Impact of kidney transplantation on the progression of cardiovascular disease.
Kidney transplantation, of all the treatment modalities for end-stage renal disease, affords the greatest potential for prolonged survival and improved quality of life. Great strides in immunosuppressant therapy have improved graft survival and forced clinicians to consider other health-care needs of kidney transplant recipients. Chief among these needs is the prevention and treatment of cardiovascular disease. Cardiovascular disease is the most common cause of death among patients with a working renal allograft. Because therapies for primary and secondary prevention are successful in the general population, transplant clinicians are increasingly focused on preventing or limiting the progression of cardiovascular disease. Initiation of aggressive management of conventional atherosclerotic risk factors and uremia-related risk factors, ideally during the early stages of chronic kidney disease (CKD) or after kidney transplantation, and efforts to delay the progression of kidney disease will hopefully reduce the cardiovascular burden in transplant recipients.


Microstructure Manipulation for Enhancing the Resistance of Garnet-Type Solid Electrolytes to "Short Circuit" by Li Metal Anodes.
Al-contained Li7- xLa3Zr2- xTa xO12 ( xTa-LLZO) powder was synthesized via solid-state reaction, where increasing the Ta doping level was found to reduce the average particle size and facilitate a higher relative density in the sintered pellet. 0.8Ta-LLZO pellets sintered at 1150 °C achieved a relative density of 96.2 ± 0.2% and survived the Li striping/plating test under a unidirectional current polarization of 0.5 mA/cm2 for more than 8 h without short-circuiting. In contrast, other xTa-LLZO sintered pellets with lower Ta doping levels were short-circuited by lithium dendrites after polarization for much shorter time periods. The microstructure of the sintered body played a more essential role in lithium dendrite prevention compared to relative density alone. By characterizing the microstructure of xTa-LLZO sintered pellets, we proposed a formation mechanism of the pathways for lithium dendrite growth.


Quantum observable homotopy tracking control.
This paper presents a new tracking method where the target observable O(s,T) at the final dynamical time T follows a predefined track P(s) with respect to a homotopy tracking variable s>or=0. The procedure calculates the series of control fields E(s,t) required to accomplish observable homotopy tracking by solving a first-order differential equation in s for the evolution of the control field. Controls produced by this technique render the desired track for all s without encountering field singularities. This paper also extends the technique to the case where the field-free Hamiltonian and dipole moment operator change with s in order to explore the control of new physical systems along the track. Several simulations are presented illustrating the various uses for this quantum tracking control technique.


Hepatitis C Virus Screening Among Adolescents Attending a Drug Rehabilitation Center.
Hepatitis C virus (HCV) infection has a strong association with intravenous drug use (IVDU). IVDU is a growing public health concern, even in the adolescent population. To our knowledge, there are no published HCV screening studies targeting high-risk adolescents who attend drug rehabilitation centers.This study was designed to determine the seroprevalence of HCV infection utilizing point-of-care (POC) testing at an adolescent drug rehabilitation center and gain a preliminary understanding of the acceptance rate for HCV screening in this high-risk population. This single-center, observational study was conducted at a major drug rehabilitation center in northeast Ohio from July 2016 to June 2017. The consented adolescents who presented at the center were recruited to participate in HCV screening. The participants were administered a survey to assess their demographics and risk behavior profile followed by HCV testing utilizing a POC test. During the study period, 150 adolescents were admitted to the drug rehabilitation center, of whom 100 were approached and 85 agreed to participate. Forty percent of the participants (34/85) were females, and 78% (66/85) were white. HCV prevalence among participants was 5% (4/85), all of whom were females. History of heroin use was reported by 15% (13/85) and it was associated with HCV seropositivity; 100% (4/4) of all HCV-positive individuals reported the use of heroin vs only 11% (9/81) of HCV-negative individuals (P = .0004). Our study showed a high prevalence of HCV among adolescents attending a drug rehabilitation center with high acceptance of POC HCV testing.


Ethno-Caste Influences on Migration Rates and Destinations.
While studies commonly show differences in out-migration between ethnic groups, ethnicity most often features no more than a side note in the emigration literature, and we have very little insight about why people from different ethnic groups migrate at different rates. Understanding ethnic differences in migration rates and destination choice has important implications for the present-day and future potential for either dampening or exacerbating ethnic discrimination and opportunity structures. Building on existing migration theory, we identify three possible mechanisms through which ethnicity might influence out-migration rates and destination choice: human and economic capital, contemporary discrimination, and historical legacies that are perpetuated through social networks. Our empirical investigation uses longitudinal panel survey data from Nepal and we find that all three of these mechanisms likely influence out-migration and destinations of the five major ethno-caste groups. However, we show that historical legacy and human and economic capital emerge as the key drivers of ethnic differences in out-migration here. We discuss what these results mean for migration studies as well as the potential for the institution of migration to affect patterns of ethno-caste-based disadvantage in Nepal. The theoretical basis and empirical evidence from our study also suggest ways to understand the reasoning for and consequence of ethnic and racial differentials in migration patterns in other areas of the world.


Clinical and endoscopic evaluation of gastroesophageal reflux disease in patients successfully treated with esomeprazole.
Esomeprazole, an S-isomer of omeprazole, is the first proton pump inhibitor developed as an optical isomer, and it has shown high healing rates in erosive esophagitis. To evaluate the efficacy and tolerability of esomeprazole in subjects with erosive esophagitis, according to the Los Angeles classification study design: an open, multi-center clinical study. Two hundred and eighteen subjects with reflux esophagitis confirmed by endoscopy were included in an open, multi-center study in Brazil. All of them received esomeprazole 40 mg, once daily, for a 4-week period. Subjects who had unhealed esophagitis by week 4 continued the treatment for another 4 weeks. The primary efficacy endpoint was the healing rates by weeks 4 and 8. The secondary endpoints were the number of patients with symptom resolution by week 4, the number of days to sustained symptom resolution, number of symptom-free days and nights and safety and tolerability of the drug. Healing rates by weeks 4 and 8 were 82% (confidence interval: 77.4%-87.6%) and 96.1% (confidence interval: 93.5% - 98.8%), respectively. Ninety-nine (99%) of the patients had heartburn resolution by week 2. The most common adverse events were headache (4%), diarrhea (2.6%) and epigastric pain (2.2%). For the studied period, esomeprazole was shown to be a safe and well-tolerated drug, providing significant healing rates of mucosal breaks, regardless of LA classification, in patients with erosive esophagitis. Esomeprazole was also shown to be effective in quickly relieving symptoms.


Temporal dynamics of the gut microbiota in people sharing a confined environment, a 520-day ground-based space simulation, MARS500.
The intestinal microbial communities and their temporal dynamics are gaining increasing interest due to the significant implications for human health. Recent studies have shown the dynamic behavior of the gut microbiota in free-living, healthy persons. To date, it is not known whether these dynamics are applicable during prolonged life sharing in a confined and controlled environment. The MARS500 project, the longest ground-based space simulation ever, provided us with a unique opportunity to trace the crew microbiota over 520 days of isolated confinement, such as that faced by astronauts in real long-term interplanetary space flights, and after returning to regular life, for a total of 2 years. According to our data, even under the strictly controlled conditions of an enclosed environment, the human gut microbiota is inherently dynamic, capable of shifting between different steady states, typically with rearrangements of autochthonous members. Notwithstanding a strong individuality in the overall gut microbiota trajectory, some key microbial components showed conserved temporal dynamics, with potential implications for the maintenance of a health-promoting, mutualistic microbiota configuration. Sharing life in a confined habitat does not affect the resilience of the individual gut microbial ecosystem, even in the long term. However, the temporal dynamics of certain microbiota components should be monitored when programming future mission simulations and real space flights, to prevent breakdowns in the metabolic and immunological homeostasis of the crewmembers.


