Cryoglobulinemic Vasculitis in Disguise: Cryofibrinogenemia as Variant of Monoclonal Gammopathy of Renal Significance.
Monoclonal gammopathy with cryoactivity (ie, cryoglobulins) that causes glomerulonephritis is considered within the spectrum of monoclonal gammopathy of renal significance. Cryofibrinogenemia (cryoactivity of coagulation factors) is very rarely associated with glomerulonephritis. We present a 39-year-old woman with a relapsing nephrotic syndrome. Laboratory investigation detected cryofibrinogen; the precipitate consisted of fibrinogen and a monoclonal immunoglobulin (M-protein; IgG-λ), and the latter was also detected in serum (4g/L). Initial conventional immunosuppressive therapy resulted in temporary renal remission. In view of the M-protein, subsequent therapy consisted of bortezomib/dexamethasone and high-dose melphalan followed by autologous hematopoietic stem cell transplantation, and resulted in a very good partial hematological response and temporary renal remission. However, after hematological and renal relapse, we performed unique experiments to clarify the role of the M-protein. Mixing patient serum with donor plasma resulted in cryoactivity, composed of M-protein+fibrinogen. Patient plasma deprived of M-protein did not have cryoactivity. Therefore, cryoactivity was dependent on the M-protein. We started lenalidomide, which resulted in very good partial hematological and renal remission. Thus, cryofibrinogenemia can be the consequence of an M-protein, which we suggest should be defined as monoclonal gammopathy of renal significance.


An adjustable, high sensitivity, wide dynamic range two channel wave-front sensor based on moiré deflectometry.
An adjustable, high sensitivity, wide dynamic range two channel wave-front sensor based on moiré deflectometry has been constructed for measuring distortions of light wave-front transmitted through the atmosphere. In this approach, a slightly divergent laser beam is passed through the turbulent ground level atmosphere and then a beam-splitter divides it into two beams. The beams pass through a pair of moiré deflectometers which are installed parallel and close together. From deviations in the moiré fringes we calculate the two orthogonal components of angle of arrival at each location across the wave-front. The deviations have been deduced in successive frames which allows evolution of the wave-front shape to be determined. The dynamic range and sensitivity of detection are adjustable by merely changing the separation of the gratings and the angle between the rulings of the gratings in both of channels. The spatial resolution of the method is also adjustable by means of bright, dark, and virtual traces for given moiré fringes without paying a toll in the measurement precision.


The effect of hyperbaric oxygen therapy on the pathophysiology of skin aging: a prospective clinical trial.
Skin biopsies can be used to evaluate physiological effects of aging targeted intervention at the tissue/cellular levels. Recent clinical trials have shown that hyperbaric oxygen therapy (HBOT) can target aging hallmarks, including telomere shortening, senescent cells clearance and angiogenesis. The aim of this study was to evaluate the effects of HBOT on the skin of a normal, non-pathological, aging population. The study was performed as a prospective clinical trial. After signing informed consent and undergoing baseline evaluations, the subjects were assigned to a three-month control period followed by three months of HBOT daily sessions. Skin biopsies were taken at baseline, after three months of no intervention (control) and 1-2 weeks following the last HBOT session. Trichrome, Orecin, lipofuscin and CD31 staining were used to evaluate collagen fibers, elastic fibers, senescent cells and blood vessels, respectively. Out of the cohort of 70 participants in the normal aging population study, thirteen male patients (age 68.07±2.5y) gave consent for repeated skin biopsies. Following HBOT, there was a significant increase in collagen density (p<0.001, effect size(es)=1.10), elastic fiber length (p<0.0001, es=2.71) and the number of blood vessels (p=0.02, es=1.00). There was a significant decrease in fiber fragmentation (p=0.012) and in tissue senescent cells (p=0.03, es=0.84) post-HBOT. No changes were noted in elastic fiber density or thickness. The study indicates, for the first time in humans, that HBOT can significantly modulate the pathophysiology of the skin aging in a healthy aging population. The demonstrated mechanisms include angiogenesis and senescent cell clearance.


TRIM22 activates NF-κB signaling in glioblastoma by accelerating the degradation of IκBα.
NF-κB signaling plays a critical role in tumor growth and treatment resistance in GBM as in many other cancers. However, the molecular mechanisms underlying high, constitutive NF-κB activity in GBM remains to be elucidated. Here, we screened a panel of tripartite motif (TRIM) family proteins and identified TRIM22 as a potential activator of NF-κB using an NF-κB driven luciferase reporter construct in GBM cell lines. Knockout of TRIM22 using Cas9-sgRNAs led to reduced GBM cell proliferation, while TRIM22 overexpression enhanced proliferation of cell populations, in vitro and in an orthotopic xenograft model. However, two TRIM22 mutants, one with a critical RING-finger domain deletion and the other with amino acid changes at two active sites of RING E3 ligase (C15/18A), were both unable to promote GBM cell proliferation over controls, thus implicating E3 ligase activity in the growth-promoting properties of TRIM22. Co-immunoprecipitations demonstrated that TRIM22 bound a negative regulator of NF-κB, NF-κB inhibitor alpha (IκBα), and accelerated its degradation by inducing K48-linked ubiquitination. TRIM22 also formed a complex with the NF-κB upstream regulator IKKγ and promoted K63-linked ubiquitination, which led to the phosphorylation of both IKKα/β and IκBα. Expression of a non-phosphorylation mutant, srIκBα, inhibited the growth-promoting properties of TRIM22 in GBM cell lines. Finally, TRIM22 was increased in a cohort of primary GBM samples on a tissue microarray, and high expression of TRIM22 correlated with other clinical parameters associated with progressive gliomas, such as wild-type IDH1 status. In summary, our study revealed that TRIM22 activated NF-κB signaling through posttranslational modification of two critical regulators of NF-κB signaling in GBM cells.


Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75.
VA Cooperative Study #75 was established to test in a controlled, randomized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy. No differences in survival were observed between warfarin-treated and control groups for advanced non-small cell lung, colorectal, head and neck and prostate cancers. However, warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression (P = 0.016) and a significant improvement in survival (P = 0.018) for patients with small cell carcinoma of the lung, including the subgroup of patients with disseminated disease at the time of randomization (P = 0.013). A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non-small cell lung cancer who had minimal disease at randomization. These results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung. Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present.


Use of MRF residue as alternative fuel in cement production.
Single-stream recycling has helped divert millions of metric tons of waste from landfills in the U.S., where recycling rates for municipal solid waste are currently over 30%. However, material recovery facilities (MRFs) that sort the municipal recycled streams do not recover 100% of the incoming material. Consequently, they landfill between 5% and 15% of total processed material as residue. This residue is primarily composed of high-energy-content non-recycled plastics and fiber. One possible end-of-life solution for these energy-dense materials is to process the residue into Solid Recovered Fuel (SRF) that can be used as an alternative energy resource capable of replacing or supplementing fuel resources such as coal, natural gas, petroleum coke, or biomass in many industrial and power production processes. This report addresses the energetic and environmental benefits and trade-offs of converting non-recycled post-consumer plastics and fiber derived from MRF residue streams into SRF for use in a cement kiln. An experimental test burn of 118 Mg of SRF in the precalciner portion of the cement kiln was conducted. The SRF was a blend of 60% MRF residue and 40% post-industrial waste products producing an estimated 60% plastic and 40% fibrous material mixture. The SRF was fed into the kiln at 0.9 Mg/h for 24h and then 1.8 Mg/h for the following 48 h. The emissions data recorded in the experimental test burn were used to perform the life-cycle analysis portion of this study. The analysis included the following steps: transportation, landfill, processing and fuel combustion at the cement kiln. The energy use and emissions at each step is tracked for the two cases: (1) The Reference Case, where MRF residue is disposed of in a landfill and the cement kiln uses coal as its fuel source, and (2) The SRF Case, in which MRF residue is processed into SRF and used to offset some portion of coal use at the cement kiln. The experimental test burn and accompanying analysis indicate that using MRF residue to produce SRF for use in cement kilns is likely an advantageous alternative to disposal of the residue in landfills. The use of SRF can offset fossil fuel use, reduce CO2 emissions, and divert energy-dense materials away from landfills. For this test-case, the use of SRF offset between 7700 and 8700 Mg of coal use, reduced CO2 emissions by at least 1.4%, and diverted over 7950 Mg of energy-dense materials away from landfills. In addition, emissions were reduced by at least 19% for SO2, while NOX emissions increased by between 16% and 24%. Changes in emissions of particulate matter, mercury, hydrogen chloride, and total-hydrocarbons were all less than plus or minus 2.2%, however these emissions were not measured at the cement kiln. Co-location of MRFs, SRF production facilities, and landfills can increase the benefits of SRF use even further by reducing transportation requirements.


Change, lack of change, and creating optimal change out of chaos.
Once again, we consider how to effect practice change at the local and national levels. This issue includes several articles that relate to quality improvement. Some physician actions seem resistant to change, as do the underlying social determinants and processes that lead to what are thought to be avoidable hospitalizations, but we also find that concerted effort, along with standardized orders sets and other avenues, can make a difference. Sometimes, however, our attempts at change can lead to more distraction then efficacy. Here we include articles that place the quality issues in context, report interventions, and advance the types of specific knowledge that allow interventional trials. We also have several articles about cancer screening and follow-up, a subset of quality improvement.


[Comparative analysis of parametric images in patients with dilated cardiomyopathy and coronary heart disease by radionuclide ventriculography].
After equiponderant radionuclide ventriculography the parametric images (phasic and amplitude) of heart function were estimated in 20 patients with dilated cardiomyopathy and in 17 patients with coronary heart disease associated with cardiomegaly. The patients with dilated cardiomyopathy and those with coronary heart disease showed principal differences in local disturbances of the amplitude of movements of left ventricle myocardium walls. While assessing synchronism of myocardial contraction in the patients with dilated cardiomyopathy the presence of the zones of myocardial asynchronism appeared to be a suggestive sign. At the same time the phenomena of asynchronism were not directly connected with impairment of heart conduction and became aggravated as dilatation of the left ventricle progressed, being often coupled with the ECG signs of cicatrical alterations in the myocardium, which came on the phasic images in the form of dyssynergia areas.


