Clotting factor deficiency in early trauma-associated coagulopathy.
Coagulopathic bleeding is a leading cause of in-hospital death after injury. A recently proposed transfusion strategy calls for early and aggressive frozen plasma transfusion to bleeding trauma patients, thus addressing trauma-associated coagulopathy (TAC) by transfusing clotting factors (CFs). This strategy may dramatically improve survival of bleeding trauma patients. However, other studies suggest that early TAC occurs by protein C activation and is independent of CF deficiency. This study investigated whether CF deficiency is associated with early TAC. This is a prospective observational cohort study of severely traumatized patients (Injury Severity Score ≥ 16) admitted shortly after injury, receiving minimal fluids and no prehospital blood. Blood was assayed for CF levels, thromboelastography, and routine coagulation tests. Critical CF deficiency was defined as ≤ 30% activity of any CF. Of 110 patients, 22 (20%) had critical CF deficiency: critically low factor V level was evident in all these patients. International normalized ratio, activated prothrombin time, and, thromboelastography were abnormal in 32%, 36%, and 35%, respectively, of patients with any critically low CF. Patients with critical CF deficiency suffered more severe injuries, were more acidotic, received more blood transfusions, and showed a trend toward higher mortality (32% vs. 18%, p = 0.23). Computational modeling showed coagulopathic patients had pronounced delays and quantitative deficits in generating thrombin. Twenty percent of all severely injured patients had critical CF deficiency on admission, particularly of factor V. The observed factor V deficit aligns with current understanding of the mechanisms underlying early TAC. Critical deficiency of factor V impairs thrombin generation and profoundly affects hemostasis.


Chlamydia and Borrelia DNA in synovial fluid of patients with early undifferentiated oligoarthritis: results of a prospective study.
More than 50% of patients with synovitis involving 1-4 joints remain classified as having undifferentiated oligoarthritis (UOA) after 1 year of disease. The clinical presentation is often similar to that of reactive arthritis (ReA) and other spondylarthropathies or to Lyme arthritis. We therefore determined how often Chlamydia trachomatis (Ct) and Borrelia burgdorferi (Bb) can be identified in patients with UOA, by using an extensive laboratory approach. We prospectively studied 52 patients with UOA who presented at an early synovitis clinic in a region highly endemic for Lyme disease. Patients were examined by standardized clinical and immunoserologic procedures. Synovial fluid was screened for the presence of Ct and Bb DNA by polymerase chain reaction (PCR). Urine was tested for Ct DNA by ligase chain reaction, and serum was tested for Ct antibodies by enzyme-linked immunosorbent assay and Bb antibodies by hemagglutination test and Western blotting. PCR results in the UOA patients were compared with the results in cohorts of patients with definite rheumatoid arthritis (RA), Lyme arthritis, and Chlamydia-induced arthritis (CIA). In the synovial fluid of 9 of 52 patients with UOA (17%), we found Ct DNA, and in 6 of the 52 patients (12%), Bb DNA was found. The frequency of bacteria-specific DNA was 50% (7 of 14) in CIA patients and 69% (11 of 16) in patients with Lyme arthritis. No Bb or Ct DNA was found in the synovial fluid of the 31 RA patients. With optimized PCR protocols, it is possible to detect considerable levels of Bb and Ct DNA in the synovial fluid of patients with UOA. Although the presence of bacterial DNA does not unequivocally prove its etiologic significance, we suggest that at least one-third of patients with UOA may have a form of ReA that involves asymptomatic primary infection.


The Roles of Cruciferae Glucosinolates in Disease and Pest Resistance.
With the expansion of the area under Cruciferae vegetable cultivation, and an increase in the incidence of natural threats such as pests and diseases globally, Cruciferae vegetable losses caused by pathogens, insects, and pests are on the rise. As one of the key metabolites produced by Cruciferae vegetables, glucosinolate (GLS) is not only an indicator of their quality but also controls infestation by numerous fungi, bacteria, aphids, and worms. Today, the safe and pollution-free production of vegetables is advocated globally, and environmentally friendly pest and disease control strategies, such as biological control, to minimize the adverse impacts of pathogen and insect pest stress on Cruciferae vegetables, have attracted the attention of researchers. This review explores the mechanisms via which GLS acts as a defensive substance, participates in responses to biotic stress, and enhances plant tolerance to the various stress factors. According to the current research status, future research directions are also proposed.


Dorsally exophytic glioblastoma of the pons.
Brainstem gliomas are rare tumours in adults, accounting for only 1%-2% of all intracranial gliomas. They are recognised as a heterogeneous group, in which most are malignant tumours. Brainstem gliomas are classified into four major groups according to the growth pattern on imaging, namely diffuse, focal, exophytic and cervicomedullary. Such a classification system is also useful for surgical decision making. The exophytic variant is extremely rare having anecdoctal reports in the literature. We report the case of an adult patient affected by an exophytic glioblastoma of the pons, which was submitted to subtotal resection followed by radiation therapy and chemotherapy with a longer overall survival. To the best of our knowledge, this is the seventh adult patient reported of an exophytic brainstem glioblastoma.


A multi-step education model for advancing competencies in geriatrics and interprofessional collaboration for health students.
At a time when the older adult population is increasing exponentially and health care agencies are fraught with crisis-level short-handedness and burnout, addressing the Quadruple Aim of enhancing patient experience, improving population health, reducing costs, and improving the work life of health care providers is more crucial than ever. A multi-step education model was designed to advance competencies in geriatrics and Interprofessional Collaborative Practice (IPCP) for health profession students focused on each element of the Quadruple Aim. The goals of this education were to equip students with knowledge and experience to provide team-based care for older adults and achieve satisfaction with the education program. The education steps consisted of online didactics, team icebreaker, skills practice, professional huddles, and interprofessional simulation with debriefing. Over 2,300 students and 87 facilitators from 16 professions completed the training over three years. A positive statistically significant increase was found between pre- and post-measures of IPCP competency, knowledge, and attitudes. Additionally, high satisfaction with the education was reported by students and facilitators. By providing positive geriatric education and experiences for health students to work in interprofessional teams, it can translate into future improvements in older adult population health, health care provider job satisfaction, and reduced health care costs.


Assessment of two theoretical methods to estimate potentiometric titration curves of peptides: comparison with experiment.
We compared the ability of two theoretical methods of pH-dependent conformational calculations to reproduce experimental potentiometric titration curves of two models of peptides: Ac-K5-NHMe in 95% methanol (MeOH)/5% water mixture and Ac-XX(A)7OO-NH2 (XAO) (where X is diaminobutyric acid, A is alanine, and O is ornithine) in water, methanol (MeOH), and dimethyl sulfoxide (DMSO), respectively. The titration curve of the former was taken from the literature, and the curve of the latter was determined in this work. The first theoretical method involves a conformational search using the electrostatically driven Monte Carlo (EDMC) method with a low-cost energy function (ECEPP/3 plus the SRFOPT surface-solvation model, assumming that all titratable groups are uncharged) and subsequent reevaluation of the free energy at a given pH with the Poisson-Boltzmann equation, considering variable protonation states. In the second procedure, molecular dynamics (MD) simulations are run with the AMBER force field and the generalized Born model of electrostatic solvation, and the protonation states are sampled during constant-pH MD runs. In all three solvents, the first pKa of XAO is strongly downshifted compared to the value for the reference compounds (ethylamine and propylamine, respectively); the water and methanol curves have one, and the DMSO curve has two jumps characteristic of remarkable differences in the dissociation constants of acidic groups. The predicted titration curves of Ac-K5-NHMe are in good agreement with the experimental ones; better agreement is achieved with the MD-based method. The titration curves of XAO in methanol and DMSO, calculated using the MD-based approach, trace the shape of the experimental curves, reproducing the pH jump, while those calculated with the EDMC-based approach and the titration curve in water calculated using the MD-based approach have smooth shapes characteristic of the titration of weak multifunctional acids with small differences between the dissociation constants. Nevertheless, quantitative agreement between theoretically predicted and experimental titration curves is not achieved in all three solvents even with the MD-based approach, which is manifested by a smaller pH range of the calculated titration curves with respect to the experimental curves. The poorer agreement obtained for water than for the nonaqueous solvents suggests a significant role of specific solvation in water, which cannot be accounted for by the mean-field solvation models.


Degradation of textile dyes from aqueous solution using tea-polyphenol/Fe loaded waste silk fabrics as Fenton-like catalysts.
In this study, waste silk fabrics (SF) were modified with tea-polyphenols (TPs) and then iron (Fe2+). The modified silk fabrics (TP-SF/Fe) were characterized via Fourier-transform infrared (FTIR), energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) analysis. TP-SF/Fe was used in the Fenton-like removal of dyes (methylene blue, reactive orange GRN, and cationic violet X-5BLN) from aqueous solutions with catalyst-like activity. The effects of different catalyst samples, contact time, H2O2 concentration, initial dye concentration, and pH values on dye removal were investigated. The results showed that the dye removal percentages with the TP-SF/Fe-H2O2 sample reached 98%, 97%, and 95% in 5-40 min for methylene blue, reactive orange GRN, and cationic violet X-5BLN, respectively. Different thermodynamic and kinetic models were used to check the best fit of the adsorption data. The results indicated that the Freundlich isotherm and pseudo first-order kinetics models were the best fits. Moreover, it was also proved that TP-SF/Fe would be quite an effective and economical adsorbent for the treatment of textile dye wastewater. This work provides the basis for waste silk application in the removal of dyes from wastewater.


Capturing conformational States in proteins using sparse paramagnetic NMR data.
Capturing conformational changes in proteins or protein-protein complexes is a challenge for both experimentalists and computational biologists. Solution nuclear magnetic resonance (NMR) is unique in that it permits structural studies of proteins under greatly varying conditions, and thus allows us to monitor induced structural changes. Paramagnetic effects are increasingly used to study protein structures as they give ready access to rich structural information of orientation and long-range distance restraints from the NMR signals of backbone amides, and reliable methods have become available to tag proteins with paramagnetic metal ions site-specifically and at multiple sites. In this study, we show how sparse pseudocontact shift (PCS) data can be used to computationally model conformational states in a protein system, by first identifying core structural elements that are not affected by the environmental change, and then computationally completing the remaining structure based on experimental restraints from PCS. The approach is demonstrated on a 27 kDa two-domain NS2B-NS3 protease system of the dengue virus serotype 2, for which distinct closed and open conformational states have been observed in crystal structures. By changing the input PCS data, the observed conformational states in the dengue virus protease are reproduced without modifying the computational procedure. This data driven Rosetta protocol enables identification of conformational states of a protein system, which are otherwise difficult to obtain either experimentally or computationally.