Interferon-alpha therapy of recurrent conjunctival papillomas.
Five patients with multiple, recurrent conjunctival papillomas underwent surgical excision of their tumor and then received interferon alpha-N1, 5 X 10(6) units/m2 (5 Mu/m2), intramuscularly daily for one month. A similar dose was given two to three times per week for the next six months and tapered off or discontinued thereafter. The follow-up period varied from one to four years. Two patients have had no recurrence of tumor. The other three patients have had recurrences of lesser severity upon tapering or discontinuing the interferon, and repeat surgical or laser excision of these lesions has been performed. The presence of koilocytosis and human papillomavirus type 11a DNA sequences was noted in all specimens large enough to examine, whereas papillomavirus structural antigens were detected in only two of five specimens. A regimen of interferon therapy appears to be tumor suppressive, but not curative.


Biological potency of selenium from sodium selenite, selenomethionine, and selenocystine in the chick.
Experiments were conducted to determine the relative effectiveness of selenium (Se) from sodium selenite, selenomethionine and selenocystine for promoting weight gain and preventing exudative diathesis. The chicks used were hatched from eggs low in Se. They were fed a basal diet made up mostly of corn (low in Se) and torula yeast or the basal diet supplemented with various levels of Se from sodium selenite, selenomethionine, or selenocystine. At 10 mug. of added Se per kg of diet, sodium selenite and selenocystine were about equal in promoting weight gain and preventing exudative diathesis. Selenomethionine was less effective. Tissues from chicks fed the various Se sources providing 60 mug. Se per kg of diet for four weeks were analyzed for Se. The content of tissues from chicks fed sodium selenite or selenocystine was similar. Chicks fed selenomethionine had a higher concentration of Se in the pancreas and breast muscle than chicks fed the other two Se sources, but a lower concentration in the kidney, liver, and heart. The level of Se in the kidney, liver, or heart which a Se source produces seems to be more important for preventing exudative diathesis than that which is found in the pancreas or muscle.


Photo-assisted removal of fuel oil hydrocarbons from wood and concrete.
A novel photo-treatment to decontaminate building structural elements polluted with fuel oil hydrocarbons as a result of spillage and/or a catastrophic flood was examined. A proof-of-concept study evaluating the photocatalytic removal of hydrocarbons (n-hexadecane and fuel oil #2) from contaminated wood (southern yellow pine) and concrete was conducted using scintillation counting (with (14)C-labeled n-hexadecane) and gas chromatography. Contaminated samples were irradiated by UV or fluorescent light in the absence or presence of a photocatalyst, TiO(2). As a result of the treatment, under various scenarios, up to 80-98% of the originally applied n-hexadecane was removed, within a wide range of contaminant concentrations (4-250 mg/g wood). The essential treatment time increased from 1-7 days for low concentrations to several weeks for high concentrations. Mass balance experiments showed that the only product formed from (14)C-labeled n-hexadecane in detectable amounts was (14)CO(2). For low amounts of applied hydrocarbon (4-20 mg/g wood), the overall process rate was limited by the contaminant transport/mobility whereas for high n-hexadecane concentrations (150-250 mg/g, corresponding to 50-80% filling of wood pores), the key factor was the photochemical reaction. Photodegradation experiments conducted with standard heating fuel oil #2 (a representative real-world contaminant) resulted in a significant (up to 80%) photochemical removal of mid-size hydrocarbons (C(13)-C(17)) in 3 weeks whereas heavier hydrocarbons (> C(17)) were not affected; light hydrocarbons (< C(12)) were removed by evaporation. These results point toward a promising technique to reclaim wooden and concrete structures contaminated with semi-volatile chemicals.


Human population genetic structure and diversity inferred from polymorphic L1(LINE-1) and Alu insertions.
The L1 retrotransposable element family is the most successful self-replicating genomic parasite of the human genome. L1 elements drive replication of Alu elements, and both have had far-reaching impacts on the human genome. We use L1 and Alu insertion polymorphisms to analyze human population structure. We genotyped 75 recent, polymorphic L1 insertions in 317 individuals from 21 populations in sub-Saharan Africa, East Asia, Europe and the Indian subcontinent. This is the first sample of L1 loci large enough to support detailed population genetic inference. We analyzed these data in parallel with a set of 100 polymorphic Alu insertion loci previously genotyped in the same individuals. The data sets yield congruent results that support the recent African origin model of human ancestry. A genetic clustering algorithm detects clusters of individuals corresponding to continental regions. The number of loci sampled is critical: with fewer than 50 typical loci, structure cannot be reliably discerned in these populations. The inclusion of geographically intermediate populations (from India) reduces the distinctness of clustering. Our results indicate that human genetic variation is neither perfectly correlated with geographic distance (purely clinal) nor independent of distance (purely clustered), but a combination of both: stepped clinal.


[Right ventricular function during and after aortocoronary bypass].
A transient depression of right ventricule (RV) function following aortocoronary bypass operation is a common event. Occasionally, RV failure may be responsible for postoperative low cardiac output syndrome, cardiogenic shock or intracardiac right-left shunt. Understanding and monitoring of RV function is essential for proper management of patients during and after aortocoronary bypass operation.


Helix geometry and hydration in an A-DNA tetramer: IC-C-G-G.
The DNA oligomer of sequence IC-C-G-G has been synthesized, and its X-ray crystal structure solved at a resolution of 2.0 A, using anomalous scattering from iodines in phase analysis: 48 cycles of Jack-Levitt restrained least-squares refinement resulted in a residual error of 19.9% over all data, or 16.5% for two-sigma data. Two double-helical tetramers stack in the crystal to form a continuous octamer, except for the two missing phosphate connections across the center. The octamer has a mean helix rotation of 33.7 degrees (10.7 base-pairs per turn), rise of 2.87 A, mean inclination angle of base-pairs of 14 degrees, and mean base-pair propeller twist of +16.3 degrees. Local variations in both helix rotation and base plane roll angles, including those across the center of the octamer, are as predicted from base sequence by sum functions sigma 1 and sigma 2. The three known DNA octamers: IC-C-G-G/IC-C-G-G, G-G-T-A-T-A-C-C and G-G-C-C-G-G-C-C, make up a graded series in this order, with monotonically changing structural parameters. An exhaustive comparison of torsion angle correlations among the known A helices confirms some structural expectations and reveals some new features. 86 water molecules have been located per double-helical IC-C-G-G tetramer (the asymmetric unit), of which 451/2 per tetramer lie within a first hydrogen-bonded shell of hydration. No ordered water structure is observed comparable to the minor groove spine of hydration in B-DNA.


Vaccination against human genital papillomaviruses. More than a hypothesis.
Human genital papillomaviruses are the necessary cause of cervical cancer. A prophylactic vaccine designed to prevent genital HPV disease by inducing virus neutralizing antibodies has been proposed. Studies on animal models have produced relevant data on the efficacy of HPV vaccine. The results of HPV clinical studies suggest that it will be possible to develop an effective vaccine. Nevertheless the number of subjects analyzed in the full text published clinical studies is still poor. Although a recently presented phase III study appears satisfied, it is probably necessary for a larger phase III study. Besides the choice of the geographical area for a very large clinical trial, there are different aspects to consider, such as the identification of the target population, identification of the endpoints, composition of the vaccine and marketing of the vaccine. Furthermore there are two open questions: the duration of protection and the behavioral modifications. All these issues are discussed in this review.


Clinical and Molecular Variability in Patients with PHKA2 Variants and Liver Phosphorylase b Kinase Deficiency.
Glycogen storage disease (GSD) type IX is a rare disease of variable clinical severity affecting primarily the liver tissue. Individuals with liver phosphorylase b kinase (PhK) deficiency (GSD IX) can present with hepatomegaly with elevated serum transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth with considerable variation in clinical severity. PhK is a cAMP-dependent protein kinase that phosphorylates the inactive form of glycogen phosphorylase, phosphorylase b, to produce the active form, phosphorylase a. PhK is a heterotetramer; the alpha 2 subunit in the liver is encoded by the X-linked PHKA2 gene. About 75% of individuals with liver PhK deficiency have mutations in the PHKA2 gene; this condition is also known as X-linked glycogenosis (XLG). Here we report the variability in clinical severity and laboratory findings in 12 male patients from 10 different families with X-linked liver PhK deficiency caused by mutations in PHKA2. We found that there is variability in the severity of clinical features, including hypoglycemia and growth. We also report additional PHKA2 variants that were identified in 24 patients suspected to have liver PhK deficiency. The basis of the clinical variation in GSDIX due to X-linked PHKA2 gene mutations is currently not well understood. Creating systematic registries, and collecting longitudinal data may help in better understanding of this rare, but common, glycogen storage disorder. Liver phosphorylase b kinase (PhK) deficiency caused due to mutations in X-linked PHKA2 is highly variable.