Antibacterial and dermal toxicological profiles of ethyl acetate extract from Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae).
The emergence in recent years of numerous resistant strains of pathogenic bacteria to a range of formerly efficient antibiotics constitutes a serious threat to public health. Crassocephalum bauchiense, a medicinal herb found in the West Region of Cameroon is used to treat gastrointestinal infections as well as liver disorders. The ethyl acetate extract from the leaves of C. bauchiense was evaluated for its antibacterial activity as well as acute and sub-acute toxicities. The plant extract was prepared by maceration in ethyl acetate. Its phytochemical screening was done by standard methods. The broth microdilution method was used to evaluate the in vitro antibacterial activity. The in vivo antibacterial activity of a gel formulation (0.05, 1 and 2% w/v) of this extract was evaluated using a Staphylococcus aureus-induced dermatitis in a murine model. Selected haematological and biochemical parameters were used to evaluate the dermal sub-acute toxicity of the extract in rats. Phytochemical screening of the C. bauchiense extract revealed the presence of alkaloids, phenols, tannins and sterols. In vitro antibacterial activities were observed against all the tested microorganisms (MIC = 0.04-6.25 mg/ml). Formulated extract-gel (2% w/v) and gentamycin (reference drug) eradicated the microbial infection after five days of treatment. A single dermal dose of this extract up to 32 g/kg body weight (bw) did not produce any visible sign of toxicity. Also, daily dermal application of the C. bauchiense extract gel formulation for 28 days did not show any negative effect, instead some biochemical parameters such as alanine aminotransferase (ALT and AST), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides were significantly (p < 0.05) affected positively. These results indicate that the C. bauchiense ethyl acetate extract can be used safely for the treatment of some bacterial infections.


Packaging sensing cells in spores for long-term preservation of sensors: a tool for biomedical and environmental analysis.
Whole-cell sensing systems have successfully been employed for detection of various biologically and environmentally important analytes. A limitation to their use for on-field analysis is the paucity of preservation methods for long-term storage and transport. For that, we have previously developed spore-based genetically engineered whole-cell sensing systems that are able not only to maintain the activity of the sensing cells but also to preserve it for long periods of time in normal and extreme environmental conditions. Herein, we have employed these spore-based sensing systems for analysis of real samples, such as blood serum and freshwater. Spores were able to germinate in the presence of the sample matrix, and the minimum time required for the spores to germinate and generate vegetative sensing cells able to elicit a measurable response to target analytes resulted to be around 2 h. Of the two spore-based sensing systems selected to detect model analytes in real samples, one was able to detect arsenic concentrations as low as 1 x 10(-7) M in freshwater and serum samples, and the other one could sense down to 1 x 10(-6) M of zinc in serum. The analysis of human serum samples from healthy subjects for their zinc content proved the viability of spore-based sensing systems. The complete assays, including spore germination and analyte detection, were performed in 2.5 h or less for arsenic and zinc. Furthermore, the assay is inexpensive and simple to carry out and offers unique advantages for the incorporation of the spore-based sensing systems into portable analytical platforms, such as microfluidic devices, to be employed for on-site analysis.


Propylthiouracil-induced diffuse interstitial pneumonitis.
Cough productive of sputum, exertional dyspnea, and hypoxemia developed in two patients with Graves' disease after six months (patient 1) or three weeks (patient 2) of treatment with propylthiouracil, 300 mg/day. Chest roentgenograms and transbronchial lung biopsy specimens revealed diffuse interstitial pneumonitis. Lymphocyte transformation by phytohemagglutinin was highly stimulated by propylthiouracil. Symptoms and signs improved after cessation of the drug therapy and administration of prednisolone acetate. These cases represent the first report of a complication of diffuse interstitial pneumonitis induced by propylthiouracil.


CME Planning Series: article one of five, conducting a needs assessment.
Conducting a needs assessment is the first step in the process of planning a CME activity or program. Performing a needs assessment requires a clear sense of one's target audience. Having more than one perspective, with at least one data source being subjective and another being objective, helps educators offer a program that is meaningful and relevant to participants. A root cause analysis represents an additional step of needs assessment that offers critical details about the educational needs of the target audience.


Renal failure after ruptured aneurysm.
The effectiveness of an intravenous nutritional program plus aggressive dialysis was studied in 32 patients with renal failure following ruptured abdominal aortic aneurysm. Each patient was managed postoperatively with a renal failure fluid regimen, consisting of the eight essential amino acids plus dextrose in conjunction with peritoneal dialysis and hemodialysis. This regimen induced salutary metabolic effects temporarily improving the patient's condition in most instances. No technical or septic complications associated with the intravenous dietary therapy occurred. However, the incidence of recovery of renal function was low, and the overall patient survival was only 12.5%. The experience indicates that although this program has been shown to be efficacious in some patients with acute renal failure, it seems of little benefit in those whose renal failure follows ruptured aortic aneurysm.


The development and recovery of motor function in spinal cats. II. Pharmacological enhancement of recovery.
The effects of the gamma-aminobutyric acid (GABA) antagonist bicuculline (BCC) on hindlimb motor performance was examined in mature spinal cats with spinal cord transections made either on the day of birth or at approximately two weeks postpartum and in chronic adult cats with spinal transections made in adulthood. In those adult operates, whose pre-drug performance was poor compared to neonatal operates, treadmill locomotion and weight support were improved dramatically by BCC administration. In neonatal operates (examined as adults), BCC administration increased the force of extension to abnormal levels and this increase appeared to disrupt locomotion. Immunocytochemical localization of GABA's synthetic enzyme, glutamic acid decarboxylase (GAD) within the spinal cords of these animals revealed an abnormal distribution of GAD reaction product only in newborn operates. The behavioral results indicate that the full extent of recovery in adult operates is prevented by inhibitory influences and this may contribute to the comparatively superior performance of neonatal operates i.e., the infant lesion effect. The anatomical results suggest that one requirement for the normal development of some intrinsic spinal circuitry is transneuronal regulation mediated by the maturation of descending systems.


Investigating Nanoparticle Organization in Polymer Matrices during Reaction-Induced Phase Transitions and Material Processing.
Controlling nanoparticle organization in polymer matrices has been and is still a long-standing issue and directly impacts the performance of the materials. In the majority of instances, simply mixing nanoparticles and polymers leads to macroscale aggregation, resulting in deleterious effects. An alternative method to physically blending independent components such as nanoparticle and polymers is to conduct polymerizations in one-phase monomer/nanoparticle mixtures. Here, we report on the mechanism of nanoparticle aggregation in hybrid materials in which gold nanoparticles are initially homogeneously dispersed in a monomer mixture and then undergo a two-step aggregation process during polymerization and material processing. Specifically, oleylamine-functionalized gold nanoparticles (AuNP) are first synthesized in a methyl methacrylate (MMA) solution and then subsequently polymerized by using a free radical polymerization initiated with azobis(isobutyronitrile) (AIBN) to create hybrid AuNP and poly(methyl methacrylate) (PMMA) materials. The resulting products are easily pressed to obtain bulk films with nanoparticle organization defined as either well-dispersed or aggregated. Polymerizations are performed at various temperatures (T) and MMA volume fractions (ΦMMA) to systematically influence the final nanoparticle dispersion state. During the polymerization of MMA and subsequent material processing, the initially homogeneous AuNP/MMA mixture undergoes macrophase separation between PMMA and oleylamine during the polymerization, yet the AuNP are dispersed in the oleylamine phase. The nanoparticles then aggregate within the oleylamine phase when the materials are processed via vacuum drying and pressing. Nanoparticle organization is tracked throughout the polymerization and processing steps by using a combination of transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). The resulting dispersion state of AuNPs in PMMA bulk films is ultimately dictated by the thermodynamics of mixing between the PMMA and oleylamine phases, but the mechanism of nanoparticle aggregation occurs in two steps that correspond to the polymerization and processing of the materials. Flory-Huggins mixing theory is used to support the PMMA and oleylamine phase separation. The reported results highlight how the integration of nonequilibrium processing and mean-field approximations reveal nanoparticle aggregation in hybrid materials synthesized by using reaction-induced phase transitions.


Apertureless scanning near-field optical microscopy: the need for probe-vibration modeling.
In apertureless scanning near-field optical microscopy (ASNOM), the probe vibration is often used to increase the detected signal. The useful signal is detected at the probe-vibration frequency by a lock-in amplifier. By comparing two-dimensional numerical results with an experimental scan, we show numerically that, to explain or predict the detected signal, a realistic model of ASNOM should take into account the scan of the probe as well as the probe vibration and the material properties.


Can inhaled cannabis users accurately evaluate impaired driving ability? A randomized controlled trial.
To study the effect of inhaled cannabis on self-assessed predicted driving ability and its relation to reaction times and driving ability on a driving simulator. 30 healthy male volunteers aged 18-34: 15 chronic (1-2 joints /day) and 15 occasional (1-2 joints/week) consumers. Self-assessed driving confidence (visual analog scale), vigilance (Karolinska), reaction time (mean reciprocal reaction time mRRT, psychomotor vigilance test), driving ability (standard deviation of lane position SDLP on a York driving simulator) and blood concentrations of delta-9-tétrahydrocannabinol (THC) were measured before and repeatedly after controlled inhalation of placebo, 10 mg or 30 mg of THC mixed with tobacco in a cigarette. Cannabis consumption (at 10 and 30 mg) led to a marked decrease in driving confidence over the first 2 h which remained below baseline at 8 h. Driving confidence was related to THC dose and to THC concentrations in the effective compartment with a low concentration of 0.11 ng/ml for the EC50 and a rapid onset of action (T1/2 37 min). Driving ability and reaction times were reduced by cannabis consumption. Driving confidence was shown to be related to driving ability and reaction times in both chronic and occasional consumers. Cannabis consumption leads to a rapid reduction in driving confidence which is related to reduced ability on a driving simulator. ClinicalTrials.gov, identifier: NCT02061020.


