Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study.
To evaluate the ability of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) to detect concussion in children and adult trauma patients with a normal mental status and assess biomarker concentrations over time as gradients of injury in concussive and non-concussive head and body trauma. Large prospective cohort study. Three level I trauma centres in the USA. Paediatric and adult trauma patients of all ages, with and without head trauma, presenting with a normal mental status (Glasgow Coma Scale score of 15) within 4 hours of injury. Rigorous screening for concussive symptoms was conducted. Of 3462 trauma patients screened, 751 were enrolled and 712 had biomarker data. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours postinjury in adults. Detection of concussion and gradients of injury in children versus adults by comparing three groups of patients: (1) those with concussion; (2) those with head trauma without overt signs of concussion (non-concussive head trauma controls) and (3) those with peripheral (body) trauma without head trauma or concussion (non-concussive body trauma controls). A total of 1904 samples from 712 trauma patients were analysed. Within 4 hours of injury, there were incremental increases in levels of both GFAP and UCH-L1 from non-concussive body trauma (lowest), to mild elevations in non-concussive head trauma, to highest levels in patients with concussion. In concussion patients, GFAP concentrations were significantly higher compared with body trauma controls (p<0.001) and with head trauma controls (p<0.001) in both children and adults, after controlling for multiple comparisons. However, for UCH-L1, there were no significant differences between concussion patients and head trauma controls (p=0.894) and between body trauma and head trauma controls in children. The AUC for initial GFAP levels to detect concussion was 0.80 (0.73-0.87) in children and 0.76 (0.71-0.80) in adults. This differed significantly from UCH-L1 with AUCs of 0.62 (0.53-0.72) in children and 0.69 (0.64-0.74) in adults. In a cohort of trauma patients with normal mental status, GFAP outperformed UCH-L1 in detecting concussion in both children and adults. Blood levels of GFAP and UCH-L1 showed incremental elevations across three injury groups: from non-concussive body trauma, to non-concussive head trauma, to concussion. However, UCH-L1 was expressed at much higher levels than GFAP in those with non-concussive trauma, particularly in children. Elevations in both biomarkers in patients with non-concussive head trauma may be reflective of a subconcussive brain injury. This will require further study.


Salmonella enterica Phylogeny Based on Whole-Genome Sequencing Reveals Two New Clades and Novel Patterns of Horizontally Acquired Genetic Elements.
Using whole-genome sequence (WGS) data from the GenomeTrakr network, a globally distributed network of laboratories sequencing foodborne pathogens, we present a new phylogeny of Salmonella enterica comprising 445 isolates from 266 distinct serovars and originating from 52 countries. This phylogeny includes two previously unidentified S. enterica subsp. enterica clades. Serovar Typhi is shown to be nested within clade A. Our findings are supported by both phylogenetic support, based on a core genome alignment, and Bayesian approaches, based on single-nucleotide polymorphisms. Serovar assignments were refined by in silico analysis using SeqSero. More than 10% of serovars were either polyphyletic or paraphyletic. We found variable genetic content in these isolates relating to gene mobilization and virulence factors which have different distributions within clades. Gifsy-1- and Gifsy-2-like phages appear more prevalent in clade A; other viruses are more evenly distributed. Our analyses reveal IncFII is the predominant plasmid replicon in S. enterica Few core or clade-defining virulence genes are observed, and their distributions appear probabilistic in nature. Together, these patterns demonstrate that genetic exchange within S. enterica is more extensive and frequent than previously realized, which significantly alters how we view the genetic structure of the bacterial species.IMPORTANCE Rapid improvements in nucleotide sequencing access and affordability have led to a drastic increase in availability of genetic information. This information will improve the accuracy of molecular descriptions, including serovars, within S. enterica Although the concept of serovars continues to be useful, it may have more significant limitations than previously understood. Furthermore, the discrete absence or presence of specific genes can be an unstable indicator of phylogenetic identity. Whole-genome sequencing provides more rigorous tools for assessing the distributions of these genes. Our phylogenetic and genetic content analyses reveal how active genetic elements are dynamically distributed within a species, allowing us to better understand genetic reservoirs and underlying bacterial evolution.


Intermediate Hamiltonian Fock-space multireference coupled-cluster method with full triples for calculation of excitation energies.
The intermediate Hamiltonian multireference coupled-cluster (CC) method with singles, doubles, and triples within the excited (1,1) sector of Fock space (FS) is implemented and formulated to calculate excitation energies (EEs). Due to the intermediate Hamiltonian formulation, which provides a robust computational scheme for solving the FS-CC equations, coupled to an efficient factorization strategy, relatively large basis sets and model spaces are employed permitting basis set converged comparisons of the calculated vertical EEs, which can be compared to the experimental data for the N(2) and CO molecules. The issue of charge-transfer separability is also addressed.


The influence of storage time upon the real thickness of the histological brain sections.
The aim of the study was to assess the effect of storage time on the actual thickness of the histological sections. The study was performed on 5 brains of adult Wistar rats. The most rapid changes occur at the beginning of the storage process, after about one month the dynamics of changes decreases, but still the thickness of the sections diminishes. It is suggested that quantitative analyses should be performed in similar period of time and the critical care should be taken not only of the chemicals and procedures used, but also of the control of environmental factors.


An exegesis of bacteriophage therapy: An emerging player in the fight against anti-microbial resistance.
Bacteriophages (simply referred to as Phages) are a class of viruses with the ability to infect and kill prokaryotic cells (bacteria), but are unable to infect mammalian cells. This unique ability to achieve specific infectiousness by bacteriophages has been harnessed in antibacterial treatments dating back almost a decade before the antibiotic era began. Bacteriophages were used as therapeutic agents in treatment of dysentery caused by Shigella dysenteriae as far back as 1919 and in the experimental treatment of a wide variety of other bacterial infections caused by Vibrio cholerae, Staphylococcus sp., Pseudomonas sp. etc, with varying degrees of success. Phage therapy and its many prospects soon fell out of favour in western medicine after the Second World War, with the discovery of penicillin. The Soviet Union and other countries in Eastern Europe however mastered the craft of bacteriophage isolation, purification and cocktail preparation, with phage-based therapeutics becoming widely available over-the-counter. With the recent rise in cases of multi-drug resistant bacterial infections, the clamour for a return to phage therapy, as a potential solution to the anti-microbial resistance (AMR) crisis has grown louder. This review provides an extensive exposé on phage therapy, addressing its historical use, evidences of its safety and efficacy, its pros and cons when compared with antibiotics, cases of compassionate use for treating life-threatening antibiotic-resistant infections, the limitations to its acceptance and how these may be circumvented.


Optimized culture conditions for bacterial cellulose production by Acetobacter senegalensis MA1.
Cellulose, the most versatile biomolecule on earth, is available in large quantities from plants. However, cellulose in plants is accompanied by other polymers like hemicellulose, lignin, and pectin. On the other hand, pure cellulose can be produced by some microorganisms, with the most active producer being Acetobacter xylinum. A. senengalensis is a gram-negative, obligate aerobic, motile coccus, isolated from Mango fruits in Senegal, capable of utilizing a variety of sugars and produce cellulose. Besides, the production is also influenced by other culture conditions. Previously, we isolated and identified A. senengalensis MA1, and characterized the bacterial cellulose (BC) produced. The maximum cellulose production by A. senengalensis MA1 was pre-optimized for different parameters like carbon, nitrogen, precursor, polymer additive, pH, temperature, inoculum concentration, and incubation time. Further, the pre-optimized parameters were pooled, and the best combination was analyzed by using Central Composite Design (CCD) of Response Surface Methodology (RSM). Maximum BC production was achieved with glycerol, yeast extract, and PEG 6000 as the best carbon and nitrogen sources, and polymer additive, respectively, at 4.5 pH and an incubation temperature of 33.5 °C. Around 20% of inoculum concentration gave a high yield after 30 days of inoculation. The interactions between culture conditions optimized by CCD included alterations in the composition of the HS medium with 50 mL L- 1 of glycerol, 7.50 g L- 1 of yeast extract at pH 6.0 by incubating at a temperature of 33.5 °C along with 7.76 g L- 1 of PEG 6000. This gave a BC yield of wet weight as 469.83 g L- 1. The optimized conditions of growth medium resulted in enhanced production of bacterial cellulose by A. senegalensis MA1, which is around 20 times higher than that produced using an unoptimized HS medium. Further, the cellulose produced can be used in food and pharmaceuticals, for producing high-quality paper, wound dressing material, and nanocomposite films for food packaging.


The misidentification syndromes as mindreading disorders.
The patient with Capgras' syndrome claims that people very familiar to him have been replaced by impostors. I argue that this disorder is due to the destruction of a representation that the patient has of the mind of the familiar person. This creates the appearance of a familiar body and face, but without the familiar personality, beliefs, and thoughts. The posterior site of damage in Capgras' is often reported to be the temporoparietal junction, an area that has a role in the mindreading system, a connected system of cortical areas that allow us to attribute mental states to others. Just as the Capgras' patient claims that that man is not his father, the patient with asomatognosia claims that his arm is not really his. A similar account applies here, in that a nearby brain area, the supramarginal gyrus, is damaged. This area works in concert with the temporoparietal junction and other areas to produce a large representation of a mind inside a body situated in an environment. Damage to the mind-representing part of this system (coupled with damage to executive processes in the prefrontal lobes) causes Capgras' syndrome, whereas damage to the body-representing part of this system (also coupled with executive damage) causes asomatognosia.