Amoxycillin-clavulanic acid (Augmentin) antibiotic prophylaxis against wound infections in renal failure patients.
A randomized, controlled trial of the use of amoxycillin with clavulanic acid (Augmentin) for prophylaxis against wound infections following major surgery, including transplantation, in patients with chronic renal failure, was undertaken. Six of 22 control patients developed wound infections (27%) whereas no patient in the treatment group (24) developed a wound infection (P less than 0.05). After the termination of this trial, the next 35 consecutive patients received prophylactic amoxycillin/clavulanate; of these only two developed wound infections associated with leakage from their pancreatic anastomoses. All the wound infections were shown to be caused by bacteria sensitive to amoxycillin/clavulanate. Pharmacokinetic studies in patients have shown that a bactericidal concentration of the drugs was present for up to 20 h post-operatively in patients on dialysis, and in recipients of non-functioning renal transplants. In patients with normal renal transplant function excretion of the drug within 12 h was observed.


Orbital lipogranulomatous inflammation harboring Mycobacterium abscessus.
A case of iatrogenic Mycobacterium abscessus orbital infection is presented to call attention to its distinct histopathologic appearance, mechanism of organism, virulence, and clinical management. Clinicopathologic analysis of an orbital infection caused by M. abscessus is described. Detailed histologic analysis is performed to provide insight into the mechanism of infection and correlate the features of the orbital infection with that of atypical mycobacteriosis at other body sites. A 71-year-old woman had an orbital mass in the supranasal orbit after a blepharoplasty. The mass consisted of a dimorphic inflammatory reaction with a superficial purulent reaction and a deeper granulomatous process consisting of epithelioid tubercles, each centered about a lipid vacuole. Acid-fast bacilli were found in the lipid vacuoles but not elsewhere in the specimen. Each tubercle was surrounded by a zone of lymphocytes and a desmoplastic reaction. Microbiologic culture studies identified M. abscessus. A combination of surgical intervention and antibiotic therapy for 4 weeks eliminated the infection. Acid-fast stains should be performed on any orbital lesion showing an apparent lipogranulomatous reaction. Although clinical management of orbital atypical microbacteriosis is difficult, the combination of surgical and specific antimicrobial intervention is effective. Our study contributes to an evolving understanding of the mechanism of human infectivity of these low-virulence organisms by suggesting that the orbital fat is a source of lipid material that can harbor the organisms, allowing them to escape host immunosurveillance.


[Management of thyroglossal duct carcinoma: report of five cases].
To study the clinical characteristic, diagnosis, surgical treatment and prognosis of thyroglossal duct carcinoma (TDCa). A total of 110 patients with thyroglossal duct remanat in our hospital between 1991 and 2011 was reviewed. Five patients of them were diagnosed with TDCa by pathological examination, including 4 cases of papillary carcinoma and 1 case of squamous cell carcinoma. All five patients were men and the median age was 41 years (range from 17 - 73 years). Pulmonary metastasis was found preoperatively in one patient with papillary carcinoma. All five patients were managed by surgical treatment. Sistrunk operation was performed with resection of the tumor, thyroglossal remanat and partial hyoid bone in 2 patients, with resection of thyroid nodule in one patient, with total thyroidectomy and central neck dissection in one patient with pulmonary metastasis, with extensive resection of invading tissues in one patient with squamous TDCa. Two patients with papillary carcinoma underwent the treatment with TSH suppression postoperatively, of them one with pulmonary metastasis received radioactive iodine therapy simultaneously. The remaining three patients did not receive any further treatment. With follow-up of 14 - 45 months, local recurrence occurred in one patient with squamous TDCa after two months and caused death seven months after surgery, and the other four patients survived. TDCa is a rare malignant tumor that is usually diagnosed after surgery. The Sistrunk operation may be adequate for low-risk cases.


Persistence of microbial and chemical pig manure markers as compared to faecal indicator bacteria survival in freshwater and seawater microcosms.
Natural seawater and freshwater microcosms inoculated with pig manure were set up to determine the persistence of pig faecal microbial and chemical markers in these two types of surface water. The concentrations of Lactobacillus amylovorus, the Bacteroidales Pig-2-Bac 16S rRNA genetic marker, five stanols and the evolution of two ratios of stanols, R1 (coprostanol to the sum of coprostanol and 24-ethylcoprostanol) and R2 (sitostanol to coprostanol) were analyzed during two months along with the concentration of Faecal Indicator Bacteria (FIB). Pig manure was inoculated to unfiltered water microcosms incubated aerobically at 18 °C in the dark. The faecal contamination load represented by the concentrations of culturable Escherichia coli and/or enterococci remained for two months in the freshwater and seawater microcosms water column. These concentrations followed a biphasic decay pattern with a 97% reduction of the initial amount during a first rapid phase (<6 days) and a remaining proportion undergoing a slower or null second decline. The L. amylovorus marker and five stanols persisted as long as the indicators in both treatments. The Pig-2-Bac marker persisted 20 and 27 days in seawater and freshwater, respectively. The ratios R1 and R2 were in the range specific to pig manure until day 6 in both types of water. These results indicate that Pig-2-Bac, L. amylovorus and stanol ratios might be used in combination to complement FIB testing to determine the pig source of fecal pollution. However, stanol ratios are to be used when the time point of the discharge is known.


Factors affecting fracture position at cast removal after pediatric forearm fracture.
The outcome of a pediatric forearm fracture is related to the angulation of that fracture at the time of union. We discuss the factors affecting the position of the fracture at union. Three hundred forty-six children with 369 reductions of forearm fractures were reviewed retrospectively. Quality of reduction at the time of operation and loss of reduction during the period of cast immobilization were assessed using axis deviation. Loss of reduction had a greater influence on the final position of the fracture at union than did the position of the fracture at initial reduction. To ensure a satisfactory outcome, all pediatric forearm fractures should be monitored with radiologic review and remanipulation if their axis deviation is > 5 in younger patients or > 3 in patients with fractures close to or after growth-plate closure. Right forearm fractures in boys were identified as a subgroup at greater risk for redisplacement.


Functional impact of navigation-assisted minimally invasive total knee arthroplasty.
The functional results of 47 navigation-assisted minimally invasive total knee arthroplasties (TKAs) were compared with results of 50 conventionally performed TKAs with a minimum 1-year follow-up. Navigation-assisted minimally invasiveTKA showed better functional results than conventionally performed TKA at 1 year after surgery with regard to the Hospital for Special Surgery (HSS) score, Western Ontario and McMaster Universities (WOMAC) pain and function score, flexion range, and less outliers of leg and component alignment. Among the bilateral cases (one side by navigation-assisted minimally invasive TKA and the other side by conventionally performed TKA), more patients preferred the navigation-assisted minimally invasive side to the conventionally performed side.


Successful aging among the young-old, old-old, and oldest-old Chinese.
In this study, successful aging was defined by four dimensions including functional status, affective status, cognitive status, and productive involvement status. This study examined successful aging among Hong Kong Chinese old people in three different age cohorts: young-old, old-old, and oldest-old. The respondents were 1106 people aged 60 years or older from a cross-sectional study of a representative community sample of the elderly population in Hong Kong. We found modest associations between four dimensions of successful aging, indicating the relative independence of these four criteria for successful aging. Using multiple regression models, we found that age, gender, years of education, number of close relatives, frequency of contact with friends, financial strain, number of chronic illnesses, self-rated health, hearing impairment, and life satisfaction were associated with the successful aging indicator.