Studies on digestive proteases from midgut glands of a shrimp, Penaeus indicus, and a lobster, Nephrops norvegicus: Part 1. Proteolytic activity.
Digestive gland protease pH optima and specific activities determined in Penaeus indicus with casein, azocasein, Azocoll, and Congo red fibrin as substrates were pH 7.7-9.2, 210-371 micromol of tyrosine/mg of homogenate protein/min; pH 7.8, 36; pH 6.0-7.0, 7; and pH 8.9-9.2, 7A delta0.001 U/mg of homogenate protein/min, respectively. Activity in the shrimp was stable during frozen storage but relatively labile and very low (1.043 azocasein units) in the Norwegian lobster, Nephrops norvegicus. The high activity in shrimp is significant in aquaculture and may be a source of proteolytic enzymes for industrial use. The rapid deterioration after landing may be a consequence of the high and stable activity. The low activity in the lobster may present a problem in culture and requires a more critical choice of feed as well as further investigation. 4-(2-Aminoethyl)-benzenesulfonyl fluoride hydrochloride was a very convenient, fast-acting, and effective inhibitor of shrimp trypsin and chymotrypsin but did not completely inhibit general protease activity in shrimp and had a negligible effect on the lobster. A significant component of that activity may be from nonserine proteases (such as the exoproteases carboxypeptidase A and B and the leucine aminopeptidases), whose proportion relative to the serine proteases may be greater in the lobster.


The role of beliefs about the impact of illness on fertility and close relationships for psychopathological symptoms in women treated for hypothyroidism.
As demonstrated in a pilot study, hypothyroidism has a highly stressful impact on some areas of functioning. This study aims to evaluate the connection between illness-related beliefs (IRBs) and the impact of hypothyroidism on fertility and close relationships, which were the strongest stressors, and the level of depressive, anxiety, and anger symptoms. Two hundred and thirteen women being treated for hypothyroidism took part in an online survey and completed the modified Hospital Anxiety and Depression Scale, Hypothyroidism Symptoms Severity rating scales, and a measure of IRBs. Other relevant clinical data were also collected. Mean levels of thyroid-stimulating hormone indicated that the women were euthyroid. Four groups of participants were identified based on IRBs. The group holding a strong IRB about the negative impact of illness only on close relationships scored significantly higher on depressive symptoms than women in the other groups. The group holding strong IRBs about the negative impact of illness on both close relationships and fertility scored significantly higher on anxiety symptoms than the women in the other groups. Regression analysis showed that IRBs about the negative impact of hypothyroidism predicted anxiety, depressive, and anger symptoms. Negative IRBs about the impact of illness on fertility and close relationships contribute to increased levels of emotional distress symptoms in women being treated for hypothyroidism.


Electronic Antiretroviral Therapy Adherence Monitors and Associated Interventions Improve Adolescent-Caregiver Relationships and Self-Efficacy Among Adolescents and Young Adults with HIV in Uganda.
Many adolescents and young adults with HIV (AYWH) struggle with antiretroviral therapy (ART) adherence and experience poorer outcomes than adults. Relevant factors include forgetfulness and poor self-efficacy related to their evolving neurobiology. We qualitatively explored experiences of AYWH-caregivers dyads using real-time ART adherence monitors and associated reminder functions in the home setting. As part of an implementation science-oriented study, AYWH used the Wisepill adherence monitor for 3 months. AYWH could also opt for short message service (SMS) self-reminders, a self-selected social supporter for delayed or missed doses, or an alarm reminder. We conducted in-depth interviews with randomly selected AYWH-caregiver dyads regarding their experience using the monitor. Qualitative data were analyzed using inductive content analysis. We completed 15 AYWH-caregiver dyad interviews. Of the AYWH, 67% were female, mean age was 16 years, 56% lived with their biological mother, and 86% were virologically suppressed. AYWH and their caregivers generally found the adherence monitors acceptable, though some had privacy concerns. AYWH felt the monitors helped them take charge of their medication, largely through the real-time alarm and SMS reminders; this took the burden of adherence reminders away from the caregivers, improving strained AYWH-caregiver relationships. Two adolescents reported rebound poor adherence after monitor withdrawal. ART adherence monitors and associated tools were largely acceptable to AYWH and their caregivers in home settings. The intervention helped improve AYWH self-efficacy and alleviated burden from some AYWH-caregiver relationships. Rebound poor adherence suggests the need for on-going support and/or other means to achieve intrinsic mechanisms for sustained adherence. Clinical Trial Registration number: NCT03825952.


Passive sensitization of tissue cells. V. The detection of chicken antibodies cytophilic for basophils and eosinophils.
Basophil-cytophilic antibodies were domonstrated in sera of chickens injected with either sheep erythrocytes or avian tuberculin. Normal chicken basophils were passively sensitized in vitro, and two types of cytophilic antibodies were shown by rosette-formation: (a) heat-stable, mercaptoethanol-resistant antibodies, and (b) heat-labile, mercaptoethanol-sensitive antibodies. Serum from one of the chickens injected with sheep erythrocytes also passively sensitized normal, non-basophilic granulocytes which would appear from stained smears to be eosinophils. Cytophilic activity in the serum correlated with the rosette-forming reactions of circulating eosinophils and/or basophils from each of the sensitized donor birds.


Control of trachoma in Australia: a model based evaluation of current interventions.
Australia is the only high-income country in which endemic trachoma persists. In response, the Australian Government has recently invested heavily towards the nationwide control of the disease. A novel simulation model was developed to reflect the trachoma epidemic in Australian Aboriginal communities. The model, which incorporates demographic, migration, mixing, and biological heterogeneities, was used to evaluate recent intervention measures against counterfactual past scenarios, and also to assess the potential impact of a series of hypothesized future intervention measures relative to the current national strategy and intensity. The model simulations indicate that, under the current intervention strategy and intensity, the likelihood of controlling trachoma to less than 5% prevalence among 5-9 year-old children in hyperendemic communities by 2020 is 31% (19%-43%). By shifting intervention priorities such that large increases in the facial cleanliness of children are observed, this likelihood of controlling trachoma in hyperendemic communities is increased to 64% (53%-76%). The most effective intervention strategy incorporated large-scale antibiotic distribution programs whilst attaining ambitious yet feasible screening, treatment, facial cleanliness and housing construction targets. Accordingly, the estimated likelihood of controlling trachoma in these communities is increased to 86% (76%-95%). Maintaining the current intervention strategy and intensity is unlikely to be sufficient to control trachoma across Australia by 2020. However, by shifting the intervention strategy and increasing intensity, the likelihood of controlling trachoma nationwide can be significantly increased.


How much does vaccination reduce the rate of HBV infection in Iranian population? a Bayesian adjustment analysis.
The aim of this research was to estimate the changing rate of odds ratio (OR) by varying degrees of hepatitis B virus (HBV) underreporting. Data registering is usually associated with extensive errors such as misclassification, under-reporting, missing data due to lack of co-operation, error prone factors, and in medical studies, inadequate diagnosis of physicians or low accuracy of laboratory tests. In the present study, which discuss the actual impact of vaccination on HBV prevention, exposure and response were prone to various errors. Furthermore, some people in the community are possibly infected to the virus while were not reported in the count of patients with HBV infection. This was a case control study. Cases included patients with HBV referring to the gastroenterology and liver disease research center. The control group included patients without HBV who underwent a fatty liver test at Taleghani hospital laboratory. Bayesian approach and Gibbs sampling algorithm were used to estimate OR. According to results, misclassification rate was mild in raw data, but with an increase in degree of underreporting for 50 and 500 of unreported cases, OR increased by about half and more than double, respectively, while sensitivity diminished strikingly. Our analysis asserted that knowing the degree of underreporting is essential to accurately calculate OR and sensitivity. In addition, despite varying OR in different samples, overall the results were similar according to the pattern of exposure and response association.


A multicomponent intervention program to Prevent and Reduce AgItation and phySical rEstraint use in the ICU (PRAISE): study protocol for a multicenter, stepped-wedge, cluster randomized controlled trial.
Physical restraints remain to be commonly used in agitated intensive care unit (ICU) patients worldwide, despite a lack of evidence on efficacy and safety and reports of detrimental short and long-term consequences, such as prolonged delirium and a longer ICU length of stay. Physical restraint minimization approaches have focused mainly on educational strategies and other non-pharmacological interventions. Combining these interventions with goal-directed light sedation therapy if needed may play an important contributory role in further reducing the use of physical restraints. The aim of the study is to determine the effectiveness of a multicomponent intervention (MCI) program, combining person-centered non-pharmacological interventions with goal-directed light sedation, compared to physical restraints. A multicenter stepped-wedge cluster randomized controlled trial will be conducted in six Dutch ICUs. A power calculation based total of 480 (expected to become) agitated adult patients will be included in 26 months with a subsequent 2-year follow-up. Patients included in the control period will receive standard care with the current agitation management protocol including physical restraints. Patients included in the intervention period will be treated with the MCI program, consisting of four components, without physical restraints: education of ICU professionals, identification of patients at risk for agitation, formulation of a multidisciplinary person-centered care plan including non-pharmacological and medical interventions, and protocolized goal-directed light sedation using dexmedetomidine. Primary outcome is the number of days alive and outside of the ICU within 28 days after ICU admission. Secondary outcomes include length of hospital stay; 3-, 12-, and 24-month post-ICU quality of life; physical (fatigue, frailty, new physical problems), mental (anxiety, depression, and post-traumatic stress disorder), and cognitive health; and 1-year cost-effectiveness. A process evaluation will be conducted. This will be the first multicenter randomized controlled trial determining the effect of a combination of non-pharmacological interventions and light sedation using dexmedetomidine compared to physical restraints in agitated ICU patients. The results of this study, including long-term patient-centered outcomes, will provide relevant insights to aid ICU professionals in the management of agitated patients. NCT05783505, registration date 23 March 2023.


Stimulatory effect of calponin on myosin ATPase activity.
Calponin, a calmodulin-binding protein of smooth muscle that inhibits the actin-myosin interaction by binding to actin, was shown to bind to myosin and to stimulate the ATPase activity of myosin to some extent. Actin abolished this myosin-linked, stimulatory effect of calponin. Ca(2+)-calmodulin affected neither the myosin-binding activity nor the stimulatory effect of calponin. We further presented a few data which suggest that calponin may exert regulatory activity toward myosin in quite a different way from caldesmon, another smooth muscle protein that binds to myosin, actin, and calmodulin.


