Co-production of GroELS discriminates between intrinsic and thermally-induced recombinant protein aggregation during substrate quality control.
The effects and effectiveness of the chaperone pair GroELS on the yield and quality of recombinant polypeptides produced in Escherichia coli are matter of controversy, as the reported activities of this complex are not always consistent and eventually indicate undesired side effects. The divergence in the reported data could be due, at least partially, to different experimental conditions in independent research approaches. We have then selected two structurally different model proteins (namely GFP and E. coli β-galactosidase) and two derived aggregation-prone fusions to explore, in a systematic way, the eventual effects of GroELS co-production on yield, solubility and conformational quality. Host cells were cultured at two alternative temperatures below the threshold at which thermal stress is expected to be triggered, to minimize the involvement of independent stress factors. From the analysis of protein yield, solubility and biological activity of the four model proteins produced alone or along the chaperones, we conclude that GroELS impacts on yield and quality of aggregation-prone proteins with intrinsic determinants but not on thermally induced protein aggregation. No effective modifications of protein solubility have been observed, but significant stabilization of small (encapsulable) substrates and moderate chaperone-induced degradation of larger (excluded) polypeptides. These findings indicate that the activities of this chaperone pair in the context of actively producing recombinant bacteria discriminate between intrinsic and thermally-induced protein aggregation, and that the side effects of GroELS overproduction might be determined by substrate size.


Requirement for Vibrio cholerae integration host factor in conjugative DNA transfer.
The requirement for host factors in the transmission of integrative and conjugative elements (ICEs) has not been extensively explored. Here we tested whether integration host factor (IHF) or Fis, two host-encoded nucleoid proteins, are required for transfer of SXT, a Vibrio cholerae-derived ICE that can be transmitted to many gram-negative species. Fis did not influence the transfer of SXT to or from V. cholerae. In contrast, IHF proved to be required for V. cholerae to act as an SXT donor. In the absence of IHF, V. cholerae displayed a modest defect for serving as an SXT recipient. Surprisingly, SXT integration into or excision from the V. cholerae chromosome, which requires an SXT-encoded integrase related to lambda integrase, did not require IHF. Therefore, the defect in SXT transmission in the V. cholerae IHF mutant is probably not related to IHF's ability to promote DNA recombination. The V. cholerae IHF mutant was also highly impaired as a donor of RP4, a broad-host-range conjugative plasmid. Thus, the V. cholerae IHF mutant appears to have a general defect in conjugation. Escherichia coli IHF mutants were not impaired as donors or recipients of SXT or RP4, indicating that IHF is a V. cholerae-specific conjugation factor.


Endometriosis and infertility: a review.
The objective of this article is to review the current understanding of the relationship between endometriosis and infertility and the recommended management based on the latest evidence. The article is based on a MEDLINE search and bibliography review of the relevant literature from 1960 to 2003. The exact nature of the relationship between endometriosis and infertility remains uncertain. Surgical treatment of moderate and severe endometriosis improves the monthly fecundity rate. Surgical ablation of minimal and mild endometriosis seems superior to expectant management. Infertile patients with minimal and mild endometriosis can benefit from using clomiphene citrate and intrauterine insemination (IUI) or gonadotropins and IUI. Ovarian suppression should not be used in asymptomatic patients wishing to become pregnant except in the setting of in vitro fertilization and embryo transfer (IVF/ET). Prolonged suppression with gonadotropic-releasing hormone analogues should be considered for endometriosis patients about to undergo an IVF/ET cycle. IVF seems to be effective in endometriosis patients.


Advances in Brain Metastases Diagnosis: Non-coding RNAs As Potential Biomarkers.
Brain metastasis is considered the most common brain tumor. They arise from different primary cancers. The most common primary tumors giving brain metastases include breast, colorectal, lung, melanoma, and renal cancer. Depending only on history, physical examination, and conventional imaging modalities makes brain tumors diagnosis difficult. Rapid and non-invasive promising modalities could diagnose and differentiate between different brain metastases without exposing the patients to unnecessary brain surgeries for biopsies. One of these promising modalities is non-coding RNAs (ncRNAs). NcRNAs can determine brain metastases' prognosis, chemoresistance, and radioresistance. It also helps us to understand the pathophysiology of brain metastases development. Additionally, ncRNAs may work as potential therapeutic targets for brain metastases treatment and prevention. Herein, we present deregulated ncRNAs in different brain metastases, including microRNAs and long non-coding RNAs (lncRNAs), such as gastric adenocarcinoma, colorectal, breast, melanoma, lung, and prostate cancer. Additionally, we focus on serum and cerebrospinal fluid (CSF) expression of these ncRNAs in patients with brain metastases compared to patients with primary tumors. Moreover, we discuss the role of ncRNAs in modulating the immune response in the brain microenvironment. More clinical studies are encouraged to assess the specificity and sensitivity of these ncRNAs.


Diagnostic performance of dental students in identifying mandibular condyle fractures by panoramic radiography and the usefulness of reference images.
The purpose of this study was to evaluate the diagnostic performance of dental students in detection of mandibular condyle fractures and the effectiveness of reference panoramic images. Forty-six undergraduates evaluated 25 panoramic radiographs for condylar fractures and the data were analyzed through receiver operating characteristic (ROC) analysis. After a month, they were divided into two homogeneous groups based on the first results and re-evaluated the images with (group A) or without (group B) reference images. Eight reference images included indications showing either typical condylar fractures or anatomic structures which could be confused with fractures. Paired t-test was used for statistical analysis of the difference between the first and the second evaluations for each group, and student's t-test was used between the two groups in the second evaluation. The intra- and inter-observer agreements were evaluated with Kappa statistics. Intra- and inter-observer agreements were substantial (k=0.66) and moderate (k=0.53), respectively. The area under the ROC curve (Az) in the first evaluation was 0.802. In the second evaluation, it was increased to 0.823 for group A and 0.814 for group B. The difference between the first and second evaluations for group A was statistically significant (p<0.05), however there was no statistically significant difference between the two groups in the second evaluation. Providing reference images to less experienced clinicians would be a good way to improve the diagnostic ability in detecting condylar fracture.


C2H2 Zinc Finger Proteins Response to Abiotic Stress in Plants.
Abiotic stresses have already exhibited the negative effects on crop growth and development, thereby influencing crop quality and yield. Therefore, plants have developed regulatory mechanisms to adopt against such harsh changing environmental conditions. Recent studies have shown that zinc finger protein transcription factors play a crucial role in plant growth and development as well as in stress response. C2H2 zinc finger proteins are one of the best-studied types and have been shown to play diverse roles in the plant abiotic stress responses. However, the C2H2 zinc finger network in plants is complex and needs to be further studied in abiotic stress responses. Here in this review, we mainly focus on recent findings on the regulatory mechanisms, summarize the structural and functional characterization of C2H2 zinc finger proteins, and discuss the C2H2 zinc finger proteins involved in the different signal pathways in plant responses to abiotic stress.


Disinfecting activities of non-peroxide soft contact lens cold disinfection solutions.
The antimicrobial activities of three non-peroxide soft contact lens chemical disinfection systems--ReNu Multi-Purpose Solution (0.00005% polyaminopropyl biguanide), Opti-Soft Disinfecting Solution (0.001% polyquaternium-1), and Opti-Free Rinsing, Disinfecting & Storage Solution (0.001% polyquaternium-1)--were compared to Soft Mate Disinfecting Solution (0.005% chlorhexidine digluconate). Each product was separately inoculated with each of five microorganisms at approximately 10(6) microorganisms per mL. All of the solutions demonstrated excellent disinfecting activity against Pseudomonas aeruginosa and Staphylococcus epidermidis, with complete disinfection occurring within 4 hours. Only Soft Mate disinfected Serratia marcescens within 4 hours. ReNu reduced the microorganisms to 10-100 cells/mL and Opti-Soft and Opti-Free reduced the number to 10(2)-10(3) cells/mL. For the fungal species, Soft Mate showed excellent activity against Candida albicans (disinfection in 4 hours) and reduced Aspergillus fumigatus to 10(3) spores/mL in 4 hours. After 4 hours ReNu, Opti-Soft, and Opti-Free had reduced C. albicans only slightly, to 10(5) cells/mL and displayed virtually no disinfecting activity against A. fumigatus. For these newer chemical disinfection systems, diligent cleaning and rinsing of the soft contact lenses are the most important steps in the patient care regimen.


Silent cardiac ischemia in cervical spinal cord injury: case study.
The management of ischemic heart disease in patients with chronic spinal cord injury (SCI) will become an increasingly major concern as this population ages. Although silent ischemia has become an important topic in the medical literature, the relationship with cervical SCI has not been adequately explored. A literature search revealed no case reports of documented asymptomatic cardiac ischemia in SCI patients. This is a case report of a 65-year-old patient with chronic C7 incomplete SCI who had multiple risk factors for coronary artery disease and an abnormal electrocardiogram. Despite being completely asymptomatic, the patient was found to have significant myocardial ischemia induced by minimal stress using atrial paced thallium scintigraphy. This finding led to the cancellation of an elective surgical procedure. This case illustrates the importance of suspecting silent myocardial ischemia in cervical SCI patients.


A method to evaluate cardiac surgery mortality: phase of care mortality analysis.
This is a study of a method of mortality review, adopted by the Michigan Society of Thoracic and Cardiovascular Surgeons, to enhance understanding of mortality and potentially avoidable deaths after cardiac surgery, utilizing a voluntary statewide database. A system to categorize mortality was developed utilizing a phase of care mortality analysis approach as well as providing criteria to classify mortality as potentially "avoidable." For each mortality, the operating surgeon categorized a cardiac surgery mortality trigger into 1 of 5 time frames: preoperative, intraoperative, intensive care unit (ICU), postoperative floor, and discharge. A total of 53,674 adult cardiac operations were performed from January 1, 2006 to June 30, 2010 with a crude mortality of 3.5% (1,905 of 53,674). Of the mortalities analyzed, 35% (618 of 1,780) were preoperative, 25% (451 of 1,780) were ICU, 19% (333 of 1,780) were intraoperative, 11% (198 of 1,780) were floor, and 10% (180 of 1,780) were discharge phase. "Avoidable" mortality triggers occurred in 53% (174 of 333) of the intraoperative, 41% (253 of 618) and (184 of 451) of the preoperative and ICU phases, 42% (83 of 198) of the floor, and 19% (35 of 180) of the discharge phase. Overall potentially avoidable mortality was 41% (729 of 1780). Thirty-six percent (644 of 1,780) of the mortalities were coronary artery bypass grafting patients and 29% (188 of 644) of these were in the preoperative phase, with a mean predicted risk of 16%. This analysis identifies the occurrence of potentially avoidable mortalities in the 4 hospital phases of care, with the largest absolute number of avoidable mortalities occurring in the preoperative phase. A focus on these phases of care provides significant opportunity for quality improvement initiatives. Utilizing phase of care mortality analysis stimulates surgeons and hospitals to develop and refine mortality reviews and provides a structured statewide platform for discussion, education, quality improvement, and enhanced outcomes.