[Future and needs of regenerative therapy in prosthetic treatment].
Bone regeneration is currently considered to be most significant in implantology as regenerative therapy is directly involved and essential in dental prosthetics. The following factors, however, must be clarified before prosthetic treatment can be performed; 1. Necessity of bone regeneration and recovery with individual method. 2. Change of regenerated bone. 3. Analysis of dynamics which will affect bone resorption. Though these factors are important in prosthetics, dynamic analysis is not performed well even in the existing bone. Clinical follow-ups so far indicate that not only infection but also excessive loading influence most of the cases whose progress is not good. Moreover, there are many challenges to be solved for bone generated by regenerative therapy such as the timing of placing the implant, the timing of loading, conditions for loading and occlusal control.


Transcriptional analysis of a whole-body form of long-term habituation in Aplysia californica.
Habituation is the simplest form of learning, but we know little about the transcriptional mechanisms that encode long-term habituation memory. A key obstacle is that habituation is relatively stimulus-specific and is thus encoded in small sets of neurons, providing poor signal/noise ratios for transcriptional analysis. To overcome this obstacle, we have developed a protocol for producing whole-body long-term habituation of the siphon-withdrawal reflex (SWR) of Aplysia californica. Specifically, we constructed a computer-controlled brushing apparatus to apply low-intensity tactile stimulation over the entire dorsal surface of Aplysia at regular intervals. We found that 3 d of training (10 rounds of stimulation/day; each round = 15 min brushing at a 10-sec ISI; 15-min rest between rounds) produces habituation with several characteristics favorable for mechanistic investigation. First, habituation is widespread, with SWR durations reduced whether the reflex is evoked by tactile stimulation to the head, tail, or the siphon. Second, long-term habituation is sensitive to the pattern of training, occurring only when brushing sessions are spaced out over 3 d rather than massed into a single session. Using a custom-designed microarray and quantitative PCR, we show that long-term habituation produces long-term up-regulation of an apparent Aplysia homolog of cornichon, a protein important for glutamate receptor trafficking. Our training paradigm provides a promising starting point for characterizing the transcriptional mechanisms of long-term habituation memory.


Medical aspects of liver transplantation.
The methods used to screen prospective candidates for orthotopic liver transplantation are described. Both the indication and the contraindications for the procedure are discussed. The timing of the procedure during the course of an individual candidate's liver disease is also discussed. Additionally, the institutional requirements of a liver transplant center are identified. Finally, the problems experienced by a liver transplant patient and his physician during the postoperative period are identified and discussed.


Tumor invasive ability of papillary thyroid carcinomas is not conferred by acquired gene mutations.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The ability to predict whether a carcinoma would exhibit invasive ability in patients with PTC is important and has clinical implications for the selection of therapeutic strategies. Although several studies have focused on the genetic characterization of invasive cancer cells, the factors critical to the origination of invasive cancer cells are still unclear. This study aimed to determine whether genomic mutations contribute to the acquisition of the tumor invasion phenotype and to investigate the genetic features of invasive cancer cells in patients with PTC. We performed customized 48-gene deep exon sequencing in samples obtained from 88 patients with PTC via fine needle aspiration; the results revealed that no genetic changes were specifically associated with the tumor aggressiveness phenotype. Our results indicate that genetic mutations do not cause indolent PTCs to become invasive.


Low-Level Prenatal Toxin Exposures and Breastfeeding Duration: A Prospective Cohort Study.
Introduction Maternal exposure to tobacco smoke is associated with shortened breastfeeding duration, but few studies have examined the effects on breastfeeding outcomes of low level exposures to other toxic chemicals. Moreover, it is unclear if passive smoking is associated with duration of breastfeeding. Our objective was therefore to examine the effect of low-level prenatal exposures to common environmental toxins (tobacco smoke, lead, and phthalates) on breastfeeding exclusivity and duration. Methods We conducted an analysis of data from the Health Outcomes and Measures of the Environment (HOME) Study. Serum and urine samples were collected at approximately 16 and 26 weeks gestation and at delivery from 373 women; 302 breastfed their infants. Maternal infant feeding interviews were conducted a maximum of eight times through 30 months postpartum. The main predictor variables for this study were gestational exposures to tobacco smoke (measured by serum cotinine), lead, and phthalates. Passive smoke exposure was defined as cotinine levels of 0.015-3.0 μg/mL. Primary outcomes were duration of any and exclusive breastfeeding. Results Serum cotinine concentrations were negatively associated with the duration of any breastfeeding (29.9 weeks unexposed vs. 24.9 weeks with passive exposure, p = 0.04; and 22.4 weeks with active exposure, p = 0.12; p = 0.03 for linear trend), but not duration of exclusive breastfeeding. Prenatal levels of blood lead and urinary phthalate metabolites were not significantly associated with duration of any or exclusive breastfeeding. Conclusions Passive exposure to tobacco smoke during pregnancy was associated with shortened duration of any breastfeeding.


Metabolic and body composition changes in first year following traumatic amputation.
Body composition and metabolism may change considerably after traumatic amputation because of muscle atrophy and an increase in adiposity. The purpose of this study was to quantify changes in weight, body composition, and metabolic rate during the first year following traumatic amputation in military servicemembers. Servicemembers without amputation were included for comparison. Participants were measured within the first 12 wk after amputation (baseline) and at 6, 9, and 12 mo after amputation. Muscle mass, fat mass, weight, and metabolic rate were measured at each time point. There was a significant increase in weight and body mass index in the unilateral group between baseline and all follow-up visits (p < 0.01). Over the 12 mo period, total fat mass and trunk fat mass increased in both unilateral and bilateral groups; however, these changes were not statistically significant over time. Muscle mass increased in both the unilateral and bilateral group despite percent of lean mass decreasing. No changes in resting metabolism or walking energy expenditure were observed in any group. The results of this study conclude that weight significantly increased because of an increase in both fat mass and muscle mass in the first year following unilateral and bilateral amputation.


Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits.
The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation.


Quantification of zolpidem in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry.
A simple and robust method for quantification of zolpidem in human plasma has been established using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS). Es-citalopram was used as an internal standard. Zolpidem and internal standard in plasma sample were extracted using solid-phase extraction cartridges (Oasis HLB, 1 cm3/30 mg). The samples were injected into a C8 reversed-phase column and the mobile phase used was acetonitrile-ammonium acetate (pH 4.6; 10 mm) (80:20, v/v) at a flow rate of 0.7 mL/min. Using MS/MS in the selected reaction-monitoring (SRM) mode, zolpidem and Es-citalopram were detected without any interference from human plasma matrix. Zolpidem produced a protonated precursor ion ([M+H]+) at m/z 308.1 and a corresponding product ion at m/z 235.1. The internal standard produced a protonated precursor ion ([M+H]+) at m/z 325.1 and a corresponding product ion at m/z 262.1. Detection of zolpidem in human plasma by the LC-ESI MS/MS method was accurate and precise with a quantification limit of 2.5 ng/mL. The proposed method was validated in the linear range 2.5-300 ng/mL. Reproducibility, recovery and stability of the method were evaluated. The method has been successfully applied to bioequivalence studies of zolpidem.


Maternal rearing environment impacts autonomic nervous system activity.
While it is now well known that social deprivation during early development permanently perturbs affective responding, accumulating evidence suggests that less severe restriction of the early social environment may also have deleterious effects. In the present report, we evaluate the affective responding of rhesus macaque (Macaca mulatta) infants raised by their mothers in restricted social environments or by their mothers in large social groups by indexing autonomic nervous system activity. Following a 25-hr evaluation of biobehavioral organization, electrocardiogram, and an index of respiration were recorded for 10 min. This allowed for an evaluation of both heart rate and respiratory sinus arrhythmia (RSA), an index of parasympathetic activity, during a challenging situation. Three- to four-month-old infants raised in restricted social environments had significantly higher heart rates and lower RSA as compared to infants raised in unrestricted social environments, consistent with a more potent stress response to the procedure. These results are consistent with mounting evidence that the environment in which individuals are raised has important consequences for affective processing.