Nosocomial Candida krusei fungemia in cancer patients: report of 10 cases and review.
The risk factors, therapy and outcome of ten cases of fungemia due to Candida krusei, appearing during the last 10 years in a single national cancer institution, are analyzed. Univariate analyses did not find any specific risk factors in comparison to 51 Candida albicans fungemias appearing at the same institution and with a similar antibiotic policy. Association with prior fluconazole prophylaxis was not confirmed because only one case appeared in a patient previously treated with fluconazole. However, attributable and crude mortality due to C. krusei fungemias was higher than for C. albicans fungemia. The authors review 172 C. krusei fungemias published within the last 10 years to compare with the incidence, therapy and outcome of C. krusei fungemia from our cancer institute.


Role of radiation therapy as immune activator in the era of modern immunotherapy for metastatic malignant melanoma.
Metastatic melanoma is difficult to treat, and often portends a grim prognosis. For patients with cerebral metastases, the prognosis is even more dire. Systemic immunotherapy and targeted agents are emerging as the mainstay of treatment for metastatic melanoma. Although immunotherapy has been shown to prolong relapse-free survival and long-term control of micrometastatic disease, the response rate is suboptimal, prompting the need to optimize and improve therapy. Accumulating evidence suggests that in addition to effective locoregional control, radiation therapy (RT) may induce immune activation and expansion of T lymphocytes recognizing melanocyte-specific antigens including activated cytotoxic T lymphocytes that can potentially kill melanoma cells. In some cases, RT contributes to the clearance of metastatic disease in distant, nonirradiated regions, a bystander phenomenon called the abscopal effect. Here, we evaluate the potential promise of ablative radiation treatment in the era of modern immunotherapy by presenting a patient with metastatic melanoma who remained disease free for over 3 years after an initial diagnosis of advanced metastatic melanoma with brain, subcutaneous tissue, mesenteric, pelvic, and retroperitoneal involvement. The patient failed initial stereotactic radiosurgery, but responded to whole-brain RT in combination with interleukin-2 immunotherapy. Thus, combination RT with immunotherapy may be synergistic by promoting the release and processing of melanoma antigens that can be presented by dendritic cells. This in turn may augment the response to therapies that center on expansion and/or activation of antitumor T cells.


The development of telemedicine programs in Sub-Saharan Africa: Progress and associated challenges.
Monitoring the progress of telemedicine use in Sub-Saharan Africa (SSA) countries has received a considerable attention from many health organizations and governmental agencies. This study reviewed the current progress and challenges in relation to the development of telemedicine programs in SSA. The results from reviewing 66 empirical studies revealed an unbalanced progress across SSA countries. Further, technological, organisational, legal and regulatory, individual, financial, and cultural aspects were identified as the major barriers to the success of telemedicine development in SSA. This study reported the current trends in telemedicine application, as well as highlighting critical barriers for consideration by healthcare decision makers. The outcomes from this study offer a number of recommendations to support wider implementation and sustainable usage of telemedicine in SSA.


Conservative interventions for treating functional daytime urinary incontinence in children.
In children, functional daytime urinary incontinence is the term used to describe any leakage of urine while awake that is not the result of a known underlying neurological or congenital anatomic cause (such as conditions or injuries that affect the nerves that control the bladder or problems with the way the urinary system is formed). It can result in practical difficulties for both the child and their family and can have detrimental effects on a child's well-being, education and social engagement. To assess the effects of conservative interventions for treating functional daytime urinary incontinence in children. We searched the Cochrane Incontinence Specialised Register, which contains studies identified from CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 11 September 2018). We also searched Chinese language bibliographic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang. No language restrictions were imposed. We included randomised controlled trials (RCTs), quasi-randomised, multi-arm studies, cross-over studies and cluster-randomised studies that included children aged between 5 and 18 years with functional daytime urinary incontinence. Two review authors independently screened records and determined the eligibility of studies for inclusion according to predefined criteria. Where data from the study were not provided, we contacted the study authors to request further information. Two review authors assessed risk of bias and processed included study data as described in the Cochrane Handbook for Systematic Reviews of Interventions. Where meta-analysis was possible, we applied random-effects meta-analysis using the Mantel-Haenszel method for dichotomous outcomes. The review included 27 RCTs involving 1803 children. Of these, six were multi-arm and one was also a cross-over study. Most studies were small, with numbers randomised ranging from 16 to 202. A total of 19 studies were at high risk of bias for at least one domain. Few studies reported data suitable for pooling due to heterogeneity in interventions, outcomes and measurements.Individual conservative interventions (lifestyle, behavioural or physical) versus no treatmentTranscutaneous electrical nerve stimulation (TENS) versus sham (placebo) TENS. More children receiving active TENS may achieve continence (risk ratio (RR) 4.89, 95% confidence interval (CI) 1.68 to 14.21; 3 studies; n = 93; low-certainty evidence).One individual conservative intervention versus another individual or combined conservative interventionPelvic floor muscle training (PFMT) with urotherapy versus urotherapy alone. We are uncertain whether more children receiving PFMT with urotherapy achieve continence (RR 2.36, 95% CI 0.65 to 8.53, 95% CI 25 to 100; 3 studies; n = 91; very low-certainty evidence).Voiding education with uroflowmetry feedback and urotherapy versus urotherapy alone. Slightly more children receiving voiding education with uroflow feedback and urotherapy may achieve continence (RR 1.13, 95% CI 0.87 to 1.45; 3 studies; n = 151; low-certainty evidence).Urotherapy with timer watch versus urotherapy alone. We are uncertain whether urotherapy plus timer watch increases the number of children achieving continence compared to urotherapy alone (RR 1.42, 95% CI 1.12 to 1.80; 1 study; n = 58; very low-certainty evidence).Combined conservative interventions versus other combined conservative interventionsTENS and standard urotherapy versus PFMT with electromyographic biofeedback and standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.11, 95% CI 0.73 to 1.68; 1 study; n = 78; very low-certainty evidence).PFMT with electromyography biofeedback and standard urotherapy versus PFMT without feedback but with standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.05, 95% CI 0.72 to 1.52; 1 study; n = 41; very low-certainty evidence).Individual conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions)PFMT versus anticholinergics. We are uncertain whether more children receiving PFMT than anticholinergics achieve continence (RR 1.92, 95% CI 1.17 to 3.15; equivalent to an increase from 33 to 64 per 100 children; 2 studies; n = 86; very low-certainty evidence).TENS versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 0.81, 95% CI 0.05 to 12.50; 2 studies; n = 72; very low-certainty evidence).Combined conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions)Voiding education with uroflowmetry feedback versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportion of children achieving continence (RR 1.02, 95% CI 0.58 to 1.78; 1 study; n = 64; very low-certainty evidence). The review found little reliable evidence that can help affected children, their carers and the clinicians working with them to make evidence-based treatment decisions. In this scenario, the clinical experience of individual clinicians and the support of carers may be the most valuable resources. More well-designed research, with well-defined interventions and consistent outcome measurement, is needed.


Aspergillus asper sp. nov. and Aspergillus collinsii sp. nov., from Aspergillus section Usti.
In sampling fungi from the built environment, two isolates that could not confidently be placed in described species were encountered. Phenotypic analysis suggested that they belonged in Aspergillus sect. Usti. In order to verify the sectional placement and to assure that they were undescribed rather than phenotypically aberrant isolates, DNA was isolated and sequenced at the beta-tubulin, calmodulin, internal transcribed spacer and RNA polymerase II loci and sequences compared with those from other species in the genus Aspergillus. At each locus, each new isolate was distant from existing species. Phylogenetic trees calculated from these data and GenBank data for species of the section Usti excluded the placement of these isolates in existing species, with statistical support. Because they were excluded from existing taxa, the distinct species Aspergillus asper (type strain NRRL 35910T) and Aspergillus collinsii (type strain NRRL 66196T) in sect. Usti are proposed to accommodate these strains.


An Improved Vision Method for Robust Monitoring of Multi-Point Dynamic Displacements with Smartphones in an Interference Environment.
Current research on dynamic displacement measurement based on computer vision mostly requires professional high-speed cameras and an ideal shooting environment to ensure the performance and accuracy of the analysis. However, the high cost of the camera and strict requirements of sharp image contrast and stable environment during the shooting process limit the broad application of the technology. This paper proposes an improved vision method to implement multi-point dynamic displacement measurements with smartphones in an interference environment. A motion-enhanced spatio-temporal context (MSTC) algorithm is developed and applied together with the optical flow (OF) algorithm to realize a simultaneous tracking and dynamic displacement extraction of multiple points on a vibrating structure in the interference environment. Finally, a sine-sweep vibration experiment on a cantilever sphere model is presented to validate the feasibility of the proposed method in a wide-band frequency range. In the test, a smartphone was used to shoot the vibration process of the sine-sweep-excited sphere, and illumination change, fog interference, and camera jitter were artificially simulated to represent the interference environment. The results of the proposed method are compared to conventional displacement sensor data and current vision method results. It is demonstrated that, in an interference environment, (1) the OF method is prone to mismatch the feature points and leads to data deviated or lost; (2) the conventional STC method is sensitive to target selection and can effectively track those targets having a large proportion of pixels in the context with motion tendency similar to the target center; (3) the proposed MSTC method, however, can ease the sensitivity to target selection through in-depth processing of the information in the context and finally enhance the robustness of the target tracking. In addition, the MSTC method takes less than one second to track each target between adjacent frame images, implying a potential for online measurement.


[Metastatic sternal tumor from thyroid papillary carcinoma; report of a case].
A 68-year-old male was referred to our department for treatment of a metastatic sternal tumor in the manubrium sterni. Primary lesion was papillary carcinoma of the left lobe of the thyroid gland. Total thyroidectomy, cervical lymph node dissection, resection of manubrium sterni with concomitant resection of bilateral clavicles, 1st ribs and 2nd ribs, and chest wall reconstruction using Marlex Mesh were performed on January 29, 2001. Considering relatively good prognosis and good response to multimodality therapy, surgical resection of sternal metastatic lesion from differentiated thyroid cancer seems to be a choice of therapy as a part of multimodality approach, including surgery, radioiodine and external radiation therapy, to thyroid cancer with systemic spread.


