predictors of coronary artery disease in patients with psoriasis (F = 30.9; P = 0.001; adjusted R(2) = 0.49). Patients with psoriasis had the same prevalence of calcified and non-calcified atherosclerotic coronary lesions as compared to controls. Our results demonstrated the necessity of considering the age and fasting blood glucose of patients with psoriasis in a decision for further cardiovascular evaluation.


Association between depressive mood and cigarette smoking in a large Italian sample of smokers intending to quit: implications for treatment.
The aim of the study is to assess the prevalence and degree of depression at baseline of a large cohort of smokers intending to quit. A cross-sectional investigation was carried out on a population of 757 smokers attending the Medical Service for Addictive Disorders, at Verona University Hospital. The degree of nicotine addiction was measured by the Fagerstrom Test of Nicotine Dependence (FTND) and current mood tested by the Self-rating Depression Scale (SDS), a commonly used and well validated instrument to assess depressive mood. Two hundred and twenty-two subjects (30.3%) were depressed at baseline (SDS test score > or = 50). Bivariate analysis, using the SDs score dichotomised at the cut-off of 50 as dependent variable, shows that female gender (p=0.01) and widowhood (p<0.001) were correlated to depression. Logistic regression analysis confirms the correlation between depression and female gender (OR=2.03, IC 95%=1.42-2.88, p<0.001) and between depression and widowhood, with the greatest risk of depression among widows and widowers (OR=3.22, IC 95%=1.01-10.27, p<0.048). The study showed a high degree of pre-treatment depression in smokers intending to quit. Although the association between depression and nicotine dependence has been consistently reported many times, and it is well known that depressed subjects find it more difficult to quit, most guidelines seem not to consider this connection. These findings suggest the need for baseline assessment of depression by screening all smokers seeking assistance in quitting, a priority health objective because smoking is the number one avoidable killer in developed countries.


Functional MRI in the investigation of blast-related traumatic brain injury.
This review focuses on the application of functional magnetic resonance imaging (fMRI) to the investigation of blast-related traumatic brain injury (bTBI). Relatively little is known about the exact mechanisms of neurophysiological injury and pathological and functional sequelae of bTBI. Furthermore, in mild bTBI, standard anatomical imaging techniques (MRI and computed tomography) generally fail to show focal lesions and most of the symptoms present as subjective clinical functional deficits. Therefore, an objective test of brain functionality has great potential to aid in patient diagnosis and provide a sensitive measurement to monitor disease progression and treatment. The goal of this review is to highlight the relevant body of blast-related TBI literature and present suggestions and considerations in the development of fMRI studies for the investigation of bTBI. The review begins with a summary of recent bTBI publications followed by discussions of various elements of blast-related injury. Brief reviews of some fMRI techniques that focus on mental processes commonly disrupted by bTBI, including working memory, selective attention, and emotional processing, are presented in addition to a short review of resting state fMRI. Potential strengths and weaknesses of these approaches as regards bTBI are discussed. Finally, this review presents considerations that must be made when designing fMRI studies for bTBI populations, given the heterogeneous nature of bTBI and its high rate of comorbidity with other physical and psychological injuries.


[Posterior reversible encephalopathy in infancy].
Posterior reversible encephalopathy (PRE) is a radiological clinical syndrome that was initially reported in adults and which is characterised by seizures, headache, visual disorders, decreased awareness and anomalous neuroimages. It is an acute transient disorder. The most frequent causes are arterial hypertension (AHT) and immunosuppressive therapy. The aim of this study is to describe the characteristics of PRE in patients of paediatric age. From a total of 109,267 patients admitted to hospital between 1/1/1999 and 1/8/2002, we reviewed the case histories of seven patients who satisfied PRE criteria. Seven patients presented AHT associated with kidney disease (6) and with an undetermined causation (1). The initial symptoms were vomiting in seven and headaches in five patients, followed by seizures in six cases, which were partial (4), generalised (1), motor status (1). Five of them suffered visual disorders. All of them had decreased awareness and one of them required the assistance of mechanical ventilation. The condition cleared within 3 to 12 days after antihypertensive therapy. The anomalies that showed up in the neuroimaging studies (hypodensities in CAT, hyperintensities in T2 and hypointensities in T1 in MR) revealed the involvement of cortical and parieto occipital cortico subcortical regions asymmetrically. Frontal (2), temporal (2) and cerebellous (1) involvement was also observed. These disorders disappeared in patients from whom control images were obtained. PRE must be considered in the presence of the symptoms and the anomalous neuroimages described above, when associated with acute AHT. With correct management of arterial hypertension it is possible to clear the neurological symptoms and normalise the neuroimages that confirm this diagnosis.


What if the Women's Health Initiative had used transdermal estradiol and oral progesterone instead?
The author considers hypothetical comparisons between oral conjugated equine estrogens and transdermal estradiol and between oral medroxyprogesterone acetate and oral micronized progesterone for their effects on four primary outcomes of the Women's Health Initiative (WHI): cardiovascular disease risk, cerebrovascular disease risk, venous thromboembolism risk, and breast cancer risk. Although the discussion in this article focuses on transdermal estradiol delivered through patches, gels, or lotions, it could be broadened to include all forms of nonoral estrogen administration. After a brief review of the WHI and a survey of the relevant literature in which the safety of these various hormone therapies is assessed or compared, the author uses statistical methods to ascertain the attributable risk of venous thromboembolism for transdermal estradiol versus oral hormone therapy and imputes those risks into the WHI primary outcomes.