Ciprofloxacin/dexamethasone precipitate formation in the ear canal of a paediatric patient.
This case report describes a paediatric patient diagnosed with otitis externa and treated with topical ciprofloxacin/dexamethasone. The patient completed the course of therapy and then developed precipitate formation from the pharmacological treatment. Laboratory testing of the precipitate confirmed the presence of a large quantity of ciprofloxacin. Removal of the precipitate required the use of an elephant ear washer system and removal with surgical tweezers. This case report investigated a probable topical ciprofloxacin/dexamethasone-induced ear precipitate formation in the ear canal, which, subsequently, was successfully removed from the patient's ear canal.


Effect of peracetic acid on ascospore-forming molds and test microorganisms used for bio-validations of sanitizing processes in food plants.
Industrial sterilization of packaging and filling machineries by peracetic acid (PAA) is a widespread practice. In our study we assessed the resistance to PAA of three ascospore-forming molds (Chaetomium globosum ATCC 6205; Talaromyces bacillisporus SSICA 10915; Aspergillus hiratsukae SSICA 3913) compared to that of Aspergillus brasiliensis ATCC 16404 and Bacillus atrophaeus DSM 675, that are currently used as test microorganisms during industrial bio-validations of food packaging and machineries. Tests were carried out at 40 °C using 1,000 mg/l of PAA, with or without a supporting material (aluminium, tin-plate, PET). At all conditions tested, a greater resistance to PAA was registered for C. globosum, followed by T. bacillisporus, A. hiratsukae, A. brasiliensis and B. atrophaeus. D-values of C. globosum varied from 23 to 68 min, whereas T. bacillisporus showed D-values from 83 to 352 s and A. hiratsukae showed D-values from 32 to 65 s. Surprisingly, both test microorganisms (A. brasiliensis and B. atrophaeus) proved less resistant than ascospore-forming molds tested, their D-values being always lower than 30 s. Cells treated without a supporting material proved more resistant than those deposited on plastic or metallic strips, with the exception of tin-plate, where results approaching those obtained without a supporting materials were obtained. Based on the results obtained in this paper, test microorganisms currently used for bio-validations in industrial plants and also heat-resistant strains proved sensibly less resistant to PAA than C. globosum. Therefore, for practical purposes C. globosum should be furtherly studied to understand if its use during bio-validations of sanitizing processes could lead to more performing results.


Developing irreversible inhibitors of the protein kinase cysteinome.
Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a γ-phosphate group from ATP to a variety of amino acid residues, such as tyrosine, serine, and threonine, that serves as a ubiquitous mechanism for cellular signal transduction. The clinical success of a number of kinase-directed drugs and the frequent observation of disease causing mutations in protein kinases suggest that a large number of kinases may represent therapeutically relevant targets. To date, the majority of clinical and preclinical kinase inhibitors are ATP competitive, noncovalent inhibitors that achieve selectivity through recognition of unique features of particular protein kinases. Recently, there has been renewed interest in the development of irreversible inhibitors that form covalent bonds with cysteine or other nucleophilic residues in the ATP-binding pocket. Irreversible kinase inhibitors have a number of potential advantages including prolonged pharmacodynamics, suitability for rational design, high potency, and ability to validate pharmacological specificity through mutation of the reactive cysteine residue. Here, we review recent efforts to develop cysteine-targeted irreversible protein kinase inhibitors and discuss their modes of recognizing the ATP-binding pocket and their biological activity profiles. In addition, we provided an informatics assessment of the potential "kinase cysteinome" and discuss strategies for the efficient development of new covalent inhibitors.


Components of the cannabinoid system in the dorsal periaqueductal gray are related to resting heart rate.
The present study was undertaken to examine whether variations in endocannabinoid signaling in the dorsal periaqueductal gray (dPAG) are associated with baseline autonomic nerve activity, heart rate, and blood pressure. Blood pressure was recorded telemetrically in rats, and heart rate and power spectral analysis of heart rate variability were determined. Natural variations from animal to animal provided a range of baseline values for analysis. Transcript levels of endocannabinoid signaling components in the dPAG were analyzed, and endocannabinoid content and catabolic enzyme activity were measured. Higher baseline heart rate was associated with increased anandamide content and with decreased activity of the anandamide-hydrolyzing enzyme, fatty acid amide hydrolase (FAAH), and it was negatively correlated with transcript levels of both FAAH and monoacylglycerol lipase (MAGL), a catabolic enzyme for 2-arachidonoylglycerol (2-AG). Autonomic tone and heart rate, but not blood pressure, were correlated to levels of FAAH mRNA. In accordance with these data, exogenous anandamide in the dPAG of anesthetized rats increased heart rate. These data indicate that in the dPAG, anandamide, a FAAH-regulated lipid, contributes to regulation of baseline heart rate through influences on autonomic outflow.


Combination of the AO-Magerl and load-sharing classifications for the management of thoracolumbar burst fractures.
The AO-Magerl classification is widely accepted for the appropriate management of patients with thoracolumbar burst fractures; however, it fails to assess the ability of the injured spine to withstand compressive loading and cannot predict instrumentation failure after short-segment posterior fixation. The load-sharing classification depends on the degree of comminution and apposition of bony fragments.We retrospectively classified according to both classifications 100 consecutive patients with 1-level thoracolumbar burst fractures treated nonoperatively or operatively within a 7-year period. Sixty neurologically intact patients (60%) were treated nonoperatively, 15 (15%) had short posterior instrumentation, 15 (15%) had short anterior instrumentation, and 10 (10%) had combined short posterior instrumentation and anterior strut grafting. Twenty-five of the 40 (60%) surgically treated patients had neurological impairment on admission. Clinical outcome was assessed using a pain and working ability scale. Mean follow-up was 52 months (range, 24-70 months). Function was satisfactory in 55 (92%) nonoperatively treated patients and in 33 (83%) surgically treated patients. Neurological improvement by American Spinal Injury Association (ASIA) grade was observed in patients with incomplete paraplegia (70% of neurologically impaired patients) who were treated operatively.The combination of AO-Magerl and load-sharing classifications provides for accurate selection of treatment, surgical approach, and length of instrumentation, and can guide the decision for additional anterior surgery.


Testing Spirotetramat as an Alternative Solution to Abamectin for Cacopsylla pyri (Hemiptera: Psyllidae) Control: Laboratory and Field Tests.
Aim of the study was to investigate the performance of the new insecticide "spirotetramat" as an alternative solution of "abamectin" for the control of Cacopsylla pyri L. (Hemiptera: Psyllidae) in the context of an IPM program in European pear, Pyrus communis L.. Laboratory bioassays for the estimation of LC50 and LC90 of both insecticides were performed using four populations collected in Emilia-Romagna (Italy) orchards where different pest management strategies were used (organic, integrated, and conventional). The same populations were also analyzed for the main insecticide detoxifying activities in nymphs by spectrofluorimetric in vitro assays. The performance of the two insecticides was also tested on field on one population under integrated pest management conditions. The laboratory experiments showed that the LC90 of spirotetramat were lower than the highest field concentration allowed in Europe (172.80 mg AI liter(-1)) giving reassurance about the efficacy of the product. Concerning the abamectin, the laboratory bioassays did not show strong indications of resistance development of C. pyri populations of Emilia-Romagna. A similarity in enzyme detoxifying activity was observed in both insecticides indicating a general absence of a significant insecticide resistance. The field trial showed a high efficacy (>90 %) of spirotetramat on C. pyri already after 15 d from application, and it was significantly higher from abamectin. Overall, spirotetramat is one more choice for C. pyri control, as well as abamectin in order to minimize the risks of occurrence of insecticide resistance.