[Changes of right atrial myoendocrine cells during hypertension and after arterial pressure decrease].
It is well known now that atrial cardiomyocytes carry out both contractile and endocrine activities--they synthesize, accumulate in specific secretory granules and release the natriuretic peptides. The main physiological effects of natriuretic peptides are antagonistic to the renin-angiotensin-aldostrol system, but their role in the development of hypertension is still disputable. The aim of this investigation is to estimate using electron microscopy the secretory activities of atrial myoendocrine cells in rats with inherited stress-induced arterial hypertension (ISIAH stain). It has been shown that myoendocrine cells in the ISIAH rats with arterial pressure about 180 mm Hg reveal morphological features of increased synthesis, extra accumulation and release of natriuretic peptides compared with normotensive control rats. In the ISIAH rats treated with losartan (angiotensin II receptor blocker) and therefore having a sustained decrease in arterial pressure to 140 mm Hg, changes in granular pool composition, reduction of the number and diameter of the secretory granules, reduction of Golgi complexes, and increased intracellular degradation of secretory stores were found in the myoendocrine cells. At the same time the marked capillary hyperemia and interstitial edema in the myocardium were observed. Thus, in rats with severe inherited hypertension, the secretory activity of heart myoendocrine cells is sharply increased and directly depends on the arterial blood pressure level. This proves that natriuretic peptides actively participate in the regulation of hemodynamics during with cardiovascular pathology.


Combining antigen-based therapy with GABA treatment synergistically prolongs survival of transplanted ß-cells in diabetic NOD mice.
Antigen-based therapies (ABTs) very effectively prevent the development of type 1 diabetes (T1D) when given to young nonobese diabetic (NOD) mice, however, they have little or no ability to reverse hyperglycemia in newly diabetic NOD mice. More importantly, ABTs have not yet demonstrated an ability to effectively preserve residual ß-cells in individuals newly diagnosed with type 1 diabetes (T1D). Accordingly, there is great interest in identifying new treatments that can be combined with ABTs to safely protect ß-cells in diabetic animals. The activation of γ-aminobutyric acid (GABA) receptors (GABA-Rs) on immune cells has been shown to prevent T1D, experimental autoimmune encephalomyelitis (EAE) and rheumatoid arthritis in mouse models. Based on GABA's ability to inhibit different autoimmune diseases and its safety profile, we tested whether the combination of ABT with GABA treatment could prolong the survival of transplanted ß-cells in newly diabetic NOD mice. Newly diabetic NOD mice were untreated, or given GAD/alum (20 or 100 µg) and placed on plain drinking water, or water containing GABA (2 or 6 mg/ml). Twenty-eight days later, they received syngenic pancreas grafts and were monitored for the recurrence of hyperglycemia. Hyperglycemia reoccurred in the recipients given plain water, GAD monotherapy, GABA monotherapy, GAD (20 µg)+GABA (2 mg/ml), GAD (20 µg)+GABA (6 mg/ml) and GAD (100 µg)+GABA (6 mg/ml) about 1, 2-3, 3, 2-3, 3-8 and 10-11 weeks post-transplantation, respectively. Thus, combined GABA and ABT treatment had a synergistic effect in a dose-dependent fashion. These findings suggest that co-treatment with GABA (or other GABA-R agonists) may provide a new strategy to safely enhance the efficacy of other therapeutics designed to prevent or reverse T1D, as well as other T cell-mediated autoimmune diseases.


Tyrosine kinase inhibitors in the treatment of advanced renal cell carcinoma: focus on pazopanib.
Advances in our understanding of renal cancer biology have led to a new treatment paradigm in renal cancer. Tyrosine kinase inhibitors (TKI), that target the intracellular kinase domain of the VEGF receptor, have become established as the most successful class of agent in this disease. Three TKIs are currently approved for use in patients with advanced disease. Newer, more potent inhibitors have reached phase III clinical testing, meaning others are likely to follow. In 2009, pazopanib became the most recent TKI to receive FDA approval. This review sets out to discuss the key opportunities and challenges associated with TKI use in RCC, focusing particularly on pazopanib. We also review the current place of pazopanib in the management of patients with advanced disease, in what is a rapidly evolving therapeutic landscape.


Intra-specific variation in xylem cavitation in interior live oak (Quercus wislizenii A. DC.).
Xylem cavitation induced by water stress reduces plant hydraulic conductance and can indicate the habitat a species evolved in and its phylogenetic background. Species differ widely in cavitation resistance, but less is known about intra-specific variation. Cavitation resistance was assessed for field-collected adult and sapling size classes from three populations of interior live oak (Quercus wislizenii A. DC.) in California, USA. Root and stem cavitation resistance of two-year old seedlings from a greenhouse experiment was also measured. Cavitation resistance curves were determined by injecting air into the vascular system to induce cavitation and measuring the subsequent decline in hydraulic conductance. Based on the air-seeding hypothesis, the absolute value of the air pressures should be equivalent to the tensions that cause cavitation under dehydrating conditions. Conductance declined exponentially with applied pressure for both roots and stems. Comparisons between populations did not reveal significant differences despite good statistical power. The 50% loss in conductance point occurred between 1.0-1.6 MPa; conductance declined more slowly thereafter. Conductance was 21-30% of maximum at 4.0 MPa and 7-14% at 8.0 MPa. Saplings exhibited a nearly identical pattern compared with adults except at 4.0 MPa, where saplings exhibited slightly less cavitation (7%). Greenhouse seedling stems were more resistant compared with both field-collected adults and with seedling roots. The 50% loss in conductance point occurred at 0.83 and 2.6 MPa for seedling roots and stems, respectively. Seedling stems maintained conductance of 20.9% at 8.0 MPa while most roots were fully cavitated between 5.0-8.0 MPa.


Hypervirulent Clostridium difficile PCR-ribotypes exhibit resistance to widely used disinfectants.
The increased prevalence of Clostridium difficile infection (CDI) has coincided with enhanced transmissibility and severity of disease, which is often linked to two distinct clonal lineages designated PCR-ribotype 027 and 017 responsible for CDI outbreaks in the USA, Europe and Asia. We assessed sporulation and susceptibility of three PCR-ribotypes; 012, 017 and 027 to four classes of disinfectants; chlorine releasing agents (CRAs), peroxygens, quaternary ammonium compounds (QAC) and biguanides. The 017 PCR-ribotype, showed the highest sporulation frequency under these test conditions. The oxidizing biocides and CRAs were the most efficacious in decontamination of C. difficile vegetative cells and spores, the efficacy of the CRAs were concentration dependent irrespective of PCR-ribotype. However, there were differences observed in the susceptibility of the PCR-ribotypes, independent of the concentrations tested for Virkon®, Newgenn®, Proceine 40® and Hibiscrub®. Whereas, for Steri7® and Biocleanse® the difference observed between the disinfectants were dependent on both PCR-ribotype and concentration. The oxidizing agent Perasafe® was consistently efficacious across all three PCR ribotypes at varying concentrations; with a consistent five Log10 reduction in spore titre. The PCR-ribotype and concentration dependent differences in the efficacy of the disinfectants in this study indicate that disinfectant choice is a factor for llimiting the survival and transmission of C. difficile spores in healthcare settings.


Effects of submerged macrophytes (Elodea nuttallii) on water quality and microbial communities of largemouth bass (Micropterus salmoides) ponds.
Traditional aquaculture ponds are one of the most vulnerable ecosystems; thus, ecological aquaculture is increasingly valued for its beneficial ecological properties and ecosystem services. However, little is known about ecological aquaculture of largemouth bass with submerged vegetation. Here, we designed three ecological ponds of cultured largemouth bass with submerged macrophytes (the EM group) and three ponds with traditional aquaculture (the M group) to reveal the response of water quality, and phytoplankton and bacterial communities, to submerged macrophyte bioremediation during a 90-day culture period. We observed that Cyanobacterial outbreak occurred in the M group ponds from day 7 to the end of the experiment; however, there were no Cyanobacterial blooms in the EM group ponds throughout the culture period. Compared with the M group ponds, the EM group ponds, which had submerged hydrophytes, had significantly decreased concentrations of TP, TN, and CODMn, but significantly increased DO concentrations throughout the experimental period. Moreover, ecological aquaculture with submerged macrophytes showed strong effects on the phytoplankton and bacterial community compositions. In particular, the M group ponds had higher phytoplankton density and mainly included Cyanobacteria, whereas the EM group had lower phytoplankton density and mainly included Chlorophyta. Moreover, higher alpha diversity, as determined by Ace and Simpson index values, was detected for bacterial communities in the EM group ponds. Furthermore, PCoA clearly grouped the bacterial communities according to the two culture modes throughout the culture period. These results indicate that ecological aquaculture with submerged macrophytes can improve water quality, control Cyanobacterial blooms, and affect the diversity and composition of bacterial communities. These valuable effects seem to be beneficial and consistent to maintaining aquaculture ecosystem stability.