Estimating the population mutation rate from a de novo assembled Bactrian camel genome and cross-species comparison with dromedary ESTs.
The Bactrian camel (Camelus bactrianus) and the dromedary (Camelus dromedarius) are among the last species that have been domesticated around 3000-6000 years ago. During domestication, strong artificial (anthropogenic) selection has shaped the livestock, creating a huge amount of phenotypes and breeds. Hence, domestic animals represent a unique resource to understand the genetic basis of phenotypic variation and adaptation. Similar to its late domestication history, the Bactrian camel is also among the last livestock animals to have its genome sequenced and deciphered. As no genomic data have been available until recently, we generated a de novo assembly by shotgun sequencing of a single male Bactrian camel. We obtained 1.6 Gb genomic sequences, which correspond to more than half of the Bactrian camel's genome. The aim of this study was to identify heterozygous single-nucleotide polymorphisms (SNPs) and to estimate population parameters and nucleotide diversity based on an individual camel. With an average 6.6-fold coverage, we detected over 116 000 heterozygous SNPs and recorded a genome-wide nucleotide diversity similar to that of other domesticated ungulates. More than 20 000 (85%) dromedary expressed sequence tags successfully aligned to our genomic draft. Our results provide a template for future association studies targeting economically relevant traits and to identify changes underlying the process of camel domestication and environmental adaptation.


Clinicopathological Characteristics and Survival Outcomes of Mammary Paget's Disease: A Retrospective Study Based on a Chinese Population.
Mammary Paget's disease (PD) is a rare type of breast cancer. Most cases of PD are presented with underlying ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IDC). This study aimed to investigate the clinicopathological characteristics and survival outcomes of PD patients. A total of 406 patients diagnosed with PD with IDC/DCIS at Fudan University Shanghai Cancer Center (FUSCC) were recruited as the PD group, 1218 patients diagnosed with IDC/DCIS alone during the same period were selected as the non-PD group, and the clinicopathological results of these two groups were compared. The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the clinicopathological features between PD and non-PD patients for validation. Compared with the non-PD group, the PD group was much more likely to have larger (≥2 cm: 43.1% vs 35.5%, P < 0.001), less hormone receptor (HR)-positive (68.5% vs 26.6%, P < 0.001), more human epidermal growth factor receptor-2 (HER-2)-positive (70.7% vs 27.5%, P < 0.001) and higher Ki-67 proportion (51.5% vs 42.5%, P < 0.001) tumors. The HER-2 overexpression subtype accounted for the largest proportion in the PD-IDC group and the lowest proportion in the non-PD-IDC group (54% vs 8%, P < 0.01). Moreover, the PD group had significantly worse disease-free survival (DFS) than the non-PD group (5-year DFS: 91.8% vs 97.3%, P = 0.001), and the SEER database showed a similar trend. Univariate and multivariate Cox regression analyses demonstrated that PD was an independent poor-risk factor. Our matched study showed that the PD group had worse survival than the non-PD group after excluding age, HR, HER-2, tumor size and lymph node status. PD with IDC/DCIS is associated with more aggressive tumor characteristics and worse survival outcomes. More than half of PD breast cancers are HER-2 overexpression subtype. PD is an independent poor-risk factor for breast cancer survival.


Usefulness of a Cook® airway exchange catheter in laryngeal mask airway-guided fiberoptic intubation in a neonate with Pierre Robin syndrome -A case report-.
The case of a 33-day-old boy with Pierre Robin syndrome using a Cook® airway exchange catheter in laryngeal mask airway-guided fiberoptic intubation is presented. After induction with sevoflurane, classical reusable laryngeal mask airway (LMA) #1 was inserted and ultrathin fiberoptic bronchoscope (FOB) was passed through. A Cook® airway exchange catheter (1.6 mm ID, 2.7 mm OD) was passed through the LMA under the guidance of the FOB but failed to enter the trachea despite many trials. Then, an endotracheal tube (3.0 mm ID) was mounted on the FOB and railroaded over the FOB. After successful intubation, the Cook® airway exchange catheter was placed in the midtrachea through the lumen of the endotracheal tube. Even though the tracheal tube was accidentally displaced out of the trachea during LMA removal, the endotracheal tube could be easily railroaded over the airway exchange catheter.


Improvement of coenzyme Q(10) production by increasing the NADH/NAD(+) ratio in Agrobacterium tumefaciens.
Previously screened CoQ(10)-overproducing Agrobacterium tumefaciens A603-35 showed a relatively high NADH/NAD(+) ratio (1.1), as compared to parental strain C58 (0.2) when we increased the expression levels of NADH-generating enzymes. Also, the intracellular NADH/NAD(+) ratio showed a positive correlation with the CoQ(10) content in A603-35. Overexpression of glyceraldehyde 3-phosphate dehydrogenase in A603-35 shifted the NADH/NAD(+) ratio at 48 h from 0.8 to 1.2, and thus the CoQ(10) content in flask culture increased from 2.16 to 3.63 mg/g DCW. Due to the addition of hydroxybutyrate to the culture media, the intracellular NADH/NAD(+) ratio in A603-35-gapA shifted from 1.2 to 1.4, which led to an increase CoQ(10) content (5.27 mg/g DCW).


Pharmacological activation of mGlu2/3 metabotropic glutamate receptors protects retinal neurons against anoxic damage in the goldfish Carassius auratus.
We examined the expression of mGlu2/3 metabotropic glutamate receptors in the retina of the goldfish Carassius auratus. mGlu2/3 receptors were expressed in all retinal layers internal to the photoreceptor layer, particularly in the outer and inner nuclear layers. Although the goldfish brain is able to tolerate prolonged periods of anoxia, we examined whether anoxia could induce retinal damage. Three hours of anoxia induced in the retina the development of apoptotic cell death, as assessed 48 h later by TUNEL staining. TUNEL-positive cells were particularly found in the inner and outer nuclear layers, and were also present in the ganglion cell layer. Pharmacological activation of mGlu2/3 receptors by systemic injection of LY379268 (0.5 mg/kg, i.p., 15 min before the onset of anoxia) substantially protected retinas against anoxia-induced cell death. In contrast, systemic injection of the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p., 15 min before the onset of anoxia), significantly amplified cell death. Finally, as mGlu2/3 receptors are implicated in the control of extracellular glutamate concentrations, we examined the stimulation of glutamate release in isolated goldfish retinas. Depolarizing medium containing 30 mM KCl led to a significant increase in glutamate release, which was substantially reduced by LY379268. We conclude that activation of mGlu2/3 receptors may provide a major defensive mechanism against ischemic/anoxic retinal damage.