Oxidation of 4-substituted TEMPO derivatives reveals modifications at the 1- and 4-positions.
Potenital pathways for the deactivation of hindered amine light stabilisers (HALS) have been investigated by observing reactions of model compounds--based on 4-substituted derivatives of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)--with hydroxyl radicals. In these reactions, dilute aqueous suspensions of photocatalytic nanoparticulate titanium dioxide were irradiated with UV light in the presence of water-soluble TEMPO derivatives. Electron spin resonance (ESR) and electrospray ionisation mass-spectrometry (ESI-MS) data were acquired to provide complementary structural elucidation of the odd- and even-electron products of these reactions and both techniques show evidence for the formation of 4-oxo-TEMPO (TEMPONE). TEMPONE formation from the 4-substituted TEMPO compounds is proposed to be initiated by hydrogen abstraction at the 4-position by hydroxyl radical. High-level ab initio calculations reveal a thermodynamic preference for abstraction of this hydrogen but computed activation barriers indicate that, although viable, it is less favoured than hydrogen abstraction from elsewhere on the TEMPO scaffold. If a radical is formed at the 4-position however, calculations elucidate two reaction pathways leading to TEMPONE following combination with either a second hydroxyl radical or dioxygen. An alternate mechanism for conversion of TEMPOL to TEMPONE via an alkoxyl radical intermediate is also considered and found to be competitive with the other pathways. ESI-MS analysis also shows an increased abundance of analogous 4-substituted piperidines during the course of irradiation, suggesting competitive modification at the 1-position to produce a secondary amine. This modification is confirmed by characteristic fragmentation patterns of the ionised piperidines obtained by tandem mass spectrometry. The conclusions describe how reaction at the 4-position could be responsible for the gradual depletion of HALS in pigmented surface coatings and secondly, that modification at nitrogen to form the corresponding secondary amine species may play a greater role in the stabilisation mechanisms of HALS than previously considered.


Leptospiral carrier state and seroprevalence among animal population--a cross-sectional sample survey in Andaman and Nicobar Islands.
A study was conducted with the objective of assessing the leptospiral carrier state and seroprevalence among animal population of Andaman and Nicobar Islands. A total of 494 sera samples from different domestic animals and 85 samples from rats (Rattus rattus) were tested by microscopic agglutination test using nine serogroups prevalent in these islands. Antibodies to leptospires were detected in 164 samples giving an overall seroprevalence of (33.11%). The seroprevalence was highest among cows (40.32%). Of 85 rat (Rattus rattus) samples tested for antileptospiral antibodies six (7.1%) were positive. Leptospires were isolated from kidney of two rats and urine of one cow. Isolate from urine of cow was heavily contaminated and was subsequently lost during further subculture. The two isolates were found to be pathogenic, belonging to serogroup Grippotyphosa. The isolates were further characterized by using a set of monoclonal antibodies. The agglutination patterns of isolates were similar to that of ratnapura and valbuzzi, however these did not completely match.


Geometrical Design of a Scalable Overlapping Planar Spiral Coil Array to Generate a Homogeneous Magnetic Field.
We present a design methodology for an overlapping hexagonal planar spiral coil (hex-PSC) array, optimized for creation of a homogenous magnetic field for wireless power transmission to randomly moving objects. The modular hex-PSC array has been implemented in the form of three parallel conductive layers, for which an iterative optimization procedure defines the PSC geometries. Since the overlapping hex-PSCs in different layers have different characteristics, the worst case coil-coupling condition should be designed to provide the maximum power transfer efficiency (PTE) in order to minimize the spatial received power fluctuations. In the worst case, the transmitter (Tx) hex-PSC is overlapped by six PSCs and surrounded by six other adjacent PSCs. Using a receiver (Rx) coil, 20 mm in radius, at the coupling distance of 78 mm and maximum lateral misalignment of 49.1 mm (1/√3 of the PSC radius) we can receive power at a PTE of 19.6% from the worst case PSC. Furthermore, we have studied the effects of Rx coil tilting and concluded that the PTE degrades significantly when θ > 60°. Solutions are: 1) activating two adjacent overlapping hex-PSCs simultaneously with out-of-phase excitations to create horizontal magnetic flux and 2) inclusion of a small energy storage element in the Rx module to maintain power in the worst case scenarios. In order to verify the proposed design methodology, we have developed the EnerCage system, which aims to power up biological instruments attached to or implanted in freely behaving small animal subjects' bodies in long-term electrophysiology experiments within large experimental arenas.


Chemical composition and anti-inflammatory activity of the essential oil from the leaves of Limnocitrus littoralis (Miq.) Swingle from Vietnam.
The oil from the leaves of Limnocitrus littoralis (Miq.) Swingle was obtained by hydrodistillation and investigated by gas chromatography combined with mass spectrometry (GC/MS), the anti-inflammatory effect of the oil was examined on a LPS-induced RAW264.7 cells. An aggregate of forty components were identified, representing 93.0% of the oil. This oil was subjugated by monoterpene hydrocarbons (27.7%), sesquiterpene hydrocarbons (32.3%) and oxygenated sesquiterpenes (4.6%). The significant constituents of L. littoralis essential oil were determined as follows; myrcene (24.9%), γ-muurolene (11.0%), and oleic acid (10.3%). The essential oil of L. littoralis showed activity against the nitric oxide (NO) generation with the IC50 value to 12.50 ± 1.19 µg/L. The anti-inflammatory effect of essential oil from the leaves of L. littoralis is reported for the first time.


Risk factors for depression following traumatic injury: An epidemiological study from a scandinavian trauma center.
A significant proportion of patients suffer depression following traumatic injuries. Once manifested, major depression is challenging to overcome and its presence risks impairing the potential for physical rehabilitation and functional recovery. Risk stratification for early detection and intervention in these instances is important. This study aims to investigate patient and injury characteristics associated with an increased risk for depression. All patients with traumatic injuries were recruited from the trauma registry of an urban university hospital between 2007 and 2012. Patient and injury characteristics as well as outcomes were collected for analysis. Patients under the age of eighteen, prescribed antidepressants within one year of admission, in-hospital deaths and deaths within 30days of trauma were excluded. Pre- and post-admission antidepressant data was requested from the national drugs registry. Post-traumatic depression was defined as the prescription of antidepressants within one year of trauma. To isolate independent risk factors for depression a multivariable forward stepwise logistic regression model was deployed. A total of 5981 patients met the inclusion criteria of whom 9.2% (n=551) developed post-traumatic depression. The mean age of the cohort was 42 [standard deviation (SD) 18] years and 27.1% (n=1620) were females. The mean injury severity score was 9 (SD 9) with 18.4% (n=1100) of the patients assigned a score of at least 16. Six variables were identified as independent predictors for post-traumatic depression. Factors relating to the patient were female gender and age. Injury-specific variables were penetrating trauma and GCS score of≤8 on admission. Furthermore, intensive care admission and increasing hospital length of stay were predictors of depression. Several risk factors associated with the development of post-traumatic depression were identified. A better targeted in-hospital screening and patient-centered follow up can be offered taking these risk factors into consideration.


Osteology of the prowfish, Zaprora silenus (Cottiformes: Zoarcoidei: Zaproridae).
The prowfish, Zaprora silenus, is the sole member of the family Zaproridae. It is a large, relatively elongate species with a robust head and body, and it feeds primarily on jellyfishes. Although the larvae and juveniles are pelagic, the adults are demersal, and the species is widely distributed from Southern California around the Pacific Rim to Hokkaido, Japan. The stichaeid affinities of this species have long been recognized, and the family is currently placed, along with the Stichaeidae, in the Zoarcoidei. Previous anatomical studies of Zaprora have been based on relatively few specimens from a limited geographic range and have not included cleared and stained (c&s) specimens. Here, we provide a complete description of the osteology of the prowfish, based on a large series of specimens representing a broad ontogenetic range, including a series of c&s specimens. Our results contradict the findings of previous authors in the structure of the pharyngeal teeth, presence of the pelvic girdle, and the placement of the first dorsal pterygiophore. However, we concur with the findings of previous morphological and molecular phylogenetic studies, which indicate that the prowfish is probably most closely related to at least some members of the Stichaeidae.


Adsorptive stripping voltammetric determination of zopiclone in tablet dosage forms and human urine.
Adsorptive stripping voltammetric (AdSV) techniques were proposed for the direct quantitative determination of zopiclone (ZP) in spiked human urine and tablet dosage forms for first time. The electrochemical oxidation and determination of ZP were easily carried out on glassy carbon electrode (CGE) using a variety of voltammetric techniques. Different conditions were investigated to optimize the analytical determination of ZP. The dependence of the intensities of currents and potentials on pH, concentration, scan rate, deposition time, deposition potential, and nature of the buffer were investigated. Oxidation of ZP was found to be adsorptive-controlled and irreversible. The best results for the determination of ZP were obtained by using differential pulse adsorptive stripping (DPAdSV) and osteryoung square wave voltammetric (OSWAdSV) techniques in Britton-Robinson buffer at pH 7.08 after a pre-concentration period of 120 s at 0.60 V. The peak current showed a linear dependence on the ZP concentration in the range of 6 x 10(-7) to 2 x 10(-5) mol L(-1) for both techniques. The achieved limits of detection and quantitation were 2.78 x 10(-7) and 5.28 x 10(-7) mol L(-1) for DPAdSV; 1.70 x 10(-7) and 5.78 x10(-7) mol L(-1) for OSWAdSV, respectively. The proposed techniques were successfully applied to direct determination of ZP in tablet dosage form and spiked human urine samples. Excipients did not interfere with the determination. Precision and accuracy of the developed method were checked by recovery studies in tablet dosage forms and spiked urine samples.