Optimization of Phase Space files from clinical linear accelerators.
This work proposes a methodology to produce an optimized phase-space (PhSp) for the Elekta Synergy linac by tuning the energy and direction of particles inside the 6-MV Elekta Precise PhSp, provided by the International Atomic Energy Agency (IAEA), for Monte Carlo (MC) simulations. First, the energies of the particles emerging from the original PhSp were increased by different factors, producing new PhSps. Percentage depth dose (PDD) profiles were simulated and compared to measured data from a Synergy linac for 6-MV photon beam. This process was repeated until a minimum difference was reached. Particles' directions were then manipulated following identified correlations to lateral profiles, resulting in two distinct perturbation factors based on inline and crossline profiles. Both factors were merged into one single optimal factor. For energy optimization, an increase of 0.32 MeV applied to all particles inside the original PhSp, but to 0.511 MeV annihilation photons, provided the best results. The direction optimization factor was the combination of the individual factors for inline (0.605%) and crossline (0.051%). The agreement between measured and simulated profiles, when using the optimized PhSp, improved considerably in comparison to simulations performed with the original IAEA PhSp. For all fields and depths analyzed, the discrepancies for PDD, inline and crossline profiles dropped from 11.2%, 15.7% and 27.5% to under 1.4%, 4.7% and 13.2%, respectively. The optimized PhSp should not replace the full linac modelling, however it offers an alternative for MC dose calculations when neither geometric details nor validated IAEA PhSp are available to the user.


Development of a Remote Displacement Measuring Laser System for Bridge Inspection.
Measuring displacement is essential for assessing the safety of bridges. Non-contact sensors such as vision sensors can precisely measure displacement but may be expensive or incapable of micro-scale measurement at a low cost, unlike contact displacement sensors, which are economical but challenging to install. This study proposes an economical, remote non-contact sensor system. The system comprises a laser beam transmitter and a light receiver, deriving the displacement based on the position where the laser beam is irradiated to the light-receiving surface. To measure this, the light receiver was installed at the measurement point and included a wireless communicator to transmit the displacement data. A displacement experiment was conducted to evaluate the performance. The results confirmed that precise displacement measurements were possible at a resolution of 100 µm. For bridge load tests, a light receiver under a bridge was installed, laser beams irradiated to the light-receiving surface from a distance, and the displacement was measured for each test and compared with the values measured by a conventional contact sensor. The results were highly consistent with those of the existing sensor, indicating that the proposed sensor system applies to bridge loading tests and the safety diagnosis for various structures.


Motor performance and behaviour in preterm and full-term 3-year-old children.
To compare the motor performance and behaviour at 3 years of age of very preterm, moderately preterm and full-term children (n = 221), who needed neonatal intensive care (NIC), and of 72 neonatally healthy full-term children (reference group). A model for combined assessment of motor performance and behaviour (CAMPB) was used. The children's performance was assessed on the basis of observations and documentation of categories of co-ordination, attention and social behaviour included in CAMPB. Significantly more very preterm children showed deviations in co-ordination than children in the other groups, and this difference was most evident in comparison with the reference group. No differences were found between the groups regarding attention and social behaviour during the assessment. Very preterm children differ from moderately preterm and full-term children in their motor performance at 3 years of age. By means of CAMPB, individual children with pronounced incoordination were identified in all groups, and some of them also showed pronounced lack of attention.


Familial aquagenic urticaria associated with familial lactose intolerance.
Aquagenic urticaria is a rare disorder characterized by the occurrence of pruritus and wheals after temporary contact with water. The familial occurrence of aquagenic urticaria over 3 generations is reported here in association with familial lactose intolerance, a condition in which the enzyme lactase encoded on chromosome 2, is deficient. In two patients, a young man and his mother, we verified the appearance of pruritic hives 5 to 10 minutes after contact with water of any temperature. Other types of physical urticaria were absent, and mastocytosis was excluded by extensive laboratory investigations; lactose intolerance was confirmed in both patients by H(2)-exhalation test. In these patients the clinical symptoms did not respond to antihistamines or UV-radiation therapy. Four other members of the family had wheals from water contact, two of whom had lactose intolerance. Two other members had lactose intolerance only. Although the association of aquagenic urticaria with lactose intolerance may be coincidental, attention is drawn to the fact that the 2 conditions, known to be familial, may coexist in the same family, possibly based on an association of gene loci.


DR. CARMAN'S DENTALAID and RICKSECKER'S DENTAROMA: A Connection?
The wild image on this Victorian trade card is especially eye-catching (Fig. 1A). The thirteen animals and birds casually hanging around the DR. CARMAN'S DENTALAID display booth at the 1882 AMERICAN INSTITUTE in New York, certainly drew attention by the strangeness of the illustration. The written description on the reverse of the DENTALAID card is an excellent example of good advertising by good writing and the obverse exemplifies, even without the use of color, eye-appeal. This card was undoubtedly given out at S.A. DUSTIN'S NEW DRUG STORE on Main Street in Batavia, N.Y. (see red stamp on obverse) and at the exhibit booth.


Cardinal Temperatures for Growth of Osmotolerant Yeasts in Broths at Different Water Activity Values.
All three cardinal temperatures (Tmin, Topt and Tmax) for growth of 6 strains as well as Tmin and Tmax for growth of an additional 23 strains were determined in solutions of 10, 30, 50 and 60% (w/w) glucose at aw (20°C) of 0.990, 0.970, 0.922 and 0.868, respectively. The Topt for growth of Zygosaccharomyces rouxii and Z. bisporus were 24-28.5°C at aw >0.990 and 31-33°C at aw in the range of 0.922-0.868. Z. bailii showed Topt for growth of 29-31°C and 33-35°C at aw >0.990 and aw <0.922, respectively. The Topt for growth of Torulaspora delbrueckii was 27-28.5°C at aw <0.990 and 31-33.5 at aw in the range of 0.922-0.868. Debaryomyces hansenii showed a Topt of 24°C and 27-29.5°C at aw >0.990 and aw <0.922, respectively. The Tmin and Tmax for growth were also shifted toward higher values as the aw decreased; at aw<0.922 none of the tested strains grew at 4°C within 30 d. Several strains could grow at 42°C only in the presence of high sugar concentrations.


Willingness to join community based health insurance among households in South Wollo, Northeast Ethiopia: A community-based cross-sectional study.
Poor health care financing remains a major challenge to health service utilization among the lower socioeconomic society. Consequently, countries have designed different health insurance programs to overcome financial barriers against health services utilization. Similarly, Ethiopia has been implementing community-based health insurance programs since 2011 to improve health care financing system. However, only a small number of people are enrolled which might be attributed to lack of willingness towards the program and the reasons for this remained under reported. This study was intended to examine willingness to join the community-based health insurance program and its associated factors in South Wollo, Northeast Ethiopia. A community-based cross-sectional study was conducted among 421 households. A multistage systematic random sampling technique was employed to recruit the study households. Data were entered into EpiData version 3.1 and was exported into SPSS version 24.0 for analysis. Bivariable and multivariable logistic regression analysis with a backward elimination method was performed to identify the determinants of willingness to join community-based health insurance. Finally, a statistically significant level was declared at a p-value of less than 0.05. Two hundred and ninety-three [73.6% (95%CI:68.8%-77.9%)] households were willing to join community-based health insurance programs. Being male headed household (AOR:0.2, 95%CI: 0.07-0.58), being a member of Idir (AOR:0.46, 95%CI: 0.25-.84), absence of chronic illness in the household (AOR: 0.31, 95%CI: 0.13-0.77), and family size < 4 (AOR: 0.18, 95% CI:0.08-0.41) were barriers to join community-based health insurance program whereas rural residency (AOR:1.9, 95% CI: 1.09-3.32), perceived quality health services (AOR:2.96, 95%CI:1.4-6.24), and having positive attitude (AOR:4.1, 95%CI:2.32-7.22) and good knowledge to programs (AOR:2.62, 95%CI:1.43-4.8) were enabling factors. Nearly three-fourths of the households were willing to join community-based health insurance programs. However, different household and health service-related factors affected their willingness. The ministry of health with the regional and woreda health offices should work towards improving the quality of health services, conduct program advocacy and community sensitization towards the program, and build trust with the community.


Tumour necrosis factor antagonist and tuberculosis in patients with rheumatoid arthritis: an Asian perspective.
Rheumatoid arthritis (RA) is a systemic autoimmune disease in which inflammation of the joints is one of the dominant clinical abnormalities resulting in serious morbidity. Over the past decade, tumour necrosis factor (TNF) antagonist has revolutionized the treatment of RA. However, the subsequent increased risk of developing tuberculosis is one of the major drawbacks of this otherwise effective treatment. Latent tuberculosis infection (LTBI) is an asymptomatic form of tuberculosis that is confined by the host's immune system. Active tuberculosis may develop when the immune status weakens. This risk is much higher in patients receiving TNF antagonist. Traditionally, tuberculin skin test (TST) is used to diagnose LTBI. Unfortunately, TST cannot distinguish bacillus Calmette-Guérin (BCG) vaccination from tuberculosis making it difficult to use as a reliable diagnostic tool. In addition, possible anergy and interaction of the altered autoimmune status in rheumatological diseases further complicate the interpretation of TST results. Although interferon-gamma release assay (IGRA) has improved the diagnosis of LTBI in immunocompetent individuals, its respective sensitivity/specificity values are unknown in patients with autoimmune disease due to variable pretest probability and lack of confirmatory test for LTBI. Thus, the use of IGRA for screening LTBI is variable among different countries. This review explores the prevalence of tuberculosis in patients receiving TNF antagonist in countries with different tuberculosis disease burdens and the potential mechanisms for variation in the incidence of tuberculosis with different TNF antagonists, the current practice guidelines for assessing the risk of LTBI in different countries, and the possible solutions for improving diagnosis, monitoring and management of LTBI.