Effect of serotonin on pentagastrin-stimulated gastric pepsin secretion in dogs with gastric fistula.
The effect of serotonin on pentagastrin-stimulated gastric pepsin secretion in dogs was evaluated with regard to dose-response kinetics and receptor mediation. The pepsin secretion showed a dual response to exogenous serotonin. The high and low doses of serotonin stimulated, whereas the doses in between inhibited. The inhibition was of a non-competitive type and could be significantly counteracted by beta-adrenergic blocking drugs. This study supports the concept that the serotonin effect on gastric functions is mediated via sympathetic nerves releasing noradrenaline.


[Experimental morphological rationale for the use of cultures of multipotent mesenchymal stem cells in combination with biomaterials in the reconstruction of the pelvic floor].
To date, descension of the pelvic floor is a fairly common gynecological pathology that requires surgical treatment. The development of cellular technologies suggests that the use of multipotent mesenchymal stem cells (MMSC) in the treatment of this pathology can stimulate the regeneration of damaged tissue and contribute to the reconstruction of the structures of the pelvic floor. to evaluate the effectiveness of using MMSC in combination with biological and synthetic materials in vitro and in vivo with descension of the pelvic floor. Sprague Dawley rats 10 weeks old weighing 200 grams were used in the experiment. Under sterile conditions, mechanical damage to the posterior wall of the vagina was carried out, with the restoration of which vicryl 3-0 was used. On the 2nd and 4th day, the wound was cut off in a volume of 1.5 ml with xenograft, allograft and multipotent mesenchymal stem cells (MMSC) (5 thousand cells) obtained from the adipose tissue of rats. In the control group was not used biological material. At the second stage of the experiment, the compatibility of the mesh prosthesis with MMSC and allograft in vitro was evaluated. xenograft does not lead to full tissue regeneration, but contributes to rapid epithelialization and reduces the degree of inflammatory reaction in the wound during the regeneration of connective tissue. The use of allograft leads to quick and complete epithelialization of the wound and the formation of a structurally complete connective tissue lamina of the vaginal mucosa. The introduction of MMSC resulted in complete epithelialization of the wound and the formation of a structurally complete connective tissue plate of the mucosa and submucosa, but with a slightly smaller number of blood vessels in them than with the use of a biomaterial. At the second stage of the experiment, weak cell adhesion to the polypropylene substrate of the tablet was observed during cell culture in the presence of only a fragment of the mesh prosthesis. After MMSC cultivation in the presence of a mesh prosthesis fragment and an allograft, a relatively uniform distribution of cells around the mesh prosthesis loops was observed. it was determined that the use of MMSC and allograft has a positive effect on the process of vaginal tissue regeneration in rats. When combining these materials with mesh prostheses, it was found that MMSCs are not fixed directly to the synthetic material, but when the allograft is added, they concentrate and presumably have the maximum anti-inflammatory effect and promote tissue regeneration at the site of the mesh prosthesis. Thus, the use of autologous MMSC cells in combination with allograft and mesh polymeric materials for pelvic floor reconstruction can significantly improve the results of reconstructive operations.


Effect of Functional Electrical Stimulation Cycling Exercise on Lower Limb Strength Asymmetry in Persons With Multiple Sclerosis.
Lower limb strength asymmetry (ie, significant difference between contralateral limbs) has been associated with mobility impairment in persons with multiple sclerosis (MS). However, whether an adaptive exercise modality can be used to modify lower limb strength and potentially improve mobility is unclear. The effect of functional electrical stimulation (FES) cycling on lower limb strength asymmetry in persons with MS with mobility impairment was assessed, and the association between change in lower limb strength asymmetries and changes in functional and self-reported mobility outcomes was explored. Eight adults with MS (Expanded Disability Status Scale scores, 5.5-6.5) were included. Outcomes included knee extensor and knee flexor strength asymmetry, Timed 25-Foot Walk (T25FW) test, 2-Minute Walk Test (2MWT), Timed Up and Go (TUG) test, and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Participants received 24 weeks (3 times per week) of FES cycling or passive leg cycling. The FES condition demonstrated a small decrease in knee extensor (d = -0.33) and knee flexor (d = -0.23) strength asymmetry compared with passive leg cycling. With both groups combined, weak-to-strong associations were observed between change in knee extensor asymmetry and change in T25FW test time (rs = -0.43), 2MWT time (rs = -0.24), TUG test time (rs = 0.55), and MSWS-12 score (rs = 0.43). Moderate correlations were observed between change in knee flexor asymmetry and change in T25FW test time (rs = -0.31), TUG test time (rs = 0.33), and MSWS-12 score (rs = 0.35). FES cycling may be an efficacious exercise modality for reducing lower limb strength asymmetry and improving mobility in persons with MS.


Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort.
In the ACOSOG Z0011 trial, patients with primary breast cancer and 1-2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-François Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR)=6.1; 95% confidence interval (CI): 1.4-26.7; P=0.02)) and only one SLN removed (OR=9.1; 95%CI: 2.2-33.3; P=0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR=5.1; 95%CI: 1.2-22.2; P=0.03) was associated with the failure to perform completion ALND when recommended. Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.


On the joint analysis of longitudinal responses and early discontinuation in randomized trials.
Our focus is on the joint analysis of longitudinal nonnormal responses and early discontinuation in (pre)-clinical trials. Separate models are fitted to the two series (response and discontinuation) to account for covariate and time effects. The serial dependence and the dependence between response and drop-out are also modeled. This is done using particular dependence functions, called copulas. Copulas are used to create a joint distribution with given marginal distributions. Applications are given for the analysis of heart rate/morbidity in toxicology and pain severity/intake of rescue medications in a trial on migraine. Using copulas, the level of dependence between two variables remains invariant to changes in the marginal distribution of either variable. This proves interesting in modeling the association in a longitudinal setting when responses change over time.


Bibliometric analysis of trends in cardiac aging research over the past 20 years.
In recent years, many studies have addressed cardiac aging and related diseases. This study aims to understand the research trend of cardiac aging and find new hot issues. We searched the web of science core collection database for articles published between 2003 and 2022 on the topic of "cardiac aging." Complete information including keywords, publication year, journal title, country, organization, and author were extracted for analysis. The VOS viewer software was used to generate network maps of keywords, countries, institutions, and author relationships for visual network analysis. A total of 1002 papers were analyzed in the study. Overall, the number of annual publications on cardiac aging has increased since 2009, and new hot topics are emerging. The top 3 countries with the most publications were the United States (471 articles), China (209 articles) and Italy (101 articles). The University of Washington published the most papers (35 articles). The cluster analysis with author as the keyword found that the connections among different scholars are scattered and clustered in a small range. Network analysis based on keyword co-occurrence and year of publication identified relevant features and trends in cardiac aging research. According to the results of cluster analysis, all the articles are divided into 4 topics: "mechanisms of cardiac aging", "prevention and treatment of cardiac aging", "characteristics of cardiac aging", and "others." In recent years, the mechanism and treatment of cardiac aging have attracted the most attention. In both studies, animal models are used more often than in human populations. Mitochondrial dysfunction, autophagy and mitochondrial autophagy are hotspots in current research. In this study, bibliometric analysis was used to analyze the research trend of cardiac aging in the past 20 years. The mechanism and treatment of cardiac aging are the most concerned contents. Mitochondrial dysfunction, autophagy and mitophagy are the focus of future research on cardiac aging.


Getting to Know You: Familiarity, Stereotypes, and Children's Eyewitness Memory.
The present study concerned how the acquisition of social information, specifically knowledge about personal characteristics, influences young children's memory and suggestibility. Effects of two sources of knowledge about a target person were systematically examined: familiarity and stereotypes. Children, aged 4-5 and 7-9 years (N = 145), were randomly assigned, per age group, to experimental conditions based on a familiarity (6 hours vs. no prior exposure) × stereotype (negative depiction as messy and clumsy vs. no stereotype) factorial design. Children then watched the target person engage in a target event (a series of contests) at a preschool ("Camp Ingrid"). The children's memory and suggestibility about the target person and target event were tested after a delay of 2 weeks. Results indicated that the negative stereotype resulted in an increase in children's correct responses both to free-recall stereotype-related questions (when children were unfamiliar with the target person) and to closed-ended questions overall (for younger children). However, the stereotype was associated with greater error to stereotype-related closed-ended questions. Moreover, familiarity increased children's accuracy to closed-ended questions. Implications for theory and application are discussed. Copyright © 2016 John Wiley & Sons, Ltd.


Intrinsic Sources and Functional Impacts of Asymmetry at Electrical Synapses.
Electrical synapses couple inhibitory neurons across the brain, underlying a variety of functions that are modifiable by activity. Despite recent advances, many functions and contributions of electrical synapses within neural circuitry remain underappreciated. Among these are the sources and impacts of electrical synapse asymmetry. Using multi-compartmental models of neurons coupled through dendritic electrical synapses, we investigated intrinsic factors that contribute to effective synaptic asymmetry and that result in modulation of spike timing and synchrony between coupled cells. We show that electrical synapse location along a dendrite, input resistance, internal dendritic resistance, or directional conduction of the electrical synapse itself each alter asymmetry as measured by coupling between cell somas. Conversely, we note that asymmetrical gap junction (GJ) conductance can be masked by each of these properties. Furthermore, we show that asymmetry modulates spike timing and latency of coupled cells by up to tens of milliseconds, depending on direction of conduction or dendritic location of the electrical synapse. Coordination of rhythmic activity between two cells also depends on asymmetry. These simulations illustrate that causes of asymmetry are diverse, may not be apparent in somatic measurements of electrical coupling, influence dendritic processing, and produce a variety of outcomes on spiking and synchrony of coupled cells. Our findings highlight aspects of electrical synapses that should always be included in experimental demonstrations of coupling, and when assembling simulated networks containing electrical synapses.


Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues.
Obesity-associated metabolic abnormalities comprise a cluster of conditions including dyslipidemia, insulin resistance, diabetes and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from the accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. A variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago, and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. A substantially decreased BAT activity in individuals with obesity indicates a role for BAT in the setting of human obesity. On the other hand, BAT mass and its prevalence correlate with lower body mass index (BMI), decreased age and lower glucose levels, leading to a lower incidence of cardio-metabolic diseases. The increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. A deeper understanding of the role of BAT in human metabolic health and its interrelationship with body fat distribution and deciphering proper strategies to increase energy expenditure, by either increasing functional BAT mass or inducing white adipose browning, holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.


Options for change under Medicare: impact of a cap on catastrophic illness expense.
This study analyzes the total deductibles and coinsurance Medicare beneficiaries accrued in 1980. The study shows that Part B services accounted for 70 percent of all liability and Part A for 30 percent. Only 21 percent of enrollees exceeded $270 in liability from Part A and Part B combined. In 1980, if every enrollee had paid a surcharge of about $70, all liability over $270 could have been capped--without any additional program outlays. Similarly, projections for 1984 indicate that a surcharge of $98 could cap all liability over $800. For Part B alone, a surcharge of $113 could cover all liability over $200.


Impact of Short-Term Storage on Ex Vivo Antimalarial Susceptibilities of Fresh Ugandan Plasmodium falciparum Isolates.
We measured susceptibilities of Ugandan Plasmodium falciparum isolates assayed on the day of collection or after storage at 4°C. Samples were incubated with serial dilutions of 8 antimalarials, and susceptibilities were determined from 72-h growth inhibition assays. Storage was associated with decreased growth and lower 50% inhibitory concentration values, but differences between assays beginning on day 0 or after 1 or 2 days of storage were modest, indicating that short-term storage before drug susceptibility determination is feasible.


Rugby players' satisfaction with custom-fitted mouthguards made with different materials.
This study compared the comfort of two bimaxillary custom-fitted mouthguards. One type was made with silicone rubber and the other with methyl-methacrylate (acrylic). The study was a within-subject crossover clinical trial with 52 high-school rugby players who were randomly allocated to one of two groups. The first group wore a silicone mouthguard for 4 months and an acrylic one for the following 4-month period. The second group wore an acrylic mouthguard followed by a silicone one for similar periods. Comfort, bulkiness, stability, hardness, ability to talk and to breathe, oral dryness, nausea and inclination to chew were evaluated for each period using a Visual Analogue Scale questionnaire. There was no significant difference concerning comfort, bulkiness, ability to talk and to breathe, oral dryness and nausea between silicone and acrylic mouthguards by group and time of examination (Three-way ANOVA P>0.05). Acrylic mouthguards were more stable and harder than silicone ones (Wilcoxon's test P<0.01). Tendency to chew was greater for silicone appliances (P<0.01). For stability, hardness and inclination to chew, there was no significant difference in the response of the players based on the sequence of use of the two types of mouthguard during the survey (Mann-Whitney test P>0.05). At the end of the study, 56% of the players preferred to keep the acrylic mouthguard and 44% chose the silicone one. This choice did not vary between the groups (chi2, P>0.05). Silicone rubber mouthguards were well accepted by the players but technical improvements in silicone materials are needed to improve hardness and stability of silicone mouthguards for sport.


Impact of atypical antipsychotics on quality of life in patients with schizophrenia.
Schizophrenia is a long-term disabling illness that affects approximately 1% of the population. Its course is generally chronic with acute psychotic exacerbations that may require frequent hospitalisations. The clinical picture includes a range of symptoms such as delusions, hallucinations, agitation, suspiciousness, hostility, conceptual disorganisation, blunted affect, emotional and social withdrawal, lack of spontaneity, poverty of speech and a wide range of neurocognitive deficits. Over the past 50 years, antipsychotic medications have emerged as the cornerstone of management in concert with other important interventions, such as psychosocial and economic support and rehabilitation efforts. However, the unrivalled role of conventional antipsychotic medications has been continuously challenged by the wide range of adverse effects of these medications and their lack of usefulness in the treatment of neurocognitive deficits as well as deficit and negative symptoms. In addition, the lack of subjective tolerability of these agents and their negative impact on quality of life have complicated management for a large number of patients. Over the last 15 years, several new atypical antipsychotic medications have been introduced, including amisulpride, remoxipride, risperidone, sertindole, olanzapine, zotepine, quetiapine, ziprasidone and aripiprazole. In general, the new antipsychotics have shown themselves to be at least comparable in efficacy to conventional antipsychotics but with superior subjective tolerability and a more favourable adverse effect profile. The majority of quality of life studies involving new antipsychotic agents have evaluated the benefits of risperidone, olanzapine and clozapine; only a few studies have examined the effects of other new antipsychotics. While most of these studies have methodological and design limitations, the weight of evidence from them nevertheless points to a trend towards a more positive impact on quality of life with atypical agents. A number of recommendations can be made. First, more independent well designed and controlled studies are urgently needed to evaluate the effects of antipsychotic therapy on quality of life in patients with schizophrenia. New comparative studies should explore not only the differences between new and old antipsychotics but also identify any potential differences between individual new agents. The role of cost-effectiveness studies such as cost utility approaches in schizophrenia needs to be revisited, notwithstanding the fact that these types of studies have been reported to be feasible in schizophrenia. Finally, quality-of-life-based pharmacoeconomic studies of antipsychotic agents should not concentrate solely on cost reduction or containment, as it is likely that in order to maximise the benefits of new antipsychotic medications, greater expenditure on rehabilitation programmes and other support services will be necessary in the short-term at least.


Tumor-suppressive role of HACE1 in hepatocellular carcinoma and its clinical significance.
An increasing body of evidence suggests that downregulation or deletion of HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene plays an important role in the occurrence, invasion and metastasis process in many human malignancies and is closely related to prognosis. However, sparse evidence exists concerning the precise function and clinical significance of HACE1 in hepatocellular carcinoma (HCC). In the present study, we investigated the expression pattern of HACE1 in HCC tissues and cell lines, and determined the potential functions of HACE1 in HCC cell lines and evaluated the relationships between HACE1 expression and clinicopathological characteristics. Protein and mRNA expression levels of HACE1 in human HCC tissues and cell lines were examined by western blot analysis, quantitative real‑time polymerase chain reaction and immunohistochemical (IHC) analyses. IHC was used to analyze the correlations between HACE1 expression and clinicopathological features. HACE1 was upregulated in SMCC7721 cells by transfection with pcDNA3.1-HACE1 and Huh7 cells were transfected with siRNA targeting HACE1 for downregulation. Cell Counting Κit-8, Transwell and wound healing assays were performed to investigate the effects of the overexpression and knockdown of HACE1 on cellular proliferation and migration. The results revealed that HACE1 expression was lower in the HCC tissues and cell lines at the mRNA and protein levels compared to levels noted in the matched non‑tumor tissues and the normal liver cell line L02. Knockdown of HACE1 in Huh7 cells accelerated cell proliferation and migration (P<0.05), and overexpression of HACE1 in SMCC7721 cells was found to decrease the capacity for proliferation and migration (P<0.01). The results of IHC suggested that the HACE1 expression level was closely related to the serum AFP level, tumor differentiation and vascular invasion (P<0.05). Patients with low HACE1 expression levels exhibited poorer overall survival and HACE1 was found to be an independent prognostic factor for survival. In conclusion, as a tumor suppressor, HACE1 may be a valuable prognostic biomarker and potential therapeutic target for HCC treatment.


Human neutrophils are targets to paracoccin, a lectin expressed by Paracoccidioides brasiliensis.
Paracoccin (PCN), a lectin expressed by Paracoccidioides brasiliensis (Pb), is known to exert activities on the fungal biology, as well as different immune cells of myeloid origin. The aim of this study was to investigate the direct interaction of the recombinant form of the lectin (rPCN) with neutrophils, a neglected area. Freshly isolated human neutrophils from healthy donors were used. Neutrophils were incubated with rPCN in vitro. After the treatment, the production of reactive oxygen species (ROS), DNA release, IL-8, TNF, IFN-γ, IL-10, IL-12p40, TGF-β and IL-1β production, fungicidal ability, apoptosis and de novo protein synthesis was determined. rPCN was found to induce ROS production as well as DNA release. Using the ROS inhibitor, diphenyleneiodium, both ROS production and DNA release were significantly inhibited. In addition, rPCN was found to induce IL-8 and IL1-β production, inhibit apoptosis and induce de novo protein synthesis. Addition of cycloheximide, a protein synthesis inhibitor, drastically reversed the antiapoptotic effect of rPCN. Finally, the ability to kill Pb yeasts by human neutrophils was significantly increased after rPCN stimulation. rPCN can alter the biology of human neutrophils increasing their fungicidal ability. Moreover, the ability of rPCN to increase DNA release and to induce suppression of neutrophil apoptosis occurs by a ROS- and de novo protein synthesis-dependent mechanism, respectively.


Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae.
The human nasopharynx is the natural habitat and reservoir for Neisseria meningitidis and Haemophilus influenzae type b (Hib). Meningococcal and Hib pathogenesis was studied in human nasopharyngeal tissue in organ culture. Inocula of greater than or equal to 10(6) meningococci or cfu of Hib were required for consistent production of infection in these cultures. By 24 hours meningococci and Hib grew to 10(8)-10(10) cfu/mL in culture supernatants, while 10(4)-10(7) cfu per organ culture were tissue associated. These studies further indicated that nasopharyngeal mucus contains components that specifically bind Hib; that both meningococci and Hib cause cytotoxicity, resulting in breakdown of tight junctions of epithelial cells, sloughing of ciliated cells, and ciliostasis; that pili are the most important components mediating initial attachment of meningococci to non-ciliated epithelial cells of the human nasopharynx; that Hib expresses both pilus and nonpilus adhesions that facilitate attachment to nonciliated cells; and that meningococci and Hib both invade the epithelial surface to reach the submucosa but do so by different routes. Meningococci and Hib have evolved successful, although divergent, mechanisms by which to infect the human nasopharynx.


Safety, efficacy, surgical, and radiological outcomes of short segment occipital plate and C2 transarticular screw construct for occipito-cervical instability.
Our study aims to assess the safety, efficacy, clinicoradiological, functional, neurological outcomes, and complications of posterior occipitocervical fixation using an occipital plate and C1-2 transarticular screw (TAS) construct. This was a retrospective analysis of prospectively collected data. Data of 27 patients who underwent occipital plate and C1-2 TAS construct at a single institute from 2010 to 2015 were collected and analyzed. Demographics, clinical parameters (Visual Analog Score, Oswestry Disability Index, and modified JOA score), radiological parameters - mean atlantodens interval, posterior occipitocervical angle, occipitocervical-2 angle, surgical parameters (operative time, blood loss, hospital stay, and fusion), and complications were evaluated. The mean age of the patients was 54.074 ± 16.52 years (18-81 years), the mean operative time was 116.29 ± 12.23 min, and the mean blood loss was 196.29 ± 38.94 ml. The mean hospital stay was 5.22 ± 1.28 days. The mean ± standard deviation follow-up duration was 62.52 ± 2.27 months. There was a significant improvement in clinical parameters and radiological parameters postoperatively. One patient with implant failure, one patient with pseudoarthrosis, one with neurological deterioration, two wound complications, and two dural tears were noted. Posterior occipitocervical reconstruction with O-C1-2 TAS construct provided excellent clinical outcomes, radiological outcomes, optimal correction of malalignment in the occipitocervical region, and with biomechanically sound fixation. Extending the instrumentation into the subaxial spine will lead to a decrease in the range of motion, increased surgical time, blood loss, more extensive muscle damage, and also increase the costs.


Helix unfolding in unsolvated peptides.
The conformations of unsolvated Ac-K(AGG)(5)+H(+) and Ac-(AGG)(5)K+H(+) peptides (Ac = acetyl, A = alanine, G = glycine, and K = lysine) have been examined by ion mobility measurements over a wide temperature range (150-410 K). The Ac-K(AGG)(5)+H(+) peptide remains a globule (a compact, roughly spherical structure) over the entire temperature range, while both an alpha-helix and a globule are found for Ac-(AGG)(5)K+H(+) at low temperature. As the temperature is raised the alpha-helix unfolds. Rate constants for loss of the helix (on a millisecond time scale) have been determined as a function of temperature and yield an Arrhenius activation energy and preexponential factor of 38.2 +/- 1.0 kJ mol(-1) and 6.5 +/- 3.7 x 10(9) s(-1), respectively. The alpha-helix apparently does not unfold directly into the globule, but first converts into a long-lived intermediate which survives to a significantly higher temperature before converting. According to molecular dynamics simulations, there is a partially untwisted helical conformation that has both a low energy and a well-defined geometry. This special structure lies between the helix and globule and may be the long-lived intermediate.


Case Report: Partial Response Following Nivolumab Plus Docetaxel in a Patient With EGFR Exon 20 Deletion/Insertion (p.N771delinsGF) Mutant Lung Adenocarcinoma Transdifferentiated From Squamous Cell Carcinoma.
The histological transformation from lung squamous cell carcinoma (LUSC) to lung adenocarcinoma (LUAD) and p. N771delinsGF mutations in EGFR exon 20 (ex20) are exceedingly rare in non-small cell lung carcinoma (NSCLC). EGFR ex20 mutations are insensitive to EGFR tyrosine kinase inhibitors in NSCLC. Here, we present a 76-year-old male smoker harboring LUAD with a novel p. N771delinsGF deletion/insertion mutation in EGFR ex20 transdifferentiating from advanced LUSC after chemoradiotherapy. The patient presented reduced hydrothorax and relieved tightness with the treatment of nivolumab plus docetaxel and carboplatin after the failure of second-line chemotherapy. The case highlights the importance of rebiopsy and molecular retesting after the progression of lung cancer and supports the idea that the combination of immune checkpoint blockade and chemotherapy may be an attractive option for patients with EGFR ex20 mutations associated with LUSC-LUAD transformation.


Analysis of Censored Longitudinal Data with Skewness and a Terminal Event.
In HIV/AIDS study, the measurements viral load are often highly skewed and left-censored because of a lower detection limit. Furthermore, a terminal event (e.g., death) stops the follow-up process. The time to terminal event may be dependent on the viral load measurements. In this article, we present a joint analysis framework to model the censored longitudinal data with skewness and a terminal event process. The estimation is carried out by adaptive Gaussian quadrature techniques in SAS procedure NLMIXED. The proposed model is evaluated by a simulation study and is applied to the motivating Multicenter AIDS Cohort Study (MACS).


Indomethacin and recurrent ileal perforations in a preterm infant.
This article reports a case of a very low birth weight infant who was given intravenous indomethacin for a symptomatic patent ductus arteriosus and subsequently had two isolated ileal perforations several days apart. Spontaneous or indomethacin-related ileal perforation appears to constitute a separate clinical and pathologic entity, different from necrotizing enterocolitis, with a benign clinical picture and good prognosis when promptly recognized.


Aberration in the palatal root of the maxillary first molar.
Thorough knowledge of root canal morphology is essential for the endodontic therapy. Variations in the root and root canal morphology, especially in multirooted teeth, are a constant challenge for diagnosis and management. The dentist needs to be familiar with the various root canal configurations and their variations for successful endodontic therapy. There are rare variations in canal number and configuration in maxillary molars, which could affect treatment outcome. Two lingual root structures are occasionally found on human permanent maxillary molars. One of these is the normal lingual root, which is always present, the other is a supernumerary structure which can be located either mesiolingually (radix mesiolingualis) or distolingually (radix distolingualis). The purpose of this paper is to review the literature and to demonstrate a case report which describes the successful non-surgical endodontic management of an unusual maxillary first molar with four separate roots and four canals.


Comparative Evaluation of the Predictive Performances of Three Different Structural Population Pharmacokinetic Models To Predict Future Voriconazole Concentrations.
Bayesian methods for voriconazole therapeutic drug monitoring (TDM) have been reported previously, but there are only sparse reports comparing the accuracy and precision of predictions of published models. Furthermore, the comparative accuracy of linear, mixed linear and nonlinear, or entirely nonlinear models may be of high clinical relevance. In this study, models were coded into individually designed optimum dosing strategies (ID-ODS) with voriconazole concentration data analyzed using inverse Bayesian modeling. The data used were from two independent data sets, patients with proven or suspected invasive fungal infections (n = 57) and hematopoietic stem cell transplant recipients (n = 10). Observed voriconazole concentrations were predicted whereby for each concentration value, the data available to that point were used to predict that value. The mean prediction error (ME) and mean squared prediction error (MSE) and their 95% confidence intervals (95% CI) were calculated to measure absolute bias and precision, while ΔME and ΔMSE and their 95% CI were used to measure relative bias and precision, respectively. A total of 519 voriconazole concentrations were analyzed using three models. MEs (95% CI) were 0.09 (-0.02, 0.22), 0.23 (0.04, 0.42), and 0.35 (0.16 to 0.54) while the MSEs (95% CI) were 2.1 (1.03, 3.17), 4.98 (0.90, 9.06), and 4.97 (-0.54 to 10.48) for the linear, mixed, and nonlinear models, respectively. In conclusion, while simulations with the linear model were found to be slightly more accurate and similarly precise, the small difference in accuracy is likely negligible from the clinical point of view, making all three approaches appropriate for use in a voriconazole TDM program.


A new iphiculid crab (Crustacea, Brachyura, Leucosioidea) from the Middle Miocene of Austria, with notes on palaeobiogeography of Iphiculus.
A new fossil species of the iphiculid genus Iphiculus Adams & White, 1849, (Crustacea, Brachyura) is described on the basis of three specimens from the Middle Miocene Florian Beds of Styria, Austria. Iphiculus eliasi sp. nov. constitutes the first European record of the genus. This occurrence represents the oldest record of Iphiculus, having implications for the palaeobiogeographic history of the family Iphiculidae. It is suggested that Iphiculus may have originated in the Western Tethys and migrated subsequently into the Indo-West Pacific. Alternatively, its current geographic restriction to the Indo-West Pacific can be a remnant of an ancient broader geographic distribution.


A comparison of endoscopy versus pathology sizing of colorectal adenomas and potential implications for surveillance colonoscopy.
The aim of this study was to compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy. Endoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathologic parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines. A total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, P < .001), which may result in lower accuracy. Applying a 10-mm cut-off relevant to guidelines on risk stratification, 7.3% of all adenomas and 28.3% of those 8 to 12 mm in size had discordant endoscopy and pathology size categorization. Depending on which guidelines are applied, 4.8% to 9.1% of individuals had differing risk stratification for surveillance recommendations, with the use of pathology sizing resulting in marginally fewer recommended surveillance colonoscopies. Choice of pathology or endoscopy approaches to determine adenoma size will potentially influence surveillance colonoscopy follow-up in 4.8% to 9.1% of individuals. Pathology sizing appears more accurate than endoscopy sizing, and preferential use of pathology size would result in a small, but clinically important, decreased burden on surveillance colonoscopy demand. Careful endoscopy sizing is required for adenomas removed piecemeal.