Robust classification of renal cell carcinoma based on gene expression data and predicted cytogenetic profiles.
Renal cell carcinoma (RCC) is a heterogeneous disease that includes several histologically distinct subtypes. The most common RCC subtypes are clear cell, papillary, and chromophobe, and recent gene expression profiling studies suggest that classification of RCC based on transcriptional signatures could be beneficial. Traditionally, however, patterns of chromosomal alterations have been used to assist in the molecular classification of RCC. The purpose of this study was to determine whether it was possible to develop a classification model for the three major RCC subtypes that utilizes gene expression profiles as the bases for both molecular genetic and cytogenetic classification. Gene expression profiles were first used to build an expression-based RCC classifier. The RCC gene expression profiles were then examined for the presence of regional gene expression biases. Regional expression biases are genetic intervals that contain a disproportionate number of genes that are coordinately up- or down-regulated. The presence of a regional gene expression bias often indicates the presence of a chromosomal abnormality. In this study, we demonstrate an expression-based classifier can distinguish between the three most common RCC subtypes in 99% of cases (n = 73). We also demonstrate that detection of regional expression biases accurately identifies cytogenetic features common to RCC. Additionally, the in silico-derived cytogenetic profiles could be used to classify 81% of cases. Taken together, these data demonstrate that it is possible to construct a robust classification model for RCC using both transcriptional and cytogenetic features derived from a gene expression profile.


The ins and outs of CCR7 in the thymus.
Although it is widely supposed that chemokines play a role in the thymus, most existing evidence is circumstantial. In this issue, two groups provide direct evidence that the chemokine receptor CCR7 is required for normal thymocyte migration (Ueno, T., F. Saito, D. Gray, S. Kuse, K. Hieshima, H. Nakano, T. Kakiuchi, M. Lipp, R. Boyd, and Y. Takahama. 2004. J. Exp. Med. 200:493-505; Misslitz, A., O. Pabst, G. Hintzen, L. Ohl, E. Kremmer, H. T. Petrie, and R. Forster. 2004. J. Exp. Med. 200:481-491). The two papers focus on distinct and opposite migration events, an early outward migration and a later inward migration. Together these papers provide a fascinating picture of the complex role of CCR7 in orchestrating thymocyte migration.


The forsaking of the clinical EEG by psychiatry: how justified?
Despite decades of publications attesting to the role of the clinical EEG in diagnosing and managing psychiatric disorders, the procedure remains highly underutilized in the practice of psychiatry. The visually inspected EEG (vEEG) can detect various forms of abnormalities, each with its own clinical significance. Abnormalities can be paroxysmal (i.e., suggestive of an epileptic-like process) or stationary. The most important unanswered question remains the value of detecting epileptiform activity in a nonepileptic psychiatric patient in predicting favorable responses to anticonvulsant treatment. Despite the many shortcomings of vEEG, the available evidence suggests that in the presence of paroxysmal activity in a nonepileptic psychiatric patient a trial of a psychotropic anticonvulsant may be warranted if standard treatment has failed. More research on the contribution of paroxysmal EEG abnormalities to the problem of episodic psychiatric symptoms (e.g., panic attacks, dissociative episodes, repeated violence) is sorely needed. It is postulated that at least some of these conditions may represent an epilepsy spectrum disorder. Similarly, the significance of the presence of a slow-wave activity (whether focal or generalized) also deserves further well-designed research to ascertain the exact clinical significance. Nonetheless, the available data suggest that further medical workup is necessary to ascertain the nature and degree of the pathology when present.


Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the internalization and signal transduction of amyloid beta 1-42 in glial cells.
Recent studies suggest that the formyl-peptide-receptor-like-1 (FPRL1) plays an essential role in the inflammatory responses of host defense mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD). We therefore analyzed whether amyloid beta1-42 (Abeta1-42) increased the activity of phospholipase D (PLD) via FPRL1, which is an enzyme involved in the secretion, endocytosis and receptor signaling. PLD activity was determined using a transphosphatidylation assay. The internalization of Abeta1-42 via FPRL1 was visualized using fluorescence microscopy and quantified by ELISA (Enzyme Linked Immunosorbent Assay). Determining receptor activity by extracellular-signal regulated kinases 1/2 (ERK1/2) phosphorylation and cAMP level measurement verified the Abeta1-42-induced activation of FPRL1. We were able to show that Abeta1-42 is rapidly internalized via FPRL1 in astrocytes and microglia. PLD was additionally activated by Abeta1-42 and via FPRL1 in rat glial cells. Furthermore, the ERK1/2 phosphorylation by FPRL1 agonists was dependent on the PLD product phosphatidic acid (PA). Together, these data suggest that PLD plays an important role in the regulation of Abeta1-42-induced endocytosis and FPRL1 receptor signaling.


The convergence insufficiency treatment trial: design, methods, and baseline data.
This report describes the design and methodology of the Convergence Insufficiency Treatment Trial (CITT), the first large-scale, placebo-controlled, randomized clinical trial evaluating treatments for convergence insufficiency (CI) in children. We also report the clinical and demographic characteristics of patients. We prospectively randomized children 9 to 17 years of age to one of four treatment groups: 1) home-based pencil push-ups, 2) home-based computer vergence/accommodative therapy and pencil push-ups, 3) office-based vergence/accommodative therapy with home reinforcement, 4) office-based placebo therapy. Outcome data on the Convergence Insufficiency Symptom Survey (CISS) score (primary outcome), near point of convergence (NPC), and positive fusional vergence were collected after 12 weeks of active treatment and again at 6 and 12 months posttreatment. The CITT enrolled 221 children with symptomatic CI with a mean age of 12.0 years (SD = +2.3). The clinical profile of the cohort at baseline was 9Delta exophoria at near (+/- 4.4) and 2Delta exophoria (+/-2.8) at distance, CISS score = 30 (+/-9.0), NPC = 14 cm (+/- 7.5), and near positive fusional vergence break = 13 Delta (+/- 4.6). There were no statistically significant nor clinically relevant differences between treatment groups with respect to baseline characteristics (p > 0.05). Hallmark features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a placebo treatment arm, masked outcome examinations, and the CISS score outcome measure. The baseline data reported herein define the clinical profile of those enrolled into the CITT.


Features of dermatofibroma in reflectance confocal microscopy.
Dermatofibroma (DF) is a common benign skin lesion in a majority of cases located on the legs or upper limbs. The etiology of DF is still unclear. Reflectance confocal microscopy features of DF were described. Forty patients with DF diagnosis confirmed by dermoscopy were examined using reflectance confocal microscopy VivaScope 1500 from March 2018 to April 2019. DF was more common in females (80%) than males (20%). Thirty-six lesions (90%) were located on the limbs while four (10%) were on the trunk. Dermoscopically, 18 lesions (45%) revealed typical features: central white area with a brown network in the periphery. Twenty-two DFs (55%) were found with a central white patch and globular-like structures, surrounded by a thin brown network. In reflectance confocal microscopy, all revealed a typical honeycombed pattern, although in some cases (30%), streaming was observed. In two lesions (5%) in epidermis, few dendritic cells were observed, and one DF revealed roundish pagetoid cells (2.5%). The dermoepidermal junction (DEJ) in all lesions was abounded in dilated vessels. The most common observable feature of DF was bright "rings" composed of monomorphic, regular cells surrounding dark dermal papillae. In five lesions (12.5%), rings were "double" because of exceptionally pigmented DF. Reflectance confocal microscopy enables us to describe microscopic features of DF. There are four confocal microscopic features observable in each DF: in the epidermis, normal honeycombed pattern, sometimes with local streaming, in DEJ, edged papillae, bright rings, and dilated vessels.


Providing the Gist of Medical Expertise in the Context of Laws, Rules, and Guidelines: Fuzzy-Trace Theory's Alternative Approach to Improve Patient Communication.
Current guidelines and regulatory frameworks create a dilemma that threatens the effectiveness of much needed communication between patients and medical providers: How can patients be presented with detailed facts without creating cognitive "overload"? We explain how this is a false dichotomy and illustrate, using three examples, how fuzzy-trace theory offers a third way of informing patients.


Health risk assessment of volatile organic compounds in a high risk group surrounding Map Ta Phut industrial estate, Rayong Province.
The health risks of a high-risk group, surrounding Map Ta Phut industrial estate, Rayong, which may be exposed to VOCs through inhalation of contaminated air and dermal contact of contaminated water were assessed. The health risk was assessed for 19 subjects categorized as children, adult and elderly from Ban plong and Nongfab communities following the US Environmental Protection Agency (EPA) method. The VOC concentrations in ambient air and ground water were monitored by Pollution Control Department (PCD), Ministry of Natural Resources and Environment to represent average VOC exposure of subjects. The lifetime cancer risk of VOCs exposure from inhalation and dermal contact with ground water were 1.32 x 10(-7)-5.21 x 10(6) for elderly 1.18 x 10(-7)-6.20 x 10(-6)for adult and 8.93 x 10(-7)-5.93 x 10(-6) for children. For non-cancer risk, the hazard index was 0.44 for elderly, 0.38-0.42 for adult and 0.55 for children. The lifetime cancer risk of the high-risk group living near Map Ta Phut industrial estate was in acceptable range for elderly, adult and children. For non-cancer risk, it is also acceptable.


Primary leiomyosarcoma of brain in an adolescent with common variable immunodeficiency syndrome.
A 14-year-old girl with common variable immunodeficiency syndrome was found to have a low-grade malignant neoplasm arising in the left temporal lobe of the brain. Ultrastructural and immunohistochemical studies established a diagnosis of leiomyosarcoma, despite the rarity of this tumor in children. In situ hybridization with the EBER probe revealed essentially all of the neoplastic cells to be infected with Epstein-Barr virus (EBV). Children with the acquired immunodeficiency syndrome (AIDS) are known to exhibit an increased incidence of smooth muscle tumors associated with EBV. Similar tumors have been reported in EBV-infected patients undergoing therapeutic immunosuppression. This appears to be the first reported case of childhood leiomyosarcoma where the cause of the underlying immunodeficiency was a genetic rather than acquired disorder. The authors conclude that electron microscopy, immunohistochemistry, and other ancillary techniques are essential in the evaluation of unusual tumors in immunocompromised children, whether the cause is hereditary or acquired.