Information needs on childhood TBI: survey results of experts.
Until recently, information about childhood brain injury was rarely geared toward families or educators. Yet information is critical, according to our survey of 89 experts. We asked about the type of information needed, groups needing information, and issues of timing. Respondents were most concerned about brain injury information gaps for parents, educators, and community physicians. Basic information about brain injury among children, methods of coping, and advocacy strategies were deemed most important. Good multi-media materials are needed, so people can quickly learn the basics, find where to learn more, and make contacts in the brain injury community. New Internet discussion groups, mailing lists, and websites appear almost daily. As more user-friendly information on brain injury gets placed on the Internet, more needs to be done to make this information accessible to all citizens.


Asymmetric Triblock Copolymer Nanocarriers for Controlled Localization and pH-Sensitive Release of Proteins.
Designing nanocarriers to release proteins under specific conditions is required to improve therapeutic approaches, especially in treating cancer and protein deficiency diseases. We present here supramolecular assemblies based on asymmetric poly(ethylene glycol)-b-poly(methylcaprolactone)-b-poly(2-(N,Ndiethylamino)ethyl methacrylate) (PEG-b-PMCL-b-PDMAEMA) copolymers for controlled localization and pH-sensitive release of proteins. Copolymers self-assembled in soft nanoparticles with a core domain formed by PMCL, and a hydrophilic domain based on PEG mainly embedded inside, and the branched PDMAEMA exposed at the particle surface. We selected as model proteins to be attached to the nanoparticles bovine serum albumin (BSA) and acid sphingomyelinase (ASM), the latter being an ideal candidate for protein replacement therapy. The hydrophilic/hydrophobic ratio, nanoparticle size, and the nature of biomolecules are key factors for modulating protein localization and attachment efficiency. The predominant outer shell of PDMAEMA allows efficient pH-triggered release of BSA and ASM, and in acidic conditions >70% of the bound proteins were released. Uptake of protein-attached nanoparticles by HELA cells, together with low toxicity and pH-responsive release, supports such protein-bound nanoparticles as efficient stimuli-responsive candidates for protein therapy.


An investigation into the bilateral functional differences of the lower limb muscles in standing and walking.
To date, most studies use surface electromyographic (sEMG) signals as the control source on active rehabilitation robots, and unilateral data are collected based on the gait symmetry hypothesis, which has caused much controversy. The purpose of this study is to quantitatively evaluate the sEMG activity asymmetry of bilateral muscles in lower extremities during functional tasks. Nine participants were instructed to perform static and dynamic steady state tests. sEMG signals from the tibialis anterior, soleus, medial gastrocnemius and lateral gastrocnemius muscles of bilateral lower extremities were recorded in the experiments. Muscle activities are quantified in terms of sEMG amplitude. We investigated whether characteristics of left limb and the one of the right limb have the same statistical characteristics during functional tasks using The Wilcoxon rank-sum test, and studied dynamic signal irregularity degree for sEMG activities via sample entropy. The total of muscle activities showed significant differences between left limb and right limb during the static steady state (p = 0.000). For dynamic steady states, there were significant differences for most muscle activities between left limb and right limb at different speeds (p = 0.000). Nevertheless, there was no difference between the lateral gastrocnemius for bilateral limb at 2.0 kilometers per hour (p = 0.060). For medial gastrocnemius, differences were not found between left limb and right limb at 1.0 and 3.0 kilometers per hours (p = 0.390 and p = 0.085, respectively). Similarly, there was no difference for soleus at 3.0 kilometers per hour (p = 0.115). The importance of the differences in muscle activities between left limb and right limb were found. These results can potentially be used for evaluating lower limb extremity function of special populations (elderly people or stroke patients) in an objective and simple method.


An update on the recent literature on sickle cell bone disease.
To summarize the findings of the recent publications on sickle cell bone disease (SBD). Individuals with sickle cell disease (SCD) are living longer and develop progressive organ damage including SBD with age. Recent studies suggest alternative radiological diagnostics such as ultrasound and scintigraphy can detect and differentiate between different forms of SBD. MRI with or without diffusion-weighted sequences remains the gold standard. Case reports of cranio-orofacial SBD highlight the rarity of this presentation. Vitamin D deficiency is highly prevalent at all ages, but may not be an independent risk factor for avascular necrosis (AVN). Gene polymorphisms of the Annexin A gene may predict AVN in SCD. A recent study demonstrated reduced days with pain and improved physical activity quality of life following high-dose vitamin D therapy. The high rates of osteopenia and osteoporosis in SCD support the need for research addressing this rising public health problem. Lastly, results of total hip arthroplasty for AVN in SCD has improved significantly over time with the use of cementless prosthetic material and improved supportive care. SBD remains poorly studied. Prospective randomized studies targeting predictors, diagnostics, prevention, and treatment options for SBD are sorely needed.


Semi-supervised clustering of fractionated electrograms for electroanatomical atrial mapping.
Electrogram-guided ablation procedures have been proposed as an alternative strategy consisting of either mapping and ablating focal sources or targeting complex fractionated electrograms in atrial fibrillation (AF). However, the incomplete understanding of the mechanism of AF makes difficult the decision of detecting the target sites. To date, feature extraction from electrograms is carried out mostly based on the time-domain morphology analysis and non-linear features. However, their combination has been reported to achieve better performance. Besides, most of the inferring approaches applied for identifying the levels of fractionation are supervised, which lack of an objective description of fractionation. This aspect complicates their application on EGM-guided ablation procedures. This work proposes a semi-supervised clustering method of four levels of fractionation. In particular, we make use of the spectral clustering that groups a set of widely used features extracted from atrial electrograms. We also introduce a new atrial-deflection-based feature to quantify the fractionated activity. Further, based on the sequential forward selection, we find the optimal subset that provides the highest performance in terms of the cluster validation. The method is tested on external validation of a labeled database. The generalization ability of the proposed training approach is tested to aid semi-supervised learning on unlabeled dataset associated with anatomical information recorded from three patients. A joint set of four extracted features, based on two time-domain morphology analysis and two non-linear dynamics, are selected. To discriminate between four considered levels of fractionation, validation on a labeled database performs a suitable accuracy (77.6 %). Results show a congruence value of internal validation index among tested patients that is enough to reconstruct the patterns over the atria to located critical sites with the benefit of avoiding previous manual classification of AF types. To the best knowledge of the authors, this is the first work reporting semi-supervised clustering for distinguishing patterns in fractionated electrograms. The proposed methodology provides high performance for the detection of unknown patterns associated with critical EGM morphologies. Particularly, obtained results of semi-supervised training show the advantage of demanding fewer labeled data and less training time without significantly compromising accuracy. This paper introduces a new method, providing an objective scheme that enables electro-physiologist to recognize the diverse EGM morphologies reliably.


Muscle function at the wrist after eccentric exercise.
The purpose of this experiment was to investigate the effects of eccentric exercise by the wrist extensor muscles on the function and motor control of synergist wrist extensor muscles and the antagonist wrist flexor muscles. Ten subjects were tested repeatedly over a period of 11 d, once before and four times after a bout of strenuous eccentric exercise with the wrist extensor muscles. Tests performed as indicators of muscle injury were wrist extension MVC, ROM, and soreness. Tests performed as measures of function and motor control were maximum joint velocity, ability to sustain a constant torque, and the ability to track a changing torque. Indicators of muscle injury: subjects exhibited a decline in wrist extension MVC and ROM, which peaked on day 1, and reported that muscle soreness was greatest on day 2. All measures returned to baseline values by day 10. Measures of function and motor control: subjects exhibited a greater difficulty sustaining a submaximal contraction and tracking torque after eccentric exercise. Greater torque variances in these tests were most evident at high torque levels. Subjects exhibited the greatest difficulty 24 h after eccentric exercise and had recovered by day 10. There was no change in maximal wrist extension velocity. Strenuous eccentric exercise by wrist extensors had an effect on function and motor control of the wrist extensor muscles. The effect was most evident during contractions in which high torque was required. The response of all of the wrist extensors after the exercise bout was similar, suggesting that they operated in a synergistic manner. The antagonists wrist flexors showed increased coactivation after eccentric exercise.


Theoretical comparison of real-time feedback-driven single-particle tracking techniques.
Real-time feedback-driven single-particle tracking is a technique that uses feedback control to enable single-molecule spectroscopy of freely diffusing particles in native or near-native environments. A number of different real-time feedback-driven single-particle tracking (RT-FD-SPT) approaches exist, and comparisons between methods based on experimental results are of limited use due to differences in samples and setups. In this study, we used statistical calculations and dynamical simulations to directly compare the performance of different methods. The methods considered were the orbital method, the knight's tour (grid scan) method, and MINFLUX, and we considered both fluorescence-based and interferometric scattering (iSCAT) approaches. There is a fundamental trade-off between precision and speed, with the knight's tour method being able to track the fastest diffusion but with low precision, and MINFLUX being the most precise but only tracking slow diffusion. To compare iSCAT and fluorescence, different biological samples were considered, including labeled and intrinsically fluorescent samples. The success of iSCAT as compared to fluorescence is strongly dependent on the particle size and the density and photophysical properties of the fluorescent particles. Using a wavelength for iSCAT that is negligibly absorbed by the tracked particle allows for an increased illumination intensity, which results in iSCAT providing better tracking for most samples. This work highlights the fundamental aspects of performance in RT-FD-SPT and should assist with the selection of an appropriate method for a particular application. The approach used can easily be extended to other RT-FD-SPT methods.