The Proteome and Lipidome of Thermococcus kodakarensis across the Stationary Phase.
The majority of cells in nature probably exist in a stationary-phase-like state, due to nutrient limitation in most environments. Studies on bacteria and yeast reveal morphological and physiological changes throughout the stationary phase, which lead to an increased ability to survive prolonged nutrient limitation. However, there is little information on archaeal stationary phase responses. We investigated protein- and lipid-level changes in Thermococcus kodakarensis with extended time in the stationary phase. Adaptations to time in stationary phase included increased proportion of membrane lipids with a tetraether backbone, synthesis of proteins that ensure translational fidelity, specific regulation of ABC transporters (upregulation of some, downregulation of others), and upregulation of proteins involved in coenzyme production. Given that the biological mechanism of tetraether synthesis is unknown, we also considered whether any of the protein-level changes in T. kodakarensis might shed light on the production of tetraether lipids across the same period. A putative carbon-nitrogen hydrolase, a TldE (a protease in Escherichia coli) homologue, and a membrane bound hydrogenase complex subunit were candidates for possible involvement in tetraether-related reactions, while upregulation of adenosylcobalamin synthesis proteins might lend support to a possible radical mechanism as a trigger for tetraether synthesis.


Regulation of mucosal responses by CD4+ T lymphocytes: effects of anti-L3T4 treatment on the gastrointestinal immune system.
The role of CD4+ T cells in the gastrointestinal (GI) immune system in vivo was studied in mice selectively depleted of this subset by treatment with monoclonal anti-L3T4 (GK1.5) mAb. Treatment of young BALB/c mice with weekly injections of anti-L3T4 mAb resulted in a selective depletion of CD4+ T cells in both IgA effector (lamina propria regions of the intestine; LP) and inductive (Peyer's patch; PP) sites. However, levels of CD3+CD4-CD8+ and CD4-CD8- (double negative) T cells remained constant or increased. When sections of small intestine were assessed for the isotype of Ig-containing cells, normal mice contained predominantly IgA plasma cells with small numbers of IgM and IgG plasma cells while anti-L3T4 treatment dramatically reduced the numbers of IgA plasma cells. When numbers of IgA-producing cells were assessed by the isotype-specific ELISPOT assay, the LPL of anti-L3T4 mAb-treated mice showed an 80% reduction in the number of IgA spot-forming cells. The effect of anti-L3T4 mAb treatment on IgA inductive sites was also studied and this treatment reduced the overall size of PP as well as the germinal centers in this tissue. Although anti-L3T4 treatment depleted CD3+CD4+ T cells in PP, the relative frequency of surface IgA-positive (slgA+) B cells in this tissue did not change. These results show that repeated injection of anti-L3T4 mAb results in a CD4+ T cell deficiency in both IgA inductive (PP) and effector (LP) sites. The depletion of CD4+ T cells resulted in reductions in the numbers of mature IgA plasma cells present in the LP of gut-associated tissues, and reduced the overall size of PP including germinal centers, but did not affect the frequency of sIgA+ B cells in this IgA inductive site.


Contrast and spatial resolution in MREIT using low amplitude current.
Magnetic resonance-electrical impedance tomography employs low amplitude currents injected or induced inside an object. The additional magnetic field due to these currents results in a phase in the MR images. In this study, a modified fast spin-echo sequence was used to measure this magnetic field, which is obtained by scaling the MR phase image. A finite element method with first order triangular elements was used for the solution of the forward problem. An iterated sensitivity matrix-based algorithm was developed for the inverse problem. The resulting ill-conditioned matrix equation was regularized using the Tikhonov method and solved using a conjugate gradient solver. The spatial and contrast resolution of the technique was tested using agarose gel phantoms. A circular phantom with 7 cm diameter and 1 cm thickness is used in the phantom experiments. The amplitude of the injected current was 1 mA. 3, 5 and 8 mm diameter insulators and high conductor objects are used for the spatial resolution study and an average full-width half-maximum value of 4.7 mm is achieved for the 3 mm insulator case. For the contrast analysis, the conductivity of a 15 mm object is varied between 44% and 500% with respect to the background and results are compared to the ideal reconstruction.


Fukuyama Cross-Coupling Approach to Isoprekinamycin: Discovery of the Highly Active and Bench-Stable Palladium Precatalyst POxAP.
An efficient and user-friendly palladium(II) precatalyst, POxAP (post-oxidative-addition precatalyst), was identified for use in Fukuyama cross-coupling reactions. Suitable for storage under air, the POxAP precatalyst allowed reaction between thioesters and organozinc reagents with turnover numbers of ∼90000. A series of 23 ketones were obtained with yields ranging from 53 to 99%. As proof of efficacy, an alternative approach was developed for the synthesis of a key precursor of the natural product isoprekinamycin.


Hiring a pediatric health care advocate for advisory and support services.
In this study, factors that influence a person's likelihood of hiring a pediatric health care advocate (HCA) for support and/or advisory services were examined. Participants were asked to read vignettes in which a child's symptom severity, probability of mortality, and age were manipulated. A significantly higher likelihood of hiring an HCA for advisory services than for support services was found. A significant interaction between level of mortality and type of service indicated that when mortality was depicted as high, participants reported a greater likelihood of hiring an HCA for support services than for advisory services.


Factors affecting the presentation of exogenous hepatitis B virus core antigen.
Hepatitis B virus core antigen (HBcAg) plays a critical role in terminating acute Hepatitis B virus infection and may be used as a potential vaccine candidate. The cell surface major histocompatibility complex (MHC) class 1 molecules are thought to be involved in the presentation of HBcAg. Surface MHC class 1 HLA A2 heavy chain (HC) and trimeric molecules were characterized on transfected Hela cells used as antigen presenting cells (APC) for the presentation of HBcAg. The results show that antibodies against HC HLA A2 and trimeric HLA-A2 molecules resulted in increased activation of HBcAg 18-27 minimal peptide specific cytotoxic T lymphocytes (CTLs), while the addition of exogenous beta2-microglobulin decreased the activation of HBcAg specific CTLs. Further, specific CD8+ T cells were activated only when Hela cells as APCs were primed with HBcAg (peptide, soluble or embedded on virosomes) at pH 6.5.


[Sustainability of an innovative school food program: a case study in the northeast of Brazil].
The Brazilian School Food Program (PNAE) is intersectoral innature. It encourages social participation and local economies and is considered here as a health promotionpractice. In the Northeastern State of Pernambuco, the city of Tabira acquired international renownin 2012 for the management of its school food program (PAE). This study analyzed the positive and negative factors related to the sustainability of the innovations in Tabira to understand the processes related to the continuity of the innovative actions implemented. The research used a qualitative approach with a case study strategy. A focus group, semi-structured interviews with key actors and document analysis were performed. The data were processed using content analysis and the techniques of thematic analysis. Positive organizational and socio-political factors were: the program institutionalization, the efficient use of financial resources, municipalized management, high community participation and the use of local resources. Negative factors were: weak inter-sectoral coordination and training and poor professional qualification. The strong political engagement at the local level showed both positive and negative impacts on sustainability.


A rare case of Ewing sarcoma metastasis to the oral cavity.
Ewing sarcoma in the head and neck is rare, and metastasis from other bones to the mandible accounts for 0.7% of cases. This report presents a case of oral metastasis in a 24-year-old male patient diagnosed with Ewing sarcoma of the femur (p53 gene mutation and EWSR1-ERG fusion). The chief complaint was numbness in the mandible and pain for 1 month and a hardened, ulcerated exophytic lesion in the right retromolar region. Imaging exams revealed an unspecified thinning of the cortical bone of the inferior alveolar canal in the right mandibular ramus, associated with erosion of the alveolar bone. Histopathological analysis confirmed metastasis of Ewing sarcoma. The patient presented an aggressive disease progression and died 1 month after the oral diagnosis. It is important to recognize the signs and symptoms compatible with rare clinical outcomes, leading to an early diagnosis that can improve patients' quality of life and survival.


Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing.
Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.