Trends and Challenges in Tumor Anti-Angiogenic Therapies.
Excessive abnormal angiogenesis plays a pivotal role in tumor progression and is a hallmark of solid tumors. This process is driven by an imbalance between pro- and anti-angiogenic factors dominated by the tissue hypoxia-triggered overproduction of vascular endothelial growth factor (VEGF). VEGF-mediated signaling has quickly become one of the most promising anti-angiogenic therapeutic targets in oncology. Nevertheless, the clinical efficacy of this approach is severely limited in certain tumor types or shows only transient efficacy in patients. Acquired or intrinsic therapy resistance associated with anti-VEGF monotherapeutic approaches indicates the necessity of a paradigm change when targeting neoangiogenesis in solid tumors. In this context, the elaboration of the conceptual framework of "vessel normalization" might be a promising approach to increase the efficacy of anti-angiogenic therapies and the survival rates of patients. Indeed, the promotion of vessel maturation instead of regressing tumors by vaso-obliteration could result in reduced tumor hypoxia and improved drug delivery. The implementation of such anti-angiogenic strategies, however, faces several pitfalls due to the potential involvement of multiple pro-angiogenic factors and modulatory effects of the innate and adaptive immune system. Thus, effective treatments bypassing relapses associated with anti-VEGF monotherapies or breaking the intrinsic therapy resistance of solid tumors might use combination therapies or agents with a multimodal mode of action. This review enumerates some of the current approaches and possible future directions of treating solid tumors by targeting neovascularization.


Nineteen cases of Buruli ulcer diagnosed in Japan from 1980 to 2010.
The etiology, clinical manifestations, and treatment of 19 sporadic cases of Buruli ulcer (BU) in Japan are described. The cases originated in different regions of Honshu Island, with no evidence of patient contact with an aquatic environment. The majority (73.7%) of cases occurred in females, with an average age of 39.1 years for females and 56.8 years for males. All patients developed ulcers on exposed areas of the skin (e.g., face, extremities). Most ulcers were <5 cm in diameter (category I), except in one severe progressive case (category II). Pain was absent in 10 of the 19 cases. Fourteen ulcers were surgically excised, and nine patients needed skin grafting. All cases were treated with various antibiotic regimens, with no reported recurrences as of March 2011. Mycobacterium ulcerans-specific IS2404 was detected in all cases. Ten isolates had identical 16S rRNA gene sequences, which were similar to those of M. ulcerans. However, the rpoB gene showed a closer resemblance to Mycobacterium marinum or Mycobacterium pseudoshottsii. PCR identified pMUM001 in all isolates but failed to detect one marker. DNA-DNA hybridization misidentified all isolates as M. marinum. The drug susceptibility profile of the isolates also differed from that of M. ulcerans. Sequence analysis revealed "Mycobacterium ulcerans subsp. shinshuense" as the etiologic agent of BU in Japan. Clinical manifestations were comparable to those of M. ulcerans but differed as follows: (i) cases were not concentrated in a particular area; (ii) there was no suspected connection to an aquatic environment; (iii) drug susceptibility was different; and (iv) bacteriological features were different.


Nonlinear dynamics in ventricular fibrillation.
Electrogram recordings of ventricular fibrillation appear complex and possibly chaotic. However, sequences of beat-to-beat intervals obtained from these recordings are generally short, making it difficult to explicitly demonstrate nonlinear dynamics. Motivated by the work of Sugihara on atmospheric dynamics and the Durbin-Watson test for nonlinearity, we introduce a new statistical test that recovers significant dynamical patterns from smoothed lag plots. This test is used to show highly significant nonlinear dynamics in a stable canine model of ventricular fibrillation.


Use of a postfall assessment tool to prevent falls.
Nursing research in fall prevention should not only identify etiologic risk factors to fall but seek to identify underlying causes, whenever possible. Few studies have investigated the use of a comprehensive postfall assessment tool (PFAT) by nurses as an intervention for the prevention of recurrent falls, especially one that prompts nurses to consider all potential causes through a categorization scheme. This study tested use of a comprehensive PFAT as an intervention, prospectively, facility-wide for 1 year by registered nurses using a pretest-posttest design. A 29.4% reduction in the fall rate (z = 3.89, p < .001), 27.6% decline in total falls experienced by all fallers (p < .001), and a 34.0% decline for recurrent fallers (p = .025) from preintervention to intervention year was observed when trained nurses categorized falls according to perceived causes. These declines are likely due to consistent and rigorous use by trained nursing staff, prompting their critical examination of each fall.


Protective effect of melatonin against cytotoxic actions of malondialdehyde: an in vitro study on human erythrocytes.
Malondialdehyde (MDA), a by-product of the oxidation of polyunsaturated fatty acids, is strongly cytotoxic. Here we report the in vitro ability of melatonin to protect intact human erythrocytes against the damage induced by the exposure to MDA. MDA at 20 microM caused marked variations in the red blood cell (RBC) membrane. High molecular weight fluorescent adducts were formed within minutes with membrane proteins. A 6-hr incubation led to the oxidation of membrane lipids, as reflected by the formation of conjugated diene (CD) lipid hydroperoxides and oxidation of vitamin E, and to an increase of the high molecular weight fluorescent adducts, which were an indication of MDA finally generated in the cells. Functional damage to the membrane was evident as a leakage of K+ ions into the incubation medium, and an increased resistance to osmotic lysis. A time-dependent hemolysis was observed by exposure of RBCs to 20 microM MDA for 6-12 hr. Melatonin was not a substrate for MDA, therefore it was not able to prevent the early formation of the adducts from the reaction of the MDA in the medium with membrane proteins. Melatonin, however, concentration-dependent prevented the formation of CD lipid hydroperoxides. As a consequence of counteracting the membrane lipid oxidation, the indoleamine prevented the loss of vitamin E and the increase of the fluorescent proteinaceous adducts observed after a 6-hr exposure to MDA. Melatonin also inhibited the K+ loss and returned to normal the osmotic resistance of the erythrocyte in the osmotic fragility test. By protecting membrane lipids and proteins, melatonin effectively prevented the MDA-induced time-dependent hemolysis. In the light of the known radical scavenging properties of melatonin, mechanisms of the cytoprotective effects of melatonin in our system are discussed.


Analgesic administration in the emergency department for children requiring hospitalization for long-bone fracture.
The objective of the study was to describe analgesia utilization before and during the emergency department (ED) visit and assess factors associated with analgesia use in pediatric patients with isolated long-bone fractures. This retrospective cohort study of patients aged 0 to 15 years with a diagnosis of an isolated long-bone fracture was conducted at a single, level I pediatric trauma center. Patients included were treated in the ED within 12 hours of injury and subsequently admitted to the hospital from January 2005 through August 2007. Pain medication received within the first hour after ED arrival was categorized based on prespecified standard doses as follows: adequate, inadequate, and no pain medication received. Cumulative logistic regression analysis assessed factors associated with analgesia use. There were 773 patients with isolated long-bone fracture included in the analysis. Overall, 10% of patients received adequate pain medicine; 31% received inadequate medicine; and 59% received no pain medicine within 1 hour of ED arrival. In multivariable analysis, children with younger age, longer time from injury to ED arrival, closed fractures, and upper-extremity fractures were less likely to receive adequate pain medicine during the ED visit. Of those transported by emergency medical services directly from the scene to the ED, 9 (10%) of 88 were given pain medication during transport. Pain management in pediatric patients following a traumatic injury has been recognized as an important component of care. This study suggests that alleviation of pain after traumatic injury requires further attention in both the prehospital and ED settings, especially among the youngest children.


Ethnic and gender differences in the use of coronary artery revascularisation procedures in New Zealand.
To examine ethnic and gender variations in the use of coronary artery revascularisation procedures in New Zealand and to determine whether the introduction of priority scores affected intervention trends. Analysis of the National Minimum Database for coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) intervention rates for New Zealand Pacific, Maori and other men and women aged 40 years and over during the decade 1990-1999. Coronary artery revascularisation rates were lower in women than in men in all ethnic groups and in Pacific and Maori men compared with other New Zealand men. Compared to all men, the mean age-standardised CABG and PTCA intervention rate ratios in all women were 0.34 and 0.36. Compared to other New Zealand men, the mean age-standardised CABG and PTCA intervention rate ratios were 0.64 and 0.25 in Pacific and 0.40 and 0.29 in Maori men respectively. Compared to other New Zealand women, the rate ratios for CABG and PTCA were 0.73 and 0.21 in Pacific and 0.74 and 0.43 in Maori women respectively. Introducing priority scores was neither associated with reduced cardiac procedures nor significantly reduced variation in procedures across all ethnic groups. Although Pacific and Maori peoples had higher rates of coronary artery disease morbidity and mortality, revascularisation rates were lower in both groups. Strategies beyond the use of priority scores are needed to address ethnic and gender disparities in coronary artery revascularisation procedures in New Zealand.


Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture.
Following a limited number of cell divisions, mesenchymal stem cells (MSCs) undergo senescence, and these senescent cells maintain metabolic modification and remain viable for long periods. Autophagy, an intracellular bulk degradation process, provides a survival effect for cells under stress. In this study, the effect of autophagy on senescent MSCs was analyzed. Following serial passaging, rat MSCs underwent replicative senescence, characterized by positive staining for senescence-associated β-galactosidase (SA-β-gal), and increased expression levels of p16 and p21. During MSC senescence, the levels of autophagic activity were increased, a greater number of autophagic vacuoles were observed in senescent MSCs by transmission electron microscopy, acridine orange staining was elevated and the expression levels of autophagy‑related proteins (microtubule‑associated protein 1A/1B‑light chain 3-II, Atg7 and Atg12) were increased. The role of autophagy in MSC senescence was further investigated through pharmacological inhibition of autophagy with bafilomycin A1 and 3-methyladenine. Inhibition of autophagy by pharmacological means reduced the rate of positive staining for SA-β-gal and the expression levels of senescence‑related proteins. In conclusion, these findings suggest that autophagy is activated during senescence and the autophagic activity may be a requirement for maintaining the senescent state of MSCs.