A highly effective and versatile technology for the isolation of RNAs from grapevines and other woody perennials for use in virus diagnostics.
Isolation of pure RNA from woody perennials, especially fruit crops such as grapevine rich in complex secondary metabolites, has remained very challenging. Lack of effective RNA isolation technology has resulted in difficulties in viral diagnosis and discovery as well as studies on many biological processes of these highly important woody plants. It is imperative to develop and refine methodologies with which large amounts of pure nucleic acids can be readily isolated from woody perennials. We compared five commonly used RNA isolation kits in isolating total RNA from twelve species of woody perennials. We made modifications to select RNA isolation systems to simplify and improve their efficiency in RNA isolation. The yield and quality of isolated RNAs were assessed via gel electrophoresis and spectrophotometric measurement. We also performed RT-PCR and RT-qPCR to detect several major viruses from grapevines. Two of the kits were shown to be the best in both the yield and quality of the isolated RNA from all twelve woody species. Using disposable extraction bags for tissue homogenization not only improved the yield without affecting quality, but also made the RNA isolation technology simpler, less costly, and suitable for adoption by many potential users with facility limitations. This system was successfully applied to a wide range of woody plants, including fruit crops, ornamentals and timber trees. Inclusion of polyvinylpyrrolidone in the extraction buffer drastically improved the performance of the system in isolating total RNA from old grapevine leaves collected later in the season. This modification made our system highly effective in isolating quality RNA from grapevine leaves throughout the entire growing season. We further demonstrated that the resulting nucleic acid preparations are suitable for detection of several major grapevine viruses with RNA or DNA genomes using PCR, RT-PCR and qPCR as well as for assays on plant microRNAs. This improved RNA isolation system would have wide applications in viral diagnostics and discovery, studies on gene expression and regulation, transcriptomics, and small RNA biology in grapevines. We believe this system will also be useful in diverse applications pertaining to research on many other woody perennials and recalcitrant plant species.


Modulation of cellular tropism and innate antiviral response by viral glycans.
Arthropod-borne viruses (arboviruses) are a significant cause of human and animal disease worldwide. Multiple interactions between virus and the host innate immune system ultimately determine the pathogenesis and clinical outcome of the infection. Evidence is rapidly emerging that suggests viral glycans play a key role in viral pathogenesis by regulating host cell tropism and interactions with the host innate immune response. Glycan-mediated interactions are especially important for arboviruses which must adapt to variable glycosylation systems and cellular receptors within both vertebrate and invertebrate hosts. This review focuses on emerging evidence which supports a crucial role for viral glycans in mediating host cell tropism and regulating the innate antiviral response.


Primary radio(chemo)therapy for esophageal cancer in elderly patients: are efficiency and toxicity comparable with younger patients?
In elderly patients with esophageal cancer (EC), esophagectomy is associated with an increased mortality, and therefore these patients are often treated with definite (chemo)radiation. The purpose of this study was to assess the toxicity and efficiency of definite radio(chemo)therapy in patients >75 years compared with definite radio(chemo)therapy in patients <75 years. 32 patients >75 years were treated with definite radio(chemo)therapy for EC. We compared baseline parameters, efficiency and toxicity rates of these patients to 39 patients <75 years. Patients <75 years were more likely to receive simultaneous chemotherapy, and had a lower age-adjusted Charlson comorbidity index (ACCI). 25% of elderly patients were treated in palliative intent. There was no significant difference in progression-free survival between patient groups. No significant differences were seen for overall survival (15.7 months vs. 19.9 months; p = 0.102) and progression-free survival (10.5 months vs. 9.2 months, p = 0.470) between older patients treated with curative intent and younger patients. In addition, there were no significant differences for dysphagia and hematological side effects between elderly patients and younger patients. Definite (chemo)radiation is a feasible therapy for elderly patients. OS and PFS in elderly patients with a curative treatment approach are comparable to younger patients and it is not associated with higher toxicity rates.


FDA drug labeling for pregnancy and lactation drug safety monitoring systems.
The product label required by the FDA for every drug approved for marketing in the US is a legal document that originates with the company that wants to market the drug, but it must be approved by the FDA. Despite the recognized limitations of registries, the FDA's new labeling rule, effective from July 1, 2015, has given the data available from post-marketing surveillance priority in the new label. For this information to be maximally useful to both providers and consumers, providers must refer as many exposed consumers as possible to the registries, preferably prior to knowledge of the outcomes of the pregnancies. Consumers need to cooperate with the registries to share their health information with as much detail as possible with the registries. It will take years to accumulate a meaningful quantity of information in many of the registries, but they promise to be our best hope for useful counseling information in the future.


Civil war medicine from the perspective of S. Weir Mitchell's "The case of George Dedlow".
In 1866, a year following the close of the American Civil War, an anonymous article arousing much public interest appeared in the popular magazine, The Atlantic Monthly. The real author, Silas Weir Mitchell, who became one of America's most distinguished neurologists, wrote this short story early in his career while serving as a contract army surgeon and conducting his important clinical researches in nerve injuries. This article was the first literary effort in his long and prolific career as a physician/writer. Historians citing this article have focused almost exclusively on the early descriptions of causalgia and phantom limb syndrome, appearing as it did in a popular magazine. The present author proposes to show, for the first time, that Mitchell actually intended to describe many important medical consequences of the American Civil War, which was later shown to have so profoundly affected him throughout his medical and literary career. He cleverly accomplished this through the narration of Assistant Surgeon George Dedlow, who loses all four extremities by amputation.