Multistimuli-Responsive Squaraine Dyad Exhibiting Concentration-Controlled Vapochromic Luminescence.
Stimuli-responsive organic materials with controllable luminescence are of enormous importance because of their potential applications in sensing, data security, and display devices. In this study, a multistimuli-responsive squaraine dyad (SQ-d) composed of two rigid squaraine moieties and a flexible ethylene linker was rationally designed and synthesized. SQ-d exhibits polymorphic luminescence, which can be reversibly switched by various external stimuli, including solvent vapor exposure, heat, and shear force. Unexpectedly, the weakly luminescent phase (O1) of SQ-d exhibits concentration-controlled vapochromic behavior. Film O1 can convert to a highly green-emissive phase (G1) under a low concentration of CHCl3 vapor and convert to a highly yellow-emissive phase (Y) under a high concentration of CHCl3 vapor; these originate from two distinct crystallization-induced emission enhancement processes. To the best of our knowledge, this is the first investigation of the effect of vapor concentration on the phase transitions of organic vapochromic luminophores. By analyzing the single-crystal structures and photophysical properties of SQ-d, we concluded that the green and yellow emissions probably originated from a zigzag stacking mode and an H-type π-π stacking mode, respectively. Finally, two prototypes based on SQ-d for applications in information encryption and vapor sensing were successfully demonstrated.


[Attaching importance to the health economic evaluation of minimally invasive glaucoma surgery].
Compared to traditional filtration surgery, minimally invasive glaucoma surgery (MIGS) offers several advantages, including smaller incisions, more effective intraocular pressure reduction, higher safety levels, fewer surgical complications, faster postoperative recovery, and reduced postoperative use of antiglaucoma drugs. MIGS has gained rapid popularity both domestically and internationally due to its easier operation, shorter learning curve, and reduced operation time. Considering the current clinical promotion of MIGS and the application of health economic evaluation in the glaucoma field, this article proposes the need for an emphasis on the health economic evaluation of MIGS. Conducting research in this area will provide valuable insights for related clinical diagnosis and treatment, medical pricing, and medical insurance payment, and help to further disseminate MIGS, so as to offer clinical benefits, which are aligned with national conditions and economic viability.


Effects of combined ferrous sulfate administration and exposure to static magnetic field on brain oxidative stress and emotional behavior.
The present study was done to investigate behavioral effects and oxidative stress in iron- treated and co-exposed static magnetic field (SMF)-iron rats. Anxiety in the elevated plus- maze test, and motor skills were also assessed in the stationary beam and suspended string tests. After behavioral tests, the rats were anesthetized and their brains were removed for biochemical analysis. The co-exposure to iron and SMF induced a significant difference in elevated plus-maze test in rats. The frequency of entries and time spent in the open arms was significantly reduced (p<0.05) in the iron- and SMF-exposed group compared with the group treated with iron alone and in the control group. However, no significant difference was noticed for the motor skill test between the three groups. The biochemical investigation showed that malondialdehyde level increased (p<0.001) and that glutathione level and catalase enzyme activity decreased (p<0.001) in brain of iron- and SMF-exposed group. The dose of iron alone used in present study, was unable to induce any effect. However, the 128 mT SMF in the presence of iron ions in the body can induce disruption in the emotional behavior and can produce oxidative stress in brain tissue of rats.


Poisson-Boltzmann versus Size-Modified Poisson-Boltzmann Electrostatics Applied to Lipid Bilayers.
Mean-field methods, such as the Poisson-Boltzmann equation (PBE), are often used to calculate the electrostatic properties of molecular systems. In the past two decades, an enhancement of the PBE, the size-modified Poisson-Boltzmann equation (SMPBE), has been reported. Here, the PBE and the SMPBE are reevaluated for realistic molecular systems, namely, lipid bilayers, under eight different sets of input parameters. The SMPBE appears to reproduce the molecular dynamics simulation results better than the PBE only under specific parameter sets, but in general, it performs no better than the Stern layer correction of the PBE. These results emphasize the need for careful discussions of the accuracy of mean-field calculations on realistic systems with respect to the choice of parameters and call for reconsideration of the cost-efficiency and the significance of the current SMPBE formulation.


Late Diagnosis of Maturity-Onset Diabetes of the Young (MODY) 12 With Catastrophic Consequences.
Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous group of diseases characterized by autosomal dominant monogenic non-ketogenic diabetes mellitus, usually with early-onset, with a prevalence of 1-5% of all diabetes cases. A 72-year-old female was admitted with intestinal occlusion, anorexia, vomiting, and weight loss for four months. Medical history of type 2 diabetes mellitus, chronic pancreatitis with abnormal pancreatic development, and acute obstructive jaundice due to a mass in the head of the pancreas with duodenum extension four months before. Assuming surgically unresectable pancreatic neoplasm, digestive bypass surgery was performed. The pathologic examination of surgical specimens was negative for neoplasm. Abdominal imaging showed the pancreatic mass, proximal bowel distension and ascites, which was negative for neoplastic cells. A percutaneous biopsy of the mass revealed adenocarcinoma. Palliative chemotherapy was started. Next-generation sequencing revealed the variant c.-8G>T in the 5' untranslated region (UTR) region of the adenosine triphosphate (ATP) binding cassette subfamily C member 8 (ABCC8) gene in heterozygosity, associated with the MODY 12 subtype. We report a possible case of MODY 12 diabetes with a phenotype not previously described: a non-neoplastic pancreatic mass that appears in a previously abnormally developed pancreas, with evolution to neoplasm along with the late development of diabetes mellitus. Although this ABCC8 gene mutation could be incidental, there could be a relationship between this mutation, pancreatic malformation, chronic pancreatitis and pancreatic neoplasm. Investigation of new phenotypes is critical, including the potential role of the ABCC8 gene in oncogenesis.


Aspects of the effect of metiamide on pentagastrin-stimulated and basal gastric secretion of acid and pepsin in man.
This study has examined the inhibition produced by metiamide on the gastric secretion of acid and pepsin in 13 patients with duodenal and three with gastric ulcer. The effect of metiamide on the response to a range of doses of pentagastrin in three normal individuals was determined, as was the interaction of metiamide and atropine on prolonged basal secretion. Metiamide inhibited the secretion of acid more than pepsin and the gastric secretion of patients with gastric ulcer more than duodenal ulcer. Metiamide inhibited both the maximal secretory response attainable with pentagastrin and decreased the sensitivity to pentagastrin. Atropine augmented and prolonged the action of metiamide.


Antigenic and genetic characterization of rabies viruses isolated from domestic and wild animals of Brazil identifies the hoary fox as a rabies reservoir.
Fifty Brazilian rabies viruses, collected from many different animal species and several regions of the country, were characterized by partial sequencing of the central, variable region of the P gene, a locus useful for sensitive molecular epidemiological studies. Phylogenetic analysis of the sequences, which included comparison with other rabies strains recovered from throughout the Americas, identified three main groups of Brazilian viruses, arbitrarily designated BRL-1 to BRL-3. BRL-1 was found in terrestrial carnivores and clusters with other American strains of the cosmopolitan lineage. BRL-2 comprised two distinct isolates, recovered from two species of non-haematophagous bats, that had evolutionary links to insectivorous-bat-derived strains of North America. BRL-3 consisted of isolates from vampire bats and from livestock species probably infected via contact with vampire bats. The terrestrial group was further subdivided into three subtypes: BRL-1a was associated exclusively with dogs and cats, while BRL-1b and BRL-1c were found exclusively in hoary foxes. These observations strongly support the role of the Brazilian hoary fox as a rabies reservoir. Screening of representative Brazilian rabies viruses against a collection of anti-rabies monoclonal antibodies (mAbs) identified a small panel of mAbs that could be used to discriminate between all Brazilian subgroups as defined by genetic classification in this study.