Serum Vitamin D levels and gestational diabetes mellitus: analysis of early pregnancy cohort from a teaching hospital of Kashmir Valley.
The association of gestational diabetes mellitus and serum Vitamin D levels in different trimesters of pregnancy has been studied recently. We conducted this study in an prospective observational cohort of well-characterized healthy pregnant women to examine the relationship between 1st trimester Vitamin D levels and Gestational Diabetes Mellitus (GDM) status during pregnancy. All pregnant women attending the out-patient department of Gynecology & Obstetrics, aged less than 35 years, and who were in their first trimester were included in the study. Socio-demographic, anthropometric details, clinical details, food frequency questionnaire and physical activity data was collected using validated pretested questionnaire. The comparison between those with GDM and those with normal glucose levels has been illustrated. Women in the GDM are older than those in the non-GDM group. The women in GDM group were taller, heavier and their BMI was greater than those in the non-GDM group. There were no significant differences in dietary intake at baseline between mothers with GDM and those with normal glucose levels. Further, it was found that Vitamin D concentration of <30 nmol/L was found among higher among those with GDM and the relationship was statistically significant. There is an association between maternal Vitamin D deficiency and increased risk for GDM in early pregnancy among Kashmiri women.


Factors that influence vulnerability to STDs and HIV/AIDS among Hispanic women.
Self-esteem, motivation for sexual health, and sexual risk behaviors as indicated by condom use and number of sex partners was explored in a sample of 140 Hispanic women of childbearing age (18-44 years). The researchers used Cox's Interaction Model of Client Health Behavior (IMCHB) as the conceptual framework for the study. They found that 70% (n = 79) of single women reported condom use with their most recent sexual partner, and 49% (n = 55) of single women reported more than one sexual partner in the last 12 months. Self-esteem and motivation for sexual health were significantly associated (r =.42, p =.001), although only the latter was related to condom use among single women (r =.29, p =.01). Women who reported higher self-esteem were less likely to worry about acquiring sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). Despite public information about STDs, including HIV/AIDS, a proportion of these women and their partners are vulnerable to these diseases. Health promotion implications are discussed.


[Long-term results of closed mitral commissurotomy--comparative study of closed mitral commissurotomy (CMC), open mitral commissurotomy (OMC) and mitral valve replacement (MVR)].
As the technique of open heart surgery has improved, CMC has been abandoned in favor of OMC and MVR. We evaluated and compared the results of CMC, OMC and MVR. METHOD. Between 1965 and 1978, 141 patients with mitral stenosis (MS) underwent CMC, and late follow-up obtained in 117 (83%) of them (CMC group). Between 1980 and 1989, 72 patients and 37 patients underwent OMC (OMC group) and MVR (MVR group), respectively. Cumulative follow-up periods were 1982, 632 and 200 patient-years in the CMC, OMC and MVR groups, respectively. RESULTS. (1) Survival rate; In the CMC group there were 2 operative deaths due to severe mitral regurgitation (MR). There were 17 late deaths, due to reoperations in 4 patients, cerebral infarction in 4 patients, congestive heart failure in 3 patients, myocardial infarction in 2 patients and unknown causes in 4 patients. The survival rate was 95%, 91% and 86% at 5, 10 and 15 years, respectively, in the CMC group. In the OMC and MVR groups there was no death. (2) The event free rate was 89%, 79% and 58% at 5, 10 and 15 years, respectively, in the CMC group, 97% and 97% at 5 and 10 years in the OMC group, and 95% and 90% at 4 and 5 years in the MVR group. (3) Reoperations; In the CMC group of 40 patients (34%) required reoperations in an average of 10.4 years after the initial operation, due to re-MS in 22 patients, MR in 10 patients and MRS in the 8 patients. Reoperative findings consisted of clefts in the mitral leaflets in 7 patients. There were pulmonary hypertension in 15 patients and tricuspid regurgitation in 22 patients. Fourteen patients underwent tricuspid anuloplasty and one patient underwent a tricuspid valve replacement. In the OMC group one patient required a reoperation due to MR; in the MVR group one patient required a reoperation due to a thrombosed valve. CONCLUSION. In the CMC group the survival rate and the event free rate were lower, and the rate of reoperation was higher than in the other two groups.


Conservative Solitons and Reversibility in Time Delayed Systems.
Time delayed dynamical systems have proven to be a fertile framework for the study of physical phenomena. In natural sciences, their uses have been limited to the study of dissipative dynamics. In this Letter, we demonstrate the existence of nonlinear reversible conservative time delayed systems. We consider the example of a dispersive microcavity containing a Kerr medium coupled to a distant external mirror. At low energies and in the long delay limit, a multiscale analysis shows the equivalence with the nonlinear Schrödinger equation. We unveil some of the symmetries and conserved quantities, as well as bright temporal solitons. While elastic collisions occur for shallow wave packets, we observe the lack of integrability at higher energies. We recover the Lugiato-Lefever equation in the weakly dissipative regime.


Colorimetric indicator based on purple tomato anthocyanins and chitosan for application in intelligent packaging.
Intelligent colorimetric indicator films were prepared to monitor freshness/spoilage of milk and fish by incorporating purple tomato anthocyanin (PTA) into chitosan (CS) matrix via solution casting method with PTA concentration (w/w, based on CS) of 10%, 30%, and 50%, respectively. The pH-response, UV absorption, Swelling Index, and the mechanical properties of CS/PTA films were determined. It was found that the color of the original CS/PTA films became darker with an improvement of PTA content and expressed well pH-sensitivity. With increasing of pH, the color of the CS/PTA films exposed to pH = 3-11 solutions became darker and the change in color of the CS/10% PTA film was the most discernable. The tensile strength and Young's modulus of the CS/PTA film was much lower than that of CS film, however, the elongation at breaking and Swelling Index were both improved by adding PTA. The intelligent films with 10% PTA changed their color during progressive spoilage of milk or fish, revealing their potential application for monitoring food freshness/spoilage.


[Study of interaction of umbelliferone with three aromatic amino acids by fluorescence spectroscopy].
The interaction between umbelliferone (UMB) with tryptophan (Trp), tyrosine (Tyr) and phenylalanine (Phe) was studied by using fluorescence (FS) and ultraviolet (UV) spectroscopy. The results show that UMB can strongly quench the fluorescence of the three aromatic amino acids with the maximum quenching wavelengths at 347, 303 and 282 nm, respectively. Data analyses based on the Stern-Volmer curve and the UV spectroscopy show that static quenching occurred through the formation of the complexes of UMB with each aromatic amino acid in a molar ratio of 1 : 1. The binding constant K(c) of UMB with Trp, Tyr and Phe is 2.993 x 10(6), 7.858 x 10(4) and 1.186 x 10(3) L x mol(-1) (298.15 K) and 2.702 x 10(4), 1.063 x 10(5) and 8.352 x 10(3) L x mol(-1) (310.15 K), respectively. The thermodynamic parameters indicate that UMB has a strong interaction with the three aromatic amino acids. Hydrogen bond and Van der Waals force may play a major role in the reaction of UMB with Trp, whereas hydrophobic interaction should be responsible for the binding of UMB with Tyr and Phe. In addition, the dipole-dipole interaction may be another factor in the reactions between UMB and the three aromatic aminoacids.


Decreased superoxide anion and hydrogen peroxide production by neutrophils and monocytes in human immunodeficiency virus-infected children and adults.
The higher susceptibility to serious bacterial infections of patients, particularly children, infected with the human immunodeficiency virus (HIV) may be due in part to defective function of their phagocytic cells. We examined the ability of polymorphonuclear cells and monocytes of HIV-infected children and adults to generate superoxide anion (SO) and hydrogen peroxide (HP) and compared it with that of cells from normal children and adults. SO was measured by reduction of cytochrome c and HP by horseradish peroxidase-dependent oxidation of phenol red. The cells were incubated in 96-well plates at 37 degrees C for 2 h before the assay and the nonadherent cells then removed. Readings for SO were taken at 10, 30, 60, and 120 min after stimulation with phorbol myristate acetate; HP production was assayed after 90 min. The SO and HP production by polymorphonuclear cells and monocytes from both HIV-infected children and adults was consistently found to be markedly lower than that of cells from age-matched controls. The magnitude of the difference in response between patients and control cells also increased with increasing incubation time. Thus, phagocytic cells from HIV-infected children and adults are defective in their ability to generate reactive oxygen intermediates, and this defect may make them more vulnerable to bacterial and fungal infections.


You Don't Need an App-Conducting Mobile Smoking Research Using a Qualtrics-Based Approach.
With the increasing availability of smartphones, many tobacco researchers are exploring smartphone-delivered mobile smoking interventions as a disseminable means of treatment. Most effort has been focused on the development of smartphone applications (apps) to conduct mobile smoking research to implement and validate these interventions. However, developing project-specific smartphone apps that work across multiple mobile platforms (e.g., iOS and Android) can be costly and time-consuming. Here, using a hypothetical study, we present an alternate approach to demonstrate how mobile smoking cessation and outcome evaluation can be conducted without the need of a dedicated app. Our approach uses the Qualtrics platform, a popular online survey host that is used under license by many academic institutions. This platform allows researchers to conduct device-agnostic screening, consenting, and administration of questionnaires through Qualtrics's native survey engine. Researchers can also collect ecological momentary assessment data using text messaging prompts with the incorporation of Amazon Web Services' Pinpoint. Besides these assessment capabilities, Qualtrics has the potential for delivering personalized behavioral interventions through the use of JavaScript code. By customizing the question's web elements in Qualtrics (e.g., using texts, images, videos, and buttons), researchers can integrate interactive web-based interventions and complicated behavioral and cognitive tasks into the survey. In conclusion, this Qualtrics-based methodology represents a novel and cost-effective approach for conducting mobile smoking cessation and assessment research.