Harmonic scalpel hemorrhoidectomy: preliminary results of a new alternative method.
Surgical treatment is considered to be the best therapeutic modality for severe hemorrhoidal disease. Different surgical methods of hemorrhoidectomy aim to decrease pain, bleeding, stenosis and discharge. The aim of this study was to evaluate the efficacy of harmonic scalpel hemorrhoidectomy. During a period of seven months, 54 consecutive patients with third- and fourth-degree hemorrhoids were prospectively randomized for harmonic scalpel hemorrhoidectomy (HS) or Milligan-Morgan procedure (MM). These patients were examined at one, two, and six weeks after the operation. All patients had a lower gastrointestinal investigation prior to operation to exclude other colorectal pathologies. All patients had the same kind of preoperative preparation and analgesia during the postoperative course. Pain was assessed using a visual analog scale from 0 to 10. Patient satisfaction was defined as decrease or absence of symptoms and return to normal daily activities. HS groups included 29 patients, while the MM group had 25 patients. There as no difference between the groups in terms of age, gender, hemorrhoidal degree and indication for operation. The types of intra-operative anesthesia administered to the two groups were similar. Duration of surgery was significantly higher in the MM group ( p<0.0001). Postoperative hospitalization was longer in the MM group ( p<0.0001), and the pain degree was higher in MM group ( p<0.0001). No significant difference was noted in the overall amount of analgesics used in the two groups at week 1, although it was significantly higher in the MM group 2 and 3 weeks after the operation. Early complication occurred more frequently in the MM group but overall the difference was not statistically significant. In conclusion, harmonic scalpel hemorrhoidectomy is virtually a bloodless operation with minimal tissue damage. It is associated with significant less postoperative pain and a fast return to normal activity.


Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review.
Bone grafting is a commonly performed surgical procedure to augment bone regeneration in a variety of cases in orthopaedic and maxillofacial surgery. Autologous bone graft remains to be the 'gold standard' and the iliac crest to be the most common harvesting site. The intramedullary canal of long bones represents another potential site for large volume of autologous bone graft harvesting and is recently being used as an alternative donor site. However, harvesting of autologous bone graft is associated with morbidity and a number of complications. The aim of this systematic review was to collect and summarise the existing data on reported complications after harvesting autologous bone from the iliac crest (anterior and posterior) and the long bone intramedullary canal using the RIA device. We searched the PubMed Medline and Ovid Medline databases, from January 1990 to October 2010, to retrieve all relevant articles. A total of 92 articles (6682 patients) were included in the analysis. Overall, the complication rate following RIA was 6% (14 complications in 233 patients) and 19.37% after iliac crest bone graft harvesting (1249 complications in 6449 patients). The rate of each of the reported complications was assessed and, when the donor site was properly documented, comparison within the anterior and posterior iliac crest donor sites was performed. Although the difference of the overall morbidity rates between the two harvesting sites was not statistically significant (p=0.71); the rates of certain complications were found to significantly differ when anterior or posterior iliac crest was used. The rates of infection (p=0.016), haematoma formation (p=0.002), fracture (p=0.017), and hyperthrophic scar (p=0.017) were significantly higher when the donor site was the anterior iliac crest compared to the posterior iliac crest; whereas the rates of chronic donor site pain (p=0.004) and sensory disturbances (p=0.003) were significantly lower. The incidence of bone graft harvesting related complications can be reduced further if certain principles are followed depending on the performed harvesting methods; but overall the use of RIA device as harvesting method seems a promising alternative with a low complication rate.


Prosaposin and its receptors are differentially expressed in the salivary glands of male and female rats.
Salivary glands produce various neurotrophins that are thought to regulate salivary function during normal and pathological conditions. Prosaposin (PSAP) is a potent neurotrophin found in several tissues and various biological fluids and may play roles in the regulation of salivary function. However, little is known about PSAP in salivary glands. As the functions of salivary glands are diverse based on age and sex, this study examines whether PSAP and its receptors, G protein-coupled receptor 37 (GPR37) and GPR37L1, are expressed in the salivary glands of rats and whether sex and aging affect their expression. Immunohistochemical analysis revealed that PSAP and its receptors were expressed in the major salivary glands of rats, although their expression varied considerably based on the type of gland, acinar cells, age and sex. In fact, PSAP, GPR37 and GPR37L1 were predominantly expressed in granular convoluted tubule cells of the submandibular gland and the intensity of their immunoreactivity was higher in young adult female rats than age-matched male rats, which was more prominent at older ages (mature adult to menopause). On the other hand, weak PSAP, GPR37 and GPR37L1 immunoreactivity was observed mainly in the basal layer of mucous cells of the sublingual gland. Triple label immunofluorescence analysis revealed that PSAP, GPR37 and GPR37L1 were co-localized in the basal layer of acinar and ductal cells in the major salivary glands. The present findings indicate that PSAP and its receptors, GPR37 and GPR37L1, are expressed in the major salivary glands of rats and their immunoreactivities differ considerably with age and sex.


Deconvolution of Stark broadened spectra for multi-point density measurements in a flow Z-pinch.
Stark broadened emission spectra, once separated from other broadening effects, provide a convenient non-perturbing means of making plasma density measurements. A deconvolution technique has been developed to measure plasma densities in the ZaP flow Z-pinch experiment. The ZaP experiment uses sheared flow to mitigate MHD instabilities. The pinches exhibit Stark broadened emission spectra, which are captured at 20 locations using a multi-chord spectroscopic system. Spectra that are time- and chord-integrated are well approximated by a Voigt function. The proposed method simultaneously resolves plasma electron density and ion temperature by deconvolving the spectral Voigt profile into constituent functions: a Gaussian function associated with instrument effects and Doppler broadening by temperature; and a Lorentzian function associated with Stark broadening by electron density. The method uses analytic Fourier transforms of the constituent functions to fit the Voigt profile in the Fourier domain. The method is discussed and compared to a basic least-squares fit. The Fourier transform fitting routine requires fewer fitting parameters and shows promise in being less susceptible to instrumental noise and to contamination from neighboring spectral lines. The method is evaluated and tested using simulated lines and is applied to experimental data for the 229.69 nm C III line from multiple chords to determine plasma density and temperature across the diameter of the pinch. These measurements are used to gain a better understanding of Z-pinch equilibria.


[Medullary carcinoma of the thyroid gland].
We report the experience of the Institute of Surgical Pathology of the University of Parma on three patients with sporadic medullary thyroid carcinoma (MTC). MTC is a tumor of parafollicolor cells origin (C cells). The surgical excision of the thyroid tumor and cervical node metastases is potentially curative. The other therapeutic options are limited. Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN) related MTC. Genetic screening promises earlier and accurate diagnosis (RET gene mutations are found in MEN).


Vancomycin-resistant Enterococcus bacteremia: an evaluation of treatment with linezolid or daptomycin.
Due to high rates of resistance and a limited number of efficacious antimicrobials for vancomycin-resistant Enterococcus (VRE), appropriate antibiotic selection is vital to treatment success. The purpose of this study was to assess clinical and microbiologic outcomes associated with the use of linezolid or daptomycin in the treatment of VRE bacteremia. A retrospective analysis of adult patients with VRE bacteremia between January 2004 and July 2009 was conducted at a tertiary care hospital in the United States. Clinical and microbiologic outcomes for both therapies were evaluated using multiple criteria. Of the 361 patients with VRE bacteremia identified, 201 were included in the study (linezolid group, n = 138; daptomycin group, n = 63). More patients in the daptomycin group had hematologic malignancies (33% vs 14%) or received liver transplants (13% vs 4%). There was no difference in clinical or microbiologic cure between the linezolid and daptomycin groups (74% vs 75% and 94% vs 94%, respectively). Recurrence was documented in 3% of linezolid patients vs 12% of daptomycin patients (P = 0.0321). Reinfection was noted in 1% of patients in the linezolid group vs 6% of patients in the daptomycin group (P not significant). The average length of stay (LOS) was 37 days for the linezolid group vs 40 days for the daptomycin group (P not significant). Overall mortality was 20%, occurring in 25/138 linezolid patients vs 15/63 daptomycin patients (P not significant). No differences in clinical or microbiologic cure rates, LOS, or mortality were identified between the groups. Various factors may have contributed to the significantly higher recurrence of VRE bacteremia in daptomycin patients. This study suggests that linezolid and daptomycin appear equally efficacious in the treatment of VRE bacteremia.


Assessing and managing communication needs in people with serious mental illness.
Effective communication is essential to maintain mental health and resilience. Communication can be challenging for people who experience serious mental illness (SMI), which can be a barrier to social, employment and educational opportunities, as well as increasing their risk of experiencing abuse. Therefore, it is important that nurses who work with individuals experiencing SMI understand the assessment and management of specific communication, speech and language needs. This article focuses on five areas of communication, speech and language - receptive language, expressive language, speech, social communication and swallowing - to increase nurses' confidence in assessing communication needs and making appropriate referrals to speech and language therapy services. The authors also suggest therapeutic interventions that nurses can use to reduce the effects of speech and language difficulties among people with SMI.


Patient Satisfaction in a Safety Net Urology Clinic.
Patient satisfaction has become an important metric in medicine. In this study, we aim to identify modifiable factors contributing toward poor satisfaction amongst patients in a safety net urology clinic. We hypothesize that wait times and long distances traveled to clinic will have the largest contribution toward negative patient experiences. We conducted a cross-sectional study of adult patients presenting to the urology clinic at Zuckerberg San Francisco General Hospital. Participants completed a survey using the RAND Patient Satisfaction Questionnaire-18 after their clinic visit. Associations among demographic factors, wait times, use of a translator and satisfaction were examined. Two hundred patients, 19 to 90 years old (median age 62), were enrolled. Overall, 65% of patients were satisfied with their experience in our clinic. Our results demonstrated a significant association among race, language and overall satisfaction scores (p=0.009 and p=0.003, respectively). Multivariable analysis showed that those who waited more than an hour to see a physician were less satisfied compared with those who waited less than 15 minutes (OR 0.25, 95% CI 0.08-0.74). Similarly, those who used a translator were less satisfied than those who did not use a translator (OR 0.29, 95% CI 0.08-1.01). In a safety net urology clinic, language differences and wait times may contribute to poor patient satisfaction. Future efforts toward improving language interpreter functionality and decreasing patient wait times will likely improve patient satisfaction.


Heterostructured Silk-Nanofiber-Reduced Graphene Oxide Composite Scaffold for SH-SY5Y Cell Alignment and Differentiation.
Stem cell therapy is promising for treating traumatic injuries of the central nervous system, where a major challenge is to effectively differentiate neural stem cells into neurons with uniaxial alignment. Recently, controlling stem cell fate by modulating biophysical cues (e.g., stiffness, conductivity, and patterns) has emerged as an attractive approach. Herein, we report a new heterostructure composite scaffold to induce cell-oriented growth and enhance the neuronal differentiation of SH-SY5Y cells. The scaffold is composed of aligned electrospinning silk nanofibers coated on reduced graphene paper with high conductivity and good biocompatibility. Our experimental results demonstrate that the composite scaffold can effectively induce the oriented growth and enhance neuronal differentiation of SH-SY5Y cells. Our study develops a novel scaffold for enhancing the differentiation of SH-SY5Y cells into neurons, which holds great potential in the treatment of neurological diseases and injuries.