Immediate Loaded Full-Arch Mandibular Rehabilitations in Younger vs. Elderly Patients: A Comparative Retrospective Study with 7-Year Follow-Up.
The aim of this comparative retrospective clinical study was to assess the effect of age on immediate loaded full-arch mandibular rehabilitation in younger vs. elderly patients. Patients with an age between 45 and 60 years (younger group, YG) or with an age more or equal to 75 years (older group, OG), requiring a mandibular full-arch rehabilitation were scheduled for the present study. Implant and prosthetic failure, biological and prosthetic complications, and peri-implant marginal bone level changes were recorded until a 7-year follow-up. Sixty-six patients were included in the study; a total of 264 implants were placed and, in total, 66 "all-on-four" rehabilitations were delivered. In total, 33 patients were scheduled in the YG and 33 patients in the OG. At the 7-year follow-up, an overall implant failure rate of 1.14% was reported. Moreover, at the 7-year radiographic evaluation, peri-implant crestal bone loss averaged 1.12 ± 0.91 mm for the YG and 1.04 ± 1.01 mm for the OG. No statistically significant differences were found between the YG and OG except for the rate of peri-implantitis, which was statistically higher in the YG. The present study reported that immediate fixed mandibular full-arch rehabilitation is a viable procedure in elderly people of equal or more than 75 years of age.


Toxic epidermal necrolysis in patients receiving glucocorticosteroids.
Despite the lack of evidence of an immunologically mediated mechanism for Toxic Epidermal Necrolysis (TEN), glucocorticosteroids are frequently used for the treatment of patients afflicted with TEN. We investigated the data of 216 patients with TEN for therapy with glucocorticosteroids prior to the beginning of TEN. The data had been collected between 1984 and 1985 during the epidemiological study on severe skin reactions in West-Germany spanning the years 1981-85. 11/216 (5%) patients could be traced, who had been treated with glucocorticosteroids for at least a week prior to the first dermatological sign of TEN. Glucocorticosteroids had been administered predominantly for neurological or neurosurgical conditions. The period of treatment ranged from 1 week to several months. Doses ranging between 7.5 and 325 mg prednisolone/per day were found. There were no major differences between patients with or without steroid therapy with regard to sex, age and lethality. The observation of TEN in patients receiving therapy with glucocorticosteroids raises questions about the usefulness of treating patients with TEN with glucocorticosteroids.


[Urethral opening pressure: its clinical significance in prostatic obstruction].
In the evaluation of prostatic obstruction by using the pressure-flow study (PFS), we defined intravesical pressure at initiation of voiding as urethral opening pressure. This simple parameter could reflect the degree of compressive prostatic obstruction to some extent. The aim of this study is to analyze if a correlation exsists between clinical signs and urethral opening pressure, and if they bear any prognostic value in postoperative outcome of the patients. We analyzed 46 patients with clinical benign prostatic hypertrophy who underwent urodynamic evaluations including PFS. They were divided into 2 groups according to their urethral opening pressure. The high opening pressure was defined as greater than 70 cm water, which was noted in 24 patients (group A). Twenty-two patients had lower opening pressure (group B). Comparison of the clinical findings in these patients were reviewed. Medium-filling cystometry and PFS were performed transurethrally, by using a microtip transducer and rectal balloon. Cystoscopy was performed when possible, wherein we could examined the presence or absence of detrusor trabeculation. Transurethral prostatectomy was indicated in a total of 26 patients (16 in group A and 10 in group B), in whom postoperative clinical findings were analyzed with regard to the difference in preoperative urethral opening pressure. The patients who void with straining or who void following uninhibited detrusor contraction were excluded from this study. International Prostatic Symptoms Score (I-PSS) revealed no significant difference in both groups, however, patients in group A were often suffering from urge incontinence preoperatively. Significant correlation was found among the incidence of detrusor instability, detrusor trabeculation and increased opening pressure. In PFS the patients with high opening pressure tended to have higher detrusor pressure at maximum flow and greater contractile power of the detrusor in voiding. There were no difference in Qmax and residual volume both groups. Postoperatively, symptomatic improvement was significant in both groups. There was no statistical difference in postoperative I-PSS between group A and B. Although 6 patients in group A demonstrated poor urinary control at 1 month, only two patients remained incontinent at 6 months postoperatively. As to urodynamic findings, the difference in PFS were markedly reduced between both groups. No difference was noted in postoperative Qmax as well. Significant difference was found in preoperative objective findings except the flow rate between the patients with and without high urethral opening pressure, while no symptomatic difference was noted except urege incontinence in both groups. No prognostic value was demonstrated in urethral opening pressure, however, poor postoperative urinary control was often associated with initial high opening pressure in the short term. It was suggested that 1) compensatory detrusor hyperactivity improved voiding efficacy in the patients with prostatic obstruction, which was gradually normalized after the relief of obstruction, 2) symptomatic improvement was highly related to the relative improvement of the obstructive findings on PFS.


Effect of a Wearable Device-Based Physical Activity Intervention in North Korean Refugees: Pilot Randomized Controlled Trial.
Effective health interventions for North Korean refugees vulnerable to metabolic disorders are currently unelucidated. This study aimed to evaluate the effects of digital health interventions in North Korean refugees using a wearable activity tracker (Fitbit device). We conducted a prospective, randomized, open-label study on North Korean refugees aged 19-59 years between June 2020 and October 2021 with a 12-week follow-up period. The participants were randomly assigned to either an intervention group or a control group in a 1:1 ratio. The intervention group received individualized health counseling based on Fitbit data every 4 weeks, whereas the control group wore the Fitbit device but did not receive individualized counseling. The primary and secondary outcomes were the change in the mean daily step count and changes in the metabolic parameters, respectively. The trial was completed by 52 North Korean refugees, of whom 27 and 25 were in the intervention and control groups, respectively. The mean age was 43 (SD 10) years, and 41 (78.8%) participants were women. Most participants (44/52, 95.7%) had a low socioeconomic status. After the intervention, the daily step count in the intervention group increased, whereas that in the control group decreased. However, there were no significant differences between the 2 groups (+83 and -521 steps in the intervention and control groups, respectively; P=.500). The effects of the intervention were more prominent in the participants with a lower-than-average daily step count at baseline (<11,667 steps/day). After the 12-week study period, 85.7% (12/14) and 46.7% (7/15) of the participants in the intervention and control groups, respectively, had an increased daily step count (P=.05). The intervention prevented the worsening of the metabolic parameters, including BMI, waist circumference, fasting blood glucose level, and glycated hemoglobin level, during the study period. The wearable device-based physical activity intervention did not significantly increase the average daily step count in the North Korean refugees in this study. However, the intervention was effective among the North Korean refugees with a lower-than-average daily step count; therefore, a large-scale, long-term study of this intervention type in an underserved population is warranted. Clinical Research Information Service KCT0007999; https://cris.nih.go.kr/cris/search/detailSearch.do/23622.