Preoperative pregabalin or gabapentin for acute and chronic postoperative pain among patients undergoing breast cancer surgery: A systematic review and meta-analysis of randomized controlled trials.
Breast cancer surgery is associated with acute and chronic pain. We sought to systematically evaluate the effects of gabapentin and pregabalin on postoperative pain among patients undergoing breast cancer surgery. We searched MEDLINE, EMBASE, CENTRAL, Web of Science, and ProQuest from the inception of each database to November 2015. We included studies enrolling adult patients undergoing breast cancer surgery who were randomly assigned to preoperative gabapentin or pregabalin versus placebo or active control and assessed acute (≤24 h) or chronic (≥2 months) pain. We conducted meta-analyses when possible and rated the quality of evidence (QoE) by using the GRADE approach. Twelve studies were eligible for review, of which eight evaluated gabapentin (n = 516) and four pregabalin (n = 209). Gabapentin reduced pain scores in the recovery room (mean difference [MD] -1.68 on a 0-10 Numeric Rating Scale (NRS), 95% CI -2.59 to -0.77; minimally important difference is 1 point; relative risk [RR] for mild pain (<4/10) 1.71, 95% CI 1.33-2.02; moderate QoE) and 24 h postoperatively (MD -0.52, 95% CI -1.02 to -0.01; RR for mild pain 1.07, 95% CI 1.00-1.13; very low QoE). Pregabalin reduced pain and morphine consumption in the recovery room (MD -6.71 mg, 95% CI -10.73 to -2.70; low QoE). No significant difference was observed in pain score at 24 h (MD -0.38, 95%, CI -0.96 to 0.21; moderate QoE). Neither drug reduced the rate of chronic postoperative pain. Gabapentin and pregabalin seem to reduce opioid consumption in the recovery room. Gabapentin, but not pregabalin, reduces pain at 24 h after breast cancer surgery. Neither drug affects the development of chronic postoperative pain. Gabapentin and pregabalin administered perioperatively in patients undergoing breast cancer surgery improve acute postoperative pain as indicated by the reduction in opioid consumption. Further data are needed on reducing chronic postoperative pain.


Cognitive, neuroimaging, and pathological studies in a patient with Pick's disease.
We conducted cognitive, imaging, and neuropathological studies on a patient with Pick's disease. The patient was impaired at interpreting sentences with complex grammatical constructions, differing significantly from control subjects and patients with Alzheimer's disease (AD). Evaluation of regional brain functioning at rest, with positron emission tomography, revealed reduced left frontal activity compared with control subjects and AD patients. Autopsy demonstrated the classic pathology of Pick's disease, including massive neuron loss and gliosis in the frontal and cingulate cortex as well as numerous tau-positive hippocampal Pick bodies. The abnormal tau proteins were phosphorylated at the same amino acid residues as AD paired helical filament tau (PHFtau), but they exhibited a unique migration profile on western blot. Our observations support the hypothesis that a distinct variety of hyperphosphorylated tau in Pick's disease compromises the long-term viability of selectively vulnerable populations of neurons in frontal cortices that contribute to sentence processing.


Linking populations to landscapes: richness scenarios resulting from changes in the dynamics of an ecosystem engineer.
Predicting the effects of the loss of individual species on diversity represents one of the primary challenges facing community ecology. One pathway by which organisms of one species affect the distribution of species is ecosystem engineering. Changes in the dynamics of ecosystem engineers that lead to changes in the distribution of the patches of altered habitat are likely to lead to changes in diversity. I link data on the distribution of plant species found in the riparian zone of the Adirondacks (New York, USA) in patches modified by beaver and in unmodified forest patches to a model connecting the dynamics of ecosystem engineers to the dynamics of the patches that they create. These analyses demonstrate that changes in key parameters of the model, such as decreases in beaver colonization rates and rate of patch abandonment, lead to changes in species richness of up to 45% at the landscape scale, and that these changes are likely to occur over long time scales. This general approach of linking the population dynamics or behavior of a single species to changes in species richness at the landscape scale provides a means for both testing the importance of ecosystem engineering in different systems and developing scenarios to predict how changes in the dynamics of a single species are likely to affect species richness.


MALDI-TOF mass spectrometry identification of filamentous fungi in the clinical laboratory.
This study aimed to validate the effectiveness of a standardised procedure for the MALDI-TOF mass spectrometry (MS)-based identification on a large sample of filamentous fungi routinely identified in university hospitals' laboratories. Non-dermatophyte filamentous fungi prospectively isolated in the routine activity of five teaching hospitals in France were first identified by conventional methods in each laboratory and then by MS in one centre. DNA sequence-based identification resolved discrepancies between both methods. In this study, of the 625 analysed filamentous fungi of 58 species, 501 (80%) and 556 (89%) were correctly identified by conventional methods and MS respectively. Compared with the conventional method, MS dramatically enhanced the performance of the identification of the non-Aspergillus filamentous fungi with a 31-61% increase in correct identification rate. In conclusion, this study on a large sample of clinical filamentous fungi taxa demonstrates that species identification is significantly improved by MS compared with the conventional method. The main limitation is that MS identification is possible only if the species is included in the reference spectra library. Nevertheless, for the routine clinical laboratory, MS provides the means to attain markedly accurate results in filamentous fungi identification, which was previously restricted to only a few reference laboratories.


Appendicular tuberculosis: the resurgence of an old disease with difficult diagnosis.
Gastrointestinal tuberculosis (TB) is quite rare, representing only 3% of all extra-pulmonary cases. Blind gut and ileum are the most common gastrointestinal localizations, while appendix involvement is infrequent. Appendix involvement is usually related to symptoms of acute appendicitis since the caseous necrosis may lead to adhesions and surgical complications such as perforation. For this reason patients with suspected appendicular TB usually undergo surgery even without a secure diagnosis. In these cases, due to the absence of specific symptoms and signs, the diagnosis is delayed after surgery, thus resulting in a high percentage of important, and sometimes lethal, complications. Histopathological examination is often the only way to reach a diagnosis and to establish specific antibiotic therapy, while an early diagnosis could avoid surgical treatment. We report a case of appendicular TB not only for its rarity but also to discuss the difficulty in its diagnosis.


Otitis and meningoencephalitis associated with infectious coryza ( Avibacterium paragallinarum) in commercial broiler chickens.
Infectious coryza, caused by Avibacterium paragallinarum, is an acute respiratory disease of poultry that can result in substantial morbidity, mortality, and economic losses. In March 2017, the Turlock branch of the California Animal Health and Food Safety laboratory system encountered an unusual clinical and pathologic presentation of infectious coryza in 6 live, 29-d-old, commercial broiler chickens that were submitted for diagnostic investigation. Antemortem evaluation revealed severe neurologic signs, including disorientation, torticollis, and opisthotonos. Swollen head-like syndrome and sinusitis were also present. Histologically, severe sinusitis, cranial osteomyelitis, otitis media and interna, and meningoencephalitis were noted, explaining the clinical signs described. A. paragallinarum was readily isolated from the upper and lower respiratory tract, brain, and cranial bones. Infectious bronchitis virus (IBV) was also detected by PCR, and IBV was isolated in embryonated chicken eggs. Based on sequencing analysis, the IBV appeared 99% homologous to strain CA1737. A synergistic effect between A. paragallinarum and IBV, resulting in exacerbation of clinical signs and increased mortality, may have occurred in this case. A. paragallinarum should be considered among the possible causes of neurologic signs in chickens. Appropriate media should be used for bacterial isolation, and the role of additional contributing factors and/or complicating agents should be investigated in cases of infectious coryza.


Evaluation of Tobacco Smoke and Diet as Sources of Exposure to Two Heterocyclic Aromatic Amines for the U.S. Population: NHANES 2013-2014.
Heterocyclic aromatic amines (HAA) are a group of hazardous substances produced during combustion of tobacco or high-temperature cooking of meats. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is a major carcinogenic HAA in tobacco smoke. Urinary AαC, used as a marker of AαC exposure, was analyzed on spot urine samples from adult participants of the 2013-2014 cycle of the National Health and Nutrition Examination Survey (N = 1,792). AαC was measured using isotope-dilution liquid chromatography-tandem mass spectrometry. Exclusive combusted tobacco smokers were differentiated from nonusers of tobacco products through both self-report and serum cotinine data. Among exclusive smokers, sample-weighted median urinary AαC was 40 times higher than nonusers. Sample-weighted regression models showed that urinary AαC increased significantly with serum cotinine among both exclusive tobacco users and nonusers with secondhand smoke exposure. Among nonusers, eating beef cooked at high temperature was associated with a significant increase in urinary AαC, whereas consuming vegetables was associated with decreased AαC. In addition, smoking one-half pack of cigarettes per day was associated with a significant increase of 23.6 pg AαC/mL calculated at geometric mean of AαC, controlling for potential confounders. In comparison, increase in AαC attributable to consuming the 99th percentile of beef cooked at high temperature was 0.99 pg AαC/mL. Both exclusive smokers and nonusers of tobacco in the general U.S. population are exposed to AαC from tobacco smoke, with additional, lesser contributions from certain dietary components. AαC is an important biomarker that is associated with tobacco smoke exposure.


A national needs assessment study to determine procedures for simulation-based training in cardiology in Denmark.
New training methods such as simulation have been introduced in cardiology as in other specialties; however, the development of effective simulation-based training programs is challenging. They are often unstructured and based on convenience or coincidence. The objective of this study was to perform a nationwide general needs assessment to identify and prioritize technical procedures that should be included in a simulation-based curriculum for cardiology residency in Denmark. We completed a needs assessment using the Delphi method among key opinion leaders in cardiology. Brainstorming in round 1 identified technical procedures that future cardiologists should learn. Round 2 was a survey to examine frequency of procedure, number of cardiologists performing the procedure, operator-related risk and/or discomfort for patients and feasibility for simulation. Round 3 was final elimination and prioritization of procedures. Ninety-four key opinion leaders were included, and the response rates were 77% (round 1), 62% (Round 2), and 68% (Round 3). Twenty-four technical procedures were identified in Round 1 and pre-prioritized in Round 2. In round 3, 13 procedures were included in the final prioritized list. The five highly prioritized procedures eligible for simulation-based training were advanced life support, pleurocentesis, transesophageal echocardiography, coronary angiography, and pericardiocentesis. The general needs assessment following the Delphi process identified and prioritized 13 technical procedures in cardiology that should be integrated in a simulation-based curriculum. The final list provides educators a guide when developing simulation-based training programmes for cardiology residents.