Responses of Spring Discharge to Different Rainfall Events for Single-Conduit Karst Aquifers in Western Hunan Province, China.
It is a challenge to describe the hydrogeological characteristics of karst aquifers due to the complex structure with extremely high heterogeneity. As the response of karst aquifers to rainfall events, spring discharge variations after precipitation can be used to identify the internal structure of karst systems. In this study, responses of spring discharge to different kinds of precipitations are investigated by continuously monitoring precipitation and karst spring flow at a single-conduit karst aquifer in western Hunan province, China. Recession curves were used to analyze hydrodynamic behaviors and separate recession stages. The results show that the shape of the recession curve was changed under different rainfall conditions. Recession processes can be divided in to three recession stages under heavy rain conditions due to water drainage mainly from conduits, fracture, and matrix at each stage, but only one recession stage representing drainage mainly from matrix in the case of light rain. With the change in amount and intensity of precipitation, the calculated recession coefficient at each stage changes in an order of magnitude. The influence of precipitation on the recharge coefficient and the discharge composition at each recession are discussed, and then the conceptual model diagram of water filling and releasing in the single-conduit karst aquifers is concluded. The findings provide more insight understand on hydraulic behaviors of karst spring under different types of rainfall events and provide support for water resource management in karst regions.


The medical home bends cost curve.
While the Affordable Care Act is trying to manage health insurance, as well as mandating coverage, a number of projects around the country are trying to manage the underlying cost of health care. By bringing back the concept of a true primary care physician, who provides 90% of your care and coordinates with your specialists, these programs are bending the curve of health care cost trends. Most are seeing a reduction in emergency room visits and hospital days in the double digits. Others that are taking fee-for-service insurance out of the picture altogether are experiencing even higher reduction rates. The goal is to increase patient health, which includes the patient having an active role in understanding his or her condition, treatment options and self-care strategies. It is estimated that if all Americans had access to a medical home, our nation could save $37 billion annually.


Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.
The long history of local anesthetics (LAs) starts out in the late 19th century when the content of coca plant leaves was discovered to alleviate pain. Soon after, cocaine was established and headed off to an infamous career as a substance causing addiction. Today, LAs and related substances-in modified form-are indispensable in our clinical everyday life for pain relief during and after minor and major surgery, and dental practices. In this review, we elucidate on the interaction of modern LAs with their main target, the voltage-gated sodium channel (Navs), in the light of the recently published channel structures. Knowledge of the 3D interaction sites of the drug with the protein will allow to mechanistically substantiate the comprehensive data available on LA gating modification. In the 1970s it was suggested that LAs can enter the channel pore from the lipid phase, which was quite prospective at that time. Today we know from cryo-electron microscopy structures and mutagenesis experiments, that indeed Navs have side fenestrations facing the membrane, which are likely the entrance for LAs to induce tonic block. In this review, we will focus on the effects of LA binding on fast inactivation and use-dependent inhibition in the light of the proposed new allosteric mechanism of fast inactivation. We will elaborate on subtype and species specificity and provide insights into modelling approaches that will help identify the exact molecular binding orientation, access pathways and pharmacokinetics. With this comprehensive overview, we will provide new perspectives in the use of the drug, both clinically and as a tool for basic ion channel research.


Unveiling the Potential Role of Nanozymes in Combating the COVID-19 Outbreak.
The current coronavirus disease 2019 (COVID-19) outbreak is considered as one of the biggest public health challenges and medical emergencies of the century. A global health emergency demands an urgent development of rapid diagnostic tools and advanced therapeutics for the mitigation of COVID-19. To cope with the current crisis, nanotechnology offers a number of approaches based on abundance and versatile functioning. Despite major developments in early diagnostics and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is still a need to find effective nanomaterials with low cost, high stability and easy use. Nanozymes are nanomaterials with innate enzyme-like characteristics and exhibit great potential for various biomedical applications such as disease diagnosis and anti-viral agents. Overall the potential and contribution of nanozymes in the fight against SARS-CoV-2 infection i.e., rapid detection, inhibition of the virus at various stages, and effective vaccine development strategies, is not fully explored. This paper discusses the utility and potential of nanozymes from the perspective of COVID-19. Moreover, future research directions and potential applications of nanozymes are highlighted to overcome the challenges related to early diagnosis and therapeutics development for the SARS-CoV-2. We anticipate the current perspective will play an effective role in the existing response to the COVID-19 crisis.


Borderline ovarian tumors: a retrospective cohort study on single institution experience, practice patterns and outcomes.
Borderline ovarian tumours (BOTs) commonly affect young nulliparous women, thus making fertility-preserving approaches more desirable. Women who opt for conservative management should be counselled about disease recurrence. In this retrospective study, the medical records of 57 women with BOT treated at the American University of Beirut Medical Centre between January 1986 and May 2018 were reviewed. Clinical, pathologic, and demographic data were collected and analysed to identify variables associated with poor clinical outcomes including advanced disease and risk of recurrence. Younger and nulliparous women were more likely to undergo fertility-sparing surgery. The open approach was adopted for women with larger adnexal masses and was associated with more blood loss with a mean difference of 172 mL (95% CI [110-235], p-value < .001) but no significant difference in operative time and length of hospital stay compared to the laparoscopic approach. CA-125 correlated with an advanced International Federation of Gynaecology and Obstetrics (FIGO) stage (p = .004). The recurrence rate was found to be 7% with a median recurrence time of 41.5 months.IMPACT STATEMENTWhat is already known on this subject? BOTs are common in young nulliparous women who often desire fertility-sparing procedures. Prognostic factors associated with disease severity and recurrence remain controversial.What do the results of this study add? This study presents an opportunity to understand the disease behaviour and compare local practices and outcomes to what was reported in the literature. CA-125 appears to be a useful marker in predicting the stage of BOT.What are the implications of these findings for clinical practice and/or further research? Future research should focus on exploring whether BOTs with micropapillary features represent an aggressive histologic subtype more prone to recurrence.


[Pathologic characteristics of residual carcinoma at incisal edge after gastrectomy for gastric cancer].
To explore the reason, features and preventive measures of residual carcinoma at incisal edge after gastric cancer operation. Clinical data of 108 cases with positive incisal margin(6.47%) from December 1964 to December 2004 in Cancer Center of Sun Yat-sen were summarized and analyzed retrospectively. Positive incisal margin patients accounted for 6.5%(108/1670) of total gastric carcinoma cases during above period. There were 62 men and 46 women with median age of 54 years(ranged from 23 to 82). The residual carcinoma rates of incisal edge were 3.6%(48/1333) in radical resection group and 17.8%(60/337) in palliative resection group respectively(P=0.000). Also, the residual carcinoma rates were 2.3%(3/129) in early group, 6.8(105/1541) in advanced group(P=0.046), 4.5%(37/815) in distal gastrectomy group and 8.0%(55/689) in proximal group respectively(P=0.000). Residual carcinomas were related with pTNM stage, Borrmann type, tumor size, differentiation and invasion depth(P<0.05). Superior gastric carcinoma, Borrmann III(, IIII( type advanced cancer, tumor diameter > or =5 cm, poor differentiation or undifferentiated type and serosa invaded easily result in residual carcinoma at incisal edge. The radical preventive measure is to ensure that incisal edge ought to exceed 5 cm apart from the tumor.


[Aerodynamic effect of tracheal voice tubes].
A usual rhinomanometer was used to construct an apparatus to measure the aerodynamic resistance of a tracheostomy speaking tube lying in the trachea. This resistance, evoked by the sieve or the hole in the tube, is considerable. A model of a trachea was made from a silicone tube to assess the resistance of several types of tracheostomy speaking tubes.


Measuring toe pressures using a portable photoplethysmograph to detect arterial disease in high-risk patients: an overview of the literature.
Lower extremity arterial disease (LEAD) is estimated to affect one third of individuals older than 65 years of age, occurs in younger individuals who use tobacco or have diabetes mellitus (DM), and often remains undiagnosed until a patient pres- ents with ischemia-related symptoms or complications. Valid and reliable noninvasive tests such as the ankle-brachial index (ABI) are recommended to detect LEAD. However, ABI results can be inconclusive or the index can be elevated (i.e., >1.3) in persons with calcified ankle arteries due to DM, renal failure, or arthritis. In these instances, obtaining toe pressure (TP) measurements, which correlate well with angiographic findings, is advised, providing the patient does not have vasoconstriction with cold toes or vasospastic disease. In such cases, TP can be obtained using a portable pho- toplethysmograph (PPG), which offers a simple and inexpensive method for healthcare providers in a variety of clinical settings to assess for the presence of LEAD. Portable PPG TP measurements have been found to have a high level of agreement with vascular laboratory PPG tests to detect LEAD, as well as good sensitivity and a high specificity. Adopting a TP measurement protocol of care to assess high-risk individuals such as patients with DM and elevated ABIs potentially can have a major impact on early identification of LEAD and reduce the risk of ischemia-related complications, including lower extremity wounds and amputations.


The changing U.S. labor force and occupational differentiation by sex.
The degree of occupational differentiation by sex in the U.S. labor force is examined utilizing various measures and occupational classifications over the period 1900-1970. A consideration of comparable occupations over time indicates that while occupational differentiation by sex is still substantial, an irregular, measurable decline in that differentiation has occurred during this century. Existing labor force structure seems relatively unimportant in explaining this ongoing change. Apparently more significant are social and historical factors as they have influenced specific occupations in certain decades.