Nanopore detection of 8-oxo-7,8-dihydro-2'-deoxyguanosine in immobilized single-stranded DNA via adduct formation to the DNA damage site.
The ability to detect DNA damage within the context of the surrounding sequence is an important goal in medical diagnosis and therapies, but there are no satisfactory methods available to detect a damaged base while providing sequence information. One of the most common base lesions is 8-oxo-7,8-dihydroguanine, which occurs during oxidation of guanine. In the work presented here, we demonstrate the detection of a single oxidative damage site using ion channel nanopore methods employing α-hemolysin. Hydantoin lesions produced from further oxidation of 8-oxo-7,8-dihydroguanine, as well as spirocyclic adducts produced from covalently attaching a primary amine to the spiroiminodihydantoin lesion, were detected by tethering the damaged DNA to streptavidin via a biotin linkage and capturing the DNA inside an α-hemolysin ion channel. Spirocyclic adducts, in both homo- and heteropolymer background single-stranded DNA sequences, produced current blockage levels differing by almost 10% from those of native base current blockage levels. These preliminary studies show the applicability of ion channel recordings not only for DNA sequencing, which has recently received much attention, but also for detecting DNA damage, which will be an important component to any sequencing efforts.


Pigment epithelium-derived factor stimulates tumor macrophage recruitment and is downregulated by the prostate tumor microenvironment.
Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis but whether it has additional effects on the tumor microenvironment is largely unexplored. We show that overexpression of PEDF in orthotopic MatLyLu rat prostate tumors increased tumor macrophage recruitment. The fraction of macrophages expressing inducible nitric oxide synthase, a marker of cytotoxic M1 macrophages, was increased, suggesting that PEDF could enhance antitumor immunity. In addition, PEDF overexpression reduced vascular growth both in the tumor and in the surrounding normal tissue, slowed tumor growth, and decreased lymph node metastasis. Contrary, extratumoral lymphangiogenesis was increased. PEDF expression is, for reasons unknown, often decreased or lost during prostate tumor progression. When AT-1 rat prostate tumor cells, expressing high levels of PEDF messenger RNA (mRNA) and protein, were injected into the prostate, PEDF is markedly downregulated, suggesting that factors in the microenvironment suppressed its expression. One such factor could be macrophage-derived tumor necrosis factor alpha (TNFalpha). A fraction of the accumulating macrophages expressed TNFalpha, and TNFalpha treatment downregulated the expression of PEDF protein and mRNA in prostate AT-1 tumor cells in vitro and in the rat ventral prostate in vivo. PEDF apparently has multiple effects in prostate tumors: it suppresses angiogenesis and metastasis, but it also causes macrophage accumulation. Accumulating macrophages may inhibit tumor growth, but they may also suppress PEDF and enhance lymph angiogenesis and, in this way, eventually enhance tumor growth.


Autoantibodies against C-Reactive Protein Influence Complement Activation and Clinical Course in Lupus Nephritis.
Autoantibodies against the major acute-phase reactant C-reactive protein (CRP) are frequently found in patients with lupus nephritis. Further defining the autoimmune epitopes on CRP may not only improve patient stratification but also, hint at mechanisms of CRP action. Herein, we show that amino acids 35-47 constitute the major epitope recognized by anti-CRP autoantibodies in patients with lupus nephritis. Notably, the presence of autoantibodies against amino acids 35-47 associated with more severe renal damage and predicted worse outcome. This epitope is exposed on CRP only after irreversible structure changes, yielding a conformationally altered form termed modified or monomeric CRP (mCRP). ELISA and surface plasmon resonance assays showed that amino acids 35-47 mediate the interaction of mCRP with complement factor H, an inhibitor of alternative pathway activation, and this interaction greatly enhanced the in vitro cofactor activity of complement factor H. In contrast, autoantibodies against amino acids 35-47 inhibited these actions of mCRP. Our results thus provide evidence for the in vivo generation of mCRP in a human disease and suggest that mCRP actively controls the pathogenesis of lupus nephritis by regulating complement activation. Therefore, amino acids 35-47 constitute a functional autoimmune epitope on CRP that can be targeted therapeutically and diagnostically.


Monitoring childhood immunizations: a Canadian approach.
In Manitoba, Canada, a centralized, computerized childhood immunization monitoring system serves a population with insured medical coverage; each individual has a unique identification number. All physicians bill a single payer, and specific billing codes are used to identify immunizations given by physicians and by public health nurses. Together with dates of service, this information is used to construct immunizations-to-date and age-at-immunization profiles for individuals and groups. Reminders seeking missing information are built into the system and executed at strategic ages. The quality of input data has been assessed as high. The approach could be used readily by health maintenance organizations in the United States.


Productivity and employees' organizational justice perceptions in long-term care for the elderly.
We examined the associations between productivity, employer characteristics, and context variables, and the organizational justice perceptions of 330 female employees in long-term institutional elderly people care. The productivity measure used was the proportion of the inpatient days to total costs. Employees working in high productivity units experienced higher procedural justice than those working in low productivity units. Hostile employees experienced both the procedures and management as less fair than non-hostile employees. Unit size and resident turnover were negatively and registered nurses percentage positively associated with procedural justice perceptions.


Oil droplets of bird eyes: microlenses acting as spectral filters.
An important component of the cone photoreceptors of bird eyes is the oil droplets located in front of the visual-pigment-containing outer segments. The droplets vary in colour and are transparent, clear, pale or rather intensely yellow or red owing to various concentrations of carotenoid pigments. Quantitative modelling of the filter characteristics using known carotenoid pigment spectra indicates that the pigments' absorption spectra are modified by the high concentrations that are present in the yellow and red droplets. The high carotenoid concentrations not only cause strong spectral filtering but also a distinctly increased refractive index at longer wavelengths. The oil droplets therefore act as powerful spherical microlenses, effectively channelling the spectrally filtered light into the photoreceptor's outer segment, possibly thereby compensating for the light loss caused by the spectral filtering. The spectral filtering causes narrow-band photoreceptor spectral sensitivities, which are well suited for spectral discrimination, especially in birds that have feathers coloured by carotenoid pigments.