Evaluation of tumor-induced osteomalacia with 111In-pentetreotide scintigraphy.
In cases of nonhereditary osteomalacia associated with hypophosphatemia and inadequate response to vitamin D supplementation, one should consider the possibility of tumor-induced osteomalacia, a paraneoplastic syndrome caused by small mesenchymal tumors often found in obscure locations. We present a case of tumor-induced osteomalacia in which (111)In-pentetreotide scintigraphy aided in accurate localization of the culprit brachial plexus tumor and cure after resection.


Selection of CD133-targeted DNA aptamers for the efficient and specific therapy of colorectal cancer.
Tumor-targeted delivery of antitumor drugs is considered a promising strategy for improving the chemotherapeutic efficiency and reducing the incidence of side effects. The development of tumor-targeted aptamers to accommodate drugs has attracted great interest because of their convenience in biomedical applications. CD133 is a robust biomarker of colorectal cancer. In this study, Cs5, a novel specific aptamer with a dissociation constant in the nanomolar range, was developed using the cell-SELEX strategy from engineered CD133-expressing cells, and doxorubicin (Dox) was loaded into the Cs5 aptamer to form a chimera. The chimera showed an excellent targeting ability for CD133 through a selective killing effect in human colorectal cancer HCT116 cells expressing CD133. The in vitro and in vivo results demonstrated the highly efficient therapy and low toxicity of the chimera. Given the overexpression of CD133 in various tumors, our work provides a promising tool for specific cell identification and a wide range of applications in the field of targeted cancer therapy.


Radiosynthesis of (11)C-Levetiracetam: A Potential Marker for PET Imaging of SV2A Expression.
The multistep preparation of (11)C-levetiracetam ((11)C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.0 min. Briefly, the propionaldehyde was converted to propan-1-imine in situ as labeling precursor by incubation with ammonia. Without further separation, the imine was reacted with (11)C-HCN to form (11)C-aminonitrile. This crude was then reacted with 4-chlorobutyryl chloride and followed by hydrolysis to yield (11)C-LEV after purification by chiral high-performance liquid chromatography (HPLC). Both the radiochemical and enantiomeric purities of (11)C-LEV were >98%.


Nosocomial infection of CCHF among health care workers in Rajasthan, India.
Ever since Crimean-Congo hemorrhagic fever [CCHF] discovered in India, several outbreaks of this disease have been recorded in Gujarat State, India. During the year 2011 to 2015 several districts of Gujarat and Rajasthan state (Sirohi) found to be affected with CCHF including the positivity among ticks and livestock. During these years many infected individuals succumbed to this disease; which subsequently led to nosocomial infections. Herein, we report CCHF cases recorded from Rajasthan state during January 2015. This has affected four individuals apparently associated with one suspected CCHF case admitted in a private hospital in Jodhpur, Rajasthan. A 30-year-old male was hospitalized in a private hospital in Jodhpur, Rajasthan State, who subsequently had developed thrombocytopenia and showed hemorrhagic manifestations and died in the hospital. Later on, four nursing staff from the same hospital also developed the similar symptoms (Index case and Case A, B, C). Index case succumbed to the disease in the hospital at Jodhpur followed by the death of the case A that was shifted to AIIMS hospital, Delhi due to clinical deterioration. Blood samples of the index case and Case A, B, C were referred to the National institute of Virology, Pune, India for CCHF diagnosis from the different hospitals in Rajasthan, Delhi and Gujarat. However, a sample of deceased suspected CCHF case was not referred. Subsequently, blood samples of 5 nursing staff and 37 contacts (Case D was one of them) from Pokhran area, Jaisalmer district were referred to NIV, Pune. It clearly indicated that nursing staff acquired a nosocomial infection while attending the suspected CCHF case in an Intensive Care Unit of a private hospital in Jodhpur. However, one case was confirmed from the Pokhran area where the suspected CCHF case was residing. This case might have got the infection from suspected CCHF case or through other routes. CCHF strain associated with these nosocomial infections shares the highest identity with Afghanistan strain and its recent introduction from Afghanistan cannot be ruled out. However, lack of active surveillance, unawareness among health care workers leads to such nosocomial infections.


LiFi grid: a machine learning approach to user-centric design.
A novel machine learning (ML) clustering algorithm, named light-fidelity (LiFi) Grid, is proposed to design amorphous cells of LiFi access points (APs) in order to maximize the minimum signal-to-interference-plus-noise ratio (SINR) from the viewpoint of user-centric (UC) network design. The algorithm consists of two phases. Explicitly, the first phase consists of finding clusters of user densities based on the mean-shift (MS) clustering algorithm. In contrast to some other clustering algorithms, such as K-means, MS does not need to know the number of clusters in advance. Furthermore, the combined transmission scheme is assumed in each cell. In the second phase, this paper proposes a novel clustering algorithm that addresses the problem of grouping APs based on the positions of users-UC design-in optical wireless networks (OWNs). Hence, it addresses the dynamic resource allocation problem in OWNs if APs are considered as network resources. Based on the maximization of minimum SINR metric, LiFi Grid demonstrates the superior performance relative to conventional fixed-shape cell-centric network designs. Additionally, full compatibility of the LiFi Grid clustering algorithm with the Institute of Electrical and Electronics Engineers standard 802.15.7 is also shown.


Reducing the incidence of hematoma requiring surgical evacuation following male rhytidectomy: a 30-year review of 985 cases.
The reported incidence of hematoma following male rhytidectomy ranges from 7.9 to 12.9 percent. In 1976, it was demonstrated that postoperative hypertension is a key etiologic factor in hematoma formation and postoperative use of Thorazine was recommended to control blood pressure. This study analyzes the incidence of hematoma after male rhytidectomy at one institution after a strict and aggressive perioperative blood pressure control regimen was initiated. From 1982 to 2002, 985 patients with a mean age of 61 years (range, 49 to 72 years) underwent rhytidectomy. Thirty-six patients required surgical evacuation of expanding hematoma after rhytidectomy. Operative procedures were performed by more than 100 different plastic surgery attending surgeons, residents, and fellows. The overall incidence of hematoma during this study period was 4.24 percent. Age, medical history, medications, type of anesthesia, rhytidectomy technique and combination of procedures, and length of operation were not independent risk factors for determining who was more likely to develop a hematoma. Thirty-three percent of the patients requiring surgical evacuation had systolic blood pressure greater than 150 mmHg and diastolic blood pressure greater than 90 mmHg preoperatively, intraoperatively, and postoperatively. Over a 30-year period, the incidence of hematoma requiring surgical evacuation has decreased from 8.7 percent to 3.97 percent after initiation of a strict perioperative blood pressure control regimen. Despite the lower incidence of hematoma following male rhytidectomy today as compared with 30 years ago, the incidence in men (3.97 percent) remains higher than that in women (1 to 3 percent).


The pulsed Nd:YAG dental laser: review of clinical applications.
Since the first demonstration of a laser in 1960, numerous applications of this unique form of energy have been developed for the manufacturing, electronic, consumer and medical industries. Recent technological innovations have permitted development of lasers appropriate for use in the dental operatory. The carbon dioxide laser has been used for soft tissue surgery; the Nd:YAG laser has both soft and hard tissue applications. Advantages of laser treatment over conventional methods include minimal cellular destruction and tissue swelling, hemostasis, increased visualization of surgical sites and reduced post-operative pain. Additionally, it is possible to perform many procedures without needing anesthesia. Soft tissue clinical applications of the Nd:YAG laser include gingivectomies, gingivoplasties, operculectomies, biopsies, incising and draining procedures, frenectomies and treatment of aphthous ulcers; hard tissue clinical applications include vaporizing decay, etching enamel and dentin, desensitizing exposed root structure and creating temporary analgesia. As both clinical experiences and scientific investigations expand, possible future applications of the dental laser may well include development of new dental adhesives and composite systems, new methods for managing caries and new endodontic treatments. With its numerous benefits, the laser is having a positive impact on patients and the dental team.


Effect of Urea on Ammonium-dependent Synthesis of Carbamyl Phosphate during Spore Germination of Geotrichum candidum.
The specific activities of enzymes catalyzing the ammonium-dependent carbamyl phosphate synthesis (NH(3)-CPS) and the glutamine-dependent carbamyl phosphate synthesis (GLN-CPS) were increased during germination by approximately 5-and 1.7-fold respectively in the presence of 35 mm urea. The increase of NH(3)-CPS and GLN-CPS levels occurred immediately after the onset of germination and prior to the appearance of germ tube. Ammonium also stimulated the NH(3)-CPS activity, but the induction caused by urea was about three times higher than that by ammonium.Both NH(3)-CPS and GLN-CPS were highly labile. NH(3)-CPS was obtained free of GLN-CPS after (NH(4))(2)SO(4) fractionation and diethylaminoethyl cellulose chromatography. The optimum pH for NH(3)-CPS was 8.5 as opposed to broad pH optimum of pH 5.6-8 for the reverse reaction. The Km values obtained for NH(3), glutamine, and carbamyl phosphate were 12 mm, 0.5 mm, and 0.083 mm, respectively.