Investigating user-friendliness of the sexual and reproductive health services among youth in Botswana.
The objectives of this study were to investigate the extent of user-friendliness of sexual reproductive health services offered in Botswana. A cross-sectional study was conducted among 110 youth. A self-administered questionnaire was used to assess the friendliness of the health providers, health facility and program design using a 5-point Likert scale. The mean age of the participants was 22.1 (SD = 3.5) years. A third (33%) of participants perceived the referral system as not being youth-friendly and/or not adequate. The majority of participants (84.2%) agreed or strongly agreed that the health providers greeted youth receiving sexual and reproductive health services in a polite manner with 89.2% either agreeing or strongly agreeing that health providers told youth to return if they had concerns and 91.9% encouraging them to ask questions. More than a quarter (26%) indicated the health providers had no respect for youth; 27% of the response variables were rated lowest among the variables used to assess the friendliness of the health facility. Almost two-thirds (64%) of respondents indicated the waiting time was excessive. Fifty percent felt the sex and reproductive health services had inadequate publicity. Health provider attitudes had the greatest impact on youth perceptions (Odd ratio = 11.81; p < 0.05). Although the sexual and reproductive health service in Botswana is doing well, there are still some few weaknesses that need to be addressed, particularly working hours, and publicity of the sexual reproductive health services and information.


Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac.
The C-type lectin-like receptor 2 (CLEC-2) activates platelets through Src and Syk tyrosine kinases via a single cytoplasmic YxxL motif known as a hem immunoreceptor tyrosine-based activation motif (hemITAM). Here, we demonstrate using sucrose gradient ultracentrifugation and methyl-beta-cyclodextrin treatment that CLEC-2 translocates to lipid rafts upon ligand engagement and that translocation is essential for hemITAM phosphorylation and signal initiation. HemITAM phosphorylation, but not translocation, is also critically dependent on actin polymerization, Rac1 activation, and release of ADP and thromboxane A(2) (TxA(2)). The role of ADP and TxA(2) in mediating phosphorylation is dependent on ligand engagement and rac activation but is independent of platelet aggregation. In contrast, tyrosine phosphorylation of the GPVI-FcRgamma-chain ITAM, which has 2 YxxL motifs, is independent of actin polymerization and secondary mediators. These results reveal a unique series of proximal events in CLEC-2 phosphorylation involving actin polymerization, secondary mediators, and Rac activation.


Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in acute pyelonephritis and renal scarring.
The aim of the present study was to elucidate the role of matrix metalloproteinase-9 (MMP-9), and its main inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1), in acute pyelonephritis and the process of renal scarring. Urine samples from 40 children with acute pyelonephritis, 16 children at 6-wk follow-up and 15 children with nonrenal fever were analyzed using ELISA. MMP-9 and TIMP-1 levels were compared with the outcome of pyelonephritis as measured by renal static scintigraphy. A mouse model of acute ascending pyelonephritis was used to localize the sites of production and the kinetics of MMP-9 and TIMP-1 using immunohistochemistry and ELISA. Human renal epithelial A498 cells, primary mesangial cells and monocytic THP-1 cells were stimulated by Escherichia coli. MMP-9 and TIMP-1 mRNA was analyzed by reverse transcription-PCR (RT-PCR) and protein production by ELISA. We demonstrate a significant increase of MMP-9 and TIMP-1 in the urine of children with acute pyelonephritis. Both proteins were produced mainly by leukocytes, and TIMP-1 also by resident kidney cells. Cells reacted differently after stimulation by bacteria. In mesangial cells and monocytes a decreased constitutive TIMP-1 production was found, which was in contrast to epithelial cells. Out of 40 children with pyelonephritis, 23 had higher urinary TIMP-1 than MMP-9 levels. These children had significantly more severe changes in both acute and follow-up scintigraphy scans indicating higher degree of acute tissue damage and renal scarring. Thus, our findings suggest an association between TIMP-1 and the process of renal scarring.


The structure of the lipid anchor of Campylobacter jejuni polysaccharide.
Campylobacter jejuni is a leading cause of gastroenteritis in humans. Campylobacter jejuni produces extracellular polysaccharides that have been characterized structurally and shown to be independent of lipopolysaccharides. Furthermore, it has been suggested that these C. jejuni polysaccharides are capsular in nature, although their lipid anchor has not been identified. In this report, the occurrence of a lipid-linked capsular-like polysaccharide in C. jejuni is conclusively shown, and the lipid anchor identified as dipalmitoyl-glycerophosphate.


Dilational surface elasticity of spread monolayers of polystyrene microparticles.
The dependence of the dilational surface elasticity on the surface pressure of the spread monolayers of polystyrene microparticles is studied at the water-air interface. The surface rheological measurements together with the data from optical methods allow the division of the whole range of surface pressures into three zones characterized by different monolayer structures. The extremely high surface elasticity (∼500 mN m(-1)) at surface pressures close to 30 mN m(-1) is similar to the results for the adsorption layer of the complexes formed between silica particles and surfactant molecules and is probably caused by strong hydrophobic attraction between the particles. At the same time, some other characteristic features of the viscoelasticity of the monolayers of polysterene microparticles differ strongly from the properties of previously studied systems.


Staphylococcal Skin and Soft Tissue Infections.
Staphylococcus aureus is the most common bacteria causing purulent skin and soft tissue infections. Many disease-causing S aureus strains are methicillin resistant; thus, empiric therapy should be given to cover methicillin-resistant S aureus. Bacterial wound cultures are important for characterizing local susceptibility patterns. Definitive antibiotic therapy is warranted, although there are no compelling data demonstrating superiority of any one antibiotic over another. Antibiotic choice is predicated by the infection severity, local susceptibility patterns, and drug-related safety, tolerability, and cost. Response to therapy is expected within the first days; 5 to 7 days of therapy is typically adequate to achieve cure.


Gross elevation of TT virus genome load in the peripheral blood mononuclear cells of cancer patients.
TT virus (TTV) is a recently described circular DNA virus of about 3.8 kb, which is related to the circoviridae viruses. It is commonly detected in healthy subjects and no association with any specific disease has been established. TTV was initially thought to be hepatotropic, but subsequent reports have shown that it is detectable in other tissues, including kidney, prostate, mammary gland, brain, bone marrow, and peripheral blood mononuclear cells. Plasma samples from cancer patients and healthy subjects were tested for the presence or absence of TTV by heminested polymerase chain reaction (PCR). We also developed a quantitative competitive PCR (QC-PCR) assay for TTV that permits accurate measurement of TTV DNA load. Using this assay, the TTV genome load in peripheral blood mononuclear cells (PBMCs) of healthy control subjects (n = 50) and patients with various types of cancer (n = 148), including breast cancer, non-Hodgkin's lymphoma, colon cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and other cancers, was measured. TTV DNA was detected in 69 of 100 plasma samples (69%) of cancer patients tested and in 39 of 100 plasma samples (39%) randomly selected from 1000 plasma samples of blood donors (p < 0.05). TTV DNA was detectable in the PBMCs of 99% of the cancer patients and 86% of the controls. However, the median virus load was more than 100-fold higher in the cancer patients (3599 copies/100,000 cells) than among the controls (30 copies/100,000 cells; p < 0.0001). There was no significant difference in TTV load among the different cancer types. Using a cutoff value of >250 copies per 100,000 PBMCs, 93.2% of cancer patients were "positive" compared to only 4% of healthy control subjects. Almost all the cancer patients have TTV infection and their TTV genome load in PBMCs is significantly higher than that in control subjects. It remains to be elucidated whether such findings are specific to cancer patients or occur in all seriously ill subjects.


Functional bracing after anterior cruciate ligament reconstruction: a prospective, randomized, multicenter study.
Bracing after anterior cruciate ligament reconstruction is expensive and is not proven to prevent injuries or influence outcomes. To determine whether postoperative functional knee bracing influences outcomes. Prospective, randomized, multicenter clinical trial. One hundred volunteers from the 3 US service academies with acute anterior cruciate ligament tears were randomized into braced or nonbraced groups. Only those subjects with anterior cruciate ligament tears treated surgically within the first 8 weeks of injury were included. Patients with chondral injuries, significant meniscal tears, or multiple knee ligament injuries were excluded. Surgical procedures and the postoperative physical therapy protocols were identical for both groups. The braced group was instructed to wear an off-the-shelf functional knee brace for all cutting, pivoting, or jumping activities for the first year after surgery. Ninety-five subjects were available with a minimum 2-year follow-up. There were no statistically significant differences between groups in knee stability, functional testing with the single-legged hop test, International Knee Documentation Committee scores, Lysholm scores, knee range of motion, or isokinetic strength testing. Two braced subjects had reinjuries, and 3 nonbraced subjects had reinjuries. In this young, active population, postoperative bracing does not appear to change the clinical outcomes after anterior cruciate ligament reconstruction.


X-linked variation in immune response in Drosophila melanogaster.
This study quantifies the effects of naturally occurring X-linked variation on immune response in Drosophila melanogaster to assess associations between immunity genotypes and innate immune response. We constructed a set of 168 X-chromosomal extraction lines, incorporating X chromosomes from a natural population into co-isogenic autosomal backgrounds, and genotyped the lines at 88 SNPs in 20 X-linked immune genes. We find that genetic variation in many of the genes is associated with immune response phenotypes, including bacterial load and immune gene expression. Many of the associations act in a sex-specific or sexually antagonistic manner, supporting the theory that with the selective pressures facing genes on the X chromosome, sexually antagonistic variation may be more easily maintained.


[Statins, and the vascular and valvular calcification].
Statins are currently approved for reducing the risk of cardiovascular diseases, clinically. These evidences were thought to be due to the lipid-lowering effects of the statins. But recently, the growing evidences showed the various effects of statins, such as inhibition of vascular and valvular calcification. How statins affects the bone forming proteins and genes are still not known.


Polyols and Polyurethane Foams Obtained from Mixture of Metasilicic Acid and Cellulose.
Hydroxyalkylation of the mixture of metasilicic acid and cellulose with glycidol and ethylene carbonate leads to a polyol suitable to obtain rigid polyurethane foams. The composition, structure, and physical properties of the polyol were studied in detail. The obtained foams have apparent density, water absorption, and polymerization shrinkage, as well as heat conduction coefficients similar to conventional, rigid polyurethane foams. The polyols and foams obtained from environmentally unobtrusive substrates are easily biodegradable. Additionally, the obtained foams have high thermal resistance and are self-extinguishing. Thermal exposure of the foams leads to an increase of the compressive strength of the material and further reduces their flammability, which renders them suitable for use as heat insulating materials.