Real-time detection of caspase-2 activation in a single living HeLa cell during cisplatin-induced apoptosis.
Caspase-2 is important for the mitochondrial apoptotic pathway, however, the mechanism by which caspase-2 executes apoptosis remains obscure. We carry out the first measurements of the dynamics of caspase-2 activation in a single living cell by a FRET (fluorescence resonance energy transfer) probe. Two FRET probes are constructed that each encoded a CRS (caspase-2 or caspase-3 recognition site) fused with a cyan fluorescent protein (CFP) and a red fluorescent protein (DsRed) (CFP-CRS-DsRed). Using these probes, we found that during cisplatin-induced apoptosis, caspase-2 activation occurred more slowly than did activation of caspase-3; additionally, caspase-2 activation was initiated much earlier than that of caspase-3.


[The establishment of a modified lateral fluid percussion model of brain injury in rat and the pertinent pathologic changes].
For the purpose of studying the molecular mechanism of the traumatic brain injury, we have established a reproducible graded lateral fluid percussion model of experimental brain injury in the rat with a modified fluid percussion device. The device consists of a stainless steel cylindrical reservoir instead of the plexiglass reservoir, a steel reservoir filled with compressed gas instead of the pendulum for making more accurate percussion pressure, an apparatus for releasing the pressure immediately after the percussion, and a computer for recording and storing the percussion data. Pathologic examination demonstrated subdural hemorrhage, subarachnoid hemorrhage, and hemorrhage in the lateral ventricle and corpus callosum on the percussion side. The severity of pathologic changes increased with the magnitude of percussion. The results indicate that the new device could inflict reproducible graded lateral fluid percussion brain injury on rats and the model can be used for the studies of neuropathologic and molecular mechanism of brain injury.


Ozone concentration in leaf intercellular air spaces is close to zero.
Transpiration and ozone uptake rates were measured simultaneously in sunflower leaves at different stomatal openings and various ozone concentrations. Ozone uptake rates were proportional to the ozone concentration up to 1500 nanoliters per liter. The leaf gas phase diffusion resistance (stomatal plus boundary layer) to water vapor was calculated and converted to the resistance to ozone multiplying it by the theoretical ratio of diffusion coefficients for water vapor and ozone in air (1.67). The ozone concentration in intercellular air spaces calculated from the ozone uptake rate and diffusion resistance to ozone scattered around zero. The ozone concentration in intercellular air spaces was measured directly by supplying ozone to the leaf from one side and measuring the equilibrium concentration above the other side, and it was found to be zero. The total leaf resistance to ozone was proportional to the gas phase resistance to water vapor with a coefficient of 1.68. It is concluded that ozone enters the leaf by diffusion through the stomata, and is rapidly decomposed in cell walls and plasmalemma.


Associations between obesity, breakfast-time food habits and intake of energy and nutrients in a group of elderly Madrid residents.
The objective of this study was to gain more knowledge about the breakfast habits of different groups of elderly people and to investigate the differences in breakfast habits between overweight and normal weight elderly subjects. A study was made of the food preferences, dietary habits and the intake of energy and nutrients at breakfast in a group of 122 elderly Spanish people (65 men and 57 women) aged 75.7+/-8.7 years. Study participants were divided into two groups: overweight and obese subjects (O) with a body mass index (BMI)>or=25 kg/m2 (58% of the population), and normal weight subjects (NW) with a BMI<25 kg/m2 (42% of the population). The members of each group were further divided into subgroups according to age (>or=80 years of age (Y) and<or=79 (Z)), to determine if this factor gave rise to any differences in breakfast habits or modified existing differences between NW and O subjects. NW subjects more frequently indicated a preference for fruit (Y), juices (Y) and bread (Y and Z) as breakfast foods, and showed less preference for churros (Y) (a traditional Spanish breakfast fritter) than did O subjects. NW subjects consumed more varied breakfasts, taking both a greater number of foods and more groups of foods. They also spent a longer time eating their breakfasts and consumed greater quantities of food than did O subjects. The breakfasts of NW subjects covered a higher percentage of their theoretical energy expenditure and provided greater contributions of fiber, vitamin E and iron to meet recommended intakes than did those of O subjects. Age did not produce any statistically significant differences in subjects' breakfast habits. The shorter length of time spent eating breakfast, the consumption of smaller quantities and less varied diets and the different composition of NW and O breakfasts, could indicate the existence of less healthy breakfast habits among overweight and obese subjects. It is also possible that less adequate breakfast habits contribute to the appearance and further development of obesity.


Development of traceable measurement of the diffuse optical properties of solid reference standards for biomedical optics at National Institute of Standards and Technology.
The development of a national reference instrument dedicated to the measurement of the scattering and absorption properties of solid tissue-mimicking phantoms used as reference standards is presented. The optical properties of the phantoms are measured with a double-integrating sphere setup in the steady-state domain, coupled with an inversion routine of the adding-doubling procedure that allows for the computation of the uncertainty budget for the measurements. The results are compared to the phantom manufacturer's values obtained by a time-resolved approach. The results suggest that the agreement between these two independent methods is within the estimated uncertainties. This new reference instrument will provide optical biomedical research laboratories with reference values for absolute diffuse optical properties of phantom materials.


Nicorandil suppressed ventricular arrhythmias in a canine model of myocardial ischaemia.
These experiments were designed to explore the possibility that a K+ channel opener which also donates nitric oxide to the myocardium (nicorandil) may modify ischaemia-induced ventricular arrhythmias in a large animal model. In mongrel dogs anaesthetised with chloralose-urethane and thoracotomised, a side branch of the left anterior descending artery was catheterised for the local intracoronary infusion of nicorandil (2.5 micrograms kg-1 min-1 for 20 min prior to coronary artery occlusion and then continuing throughout the 25 min occlusion period). In this dose, nicorandil had no haemodynamic effects, increased coronary blood flow by up to 16% and significantly reduced the severity of ischaemia-induced arrhythmias (e.g. from nearly 500 ventricular premature beats in the controls to 160 +/- 60 in the nicorandil group). There was a significant reduction in the number of episodes of ventricular tachycardia during the ischaemic period and a reduced incidence of ventricular fibrillation following reperfusion resulting in a 42% survival from the combined ischaemia-reperfusion insult (cf. 0% in the control; P < 0.05). The marked changes that occurred in ST-segment elevation (mapped with epicardial electrodes) and in the inhomogeneity of electrical activation within the ischaemic area in control dogs was markedly reduced in those dogs administered nicorandil. We conclude that the local intracoronary administration of nicorandil reduces the severity of both ischaemia and the life-threatening arrhythmias that result from an abrupt reduction in coronary blood flow in this canine model. Possible mechanisms include an increase in coronary blood flow, a reduction in the severity of myocardial ischaemia and an ability of the compound to "donate' nitric oxide to the ischaemic area.


Dichloroacetate modulates the oxidative stress and inflammatory response to exercise in COPD.
Impaired skeletal muscle function contributes to exercise intolerance in patients with COPD. Exercise-induced oxidative stress may initiate or accelerate impaired muscle function. Dichloroacetate (DCA) activates muscle pyruvate dehydrogenase complex (PDC) at rest, reducing inertia in mitochondrial energy delivery at the onset of exercise and thereby diminishing anaerobic energy production. This study aimed to determine whether DCA infusion also may reduce exercise-induced systemic oxidative stress and inflammatory response in patients with COPD. A randomized, double-blind crossover design was used in which 13 patients with COPD performed maximal cycle exercise after an IV infusion of DCA (50 mg/kg body mass) or saline solution (placebo). Venous blood was sampled before exercise, and immediately, 30 min, and 2 h after exercise. Urine samples were obtained before and 2 h after exercise. Peak workload improved significantly after DCA infusion compared to placebo (10%; p < 0.01). Urinary uric acid levels after exercise were significantly lower in the DCA condition than in the placebo condition, whereas no significant difference was observed for urinary malondialdehyde levels. Oxidized glutathione (GSSG) levels were significantly increased 2 h after exercise in the placebo condition (p < 0.02) but not after DCA infusion. No changes in reduced glutathione (GSH), GSSG/GSH ratio, and superoxide dismutase activity were observed. Plasma interleukin (IL)-6 levels significantly increased 2 h after exercise only in the DCA condition (p < 0.01). This study shows that improved performance after a pharmacologic intervention known to activate PDC was accompanied by an enhanced IL-6 response and a limited reduction in exercise-induced systemic oxidative stress.


Design study of electron cyclotron resonance-ion plasma accelerator for heavy ion cancer therapy.
Electron Cyclotron Resonance-Ion Plasma Accelerator (ECR-IPAC) device, which theoretically can accelerate multiple charged ions to several hundred MeV with short acceleration length, has been proposed. The acceleration mechanism is based on the combination of two physical principles, plasma electron ion adiabatic ejection (PLEIADE) and Gyromagnetic Autoresonance (GYRAC). In this study, we have designed the proof of principle machine ECR-IPAC device and simulated the electromagnetic field distribution generating in the resonance cavity. ECR-IPAC device consisted of three parts, ECR ion source section, GYRAC section, and PLEIADE section. ECR ion source section and PLEIADE section were designed using several multi-turn solenoid coils and sextupole magnets, and GYRAC section was designed using 10 turns coil. The structure of ECR-IPAC device was the cylindrical shape, and the total length was 1024 mm and the maximum diameter was 580 mm. The magnetic field distribution, which maintains the stable acceleration of plasma, was generated on the acceleration center axis throughout three sections. In addition, the electric field for efficient acceleration of electrons was generated in the resonance cavity by supplying microwave of 2.45 GHz.


Immune modulation of collagen-induced arthritis by intranasal cytokine gene delivery: a model for the therapy of rheumatoid arthritis.
To develop a passively targeted, patient-compliant, intranasal interleukin-10 (IL-10) gene therapy delivery system and to investigate its therapeutic benefit in experimental collagen-induced arthritis, a model of rheumatoid arthritis. Arthritis was induced in DBA/1 mice and monitored following intranasal administration of an IL-10 plasmid (pG-IL-10) or the empty vector 2 days (days -2 and 19) prior to collagen injection (prophylactic group, as a single dose after collagen boost on day 21 (early therapy group, or as a single dose upon acquisition of a disease score of 3 (late therapy group. IL-10-induced alterations in cytokine secretion and proliferation by spleen and lymph node cells were assessed on days 31 and 65 and correlated with histologic changes and bone erosions assessed on day 65. Intranasal delivery of pG-IL-10 significantly delayed arthritis onset and reduced disease severity in the prophylactic group and early therapy group, reduced cellular infiltration and bone loss in the early therapy group, and reduced T cell proliferation in response to collagen on days 31 and 65 in these two groups, with a significant reduction in tumor necrosis factor alpha production on day 65. Within the late therapy group, disease progression was arrested for the rest of the study. The intranasally administered pG-IL-10 targeted monocytes and macrophages and showed dissemination to inflamed joints and draining lymph nodes in vivo. Importantly, systemic levels of IL-10 (in serum) were transient (peaking on day 2) and undetectable by day 4. Intranasal IL-10 gene delivery significantly reduces bone destruction, shows evidence of reducing joint inflammation, and may be mediated by high local levels of IL-10 produced by transfected monocytes trafficking to inflamed joints and draining lymph nodes.


IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.
Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.


The identification and partial characterisation of a novel inducible extracellular thermostable esterase from the archaeon Sulfolobus shibatae.
Extracellular esterases have so far only been reported in eubacteria, here we report the first identification and partial characterisation of a novel inducible extracellular esterase from the thermoacidophilic archaeon Sulfolobus shibatae. This esterase exhibits remarkable stability to both acid and heat. Esterase activity is induced by growth on a range of polyoxyethylenesorbitan (Tween) compounds as sole carbon source. Activity occurs over a wide temperature (25-99 degrees C) and pH (pH4.0-9.0) range and is optimal at 90 degrees C and pH6.0. It exhibits high thermal stability, with a half-life of 20 min at 120 degrees C, and shows a transient thermal activation of 60% at 90 degrees C. The thermal inactivation of function occurs by first order kinetics, and after 120 min incubation at 120 degrees C 50% of activity still remains. It is able to hydrolyse mono- and diglycerides, but is unable to hydrolyse the triglycerides olive oil and triolein, which is indicative of an esterase and not a lipase.


[Effects on extravascular lung water of lung protective ventilation strategy applied on piglets with acute respiratory distress syndrome induced by paraquat].
Objective: To study the effects on extravascular lung water of lung protective ventilation strategy applying on piglets with acute respiratory distress syndrome (ARDS) induced by paraquat (PQ) under pulse indicating continuous cardiac output (PiCCO) monitoring. Methods: The piglets models with ARDS induced by PQ were established in June 2020 and all of them were received mechanical ventilation and divided into three groups according to tidal volume (V(T)) : small V(T) group (6 ml/kg) , middle V(T) group (10 ml/kg) and large V(T) group (15 ml/kg) , there were 5 piglets in each group. The positive end expiratory pressure (PEEP) were all setup on 10 cmH(2)O. The indexes such as arterial blood gas analysis, oxygenation index (OI) , extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were monitored at time of before the model was established (baseline) , time of the model was established (t(0)) and 2 h (t(2)) , 4 h (t(4)) , 6 h (t(6)) after mechanical ventilation. Lung tissue were punctured at time of baseline, t(0) and t(6) to be stained by Hematoxylin-eosin (HE) staining and pulmonary pathology were observed under light microscopy. Results: The heart rate (HR) , mean arterial pressure (MAP) and partial pressure of carbon dioxide (PaCO(2)) of all groups were higher than the base value while the pH values, partial pressure of oxygen (PaO(2)) and OI were lower than the base value when the models were established (P<0.05) . After mechanical ventilation, the HR and MAP values of all groups at t(2), t(4) and t(6) were lower than t(0) while the PaCO(2) of t(4) and t(6) were all higher than t(0), the differences were statistically significant (P<0.05) . The PaO(2) and OI of all groups showed a trend of rising at first and then decreasing after mechanical ventilation. The MAP, PaO(2), PaCO(2) and OI of the middle V(T) group and large V(T) group were apparently lower than that of the small V(T) group at t(2), t(4) and t(6) (P<0.05) . The ELWI and PVPI at t(0) of all groups were higher than that of baseline (P<0.05) . The ELWI of the small V(T) group at t(6) were lower than t(0) of the same group and t(6) of the middle V(T) group and large V(T) group (P<0.05) . HE staining showed congestion and edema of alveolar tissue, swelling of capillaries, exudation of red blood cells and widening of alveolar septum in piglets after successful modeling. And further widening of alveolar septum and rupture of alveolar septum could be seen in the lung tissues of each group at t(6), and the injury was the slightest in the small V(T) group. Conclusion: The lung protective ventilation strategy can alleviate the extravascular lung water and ARDS induced by PQ and improve oxygenation.


Reduction mammoplasty as a treatment for symptomatic central venous stenosis.
Central venous stenosis is a rare cause of unilateral breast edema occurring in hemodialysis patients that needs to be differentiated from other differential diagnoses, including, but not limited to, inflammatory breast carcinoma, mastitis, lymphedema, and congestive heart failure. All reports of similar cases in the available literature have described improvement or resolution of the edema after treatment. Herein, we report and discuss the pathophysiology of breast edema formation in a patient who presented with massive left-sided breast edema 7 years after being diagnosed with central venous stenosis. Medical and minimally invasive therapy had not been successful, so she underwent reduction mammoplasty to relieve the symptoms.


Intra-operator and inter-operator reliability of the OSI CA 6000 Spine Motion Analyzer with a new skin fixation system.
Following the independent development in the University of Brighton of a new skin fixation system for use with the OSI CA 6000 Spine Motion Analyzer, a series of studies were initiated to test the reliability of the instrument with the new skin fixation system, and the repeatability of the results thus obtained. This paper reports on the outcome of an initial pilot study to compare the existing manufacturer-supplied strap fixation system with the new system. This was followed by a second pilot study to establish single intra-operator reliability utilising 23 asymptomatic subjects. Following successful conclusion of the pilot studies, full inter/intra-operator reliability studies were initiated, utilising 11 asymptomatic subjects. The mean ranges of motion obtained from these results are reported and analyses of variance were used to calculate Intra-class Correlation Coefficients (ICCs) as an indication of reliability. These are summarised as follows: flexion/extension ranges 0.807; lateral flexion ranges 0.923; rotation ranges 0.822. A detailed methodology is explained, along with in-depth discussion of the reasoning behind its adoption, and detailed discussion of the results obtained. This study forms a foundation for the establishment of normative data for ranges of motion and patterns of movement in the lumbar spine, as part of a long-term programme of work investigating the effects of low back pain in specific occupational groups on lumbar spine ranges of motion. It is concluded that the results reported justify progression to the collection of normative data for the lumbar spine, utilising the CA 6000 Spine Motion Analyzer with the new skin fixation system, and the widespread application of that data in the clinical setting.


Characterization of glutamate-cysteine ligase and glutathione synthetase from the δ-proteobacterium Myxococcus xanthus.
Glutathione (GSH) is synthesized in two ATP-dependent reactions by glutamate-cysteine ligase (Gcl) and glutathione synthetase (Gs). Myxococcus xanthus, a gram-negative bacterium belonging to δ-proteobacteria, possesses mxGcl and mxGs, which have high sequence identity with the enzymes from plants and bacteria, respectively. MxGcl2 was activated by Mn2+ , but not by Mg2+ , and stabilized in the presence of 5 mM Mn2+ or Mg2+ . Sequence comparison of mxGcl2 and Brassica juncea Gcl indicated that they have the same active site residues, except for Tyr330, which interacts with Cys and which in mxGcl2 is represented by Leu267. The substitution of Leu267 with Tyr resulted in the loss of mxGcl2 activity, but that with Met (found in cyanobacterial Gcls) increased the mxGcl2 affinity for Cys. GSH and its oxidized form GSSG equally inhibited the activity of mxGcl2; the inhibition was augmented by ATP at concentrations >3 mM. Buthionine sulfoximine inactivated mxGcl2 with Ki = 2.1 μM, which was lower than those for Gcls from other organisms. The mxGcl2 activity was also suppressed by pyrophosphate and polyphosphates. MxGs was a dimer, and its activity was induced by Mg2+ but strongly inhibited by Mn2+ even in the presence of 10 mM Mg2+ . MxGs was inhibited by GSSG at Ki = 3.6 mM. Approximately 1 mM GSH was generated with 3 units of mxGcl2 and 6 units of mxGs from 5 mM Glu, Cys, and Gly, and 10 mM ATP. Our results suggest that GSH production in M. xanthus mostly depends on mxGcl2 activity.


Numerical Assessment of Zebra-Stripes-Based Strategies in Buildings Energy Performance: A Case Study under Tropical Climate.
Urban growth has increased the risk of over-heating both in the microclimate and inside buildings, affecting thermal comfort and energy efficiency. That is why this research aims to evaluate the energy performance of buildings in terms of thermal comfort (operative temperature (OP) levels, satisfied hours of natural ventilation SHNV, thermal lag), and energy efficiency (roof heat gains and surface temperatures) in an urban area in Panama City, using superficial-heat-dissipation biomimetic strategies. Two case studies, a base case and a proposed case, were evaluated using the Designbuilder software through dynamic simulation. The proposed case is based on a combined biomimetic strategy; the reflective characteristics of the Saharan ant applied as a coating on the roofs through a segmented pattern such as the Zebra's stripes (one section with coating, and another without). Results showed that the OP decreased from 8 to 10 °C for the entire urban zone throughout the year. A reduction of 3.13% corresponding to 8790 kWh per year was achieved for cooling energy consumption. A difference of 5 °C in external surface temperature was obtained, having a lower temperature in which the biomimetic strategy was applied. Besides, it was evidenced that a contrasted-reflectivity-stripes pitched roof performed better than a fully reflective roof. Thus, the functionality of Zebra stripes, together with the reflective characteristics of the Saharan ant, provide better performance for buildings' thermal regulation and energy needs for cooling.


Enhanced detection of cytomegalovirus in confluent MRC-5 cells treated with dexamethasone and dimethyl sulfoxide.
Optimum growth conditions for human cytomegalovirus (HCMV) include the use of subconfluent, actively growing cultures of human embryonic fibroblasts. Many clinical virology laboratories, however, use tissue culture cells from commercial sources. These cells are usually confluent, static cultures that tend to be less sensitive to viral infection. To determine whether dimethyl sulfoxide (DMSO) or dexamethasone (DEX), which are known enhancers of HCMV, facilitates the detection of the virus in confluent cells, we tested both HCMV AD169 and a number of clinical specimens suspected to contain HCMV on MRC-5 cells in both shell vials and conventional tube cultures. We found that, in the shell vial test, treatment of the cultures with either DMSO or DEX before and after inoculation increased the number of cells staining positive by three- to sixfold compared with untreated controls. Best results were obtained by pretreating the cultures with DEX alone and by treating the cultures with a combination of DEX and 1% DMSO postinfection. In the conventional MRC-5 culture tubes, treatment with the reagents resulted in the more rapid appearance of cytopathic effect and a more extensive infection of the cell sheet. The experimental findings indicate that the enhancing effect of DEX is attributable mainly to the increased production of a cellular mRNA during the period preceding viral infection.