The perceived importance of anatomy and neuroanatomy in the practice of speech-language pathology.
The purpose of this study was to examine the application of anatomy and neuroanatomy knowledge to current practice of speech-language pathology (SLP), based on the perceptions of practicing SLPs, and to elicit information on participants' experiences of learning these subjects in their primary SLP degree with a view to inform potential curriculum development. A qualitative approach was taken to the collection of data. Eight practicing SLPs from four settings were interviewed. The critical incident technique, together with further probing, was used to elicit information. Interviews were transcribed and later thematically analyzed. This study found that knowledge of anatomy and neuroanatomy was perceived to be important by SLPs across all settings, to varying degrees, with a greater application in acute hospital settings. Negative experiences in studying this material were reported across all settings regardless of country of study. Participants discussed ways to increase students' motivation to learn this challenging material. Relevance of material demanded by students may be enhanced if active learning methods were used to teach anatomy/neuroanatomy, including case-based learning and with vertical and horizontal integration of material to provide a cohesive, spiral curriculum.


The identification of epitopic sites in human alpha 1-proteinase inhibitor.
Human alpha 1-proteinase inhibitor (alpha 1-PI) yielded nine fragments on cleavage with CNBr. The amino acid sequences of these fragments were determined. Three of these CNBr-cleavage fragments, namely fragment I (residues 64-220), fragment II (residues 243-351) and fragment III (residues 1-63), were found to bind rabbit polyclonal antibodies against chemically oxidized alpha 1-PI and mouse polyclonal antibodies against native alpha 1-PI by the Bio-Dot method (enzyme-linked immunosorbent assay on nitrocellulose). These fragments, I, II and III, inhibited by 60%, 25% and 5% respectively the binding between alpha 1-PI and the rabbit antibodies. Fragments I, II and III were subjected to proteolytic digestion, and 15, ten and five peptides were obtained from these fragments respectively. Only four of these peptides showed binding to the mouse antibodies against native alpha 1-PI. These were residues 40-63, 79-86, 176-206 and 299-323. A panel of monoclonal antibodies was prepared by conventional hybridoma technology, with chemically oxidized alpha 1-PI as the antigen. The ability of the monoclonal antibodies to bind native alpha 1-PI and CNBr-cleavage fragments I-III was determined. The monoclonal antibodies fell into three categories. Most (over 90%) belonged to group I, which was capable of binding alpha 1-PI and only fragment I. Antibodies in groups II and III bound alpha 1-PI and either fragment II or fragment III respectively. The ability of the peptides derived from proteolytic digestion of fragments I, II and III to bind three monoclonal antibodies representing each of the three groups was determined. Among all the peptides tested, only one (residues 176-206) derived from fragment I showed binding to the antibodies from group I, one (residues 299-323) derived from fragment II showed binding to the antibodies from group II, and one (residues 40-63) from fragment III showed binding to the antibodies from group III. Each of these three peptides also inhibited the binding between alpha 1-PI and the corresponding monoclonal antibodies. From these data we concluded that at least four epitopic regions (residues 40-63, 79-86, 176-206 and 299-323) were present in alpha 1-PI. Specific monoclonal antibodies to three of these sites were obtained.


[Relocation of the median nerve after scarring along the carpal tunnel with hypothenar fatty tissue flap-plasty].
In our study, we present the data of eleven patients suffering from scarring of the median nerve, predominantly after open decompression of the carpal tunnel. Dysaesthesia in the palmar region and loss of grip strength prevented performing normal daily activities. All patients except one were relieved of the palmar discomfort and experienced an increase of grip strength allowing their return to work. The hypothenar fat flap has been shown to be a reliable source of local tissue to cover the median nerve. The sprouting of nerve fibers to the skin is prevented as well as median nerve readherence. We believe that the hypothenar fat flap provides sufficient regenerative conditions and coverage of the median nerve within the carpal tunnel in the surgical treatment of abundant scarring.


Si photoanode protected by a metal modified ITO layer with ultrathin NiO(x) for solar water oxidation.
We report an ultrathin NiOx catalyzed Si np(+) junction photoanode for a stable and efficient solar driven oxygen evolution reaction (OER) in water. A stable semi-transparent ITO/Au/ITO hole conducting oxide layer, sandwiched between the OER catalyst and the Si photoanode, is used to protect the Si from corrosion in an alkaline working environment, enhance the hole transportation, and provide a pre-activation contact to the NiOx catalyst. The NiOx catalyzed Si photoanode generates a photocurrent of 1.98 mA cm(-2) at the equilibrium water oxidation potential (EOER = 0.415 V vs. NHE in 1 M NaOH solution). A thermodynamic solar-to-oxygen conversion efficiency (SOCE) of 0.07% under 0.51-sun illumination is observed. The successful development of a low cost, highly efficient, and stable photoelectrochemical electrode based on earth abundant elements is essential for the realization of a large-scale practical solar fuel conversion.


No association between two polymorphisms of the serotonin transporter gene and combined type attention deficit hyperactivity disorder.
Several independent studies have reported association between serotonin transporter gene (SLC6A4) polymorphisms and attention deficit hyperactivity disorder (ADHD). Five studies found evidence for association between the long-allele of a 44-bp insertion/deletion polymorphism (5-HTTLPR) and ADHD. Another two studies corroborated this finding while a further six studies did not find such an association. For a second polymorphism within the gene, a variable number tandem repeat (VNTR) within intron 2, one study demonstrated that the 12/12 genotype was significantly less frequent in ADHD cases compared to controls, while a second study found that the 12-allele was preferentially transmitted to offspring affected with ADHD. To provide further clarification of the reported associations, we investigated the association of these two markers with ADHD in a sample of 1,020 families with 1,166 combined type ADHD cases for the International Multi-Centre ADHD Genetics project, using the Transmission Disequilibrium Test. Given the large body of work supporting the association of the promoter polymorphism and mood disorders, we further analyzed the group of subjects with ADHD plus mood disorder separately. No association was found between either of the two markers and ADHD in our large multisite study or with depression within the sample of ADHD cases.


In Vitro Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates.
Pulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC members to some β-lactams is increased in the presence of avibactam. Therefore, we hypothesized that two new non-β-lactam-based β-lactamase inhibitors, relebactam and vaborbactam, would also increase the susceptibility of MABC organisms to β-lactams. The objective of the present study was to evaluate the in vitro activity of various marketed β-lactams alone and in combination with either relebactam or vaborbactam against multidrug-resistant MABC clinical isolates. Our data demonstrate that both β-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem-vaborbactam combination is now marketed and an imipenem-relebactam combination is currently in phase III trials, these fixed combinations may become the β-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual β-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a β-lactamase inhibitor that are deserving of further evaluation in combination with these carbapenem-β-lactamase inhibitor products.


Hyaluronic Acid-Based Theranostic Nanomedicines for Targeted Cancer Therapy.
Hyaluronic acid (HA) is a natural mucopolysaccharide and has many useful advantages, including biocompatibility, non-immunogenicity, chemical versatility, non-toxicity, biodegradability, and high hydrophilicity. Numerous tumor cells overexpress several receptors that have a high binding affinity for HA, while these receptors are poorly expressed in normal body cells. HA-based drug delivery carriers can offer improved solubility and stability of anticancer drugs in biological environments and allow for the targeting of cancer treatments. Based on these benefits, HA has been widely investigated as a promising material for developing the advanced clinical cancer therapies in various formulations, including nanoparticles, micelles, liposomes, and hydrogels, combined with other materials. We describe various approaches and findings showing the feasibility of improvement in theragnosis probes through the application of HA.


Quantification of protein deposits on silicone hydrogel materials using stable-isotopic labeling and multiple reaction monitoring.
This study was designed to use multiple reaction monitoring (MRM) for accurate quantification of contact lens protein deposits. Worn lenses used with a multipurpose disinfecting solution were collected after wear. Individual contact lenses were extracted and then digested with trypsin. MRM in conjunction with stable-isotope-labeled peptide standards was used for protein quantification. The results show that lysozyme was the major protein detected from both lens types. The amount of protein extracted from contact lenses was affected by the lens material. Except for keratin-1 (0.83 ± 0.61 vs 0.77 ± 0.20, p = 0.81) or proline rich protein-4 (0.11 ± 0.04 vs 0.15 ± 0.12, p = 0.97), the amounts of lysozyme, lactoferrin, or lipocalin-1 extracted from balafilcon A lenses (12.9 ± 9.01, 0.84 ± 0.50 or 2.06 ± 1.6, respectively) were significantly higher than that extracted from senofilcon A lenses (0.88 ± 0.13, 0.50 ± 0.10 or 0.27 ± 0.23, respectively) (p < 0.05). The amount of protein extracted from contact lenses was dependent on both the individual wearer and the contact lens material. This may have implications for the development of clinical responses during lens wear for different people and with different types of contact lenses. The use of MRM-MS is a powerful analytical tool for the quantification of specific proteins from single contact lenses after wear.


Effective e-learning for health professional and medical students: the experience with SIAS-Intelligent Tutoring System.
Current e-learning systems are still inadequate to support the level of interaction, personalization and engagement demanded by clinicians, care givers, and the patient themselves. For effective e-learning to be delivered in the health context, collaboration between pedagogy and technology is required. Furthermore, e-learning systems should be flexible enough to be adapted to the students' needs, evaluated regularly, easy to use and maintain and provide students' feedback, guidelines and supporting material in different formats. This paper presents the implementation of an Intelligent Tutoring System (SIAS-ITS), and its evaluation compared to a traditional virtual learning platform (Moodle). The evaluation was carried out as a case study, in which the participants were separated in two groups, each group attending a virtual course on the WHO Integrated Management of Childhood Illness (IMCI) strategy supported by one of the two e-learning platforms. The evaluation demonstrated that the participants' knowledge level, pedagogical strategies used, learning efficiency and systems' usability were improved using the Intelligent Tutoring System.