Solitary rib metastasis from primary nasopharyngeal carcinoma: A rare clinical presentation.
We report a case of a middle age male who presented to our tertiary care university hospital with the complaints of nasal obstruction and decrease hearing. The CT scan of head and neck exhibited a mass in nasopharynx and enlarged bilateral cervical lymph nodes. Biopsy from nasopharynx confirmed the lesion as poorly differentiated non-keratinizing squamous cell carcinoma and staged as cT2N2M0. He received neoadjuvant chemotherapy. Subsequently, he underwent chemo radiation therapy. He represented with left chest wall pain. Imaging confirmed isolated lesion on left sided 6th rib. Rib lesion was resected followed by radiation therapy to surgical bed and systemic treatment. The patient remained disease free for 4.5 years. Later, his disease relapsed, and he died of systemic disease progression. To the best of the author's knowledge, only few cases have been reported with isolated rib metastasis from nasopharyngeal carcinoma and this is the first case in which metastasectomy was considered.


Ultrasound guided high-intensity focused ultrasound combined with gonadotropin releasing hormone analogue (GnRHa) ablating uterine leiomyoma with homogeneous hyperintensity on T2 weighted MR imaging.
The study aimed to evaluate the safety and efficiency of ultrasound-guided high-intensity focused ultrasound (USgHIFU) combined with gonadotropin-releasing hormone analogue (GnRHa)-ablating symptomatic uterine leiomyoma with homogeneous hyperintensity on T2 weighted MRI prospectively. A total of 34 patients with 42 symptomatic uterine leiomyomas with homogeneous hyperintensity on T2 weighted MRI were enrolled in our study. In the patient who had multiple uterine leiomyomas, only one dominant leiomyoma was treated. According to the principles of voluntariness, 18 patients underwent a 3-month therapy of GnRHa (once a month) before the high-intensity focused ultrasound (HIFU) treatment, while 16 patients received only HIFU treatment. Enhanced MRI was performed before and after GnRHa and HIFU treatment. Evaluation of the main indicators included treatment time, sonication time, treatment efficiency, non-perfused volume (NPV) (indicative of successful ablation) ratio and energy effect ratio; adverse events were also recorded. The treatment time and sonication time of the combination group were 102.0 min (55.8-152.2 min) and 25.4 min (12.2-34.1 min); however, they were 149.0 min (87.0-210.0 min) and 38.9 min (14.0-46.7 min) in the simple USgHIFU group. The treatment and sonication time for the combination group was significantly shorter than that for the simple USgHIFU group. Treatment efficiency, NPV ratio and energy effect ratio were 46.7 mm3 s-1 (28.5-95.8 mm3 s-1), 69.2 ± 29.8% (35.5-97.4%) and 9.9 KJ mm-3 (4.5-15.7 KJ mm-3) in the combination group, respectively; but, the lowest treatment efficiency, lowest NPV ratio and more energy effect ratio were observed in the simple HIFU group, which were 16.8 mm3 s-1 (8.9-32.9 mm3 s-1), 50.2 ± 27.3% (0-78.6%) and 23.8 KJ mm-3 (12.4-46.2 KJ mm-3), respectively. Pain scores in the combination group were 3.0 ± 0.5 points (2-4 points)-significantly less than the simple USgHIFU group. There were no significant adverse reactions in either group. Our data suggest that USgHIFU combined with GnRHa may be performed to ablate symptomatic uterine leiomyoma with homogeneous hyperintensity on T2 weighted MRI. Advances in knowledge: The conclusions indicate that GnRHa can improve the effectiveness of the USgHIFU treatment of a homogeneous hyperintense leiomyoma on T2 weighted MRI, and combination treatment could be a promising alternative treatment for the uterine leiomyoma.


Effect of silver or copper middle layer on the performance of palladium modified nickel foam electrodes in the 2-chlorobiphenyl dechlorination.
To enhance the activity of chemi-deposited palladium/nickel foam (Pd/Ni) electrodes used for an electrochemical dechlorination process, silver or copper was deposited electrochemically onto the nickel foam substrate (to give Ag/Ni or Cu/Ni) before the chemical deposition of palladium. The physicochemical properties of the resulting materials (Pd/Ni, Pd/Ag/Ni and Pd/Cu/Ni) were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), and their electrochemical catalytic activities were evaluated by monitoring the electrochemical dechlorination of 2-chlorobiphenyl (2-CB) in strongly alkaline methanol/water solution. The results show that the Pd/Ag/Ni and Pd/Cu/Ni electrodes had consistently higher electrocatalytic activities and current efficiencies (CEs) compared with the untreated Pd/Ni electrode. The Pd/Ag/Ni electrode exhibited the highest activity. The dechlorination was also studied as a function of Pd loading, the Ag or Cu interlayer loadings, and the current density. The Pd loading and the interlayer loadings both had positive effects on the dechlorination reaction. Increasing the current density increased the reaction rate but reduced the CE. The improvement of the electrocatalytic activities of the Pd/Ni electrode by applying the interlayer of Ag or Cu resulted from the enlargement of the effective surface area of the electrode and the adjustment of the metal-H bond energy to the appropriate value, as well as the effective adsorption of 2-CB on Ag. Moreover, the high catalytic activity of the Pd/Ag/Ni electrode was maintained after six successive cyclic experiments, whereas Pd/Cu/Ni electrodes deactivate severely under the same conditions.


Intrapericardial teratoma presenting in fetal life: intrauterine diagnosis and neonatal management.
Intrapericardial teratoma is a rare and often fatal germ-cell tumor of neonates. It is usually histologically benign but may cause death in utero by hydrops fetalis or by pericardial tamponade in the early days of life. The etiology of these tumors is uncertain, but resection appears to be curative. However, these tumours present a challenge in terms of prenatal management. The prevention or adequate management of hydrops fetalis is essential for the gestation to proceed to term, at which point it can be managed successfully with surgical resection. We present a case of intrapericardial teratoma, diagnosed in utero on ultrasound screening and managed both prenatally by laser decompression in utero and surgically in the first days of life.