[Use of multislice spiral computed tomography to diagnose and control pulmonary complications in intensive care unit patients after neurosurgical interventions].
To perform a multifactorial analysis of the association of the development of complications in neurologic intensive care unit patients in the early (on days 1-3) postoperative period and with surgical conditions, mechanical ventilation parameters, and risk factors. The results of multislice spiral computed tomography (MSCT) of the chest and brain were analyzed in 80 patients (34 men and 46 women; mean age, 52 +/- 13 years). In the study patient group, the incidence of pulmonary edema and pneumonia was not found to depend on the type of neurosurgical intervention and that of an inhaled anesthetic. There was a significant (p < 0.05) relationship of the development of pulmonary edema to anesthesia duration exceeding 6 hours and an increase in the risk of lung pathology in the presence of extrapulmonary complications in patients with high body mass index. Some pulmonary complications in neurosurgical patients are potentially preventable. Early postoperative chest MSCT in neurosurgical patients is essential to timely diagnose lung pathology.


Somatic mutation of TRbeta can cause a defect in negative regulation of TSH in a TSH-secreting pituitary tumor.
In patients with TSH-secreting tumors (TSHomas), serum TSH is poorly suppressed by thyroid hormone. The mechanism for this defect in negative regulation of TSH secretion is not known. To investigate the possibility of a somatic mutation of TR causing this defect, we performed mutational analysis of TRbeta by RT-PCR using RNA obtained from five surgically resected TSHomas. In one TSHoma, we identified a somatic mutation in the ligand-binding domain of TRbeta that caused a His to Tyr substitution at codon 435 of TRbeta1 corresponding to codon 450 of TRbeta2. Interestingly, this mutation occurred in the same codon as two mutations (TRbetaH435L and H435Q) previously identified in patients with the syndrome of resistance to thyroid hormone. This mutant TRbeta had impaired T3 binding and T3-mediated negative regulation. It also blocked the negative regulation by wild-type TRbeta2 on glycoprotein hormone alpha-subunit and TSHbeta reporter genes in cotransfection studies. Our results demonstrate that somatic mutation of TRbeta occurred in a TSHoma and was probably responsible for the defect in negative regulation of TSH by thyroid hormone in the tumor.


Formation of polymeric toroidal-spiral particles.
Compared to spherical matrices, particles with well-defined internal structure provide large surface to volume ratio and predictable release kinetics for the encapsulated payloads. We describe self-assembly of polymeric particles, whereby competitive kinetics of viscous sedimentation, diffusion, and cross-linking yield a controllable toroidal-spiral (T-S) structure. Precursor polymeric droplets are splashed through the surface of a less dense, miscible solution, after which viscous forces entrain the surrounding bulk solution into the sedimenting polymer drop to form T-S channels. The intricate structure forms because low interfacial tension between the two miscible solutions is dominated by viscous forces. The biocompatible polymer, poly(ethylene glycol) diacrylate (PEG-DA), is used to demonstrate the solidification of the T-S shapes at various configurational stages by UV-triggered cross-linking. The dimensions of the channels are controlled by Weber number during impact on the surface, and Reynolds number and viscosity ratio during subsequent sedimentation. We anticipate applications of the T-S particle in drug delivery, wherein diffusion through these T-S channels and the polymer matrix would offer parallel release pathways for molecules of different sizes. Polyphosphate, as a model macromolecule, is entrained in T-S particles during their formation. The in vitro release kinetics of polyphosphate from the T-S particles with various channel length and width is reported. In addition, self-assembly of T-S particles occurs in a single step under benign conditions for delicate macromolecules, and appears conducive to scaleup.


The distally based radial forearm fascia-fat flap for treatment of recurrent de Quervain's tendonitis.
A radial fascial flap has been described as a valuable and versatile option to provide appropriate tissue coverage of tendons, nerves, and soft tissues in the forearm and hand. We report the use of this distally based radial forearm fascia-fat flap to create a fascial tube to treat recurrent de Quervain's tendonitis.


Biogenesis of cbb(3)-type cytochrome c oxidase in Rhodobacter capsulatus.
The cbb(3)-type cytochrome c oxidases (cbb(3)-Cox) constitute the second most abundant cytochrome c oxidase (Cox) group after the mitochondrial-like aa(3)-type Cox. They are present in bacteria only, and are considered to represent a primordial innovation in the domain of Eubacteria due to their phylogenetic distribution and their similarity to nitric oxide (NO) reductases. They are crucial for the onset of many anaerobic biological processes, such as anoxygenic photosynthesis or nitrogen fixation. In addition, they are prevalent in many pathogenic bacteria, and important for colonizing low oxygen tissues. Studies related to cbb(3)-Cox provide a fascinating paradigm for the biogenesis of sophisticated oligomeric membrane proteins. Complex subunit maturation and assembly machineries, producing the c-type cytochromes and the binuclear heme b(3)-Cu(B) center, have to be coordinated precisely both temporally and spatially to yield a functional cbb(3)-Cox enzyme. In this review we summarize our current knowledge on the structure, regulation and assembly of cbb(3)-Cox, and provide a highly tentative model for cbb(3)-Cox assembly and formation of its heme b(3)-Cu(B) binuclear center. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.


Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2.
Exposure to aristolochic acid (AA) is associated with human nephropathy and urothelial cancer. Individual susceptibility to AA-induced disease likely reflects individual differences in enzymes that metabolize AA. Herein, we evaluated AAI metabolism by human cytochrome P450 (CYP) 1A1 and 1A2 in two CYP1A-humanized mouse lines that carry functional human CYP1A1 and CYP1A2 genes in the absence of the mouse Cyp1a1/1a2 orthologs. Human and mouse hepatic microsomes and human CYPs were also studied. Human CYP1A1 and 1A2 were found to be principally responsible for reductive activation of AAI to form AAI-DNA adducts and for oxidative detoxication to 8-hydroxyaristolochic acid (AAIa), both in the intact mouse and in microsomes. Overall, AAI-DNA adduct levels were higher in CYP1A-humanized mice relative to wild-type mice, indicating that expression of human CYP1A1 and 1A2 in mice leads to higher AAI bioactivation than in mice containing the mouse CYP1A1 and 1A2 orthologs. Furthermore, an exclusive role of human CYP1A1 and 1A2 in AAI oxidation to AAIa was observed in human liver microsomes under the aerobic (i.e., oxidative) conditions. Because CYP1A2 levels in human liver are at least 100-fold greater than those of CYP1A1 and there exists a > 60-fold genetic variation in CYP1A2 levels in human populations, the role of CYP1A2 in AAI metabolism is clinically relevant. The results suggest that, in addition to CYP1A1 and 1A2 expression levels, in vivo oxygen concentration in specific tissues might affect the balance between AAI nitroreduction and demethylation, which in turn would influence tissue-specific toxicity or carcinogenicity.


ACOG Committee Opinion No. 451: Von Willebrand disease in women.
Approximately 3 million women in the United States have inherited bleeding disorders. The prevalence of bleeding disorders is particularly high among women with menorrhagia. Von Willebrand disease is the most common inherited bleeding disorder. Once a diagnosis is made, collaboration with a hematologist is helpful for long-term management. Women with von Willebrand disease may be at increased risk for gynecologic and obstetric complications. Many treatments are available for the control of menorrhagia in women with von Willebrand disease, but the first-line therapy remains combined hormonal contraception.


The physiological and psychological effects of the expression and inhibition of emotion.
Previous work has indicated that humor enhances immunity, but the immunological effects of overt crying have not been studied. Thirty-nine women viewed sad and humorous videotapes and either inhibited or expressed overt expressions of laughter and weeping; these were observed and timed. Moods and immunity (S-IgA) were repeatedly measured. The humorous stimulus resulted in improved immunity, regardless of the overt laughter expressed; overt crying was immunosuppressive, whereas the inhibition of weeping in the context of the same sad stimulus was not. Moods were more negative following the sad stimulus and in the expression condition. The results with respect to humor are consistent with previous research; the immunosuppressive effect of overt crying is discussed in the context of various types of crying that may have different effects.


Mixed-power scaling of whole-plant respiration from seedlings to giant trees.
The scaling of respiratory metabolism with body mass is one of the most pervasive phenomena in biology. Using a single allometric equation to characterize empirical scaling relationships and to evaluate alternative hypotheses about mechanisms has been controversial. We developed a method to directly measure respiration of 271 whole plants, spanning nine orders of magnitude in body mass, from small seedlings to large trees, and from tropical to boreal ecosystems. Our measurements include the roots, which have often been ignored. Rather than a single power-law relationship, our data are fit by a biphasic, mixed-power function. The allometric exponent varies continuously from 1 in the smallest plants to 3/4 in larger saplings and trees. Therefore, our findings support the recent findings of Reich et al. [Reich PB, Tjoelker MG, Machado JL, Oleksyn J (2006) Universal scaling of respiratory metabolism, size, and nitrogen in plants. Nature 439:457-461] and West, Brown, and Enquist [West GB, Brown JH, Enquist BJ (1997) A general model for the origin of allometric scaling laws in biology. Science 276:122 -126.]. The transition from linear to 3/4-power scaling may indicate fundamental physical and physiological constraints on the allocation of plant biomass between photosynthetic and nonphotosynthetic organs over the course of ontogenetic plant growth.