Inactivation of DNA polymerase by adenosine 2',3'-riboepoxide 5'-triphosphate allows estimation of the primers affinity.
Template-primer dependent inactivation of human DNA polymerase alpha and Klenow fragment of E. coli DNA polymerase I by adenosine 2',3'-riboepoxide 5'-triphosphate was used for quantitative analysis of the Kd values for oligonucleotide primers of different length. The Kd values are smaller by a factor of 2.5 than the Km values for the same primers determined in the reaction of DNA polymerization in the case of DNA polymerase alpha. The Kd and Km values are nearly the same for Klenow fragment. Such approach to the determination of Km/Kd ratio can likely be used for detailed quantitative analysis of DNA polymerases.


Malaria. Principles of prevention and treatment.
In the United States, effective malaria prevention strategies for short-term travelers are available. Monitoring trends in imported malaria and continued evaluation of the effectiveness and chemoprophylaxis will allow prevention recommendations to evolve as the risk of infection and effectiveness of antimalarial drugs change. Our challenge is to increase the number of prospective travelers receiving pre-travel advice, to disseminate this information to health care providers, and to improve the quality of the advice given. The early recognition of Plasmodium infection and the institution of prompt and effective treatment will reduce morbidity and mortality from malaria in this country.


Pet projects: animal assisted therapy in nursing homes.
1. Animal assisted therapy is an applied science using animals to solve a human problem. It is an interdisciplinary approach using animals as an adjunct to other therapies. 2. The major difference between animals as therapy and entertainment is the animal-human bond, a special relationship that develops when a person has strong feelings of psychological attachment to the animal. 3. It is essential that a complete nursing and activity assessment be made before implementation of individualized animal assisted therapy.


Acquired immunodeficiency syndrome-related intraocular B-cell lymphoma.
To present the full clinical spectrum of the acquired immunodeficiency syndrome-related intraocular lymphoma as manifested in the eye, specifically retinal lymphoma associated with primary central nervous system lymphoma, isolated ocular lymphoma, and choroidal lymphoma associated with systemic lymphoma. Three patients with acquired immunodeficiency syndrome were noted to have atypical retinal lesions. Diagnostic retinal biopsy in 2 patients and postmortem examination of the eyes in the third case were performed. Diagnostic retinal biopsy in the first 2 patients revealed retinal B-cell lymphoma. Initial systemic evaluation showed the eyes to be the sole site of disease. Later, in 1 of these patients, the lymphoma spread to the brain. The third patient developed an acute abdomen 4 months after the development of his ocular findings. The histological evaluation of the resected bowel revealed high-grade B-cell lymphoma. The patient died 1 week later and postmortem analysis of the eyes disclosed the presence of lymphoma in the choroid of both eyes. This is the most complete series of patients with acquired immunodeficiency syndrome-related intraocular B-cell lymphoma and, to our knowledge, provides the first 2 cases diagnosed by retinal biopsy. These 3 cases present the full clinical spectrum of the disease as manifested in the eye.


Donor-derived Cell-free DNA and the Prediction of BK Virus-associated Nephropathy.
Approximately 15% of kidney transplant recipients (KTRs) develop BK viremia (BKV), with 1%-10% developing BK virus-associated nephropathy (BKVAN), which histologically resembles rejection. The Diagnosing Acute Rejection in Kidney Transplant Recipients (DART) study showed that donor-derived cell-free DNA (dd-cfDNA) levels <1% have a negative predictive value of 85% for active allograft rejection. Using data from this study, we evaluated the association of dd-cfDNA with plasma BK viral loads and biopsy findings to determine if dd-cfDNA can distinguish asymptomatic BKV from BKVAN. Data on dd-cfDNA, plasma BK viral loads, and biopsy findings from patients from the DART study were retrospectively examined. BKV was defined as 500-10 000 copies/mL. Presumptive BKVAN was defined as BK >10 000 copies/mL. Of 102 participants with biopsies, 10 patients with BKV and BKVAN had paired dd-cfDNA, and viral loads available for analysis. Patients diagnosed with BKV and BKVAN had a median dd-cfDNA of 0.58% (IQR 0.43-1.15) and 3.38% (IQR 2.3-4.56, P = 0.001), respectively. dd-cfDNA titers correlated with BK PCR viral loads (R = 0.874, P = 0.01) and the presence of histologic evidence of BKVAN (100% sensitivity, 50% specificity). Five of 7 patients with BKVAN, but only 2 of 7 with BKV, had biopsies meeting Banff criteria for T-cell-mediated rejection. Median dd-cfDNA in nonrejection patients was 0.43% versus 2.84% in rejection patients (P = 0.001). Higher dd-cfDNA titers were associated with higher BK viral loads, biopsy-diagnosed BVAN, as well histologic changes meeting Banff criteria for as T-cell-mediated rejection. dd-cfDNA may be a useful noninvasive test to assess for progression of BKV to BKVAN.


[Intrinsic sympathomimetic action and its special features as demonstrated by the beta-1-receptor blocker celiprolol].
The Intrinsic Sympathetic Activity (ISA) of the beta-1-adrenoceptor blocker celiprolol was tested in a series of pharmacological and clinical investigations. Celiprolol shows much more pronounced positive chronotropic effects in spontaneously beating atria of cats than in those of guinea-pigs and rats. Positive inotropic effects of celiprolol are much pronounced in the left kitten atrium, but scarcely demonstrable in the kitten papillary muscle. Celiprolol has no influence on the adenylyl cyclase activity of the dog heart. In reserpinized rats and reserpinized, adrenalectomized, vagotomized cats celiprolol increases the heart rate to the same extent as the beta-blocker pindolol. In ganglion-blocked dogs celiprolol distinctly increases heart rate and left ventricular contraction force. Celiprolol relaxes isolated human arterial and venous strips and induces a transient increase of the femoral arterial blood flow in anaesthetized dogs. Celiprolol relaxes isolated bovine tracheal muscle preparations and reduces the airway resistance in anaesthetized cats infused with serotonin. The intrinsic chronotropic effects of celiprolol in cat atria in vitro and in reserpinized rats in vivo and the relaxing effects of celiprolol in isolated bovine tracheal muscles are antagonized by propranolol, and therefore these actions may be explained by the ISA of celiprolol. However the vascular relaxing effects of celiprolol in vitro and in vivo and the bronchodilating effects in the serotonin-infused cat are not blocked by propranolol. In order to obtain a more precise characterization of these surprising effects, further pharmacological investigations were done. In the isolated femoral artery of the dog the concentration-response curve of calcium chloride is not influenced by celiprolol while it is antagonized by verapamil. A serotonin antagonistic effect cannot be demonstrated for celiprolol either in receptor binding studies or on the blood pressure of anaesthetized dogs. Celiprolol inhibits the methacholine bronchospasm in rats and the prostaglandin F2 alpha-induced bronchoconstriction in cats. The histamine-induced bronchoconstriction in dogs is scarcely affected by celiprolol while it is enhanced by propranolol. In radioligand studies celiprolol shows a tenfold higher affinity for alpha-2 in comparison to alpha-1 receptors. Celiprolol enhances the inhibitory effect of clonidine in the electrically stimulated vas deferens of the rat in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)


Primary pulmonary lymphoma--clinical review from a single institution in Singapore.
Primary pulmonary lymphoma is a rare and vexing subset of extranodal non-Hodgkin's lymphoma. We report 11 cases and provide a brief literature review. We also highlight an unusual case of a relapsed peripheral T-cell primary lung lymphoma that underwent apparent spontaneous remission. Eleven cases of primary pulmonary lymphoma treated in our institution were studied for their clinical characteristics, behaviour, response to treatment and clinical outcome. The median duration of follow up was 26 months. The mean age was in the 50s and the presenting symptoms generally respiratory and non-specific. LDH levels did not correlate with either stage or grade of disease. Lower lobe involvement was most common and nodules and mass-like lesions the main radiologic feature. Small lymphocytic lymphoma accounted for the majority of cases and were indolent in behaviour. Good symptom control and radiologic response was achieved with chemotherapy in disseminated low grade lung lymphomas. Combination chemotherapy was effective in the aggressive lymphomas. In conclusion, Small lymphocytic lymphoma of the lung is an indolent disease with a long symptom-free survival even after recurrence. Our series confirms the clinical characteristics of primary pulmonary lymphoma. The role of Ling Zhi in effecting the spontaneous remission in the peripheral T-cell lymphoma is speculative.


Severe Heterotopic Ossification with Proximal Entrapment of the Ulnar Nerve following Primary Anterior Shoulder Dislocation.
Heterotopic ossifications (HO) in the shoulder are rare. The effectiveness of conservative treatment is limited, and therefore, symptomatic cases are usually treated surgically. However, there are no guidelines for the surgical treatment of HO. Herein, we report the case of a 45-year-old man with severe HO and proximal entrapment of the ulnar nerve following primary anterior shoulder dislocation without concomitant injuries (e.g., fracture and rotator cuff tears). Surgical intervention was indicated, including resection of HO and neurolysis of the brachial plexus. Nine months after surgery, the patient presented with restored shoulder function, pain relief, and good patient satisfaction. The case shows that the ulnar nerve can also be impaired due to HO following shoulder dislocation.


Anisotropic shift of surface plasmon resonance of gold nanoparticles doped in nematic liquid crystal.
Study of the liquid crystal (LC) director around nanoparticles has been an important topic of research very recently, since it allows design and fabrication of next-generation LC devices that are impossible in the past. In our experiment, alkanethiol-capped gold nanoparticles (GNPs) were dispersed in nematic LC. Analysis of the LC director around GNPs was performed by investigating the behavior of surface plasmon polariton (SPP) absorption peaks of the GNPs using spectrophotometry technique. It is found that the incident linearly polarized light orientated at 0°, 45°, and 90° angles with respect to the rubbing direction experiences varying interaction with the LC medium. The corresponding transmission of light reveals the anisotropic shift in wavelength of SPP peak. The anisotropic behavior of SPPs of the GNPs is in agreement with theoretical calculations.