Very brief intervention for physical activity behaviour change in cardiac rehabilitation: protocol for the 'Measure It!' effectiveness-implementation hybrid trial.
Physical inactivity is a risk factor for repeat cardiac events and all-cause mortality in coronary heart disease (CHD). Cardiac rehabilitation, a secondary prevention programme, aims to increase physical activity levels in this population from a reported low baseline. This trial will investigate the effectiveness and implementation of a very brief physical activity intervention, comparing different frequencies of physical activity measurement by cardiac rehabilitation clinicians. The Measure It! intervention (<5 min) includes a self-report and objective measure of physical activity (steps) plus very brief physical activity advice. This type 1 hybrid effectiveness-implementation study will use a two-arm multicentre assessor-blind randomised trial design. Insufficiently active (<150 min of moderate-to-vigorous physical activity per week) cardiac rehabilitation attendees with CHD (18+ years) will be recruited from five phase II cardiac rehabilitation centres (n=190). Patients will be randomised (1:1) to five physical activity measurements or two physical activity measurements in total over 24 weeks. The primary effectiveness outcome is accelerometer daily minutes of moderate-to-vigorous intensity physical activity at 24 weeks. Secondary effectiveness outcomes include body mass index, waist circumference and quality-of-life. An understanding of multilevel contextual factors that influence implementation, and antecedent outcomes to implementation of the intervention (eg, feasibility and acceptability), will be obtained using semistructured interviews and other data sources. Linear mixed-effects models will be used to analyse effectiveness outcomes. Qualitative data will be thematically analysed inductively and deductively using framework analysis, with the framework guided by the Consolidated Framework for Implementation Research and Theoretical Domains Framework. The study has ethical approval (University of Canberra (ID 11836), Calvary Bruce Public Hospital (ID 14-2022) and the Greater Western Area (ID 2022/ETH01381) Human Research Ethics Committees). Results will be disseminated in multiple formats for consumer, public and clinical audiences. ACTRN12622001187730p.


Aberrant expression of OATP1B3 in colorectal cancer liver metastases and its clinical implication on gadoxetic acid-enhanced MRI.
To investigate the factors associated with hepatobiliary phase (HBP) enhancement at gadoxetic acid-enhanced magnetic resonance imaging (MRI) and to determine whether HBP images could be used to predict prognosis in patients with colorectal cancer liver metastasis (CRLM). Of the 96 total nodules, 65 and 31 nodules were in the mixed and clearly hypointense groups, respectively. In the 55 nodules without preoperative chemotherapy, organic anionic transporting polypeptide 1B3 (OATP1B3) expression was a significant factor regarding the HBP enhancement (P=0.042). In this subgroup, nodules with OATP1B3 expression displayed a significantly higher relative intensity ratio on the HBP image (RIRpost) and relative enhancement ratio (RER) than those lacking this marker (P=0.024, 0.003, respectively). No significant factor was associated with the enhancement pattern in the chemotherapy group. The mixed hypointense group displayed worse survival rates (P=0.002). Ninety-six patients who underwent pre-operative liver MRI and surgical resection for CRLM from January 2010 to June 2012 were retrospectively analyzed. We qualitatively evaluated the HBP enhancement pattern of CRLMs and classified them into mixed and clearly hypointense groups. For quantitative measurement, the RIRpost and RER were analyzed. To investigate factors associated with HBP enhancement, tumor components (fibrosis, necrosis, and cellularity) and OATP1B3 expression were scored on a 4-point scale. Univariate and multivariate analyses were done to determine significant factors for visual enhancement and quantitative parameters. OATP1B3 expression is associated with mixed hypointense CRLMs without chemotherapy. Signal intensity on HBP has potential usefulness to predict prognosis in CRLMs.


The Sonoda-Tajima Cell Collection: a human genetics research resource with emphasis on South American indigenous populations.
The Sonoda-Tajima Cell Collection includes cell samples obtained from a range of ethnic minority groups across the world but in particular from South America. The collection is made all the more valuable by the fact that some of these ethnic populations have since died out, and thus it will be impossible to prepare a similar cell collection again. The collection was donated to our institute, a public cell bank in Japan, by Drs Sonoda and Tajima to make it available to researchers throughout the world. The original cell collection was composed of cryopreserved peripheral blood samples that would obviously have been rapidly exhausted if used directly. We, therefore, immortalized some samples with the Epstein-Barr virus and established B-lymphoblastoid cell lines (B-LCLs). As there is continuing controversy over whether the B-LCL genome is stably maintained, we performed an array comparative genomic hybridization (CGH) analysis to confirm the genomic stability of the cell lines. The array CGH analysis of the B-LCL lines and their parental B cells demonstrated that genomic stability was maintained in the long-term cell cultures. The B-LCLs of the Sonoda-Tajima Collection will therefore be made available to interested scientists around the world. At present, 512 B-LCLs have been developed, and we are willing to increase the number if there is sufficient demand.


Creutzfeldt-Jakob disease: recommendations for disinfection and sterilization.
Prion diseases constitute a unique infection control problem because prions exhibit unusual resistance to conventional chemical and physical decontamination methods. Recommendations to prevent cross-transmission of infection from medical devices contaminated by Creutzfeldt-Jakob disease (CJD) have been based primarily on prion inactivation studies. The recommendations in this article consider inactivation data but also use epidemiological studies of prion transmission, infectivity of human tissues, and efficacy of removing microbes by cleaning. On the basis of the scientific data, only critical (e.g., surgical instruments) and semicritical devices contaminated with high-risk tissue (i.e., brain, spinal cord, and eye tissue) from high-risk patients--those with known or suspected infection with CJD--require special treatment.


Shikonin enhances Adriamycin antitumor effects by inhibiting efflux pumps in A549 cells.
Shikonin (SHK) is a natural naphthoquinone pigment isolated from Lithospermum erythrorhizon, that has been reported to suppress the growth of a number of cancer cell types. Adriamycin (AD) is typically used as an effective anticancer agent; however, it has the propensity to induce drug resistance. The aim of the present study was to investigate the effects of SHK alone and in combination with AD on lung adenocarcinoma cells and the underlying molecular mechanisms of their effects. Colony formation, MTT and propidium iodide staining assays demonstrated that the co-treatment of A549 cells with SHK and AD significantly decreased cell viability and potently induced apoptosis. The mitochondrial membrane potential was assessed using 5,5', 6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide staining and fluorescence microscopy. Cells co-treated with SHK and AD exhibited marked mitochondrial membrane damage. In addition, co-treatment with SHK and AD significantly reduced ATP levels in A549 cells compared with the control. Western blot analysis revealed that SHK enhanced the antitumor effects of AD by inhibiting the expression of ATP-binding cassette transporters. These results suggest that the inhibition of glycolysis could be an effective approach for lung cancer treatment. Therefore, SHK has the potential to be used as an anticancer agent in the treatment of lung adenocarcinoma, and thus warrants further investigation and development.


Exposure in the post-operative management of surgical wounds. Report of a trial.
The ancient method of leaving operative wounds completely exposed to the air throughout the healing period is assessed on the basis of a trial in 100 surgical wounds (excluding traumatic wounds and wounds of the hand and knee). The method offers two chief advantages; the wound can be regularly and easily inspected, and any collection of secretions which can lead to skin complications and superficial sepsis can be dealt with. The results are analysed and compared favourably with those of conventional dressing techniques.


A Thioredoxin Domain-Containing Protein Interacts with Pepino mosaic virus Triple Gene Block Protein 1.
Pepino mosaic virus (PepMV) is a mechanically-transmitted tomato pathogen of importance worldwide. Interactions between the PepMV coat protein and triple gene block protein (TGBp1) with the host heat shock cognate protein 70 and catalase 1 (CAT1), respectively, have been previously reported by our lab. In this study, a novel tomato interactor (SlTXND9) was shown to bind the PepMV TGBp1 in yeast-two-hybrid screening, in vitro pull-down and bimolecular fluorescent complementation (BiFC) assays. SlTXND9 possesses part of the conserved thioredoxin (TRX) active site sequence (W__PC vs. WCXPC), and TXND9 orthologues cluster within the TRX phylogenetic superfamily closest to phosducin-like protein-3. In PepMV-infected and healthy Nicotiana benthamiana plants, NbTXND9 mRNA levels were comparable, and expression levels remained stable in both local and systemic leaves for 10 days post inoculation (dpi), as was also the case for catalase 1 (CAT1). To localize the TXND9 in plant cells, a polyclonal antiserum was produced. Purified α-SlTXND9 immunoglobulin (IgG) consistently detected a set of three protein bands in the range of 27⁻35 kDa, in the 1000 and 30,000 g pellets, and the soluble fraction of extracts of healthy and PepMV-infected N. benthamiana leaves, but not in the cell wall. These bands likely consist of the homologous protein NbTXND9 and its post-translationally modified derivatives. On electron microscopy, immuno-gold labelling of ultrathin sections of PepMV-infected N. benthamiana leaves using α-SlTXND9 IgG revealed particle accumulation close to plasmodesmata, suggesting a role in virus movement. Taken together, this study highlights a novel tomato-PepMV protein interaction and provides data on its localization in planta. Currently, studies focusing on the biological function of this interaction during PepMV infection are in progress.


Soft tissue root coverage as treatment for cervical abrasion and caries.
Root exposure caused by gingival recession may result in cervical abrasion, root caries, root sensitivity, and compromised esthetics. Although cervical root lesions can be treated with Class V restorations, there may be advantages in treating them with soft tissue grafts for root coverage since they restore the dento-gingival unit to its prerecession condition. The rationale for root coverage with soft tissue grafts is reviewed and two cases are presented of successful root coverage procedures in which gingival recession associated with cervical abrasion and caries was present.


Neutrophils play a critical role in early resistance to amebic liver abscesses in severe combined immunodeficient mice.
Animal models of liver abscess formation with Entamoeba histolytica suggest that the neutrophil is the first cell of the host immune system to interact with the invading ameba. In vitro studies have suggested that lysis of neutrophils by virulent amebae may exacerbate the damage seen in amebic liver abscesses. To investigate the role of neutrophils in vivo, we used the severe combined immunodeficient (SCID) mouse model of amebic liver abscess formation and compared liver damage in neutrophil-depleted and control mice. We found that neutrophil-depleted animals have significantly larger amebic liver abscesses at early stages of infection and that abscesses in neutrophil-depleted SCID mice lack the prominent inflammatory cell ring seen in amebic liver abscesses in control SCID mice. These data suggest that neutrophils play a protective role in the early host response to amebic infection of the liver.