Circulating interferon-alpha levels and hypertriglyceridemia in the acquired immunodeficiency syndrome.
The metabolic disturbances seen during infection are thought to be due to cytokines, modulators of the immune response. The acquired immunodeficiency syndrome (AIDS) is characterized by a high prevalence of hypertriglyceridemia and at times depletion of body cell mass (wasting). Elevated circulating levels of cytokines have also been reported in AIDS. Therefore, we determined the relationship between circulating cytokine levels and lipid levels and between circulating cytokine levels and wasting in AIDS and human immunodeficiency virus (HIV) infection. Serum samples from 45 patients with AIDS, 13 subjects with evidence of HIV infection by presence of antibody but without AIDS (HIV positive), and 17 seronegative control subjects who had previously undergone body composition analysis were analyzed for triglyceride, cholesterol, interferon, tumor necrosis factor (TNF), and interleukin-1 levels. Eleven subjects with AIDS or HIV infection had sequential measurements. Interferon was analyzed by bioassay with identification using specific antibodies. TNF and interleukin-1 were assayed by enzyme-linked immunosorbent assay. Lean body mass was assessed by total body potassium. Serum interferon-alpha levels were significantly elevated in patients with AIDS (p less than 0.001 compared to controls), with detectable levels in 84% of AIDS patients. Interferon-alpha was not detectable in serum from controls, while three of 13 HIV-positive subjects had detectable interferon-alpha levels. There was a significant correlation between interferon-alpha levels and serum triglyceride levels in AIDS and HIV-positive patients (R = 0.446, p less than 0.002). There was no relationship between interferon-alpha and serum cholesterol levels (R = -0.039, NS). In contrast only 11% of AIDS patients had detectable circulating TNF levels; the mean value for and the prevalence of detectable serum TNF levels were not significantly different from those of control subjects. Interleukin-1 was not detected in the circulation. There was no correlation between the presence of circulating TNF and serum triglycerides. There was no relationship between circulating interferon-alpha or TNF levels and the presence of wasting as measured by total body potassium. These studies suggest that interferon-alpha, which has previously been shown to modulate lipid metabolism in vivo and in vitro, may be responsible for the hypertriglyceridemia found in AIDS.


Phosphorylation via PKC Regulates the Function of the Drosophila Odorant Co-Receptor.
Insect odorant receptors (ORs) have a unique design of heterodimers formed by an olfactory receptor protein and the ion channel Orco. Heterologously expressed insect ORs are activated via an ionotropic and a metabotropic pathway that leads to cAMP production and activates the Orco channel. The contribution of metabotropic signaling to the insect odor response remains to be elucidated. Disruption of the G(q) protein signaling cascade reduces the odor response (Kain et al., 2008). We investigated this phenomenon in HEK293 cells expressing Drosophila Orco and found that phospholipase C (PLC) inhibition reduced the sensitivity of Orco to cAMP. A similar effect was seen upon inhibition of protein kinase C (PKC), whereas PKC stimulation activated Orco even in the absence of cAMP. Mutation of the five PKC phosphorylation sites in Orco almost completely eliminated sensitivity to cAMP. To test the impact of PKC activity in vivo we combined single sensillum electrophysiological recordings with microinjection of agents affecting PLC and PKC function and observed an altered response of olfactory sensory neurons (OSNs) to odorant stimulation. Injection of the PLC inhibitor U73122 or the PKC inhibitor Gö6976 into sensilla reduced the OSN response to odor pulses. Conversely, injection of the PKC activators OAG, a diacylglycerol analog, or phorbol myristate acetate (PMA) enhanced the odor response. We conclude that metabotropic pathways affecting the phosphorylation state of Orco regulate OR function and thereby shape the OSN odor response.


Mayo Clinic Clival Chordoma Case Series: Impact of Endoscopic Training on Clinical Care.
The management of clival chordoma in our group shifted around 2013 to mostly endoscopic, and proton beam was introduced for our multidisciplinary team. Consecutive patients who had surgical resection from 1987 to 2021 were reviewed. A total of 58 patients (39 patients after 2013) were analyzed. The mean tumor size was 3.7 cm, and the most common location was the upper clivus (43%). Compared to before 2013, after 2013, the endoscopic endonasal approach was more common (90%, p < 0.001), and more gross or near total resections (64%, p = 0.002) were attained. Ten cases (17%) were revision surgeries referred from elsewhere, and three cases (5%) underwent additional surgery elsewhere before adjuvant radiation. The postoperative cerebrospinal fluid leak occurred in 7%. Post-operative new cranial nerve deficits occurred in 32% before 2013, compared to 2.6% after 2013 (p = 0.004). For cases before 2013, 10 patients (53%) recurred during the median follow-up of 144 months (mean, 142 months), whereas for cases after 2013, seven patients (18%) recurred with a median follow-up of 35 months (mean, 42 months). 5-year progression-free survival was 58%, and 5-year overall survival was 87%. A specialized multidisciplinary team improved the resection rate compared to a historical cohort with an excellent morbidity profile.


Pericarditis: diagnosis, management, and return to play.
In athletes who present to their team physician with complaints of chest pain, the diagnosis of pericarditis should be entertained. Although generally self-limited, potential complications include cardiac tamponade and recurrent pericarditis. The typical scenario is of an athlete who had a recent viral upper respiratory illness and now presents with chest pain, friction rub, and characteristic electrocardiographic changes. Additional recommended testing includes complete blood count, erythrocyte sedimentation rate and/or C-reactive protein, cardiac enzymes, chest radiographs, and echocardiogram with Doppler. During acute pericarditis, participation in athletics is contraindicated. Return to play is permissible after there is no longer evidence of active disease. This is confirmed by the absence of effusion on echocardiography and normalization of serum markers of inflammation.


Inflammasomes and their roles in health and disease.
Inflammasomes are a set of intracellular protein complexes that enable autocatalytic activation of inflammatory caspases, which drive host and immune responses by releasing cytokines and alarmins into circulation and by inducing pyroptosis, a proinflammatory cell death mode. The inflammasome type mediating these responses varies with the microbial pathogen or stress factor that poses a threat to the organism. Since the discovery that polymorphisms in inflammasome genes are linked to common autoimmune diseases and less frequent periodic fever syndromes, inflammasome signaling has been dissected at the molecular level. In this review, we present recently gained insight on the distinct inflammasome types, their activation and effector mechanisms, and their modulation by microbial virulence factors. In addition, we discuss recently gained knowledge on the role of deregulated inflammasome activity in human autoinflammatory, autoimmune, and infectious diseases.


Ultrathin SnO2 nanorods: template- and surfactant-free solution phase synthesis, growth mechanism, optical, gas-sensing, and surface adsorption properties.
A novel template- and surfactant-free low temperature solution-phase method has been successfully developed for the controlled synthesis of ultrathin SnO(2) single-crystalline nanorods for the first time. The ultrathin SnO(2) single-crystalline nanorods are 2.0 +/- 0.5 nm in diameter, which is smaller than its exciton Bohr radius. The ultrathin SnO(2) nanorods show a high specific area (191.5 m(2) g(-1)). Such a thin SnO(2) single-crystalline nanorod is new in the family of SnO(2) nanostrucures and presents a strong quantum confinement effect. Its formation depends on the reaction temperature as well as on the concentration of the urea solution. A nonclassical crystallization process, Ostwald ripening process followed by an oriented attachment mechanism, is proposed based on the detailed observations from a time-dependent crystal evolution process. Importantly, such structured SnO(2) has shown a strong structure-induced enhancement of gas-sensing properties and has exhibited greatly enhanced gas-sensing property for the detection of ethanol than that of other structured SnO(2), such as the powders of nanobelts and microrods. Moreover, these ultrathin SnO(2) nanorods exhibit excellent ability to remove organic pollutant in wastewater by enormous surface adsorption. These properties are mainly attributed to its higher surface-to-volume ratio and ultrathin diameter. This work provides a novel low temperature, green, and inexpensive pathway to the synthesis of ultrathin nanorods, offering a new material form for sensors, solar cells, catalysts, water treatments, and other applications.


Inhibitory Effect of Autoclaving Whey-Based Medium on Propionic Acid Production by Propionibacterium shermanii.
Propionic acid production by Propionibacterium shermanii was compared in pasteurized and autoclaved whey-based media. Propionic acid production decreased with increasing whey concentration in autoclaved media but not in pasteurized media. Increasing the yeast extract concentration from 5 to 10 g/liter greatly reduced the inhibitory effect of autoclaving.


Design of Key Technologies for Elderly Public Network Services Based on Intelligent Recommendations.
As the world's population continues to increase, the proportion of elderly people is also rising. The existing elderly public service system is no longer able to meet the needs of the elderly for their daily lives. The elderly population is significantly less receptive to emerging matters than the younger population, resulting in the public elderly service system not being able to access the initial data of elderly users in a timely manner, which causes the system to make incorrect recommendations. Therefore, the elderly cannot enjoy all kinds of online services provided by the Internet platform. In order to solve this problem, an elderly intelligent recommendation method based on hybrid collaborative filtering is proposed. First, the data of elderly users and elderly service items are scored, and modelling is completed by a collaborative filtering algorithm. Then, the XGBoost model is combined to solve the optimal objective function, so that the recommended data set with the highest score in the nearest neighbour set is obtained. The experimental results show that the proposed hybrid algorithm effectively solves the cold start phenomenon that occurs when the elderly population uses the web to make recommendations for elderly services. In addition, the proposed hybrid algorithm has a higher recommendation footprint accuracy than other recommendation algorithms.


Scale of Adherence to Good Hospital Practices for COVID-19: Psychometric Properties.
To avoid hospital transmission, all COVID-19 prevention measures should be followed. This study aimed to evaluate the psychometric properties of a novel scale developed to assess adherence to good practices for COVID-19 in the hospital setting. A methodological cross-sectional study was conducted at a public hospital in the state of São Paulo, Brazil, with 307 healthcare providers. Data were collected using a questionnaire addressing sociodemographic/occupational data and the Adherence to Standard Precautions for COVID-19 scale. Cronbach's alpha coefficients and the intraclass correlation coefficients were used to measure internal consistency and temporal stability (test-retest analysis), respectively. Concurrent validity was evaluated using Spearman's correlation coefficients between the scores of the overall scale and its domains. Factorial structure was evaluated using exploratory factor analysis and goodness-of-fit of the model was tested using confirmatory factor analysis. Cronbach's alpha coefficients for the scale and its domains were higher than 0.7, except the psychosocial domain (0.61). All intraclass correlation coefficients were higher than 0.7. Strong correlations were found between the total score and the personal (0.84) and organizational (0.90) domains of the scale and a good correlation was found with the psychosocial domain (0.66). The fit of the multidimensional model was satisfactory for all parameters and the three-dimensional structure of the scale was confirmed by the fit of the factor loadings. The novel scale is a valid and reliable instrument for assessing adherence to good hospital practices for COVID-19.