Knockdown of p54nrb inhibits migration, invasion and TNF-α release of human acute monocytic leukemia THP1 cells.
54 kDa nuclear RNA- and DNA-binding protein (p54nrb) which is also called non-POU domain-containing octamer-binding protein (NONO) is known to be multifunctional involved in many nuclear processes. It was shown that p54nrb/NONO was closely related to the occurrence of erythroleukemia. Whether p54nrb/NONO plays a role in progress of human acute monocytic leukemia remains unknown. In the present study, we examined the effects of p54nrb/NONO silencing on the biological characteristics of human acute monocytic leukemia THP1 cells. The results showed that p54nrb was strongly expressed in THP1 cells, and knockdown of p54nrb slightly promoted proliferation and strongly inhibited motility and invasion of THP1 cells. Moreover, knockdown of p54nrb strongly decreased the release of TNF-α from THP1 cells by inhibiting certain process of TNF-α secretion, specially for the release of TNF-α induced by lipopolysaccharide (LPS). Notably, the infection of negative control shRNA-containing lentiviruses promoted the migration and the release of TNF-α induced by LPS in THP1 cells. All the above results demonstrated that p54nrb slightly inhibited THP1 cell proliferation, but significantly promoted migration, invasion and release of TNF-α induced by LPS in THP1 cells. The present study indicates that p54nrb is a powerful molecule involved in the regulation of cell motility and promotes the migration and invasion of THP1 cells, and it is more likely to be involved in the release of inflammatory mediators and the motility of inflammatory cells.


Hippocampal lesions disrupt navigation based on the shape of the environment.
Geometric information provided by the walls of an environment has a strong influence over hippocampal unit activity. This suggests that the hippocampus forms part of a cognitive mapping system that encodes geometric relationships between environmental cues and the animal's location. Here, the authors show for the first time that excitotoxic lesions of the hippocampus disrupt the ability of rats to navigate to a goal using shape information provided by a solid-walled arena and an array of identical landmarks. These results are consistent with cognitive mapping theories of hippocampal function and extend previous research by showing that hippocampal cell loss impairs navigation with respect to shape information provided by both physical barriers and an array of landmarks.


Enhanced learning strategies of undergraduate medical students with a structured case presentation format.
Improvement of the learning in undergraduate bedside teaching needs to be promoted through innovative interventions. Changes in the structured format (SF) for bedside case discussion may help students improve their learning experience and gain insights into collaborative self-directed learning. The aim of the present study was to encourage collaborative and self-directed learning strategies by MBBS undergraduate students through a new case presentation format structured for this purpose. This was an interventional study carried out in the year 2010-2011. A new SF for bedside cases presentation was developed. A comparison with the traditional format was done by holding one session in each format. Uniformity of topic and teaching style was ensured by having the sessions on pulmonary medicine cases with the same teacher. The student perspective of the educational process was analyzed using evaluation pro forma, Likert scale, and narratives. Ninety final year and prefinal year MBBS students participated in this study. There was significantly higher participation in history taking (50.7%) and clinical examination (60%) in the SF. A higher statistically significant number of clinical possibilities were considered in the SF (85.3% vs. 66.6%). Similarly, significantly higher number of students indulged in self-directed learning and referred to learning resources in the SF. The SF provided students an active role (96.9%), encouraged access to resources (93.9%), and control of learning (75.7%). The additional interactive session was productive (90.9%), discussions were streamlined (66.6%), and the role of a teacher was considered important (75.7%). The SF generated higher participation in the aspects of history taking, clinical examination, and consideration of differential diagnoses. It led to a perceived improvement in self-directed and collaborative learning among students.


The anatomical relationship between the orbicularis oculi muscle and the levator labii superioris and zygomaticus muscle complexes.
The purpose of this study was to define the anatomical relationship between the orbicularis oculi muscle and the levator labii superioris/zygomaticus major. Forty-eight sides of 24 preserved cadaver heads were evaluated. The Frankfort plane, the lateral canthus, and the midpupillary line were marked on each hemiface as landmarks. Four parallel incisions were made perpendicular to the inferior orbital rim and the Frankfort horizontal line. The incisions were midpupillary, lateral canthus, 1 cm lateral to the lateral canthus, and 2 cm lateral to the lateral canthus. Within each incision, measurements were performed that included the depth of the zygomaticus major from the orbicularis oculi (i.e., how superficial is the orbicularis above the zygomaticus complex), the superior to inferior distance between the Frankfort line and the origin of the zygomaticus major, the height of the orbicularis oculi muscle above the levator labii muscle (i.e., how superficial is the orbicularis above the levator in the midpupillary line), and how inferior to the inferior orbital rim is the origin of the levator labii superioris. The orbicularis oculi muscle was on average 0.5 cm superficial to the zygomaticus major muscle group at 2 cm lateral to the lateral canthus. At this site, the female cadaver zygomaticus muscle depth was approximately 2 mm deeper versus the male cadavers (0.60 cm versus 0.41 cm). On average, the origin of the zygomaticus major was identified 1.40 cm and 1.50 cm inferior to the Frankfort horizontal line at 1 cm lateral to and at the lateral canthus, respectively. Of note, there were 14 instances (15 percent) in which the muscle group was found to be 1 cm or less from the Frankfort horizontal line. At 1 cm lateral to the lateral canthus and at the lateral canthus, the zygomaticus muscle was seen to interdigitate with the orbicularis muscle. On average, the orbicularis oculi muscle lies 0.80 cm superficial to the levator labii muscle complex. The superficial border of the malar eminence also lies at or near the Frankfort line. An exact understanding of the location of specific muscle groups can help prevent poor outcomes, such as the lip droop occasionally seen with Botox injections. The Frankfort line may be a more appropriately used landmark for the safe placement of Botox than the commonly used malar eminence.


Posterior column dysfunction in cervical spondylotic myelopathy.
Five patients had cervical spondylotic myelopathy (CSM) with severe prorioceptive sensory loss in the upper and lower limbs. Despite an advanced age, each recovered considerable function following cervical laminectomy, in follow-up periods of 10 to 40 months. The role of newer methods of investigation including CT scanning, somatosensory evoked responses and nuclear magnetic resonance is discussed. The cause of the proprioceptive sensory loss in these patients cannot be definitively determined, but various ischemic and compressive lesions are discussed as possible pathogenetic mechanisms.


Bacterial cell division: regulating Z-ring formation.
The earliest stage of cell division in bacteria is the formation of a Z ring, composed of a polymer of the FtsZ protein, at the division site. Z rings appear to be synthesized in a bi-directional manner from a nucleation site (NS) located on the inside of the cytoplasmic membrane. It is the utilization of a NS specifically at the site of septum formation that determines where and when division will occur. However, a Z ring can be made to form at positions other than at the division site. How does a cell regulate utilization of a NS at the correct location and at the right time? In rod-shaped bacteria such as Escherichia coli and Bacillus subtilis, two factors involved in this regulation are the Min system and nucleoid occlusion. It is suggested that in B. subtilis, the main role of the Min proteins is to inhibit division at the nucleoid-free cell poles. In E. coli it is currently not clear whether the Min system can direct a Z ring to the division site at mid-cell or whether its main role is to ensure that division inhibition occurs away from mid-cell, a role analogous to that in B. subtilis. While the nucleoid negatively influences Z-ring formation in its vicinity in these rod-shaped organisms, the exact relationship between nucleoid occlusion and the ability to form a mid-cell Z ring is unresolved. Recent evidence suggests that in B. subtilis and Caulobacter crescentus, utilization of the NS at the division site is intimately linked to the progress of a round of chromosome replication and this may form the basis of achieving co-ordination between chromosome replication and cell division.


[Risk of malignant degeneration of preoperatively-classified benign large sessile rectal polyps. A comparison with adenoma size].
From January 1986 to December 1995 307 patients with preoperatively as benign classified rectal polyps underwent transanal endoscopic microsurgery or transanal excision at the Hospital of General and Abdominal Surgery, Johannes Gutenberg-University Mainz. Mean polyp size was 3.9 cm in diameter. Postoperatively in 233 patients (75.9%) a benign rectal adenoma was found. In 69 patients (22.5%) with the preoperative diagnosis "benign rectal adenoma" the postoperative histologic result was a carcinoma. No residual polyps were encountered on snare excision in 5 patients (1.6%) with inconclusive evidence of surgical margin involvement. The mean size of malignant polyps was 3.4 cm and significantly below the mean size of benign polyps (4.1 cm, p = 0.009). Especially in polyps with a size to 1 cm and from 1 to 2 cm in diameter the part of malignant rectal polyps was unexpected high (8/15 polyps, 53.3%, respectively 16/37 polyps, 43.3%. Patients with preoperatively as benign classified large sessile rectal polyps had a high risk of malignancy even when polyp's size was small. Therefore in toto excision has to be done also in small polyps.


A neuroimaging dataset of deductive reasoning in school-aged children.
Here we describe "Brain development of deductive reasoning" a pediatric neuroimaging dataset freely available on OpenNeuro.org. This dataset includes neuroimaging and standardized assessment data from 56 participants aged 8.47-15 years. Functional Magnetic Resonance Imaging (fMRI) data were collected while participants completed both set-inclusion and linear-order deductive reasoning tasks. A subset of participants (n=45) returned two years later for follow-up standardized assessment testing allowing for future research to investigate individual change in cognitive and academic skill. Previous research on this dataset has not examined the relation of skill and demographic measures to the neural basis of reasoning. Moreover, these studies have not examined the relation of the neural basis of reasoning to that of arithmetic or differences between children and adults in the neural basis of reasoning. Therefore, there are many opportunities to extend the research in the published reports on this data.