Modelling neuron fiber interaction and coupling in non-myelinated bundled fiber.
Understanding the local dynamics of a neural network relies heavily on local field potential and cell-field interaction. But it is still unclear how local the local potential is and what kinds of consequences the trans-membrane current flow and produced electric field have on the local neural fiber. Mimicking signal transmission in neighboring nerve fiber, a simulation model is built to analyze local behavior due to trans-membrane current, cell-field interactions, and their repercussions on the bundled fiber system. Simulation studies reveal that depending on the coupling parameters, activity in one fiber can depolarize or hyper-polarize adjacent fibers. The suggested cell-field interaction model was tested using an orientation-selective coupled retinal ganglion cell network, which was compared to its uncoupled counterpart. The proposed work has been used to model and simulate local signal dynamics in a bundled fiber system of an orientation-selective RGC network due to cell-field interaction, as well as to gain insight into the possible significance of dendritic fiber coupling in orientation selectivity bandwidth adjustment.


Hormonal basis of sexual differentiation in the Japanese quail.
On the 10th day of incubation, Japanese quail eggs either were injected with testosterone propionate (TP), estradiol benzoate (EB), or oil, or were not injected. When sexually mature, all birds were examined for a variety of sexually dimorphic behavioral and physical characteristics, both masculine and feminine. They were then exposed to a short photoperiod (causing gonadal regression), treated with either TP or EB, and examined again. Either androgen or estrogen administered before hatching demasculinized males, but did not masculinize females or defeminize either sex. In contrast, early sex hormones masculinize and/or or defeminize mammals. This difference is discussed in relation to other differences in avian and mammalian sexuality.


[Veno-lymphatic angiodysplasia as the cause of recurrent inguinal varicose veins].
Veno-lymphatic angiodysplasia may be the reason for the development of varicose leg veins. This form of angiodysplasia is illustrated by two case reports. Until now, angiodysplasia as possible cause of recurrent varicose veins after surgical treatment has not been included in the classification of the morphological types of recurrent varicose veins. The surgical approach exposing the common femoral vein in a first step and secondly performing a complete resection of the malformation with careful consideration of the adjacent femoral vessels is recommended as the treatment of choice.


The Relationship Between Soil Arthropods and the Overwinter Survival of Ixodes scapularis (Acari: Ixodidae) Under Manipulated Snow Cover.
We explored the relationship between the diversity and abundance of the soil arthropod predator community and the overwinter survival of engorged larval Ixodes scapularis Say under variable snow cover in a hardwood forest. We reduced the snow cover over 30 soil core field microcosms, simulating predicted changes in snow pack in the northeastern United States. An additional 29 microcosms were used as references with no snow pack manipulation. Each microcosm contained 15 engorged larval I. scapularis. We expected lower soil temperature without insulating snow cover to reduce tick survival. However, we observed that reduced snow cover had no effect, with 44.2 and 44.7% overwintering successfully in the reference and snow-removal plots, respectively. Increasing taxonomic family richness of arthropod predators and the total number of large (>1 mm) arthropod predators significantly reduced the overwinter survivorship of I. scapularis within the microcosms. Small (<1 mm) arthropod predator abundance had no effect. Our results suggest that forests with complex natural arthropod predator communities show reduced tick survival.


Inhibition of Thrombin-Activated Fibrinolysis Inhibitor Increases Survival in Experimental Kidney Fibrosis.
Uncontrolled diabetes, inflammation, and hypertension are key contributors to progressive renal fibrosis and subsequent loss of renal function. Reduced fibrinolysis appears to be a feature of ESRD, but its contribution to the fibrotic program has not been extensively studied. Here, we show that in patients with CKD, the activity levels of serum thrombin-activated fibrinolysis inhibitor and plasmin strongly correlated with the degree of renal function impairment. We made similar observations in rats after subtotal nephrectomy and tested whether pharmacologic inhibition of thrombin-activated fibrinolysis inhibitor with UK-396082 could reduce renal fibrosis and improve renal function. Compared with untreated animals, UK-396082-treated animals had reduced glomerular and tubulointerstitial fibrosis after subtotal nephrectomy. Renal function, as measured by an increase in creatinine clearance, was maintained and the rate of increase in proteinuria was reduced in UK-396082-treated animals. Furthermore, cumulative survival improved from 16% to 80% with inhibition of thrombin-activated fibrinolysis inhibitor. Taken together, these data support the importance of the fibrinolytic axis in regulating renal fibrosis and point to a potentially important therapeutic role for suppression of thrombin-activated fibrinolysis inhibitor activity.


[Phase II study of combination therapy with paclitaxel and carboplatin against postoperative small residual disease in patients with stage I c-IV ovarian cancer--KCOG 989 trial].
The tolerability and feasibility of combination therapy with paclitaxel (TXL) and carboplatin (CBDCA) against small residual disease following first-line optimal debulking of stage I c-IV ovarian cancer were evaluated in a multicenter dose-finding study. Eligibility criteria included histologically diagnosed stage I c-IV epithelial ovarian cancer with a postoperative residual lesion < or = 10 mm in diameter, no prior chemotherapy, and written informed consent of the patient and his/her family members to the chemotherapy. Twenty-two patients were enrolled and 20 of them were eligible. The patients were to receive 5 courses of TXL (175 mg/m2) and CBDCA (AUC 5) every 3 weeks. Hematological toxicities occurred in the form of grade 3 leukopenia during 25.7% of all courses, grade 3 neutropenia during 32.0% of all courses, and grade 4 neutropenia during 56.0% of all courses. No courses were associated with grade 4 leukopenia. G-CSF support was needed during 48 of 109 courses (44%) and caused normalization of the leukocyte count from a nadir of 1,921 +/- 434/mm3 after a mean time of 6 +/- 3.1 days, compared with 6 +/- 3.6 days needed for recovery from a nadir of 2, 357 +/- 360/mm3 without G-CSF support. This indicates similarly rapid recovery from severe leukopenia with the use of G-CSF. All eligible patients completed at least 5 courses of the chemotherapy. Some courses were given at a reduced dose or delayed due to toxicity but these dosage modifications were thought to be acceptable for both TXL and CBDCA. Five courses of TXL combined with CBDCA were tolerated well in this patient population.