Graded Nodal/Activin signaling titrates conversion of quantitative phospho-Smad2 levels into qualitative embryonic stem cell fate decisions.
Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of self-renewal and pluripotency in embryonic and epiblast stem cells. The molecular basis behind stem cell interpretation of Nodal/Activin signaling gradients and the undertaking of disparate cell fate decisions remains poorly understood. Here, we show that any perturbation of endogenous signaling levels in mouse embryonic stem cells leads to their exit from self-renewal towards divergent differentiation programs. Increasing Nodal signals above basal levels by direct stimulation with Activin promotes differentiation towards the mesendodermal lineages while repression of signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces trophectodermal differentiation. To address how quantitative Nodal/Activin signals are translated qualitatively into distinct cell fates decisions, we performed chromatin immunoprecipitation of phospho-Smad2, the primary downstream transcriptional factor of the Nodal/Activin pathway, followed by massively parallel sequencing, and show that phospho-Smad2 binds to and regulates distinct subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin signaling directly controls the Oct4 master regulator of pluripotency by graded phospho-Smad2 binding in the promoter region. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titrates self-renewal against alternative differentiation programs by direct regulation of distinct target gene subsets and Oct4 expression.


11-Beta Dehydrogenase Type 2 Activity Is Not Reduced in Treatment Resistant Hypertension.
Decreased renal 11-beta dehydrogenase type 2 (11β-HSD2) activity, as reflected by an increased urinary free cortisol to cortisone ratio (UFF/UFE), is associated with having hypertension (HTN). The current study was conducted to determine if reduced 11β-HSD2 activity is also associated with having resistant HTN. We evaluated 55 consecutive patients with RHTN, defined as blood pressure (BP) ≥140/90 mm Hg despite using ≥3 antihypertensive medications including a diuretic, and 38 patients whose BP was controlled on ≤3 medications to serve as a non-RHTN comparator group. All patients underwent biochemical evaluation, including measurement of 24-hour urinary UFF/UFE. The 2 study groups had similar demographic characteristics. Systolic, diastolic BP, and number of antihypertensive medications were greater in patients with uncontrolled RHTN vs. the control group (167.5 ± 28.2/91.2 ± 18.8 vs. 126.6 ± 11.4/77.8 ± 8.65 mm Hg and 4.31 ± 1.23 vs. 2.74 ± 0.6, respectively). The 24-hour UFF was 13.6 ± 11.8 vs. 14.3 ± 10.7 µg/24 h and UFE was 64.9 ± 36.3 vs. 76.1 ± 44 µg/24 h such that the UFF/UFE was 0.22 ± 0.16 vs. 0.19 ± 0.09 in RHTN vs. the control group. This ratio was not associated to age, race, gender, and body mass index. An elevated UFF/UFE was not present in this large cohort of patients with uncontrolled RHTN. This suggests that reduced conversion of cortisol to cortisone does not contribute to the development of RHTN.


[Main pharmacological roles and clinical curative effect of sanbi rebao].
Sanbi Rebao (contain 32 components, such as Radix Aconiti, Rhizoma Chuanxiong, Semen Strychni, Radix Glycyrrhizae, Radix Angelicae sinensis, Radix Ledebouriellae, Fructus Evodiae, borneolum syntheticum, etc.) had antagonistic action on the ear swollen response induced by croton oil and on the ear inflammation reaction caused by dimethylphenylene in mice. It could decrease significantly the response rate of turning its body induced by acetic acid, increase the pain threshold caused by warm, reduce the surface seepage of injure skin and accelerate the wound recovery. The above results showed Sanbi Rebao possessed the roles of dephlogisticate, analgesia and promoting wound recovery, Besides these, clinic research indicated that effective rate of Sanbi Rebao on pain or numbness caused by cold, damp and wind (rheumatism) was 97%.


Metabolic syndrome, diabetes and cardiovascular events: current controversies and recommendations.
Metabolic syndrome is now present in up to 40% of the United States adult population and is associated with a nearly a two fold increase in cardiovascular events, independent of the presence of diabetes mellitus. The concept of the metabolic syndrome as clinical syndrome has recently been challenged, however, and controversy exists as to whether the metabolic syndrome adds to cardiovascular risk above and beyond the sum of its independent metabolic components. Given the epidemic of obesity in both industrialized and third world countries, this issue is of great importance. The current article puts this controversy into perspective and explores the association of metabolic syndrome with both accelerated cardiovascular risk and the risk of development of type 2 diabetes. The pathophysiology of the increased risk of cardiovascular disease in diabetes associated with metabolic syndrome is discussed and the importance of early recognition of metabolic syndrome and potential role of addressing insulin resistance is stressed. Clearly more data is needed, but it is safe to say that metabolic syndrome is a worldwide epidemic in association with central obesity and underlying insulin resistance, which will propel a marked increase in cardiovascular events and diabetes mellitus in the years to come. Further research is needed to understand the role of more aggressive therapy in preventing type 2 diabetes and cardiovascular events in the population.


Pediatric Seymour Fractures of the Toe.
Seymour fractures of the toe are physeal fractures with often occult concomitant nail bed injuries and thus are open fractures. They are uncommon injuries that without proper treatment can result in osteomyelitis. The literature has sparse information regarding the clinical outcomes for these injuries. A single-center retrospective review included juxta-epiphyseal fractures or Salter-Harris I/II fracture of the toe with documented concomitant nail bed injury or laceration. Clinical and radiographic data were recorded for consecutive fractures. The primary outcome was the incidence of osteomyelitis. Secondary outcomes included premature physeal arrest, development of nail dystrophy, and functionality of the toe. Between 2006 and 2019, 19 patients were treated for this injury by the pediatric orthopaedic division. Complications included osteomyelitis (n=6), physeal arrest (n=4), and nail dystrophy (n=1). Days from injury to definitive treatment were significantly greater in patients who developed osteomyelitis compared with those who did not (P<0.01). Patients were significantly more likely to develop osteomyelitis if they did not receive acute definitive treatment (<48 h) (P<0.001; likelihood ratio, 17.9). Prompt definitive treatment of Seymour fractures of the toe was associated with a lower incidence of osteomyelitis. Greater awareness for these seemingly innocuous injuries is needed to provide an early treatment that may reduce the rate of osteomyelitis. Level IV-case series.


Metabolic activation of furfuryl alcohol: formation of 2-methylfuranyl DNA adducts in Salmonella typhimurium strains expressing human sulfotransferase 1A1 and in FVB/N mice.
Furfuryl alcohol, formed by acid- and heat-induced dehydration from pentoses, is found in many foodstuffs. It induced renal tubule neoplasms in male B6C3F1 mice and nasal neoplasms in male F344/N rats in a study of the National Toxicology Program (NTP). However, furfuryl alcohol was negative in the standard Ames test and in a battery of in vivo mutagenicity tests. Here, we show that furfuryl alcohol is mutagenic in Salmonella typhimurium TA100 engineered for expression of human sulfotransferase (SULT) 1A1. This finding suggests that furfuryl alcohol is converted by intracellular sulfo conjugation to 2-sulfo-oxymethylfuran, an electrophile reacting with DNA. We detected nucleoside adducts of 2'-deoxyadenosine, 2'-deoxyguanosine and 2'-deoxycytidine in porcine liver DNA incubated with freshly prepared 2-sulfo-oxymethylfuran. The main adducts, N(2)-((furan-2-yl)methyl)-2'-deoxyguanosine (N(2)-MFdG) and N(6)-((furan-2-yl)methyl)-2'-deoxyadenosine (N(6)-MFdA) were synthesized. Their structures were verified by NMR and mass spectrometry. Liquid chromatography-tandem mass spectrometry methods for the quantification of both adducts were devised. N(2)-MFdG and N(6)-MFdA were detected in DNA of furfuryl alcohol-exposed S.typhimurium TA100 expressing SULT1A1 and in DNA of liver, lung and kidney of FVB/N mice that had received ∼390 mg furfuryl alcohol/kg body wt/day via the drinking water for 28 days. In summary, furfuryl alcohol is converted by sulfo conjugation to a mutagen. The detection of N(2)-MFdG and N(6)-MFdA in renal DNA of furfuryl alcohol-treated mice suggests that the neoplasms observed in this tissue in the study of the NTP may have been induced by 2-sulfo-oxymethylfuran.


Paired Ig-like receptors bind to bacteria and shape TLR-mediated cytokine production.
The innate immune system uses a wide variety of pattern recognition receptors including TLRs, scavenger receptors, and lectins to identify potential pathogens. A carefully regulated balance between activation and inhibition must be kept to avoid detrimental and inappropriate inflammatory responses. In this study, we identify murine-paired Ig-like receptor (PIR)-B, and its human orthologs Ig-like transcript 2 and Ig-like transcript 5 as novel receptors for Staphylococcus aureus. PIR-B contains four ITIM motifs and is thought to be an inhibitory receptor. Expression of these receptors enables NIH3T3 cells to bind S. aureus. In mouse bone marrow-derived macrophages, masking of PIR-B by anti-PIR mAb or genetic deletion of PIR-B shows significantly impaired recognition of S. aureus and enhanced TLR-mediated inflammatory responses to the bacteria. These data suggest a novel mechanism for innate immune regulation by paired Ig-like receptor family members.


Glycyrrhizic acid-loaded pH-sensitive poly-(lactic-co-glycolic acid) nanoparticles for the amelioration of inflammatory bowel disease.
Aim: To fabricate and evaluate the therapeutic efficacy of glycyrrhizic acid (GA)-loaded pH-sensitive nanoformulations that specifically target and combat mucosal inflammation of the colon. Methods: GA-loaded Eudragit® S100/poly-(lactic-co-glycolic acid) nanoparticles were developed through modified double-emulsion evaporation coupled with solvent evaporation coating techniques and analyzed for physicochemical characteristics, surface chemistry, release kinetics, site-retention and therapeutic effectiveness. Results: Nanoparticles have a particle size of approximately 200 nm, high encapsulation efficiency, desired surface chemistry with pH-dependent and sustained drug release behavior following the Gompertz kinetic model. In vivo retention and therapeutic effectiveness in the inflamed colon tissues were confirmed by macroscopic and microscopic indices, cytokine analysis and antioxidant assays. Conclusion: GA-loaded Eudragit S100/poly-(lactic-co-glycolic acid) nanoparticles could efficiently deliver GA to the colon and ameliorate the mucosal inflammation for a prolonged duration.