Rate of oxygen consumption in seasonal and non-seasonal depression.
Most depressives suffer from weight loss, anorexia and insomnia, while for winter depressives the typical symptoms are weight gain, carbohydrate craving, overeating, oversleeping and extreme lack of energy. It is important to know whether winter depressives differ from most other depressives on measures of energy regulation. In wintertime, we evaluated the rate of oxygen consumption in relationship to neuro-vegetative depressive symptoms in 92 Siberian women. The seated subjects underwent oxyspirography in the mid-morning (1.5 hours after a standard breakfast). It was found that the oxygen consumption rate was similar in non-depressed women (n = 25) and depressed women with non-seasonal depression (n = 27). The comparatively lower values were obtained in women with winter depression (n = 40). This finding supports the suggestion that the behaviour disturbances typical for winter depression may represent a physiological feedback loop to energy conservation.


Nitric oxide and light co-regulate glycine betaine homeostasis in sunflower seedling cotyledons by modulating betaine aldehyde dehydrogenase transcript levels and activity.
Glycine betaine (GB), an osmolyte, is produced in chloroplasts by the action of betaine aldehyde dehydrogenase (BADH) on its precursor betaine aldehyde. The present work highlights the significance of nitric oxide (NO) in GB homeostasis as a long-distance salt (120 mM NaCl) stress-elicited response. In light-grown seedling cotyledons, both the activity and transcript levels of BADH are much higher than in dark-grown seedlings irrespective of salt stress. Significantly high accumulation of GB in dark-grown seedling cotyledons indicates its preferential mobilization from cotyledons to other plant parts in light-grown seedlings. NO donor application (diethylenetriamine) maintains high BADH activity in light, although in dark it is brought down marginally. BADH levels are maintained high in light than in dark in respective treatments. Reversal of the effect of NO donor on age-dependent GB content, BADH activity, and transcript levels by NO scavenger (diethyldithiocarbamate) further demonstrates the impact of NO on GB homeostasis in light- and dark-grown seedlings in an age-dependent manner, major modulation being observed in 4-d-old seedlings. The present work, thus, provides new information on co-regulation of GB homeostasis by NO and light. It also puts forward new information of GB-NO crosstalk in maneuvering salt stress sensing as a long-distance response in seedlings.


Rapid emission angle selection for rotating-shield brachytherapy.
The authors present a rapid emission angle selection (REAS) method that enables the efficient selection of the azimuthal shield angle for rotating shield brachytherapy (RSBT). The REAS method produces a Pareto curve from which a potential RSBT user can select a treatment plan that balances the tradeoff between delivery time and tumor dose conformity. Two cervical cancer patients were considered as test cases for the REAS method. The RSBT source considered was a Xoft Axxent(TM) electronic brachytherapy source, partially shielded with 0.5 mm of tungsten, which traveled inside a tandem intrauterine applicator. Three anchor RSBT plans were generated for each case using dose-volume optimization, with azimuthal shield emission angles of 90°, 180°, and 270°. The REAS method converts the anchor plans to treatment plans for all possible emission angles by combining neighboring beamlets to form beamlets for larger emission angles. Treatment plans based on exhaustive dose-volume optimization (ERVO) and exhaustive surface optimization (ERSO) were also generated for both cases. Uniform dwell-time scaling was applied to all plans such that that high-risk clinical target volume D90 was maximized without violating the D2cc tolerances of the rectum, bladder, and sigmoid colon. By choosing three azimuthal emission angles out of 32 potential angles, the REAS method performs about 10 times faster than the ERVO method. By setting D90 to 85-100 Gy10, the delivery times used by REAS generated plans are 21.0% and 19.5% less than exhaustive surface optimized plans used by the two clinical cases. By setting the delivery time budget to 5-25 and 10-30 min∕fx, respectively, for two the cases, the D90 contributions for REAS are improved by 5.8% and 5.1% compared to the ERSO plans. The ranges used in this comparison were selected in order to keep both D90 and the delivery time within acceptable limits. The REAS method enables efficient RSBT treatment planning and delivery and provides treatment plans with comparable quality to those generated by exhaustive replanning with dose-volume optimization.


Short review on face rejuvenation procedures: focus on preoperative antiseptic and anesthetic delivery by JetPeel™-3 (a high pressure oxygen delivery device).
Nowadays there is great attention in trying to slow and reverse the facial aging process. Esthetic medicine has been primarily based on the surgical approach for many years, but now, in order to solve the problem of aging skin, there is an increasing interest into non-invasive, possibly painless, procedures that can guarantee the patient a quick recovery. In this perspective the use of chemical peeling and dermabrasion, to achieve skin rejuvenation, is growing worldwide. These techniques are also relevant to treat skin pigmentation irregularities and to remove keratoses, lentigines, acne and other skin related conditions. One of the most interesting, safe and painless devices, useful for the effective antiaging face treatment, is JetPeel™-3. The aim of this study was to assess the device efficacy starting from a short review on face rejuvenation procedures. The basic action mechanism of this medical device is a constant high pressure air flux delivery, including oxygen, mixed with different chemical compounds such as peeling molecules, antioxidants, vitamins and hyaluronic acid, which are mechanically forced across the skin surface. Here we report a new approach in the clinical use of JetPeel™-3, tested in 20 adult volunteers, consisting in the addition to the standard protocol of an anesthetic, carbocaine and a sterilizing and disinfectant agent, that is chlorexidine. In fact disinfection and sterilization of the skin surface is a peculiar step for every antiaging or therapeutic procedure. The procedure has been completed with multiple hyaluronic acid injections of the skin in order to achieve face rejuvenation. The anesthetic power of the JetPeel™-3-carbocaine protocol has been compared to the Emla cream one. The spontaneous pain sensation perceived by the patients in the hemiface treated with JetPeel™-3 was significantly lower compared to the hemiface treated with Emla cream (P<0.001) showing, consequently, that JetPeel™-3-carbocaine protocol had the best anesthetic performance either in dermal, subdermal or subcutaneous injections compared with Emla cream. JetPeel™-3 has proved to be a good non-invasive approach and its use is recommended since it induces local anesthesia in a short time.


Outcomes of undernutrition in patients in the community with cancer or cardiovascular disease.
Public health concern has tended to focus on the dangers of obesity, but there is evidence that undernutrition may also pose a risk to physical and mental well-being, particularly in those who are already ill. Using the General Practice Research Database (see office for Population Censuses and Surveys, 1995), we followed up 10,128 men and women aged 18 years and over who had been diagnosed with cancer or cardiovascular disease to examine whether nutritional status, as indicated by BMI, affected rates of use of health care resources and mortality. In both diagnostic groups, patients with a BMI below 20 kg/m2 had higher rates of consultation with GP, higher rates of prescription and higher death rates during the follow-up period compared with those with a BMI of 20-< 25 kg/m2. In men and women with cardiovascular disease, poor nutritional status was associated with a sharply increased risk of hospital admission. Patients whose BMI was 30-< 40 kg/m2 also tended to have increased rates of GP consultation and prescription, and if they were under the age of 65 years, they had an increased risk of death. The results of the present study suggest that in men and women with cancer or cardiovascular disease, even minor degrees of undernutrition are associated with a marked increase in morbidity and mortality.


Polyelectrolyte-Coated Mesoporous Bioactive Glasses via Layer-by-Layer Deposition for Sustained Co-Delivery of Therapeutic Ions and Drugs.
In the field of bone regeneration, considerable attention has been addressed towards the use of mesoporous bioactive glasses (MBGs), as multifunctional therapeutic platforms for advanced medical devices. In fact, their extremely high exposed surface area and pore volume allow to load and the release of several drugs, while their framework can be enriched with specific therapeutic ions allowing to boost the tissue regeneration. However, due to the open and easily accessible mesopore structure of MBG, the release of the incorporated therapeutic molecules shows an initial burst effect leading to unsuitable release kinetics. Hence, a still open challenge in the design of drug delivery systems based on MBGs is the control of their release behavior. In this work, Layer-by-layer (LbL) deposition of polyelectrolyte multi-layers was exploited as a powerful and versatile technique for coating the surface of Cu-substituted MBG nanoparticles with innovative multifunctional drug delivery systems for co-releasing of therapeutic copper ions (exerting pro-angiogenic and anti-bacterial effects) and an anti-inflammatory drug (ibuprofen). Two different routes were investigated: in the first strategy, chitosan and alginate were assembled by forming the multi-layered surface, and, successively, ibuprofen was loaded by incipient wetness impregnation, while in the second approach, alginate was replaced by ibuprofen, introduced as polyelectrolyte layer. Zeta-potential, TGA and FT-IR spectroscopy were measured after the addition of each polyelectrolyte layer, confirming the occurrence of the stepwise deposition. In addition, the in vitro bioactivity and the ability to modulate the release of the cargo were evaluated. The polyelectrolyte coated-MBGs were proved to retain the peculiar ability to induce hydroxyapatite formation after 7 days of soaking in Simulated Body Fluid. Both copper ions and ibuprofen were co-released over time, showing a sustained release profile up to 14 days and 24 h, respectively, with a significantly lower burst release compared to the bare MBG particles.


Resolution of hyperthyroidism in a pregnant woman with toxic thyroid nodule by percutaneous ethanol injection.
Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who was referred to us for tachycardia, tremors, and weight loss. Clinical signs, symptoms, and laboratory findings led to the diagnosis of toxic thyroid nodule. She was treated with ultrasound guided percutaneous ethanol injection (PEI) and, after 2 weeks of treatment, the woman was completely euthyroid. These findings suggest that during pregnancy PEI appears to be a rapid and safe therapy for toxic nodular goiter and an effective alternative to the administration of antithyroid drugs.


Binding specificity and tissue-specific expression pattern of the Arabidopsis bZIP transcription factor TGA2.
The binding specificity and tissue-specific expression pattern of TGA2 (AHBP-1b), an Arabidopsis bZIP transcription factor have been determined. Filter-binding and gel-shift assays showed that TGA2 has high affinity for C-boxes (ATGACGTCAT). In this respect TGA2 is similar to other members of the Arabidopsis TGA family (such as TGA1, TGA3 and OBF4) and to tobacco TGA1a. Genomic Southern blot analysis confirmed that TGA2 is a member of the gene family. Northern blot analysis showed that the gene is expressed at similar levels in root, stem, leaf and flower t at somewhat lower levels in siliques. TGA3 was also found to be expressed at the same level throughout the plant, whereas genes encoding TGA1 and OBF4 have relatively high RNA expression levels in root. The differential expression of these genes suggests that they have distinct functions.