Clinical experience and incidence of ventilator-associated pneumonia using closed versus open suction-system.
Studies have shown a decreasing ventilator-associated pneumonia (VAP) incidence after prophylactic interventions bundles. The use of closed suction systems (CSS) has been suggested beneficial as a prophylactic measure. To investigate the effects of a CSS on VAP incidence, suction circuit contamination and adverse events (AEs) compared to an open suction system (OSS) approach in a general mixed intensive care unit (ICU). Adult patients on mechanical ventilation were consecutively included. Data were collected during four 1-month periods where CSS and OSS were used on an alternating basis. Airway cultures were obtained at intubation, after 72 h and every Monday. After changing CSS and at extubation, the catheter tip was cultured. AEs and desaturation events during suction were monitored. Descriptive analysis and differences between the groups were analysed using comparative methods. No differences in airway colonization at admission between the groups were detected (Table 2). The CSS group had a higher Simplified Acute Physiology Score (SAPS) III and also a non-significant increase in VAP incidence. Positive cultures were obtained in 50% of all the retrieved CSS catheters. There was no inter-patient contamination in either group. Six AEs versus one (CSS/OSS) related to tube-occlusion and secretion clogging was seen. Desaturations at suctioning were rare in both groups. No beneficial effects were seen on VAP incidence or inter-patient contamination compared to OSS. A high frequency of circuit contamination in the CSS group paralleled with experienced secretions clearance problems seem unfavourable and in concordance with previous studies.


Metabolic clearance rates (MCR) and production rates (PR) plasma progesterone in pregnant and pseudopregnant rabbits.
Our studies were designed to determine whether changing peripheral progesterone levels in rabbits reflected changing metabolic clearance rates (MCR) or changing production rates (PR), or both. Plasma progesterone concentrations rise from nonpregnancy levels to peak values at the end of the first third of gestation and at midpseudopregnancy. In the pregnant rabbit, these decline slowly during the second third of gestation and then more rapidly until near nonpregnancy values are reached at term. Progesterone levels decline sharply during the second half of pseudopregnancy. During pregnancy and pseudopregnancy, we found only small variations in MCRs which cannot account for the approximately 10-fold increase in plasma progesterone concentrations. The increases can, however, be accounted for by changes in PRs which rose sharply after conception of hCG injection to 14-fold the nonpregnancy level on day 16 of gestation and 11-fold on day 7 of pseudopregnancy. These results indicate that changes in ovarian PRs are the major factor for the variations in peripheral progesterone levels during pregnancy and pseudopregnancy. The rabbit differs in this respect from the guinea pig, in which changing progesterone concentrations during pregnancy were shown to reflect sharply reduced MCRs. After a single injection of progesterone in 20-day pregnant rabbits, the disappearance of the steroid from the circulation consisted of two components; an initial phase during which progesterone disappeared rapidly (t1/2 = 2.4 +/- 0.2 min) followed by a slower rate of disappearance (t1/2 = 21.5 +/- 2.2 min).


Role of aggrecanase 1 in Lyme arthritis.
Arthritis is one of the hallmarks of late-stage Lyme disease. Previous studies have shown that infection with Borrelia burgdorferi, the causative agent of Lyme disease, results in degradation of proteoglycans and collagen in cartilage. B burgdorferi do not appear to produce any exported proteases capable of digesting proteoglycans and collagen, but instead, induce and activate host proteases, such as matrix metalloproteinases (MMPs), which results in cartilage degradation. The role of aggrecanases in Lyme arthritis has not yet been determined. We therefore sought to delineate the contribution of aggrecanases to joint destruction in Lyme arthritis. We examined the expression patterns of aggrecanases 1 and 2 (ADAMTS 4 and 5, respectively) in B burgdorferi-infected primary human chondrocyte cell cultures, in synovial fluid samples from patients with active Lyme arthritis, and in the joints of mice by real-time quantitative reverse transcription-polymerase chain reaction and immunoblotting techniques. Bovine cartilage explants were used to determine the role of aggrecanases in B burgdorferi-induced cartilage degradation. ADAMTS-4, but not ADAMTS-5, was induced in human chondrocytes infected with B burgdorferi. The active forms of ADAMTS-4 were increased in synovial fluid samples from patients with active Lyme arthritis and were elevated in the joints of mice infected with B burgdorferi. Using cartilage explant models of Lyme arthritis, it appeared that the cleavage of aggrecan was predominantly mediated by "aggrecanases" rather than MMPs. The induction of ADAMTS-4 by B burgdorferi results in the cleavage of aggrecan, which may be an important first step that leads to permanent degradation of cartilage.


The cellular Pax-Hox-helix connection.
Basic helix-loop-helix (bHLH) transcription factors are important regulators of lineage determination during embryogenesis. Initial experiments in Drosophila showed that early neural selection and specification are dependent on atonal (ato) and members of the achaete-scute complex (as-c). In mammals, transcription factors homologous to as-c and ato are causally involved during development of organs throughout the body. Development of subsets of lineages in intestine, stomach, pancreas, lung, thyroid and placenta have been shown to be regulated by members of the as-c and ato families. These functional studies show that an individual bHLH transcription factor can regulate multiple developmental processes throughout the mammalian body, which implicates that extant as-c and ato transcription factors play a distinct function dependent on their cellular context. Based on the synergistic activation of the insulin, POMC and Pax4 promotors by bHLH and homeobox (Hox) protein complexes, we hypothesize that the underlying cellular function-modulating factors include members of the Hox and paired box (Pax) multigene families. These examples indicate that unique combinations of bHLH and Hox proteins, mediated by protein-protein interactions, might be responsible for activating cell-specific sets of target genes.