The Effect of Smoking on the Association between Long-Term Alcohol Consumption and Dyslipidemia in a Middle-Aged and Older Population.
The joint effects of chronic alcohol consumption and smoking on dyslipidemia remain unclear in a prospective design. This study examined the effect of smoking on the association between long-term alcohol consumption and risk of incident dyslipidemia. A total of 4467 participants (1866 men and 2601women) aged 40-69 years without dyslipidemia were recruited at baseline. Alcohol consumption was assessed biennially using a questionnaire and classified as light, moderate or heavy drinker. Smoking status was examined at baseline and categorized into non-smokers and current smokers. Dyslipidemia was defined as the presence of one or more of following: hypertriglyceridemia (triglyceride ≥200 mg/dL), hypercholesterolemia (total cholesterol ≥240 mg/dL), low high-density lipoprotein-cholesterol (HDL-C) < 40 mg/dL, or high low-density lipoprotein cholesterol ≥160 mg/dL. During a follow-up period of 12 years, 2872 (64.3%) participants developed dyslipidemia. In non-smoking men, light or moderate alcohol consumption was associated with a lower risk of incident dyslipidemia such as hypertriglyceridemia and hypercholesterolemia, whereas this association was not observed in current smoking men. Unlike non-smokers, the duration of alcohol drinking > 10 years was associated with a higher risk of hypertriglyceridemia in current smoking men (hazard ratio = 1.57, 95% confidence interval: 1.07-2.30, P = 0.020). In addition, alcohol consumption was inversely associated with low HDL-C regardless of smoking status. In women, alcohol consumption was inversely associated with dyslipidemia hypercholesterolemia and low HDL-C regardless of alcohol amount. Smoking crucially confounds the association between long-term alcohol consumption and dyslipidemia, particularly in hypertriglyceridemia and hypercholesterolemia.


Clinical Efficacy of Topical Tacrolimus on Conjunctival Hyperemia Caused by Prostaglandin Analogues.
To evaluate the clinical efficacy of tacrolimus ophthalmic solution on conjunctival hyperemia caused by prostaglandin analogues. A retrospective analysis was performed on 120 patients diagnosed with bilateral primary open-angle glaucoma (POAG). The enrolled patients developed symptoms of conjunctival hyperemia during the administration of travoprost ophthalmic solution. The patients were divided into two groups: 0.004% travoprost solution was administered in the control group. A combination of 0.004% travoprost solution with tacrolimus was administered in the experimental group. Clinopathological parameters including intraocular pressure (IOP), subjective dry eye symptom score (SDES), hyperemia score, and noninvasive tear break-up time (NIBUT) were recorded at week 0, 1, 2, and 4. Two-way ANOVA for repeated measurement was employed for statistical analysis using SPSS 22.0 software. At week 1, 2, and 4, the IOP and SDES of both the control and experimental groups were significantly lower when compared the values at week 0 (before treatment). No significant differences in the IOP values between the two groups were observed at all time points. At week 2, the SDES and hyperemia score were lower in the experimental group than those in the control group, and the NIBUT was significantly longer in the experimental group. The above parameters showed no significant difference at week 4 between the two groups, although the average SDES and hyperemia score were slightly lower in the experimental group. Tacrolimus ophthalmic solution can relieve conjunctival hyperemia, improve ocular surface conditions, and reduce discomfort caused by prostaglandin analogues.


Recent Advances in Self-Oscillating Polymer Material Systems.
In 1996, we first reported self-oscillating polymer gels exhibiting autonomous swelling-deswelling oscillations driven by the Belousov-Zhabotinsky reaction. In contrast to conventional stimuli-responsive gels, the self-oscillating gel can autonomously and periodically change its volume in a closed solution without any external stimuli. Since the first report, the novel concept of self-oscillating gels has been expanded into various polymer and gel systems. Herein, we summarize recent advances in self-oscillating polymers and gels.


Nasalance Scores as a Function of Skeletal Malocclusion of English-Speaking Adults in the North Indian Population.
The objective of this study is quantitative assessment of nasalance for skeletal Class I (normative values), Class II, and III malocclusion in the English language for the North Indian population and to compare the normative values with the nasalance scores obtained from individuals with skeletal Class II and III malocclusion and to evaluate the normative values as a function of gender. The study was conducted on a total sample of 200 patients with 100, 50, and 50 in group 1 (control group, Skeletal Class I), group 2 (Skeletal Class II), and group 3 (Skeletal Class III), respectively. ANB angle (anteroposterior angle formed by point A, nasion, and point B) measured on lateral cephalogram was used to categorize the patients into 3 groups. The normative nasalance scores were compared for males and females in the control group. The nasalance scores of skeletal Class II and III subjects were compared to the combined normative scores of the control group. The NasalView was used for the objective assessment of nasalance. Oral syllables (/pa/and/pi/), nasal syllables (/ma/and/mi/), and 3 passages (Zoo passage, Rainbow passage, and Nasal sentences) were used to determine the nasalance scores. The intragroup comparison of nasalance scores in group 1 showed statistically significant differences for different stimuli. The gender-related comparison showed no statistically significant differences in nasalance scores. The intergroup comparison of nasalance scores for skeletal malocclusion showed no statistically significant differences for different stimuli except statistically significant lower nasalance values for nasal sentences in group 3 compared to the control group. The study concluded that the nasalance scores for nasal sentences in skeletal Class III malocclusion were significantly lower than in the control group and were not statistically significant between the 3 groups for all other stimuli.


[Digital agnosia and lesions of the parietal lobe].
130 patients with focal brain damage have been submitted to non-verbal finger identification tasks. The results of this research can be summarized as follows: -when bilateral finger agnosia is studied with non-verbal tasks, no difference can be shown between right and left parietal lesions; -in left brain damaged patients the bilateral form of finger agnosia is generally due to large lesions involving the parietal lobe; -in right brain damaged patients the unilateral form of finger agnosia is almost always due to lesions centered on the parietal region.


Relationship between ferroptosis and mitophagy in cardiac ischemia reperfusion injury: a mini-review.
Cardiovascular diseases (CVD), with high morbidity and mortality, seriously affect people's life and social development. Clinically, reperfusion therapy is typically used to treat ischemic cardiomyopathy, such as severe coronary heart disease and acute myocardial infarction. However, reperfusion therapy can lead to myocardial ischemia reperfusion injury (MIRI), which can affect the prognosis of patients. Studying the mechanisms of MIRI can help us improve the treatment of MIRI. The pathological process of MIRI involves many mechanisms such as ferroptosis and mitophagy. Ferroptosis can exacerbate MIRI, and regulation of mitophagy can alleviate MIRI. Both ferroptosis and mitophagy are closely related to ROS, but there is no clear understanding of the relationship between ferroptosis and mitophagy. In this review, we analyzed the relationship between ferroptosis and mitophagy according to the role of mTOR, NLPR3 and HIF. In addition, simultaneous regulation of mitophagy and ferroptosis may be superior to single therapy for MIRI. We summarized potential drugs that can regulate mitophagy and/or ferroptosis, hoping to provide reference for the development of drugs and methods for MIRI treatment.


Manganese-Cobalt Oxido Cubanes Relevant to Manganese-Doped Water Oxidation Catalysts.
Incorporation of Mn into an established water oxidation catalyst based on a Co(III)4O4 cubane was achieved by a simple and efficient assembly of permanganate, cobalt(II) acetate, and pyridine to form the cubane oxo cluster MnCo3O4(OAc)5py3 (OAc = acetate, py = pyridine) (1-OAc) in good yield. This allows characterization of electronic and chemical properties for a manganese center in a cobalt oxide environment, and provides a molecular model for Mn-doped cobalt oxides. The electronic properties of the cubane are readily tuned by exchange of the OAc- ligand for Cl- (1-Cl), NO3- (1-NO3), and pyridine ([1-py]+). EPR spectroscopy, SQUID magnetometry, and DFT calculations thoroughly characterized the valence assignment of the cubane as [MnIVCoIII3]. These cubanes are redox-active, and calculations reveal that the Co ions behave as the reservoir for electrons, but their redox potentials are tuned by the choice of ligand at Mn. This MnCo3O4 cubane system represents a new class of easily prepared, versatile, and redox-active oxido clusters that should contribute to an understanding of mixed-metal, Mn-containing oxides.


Characterisation of proanthocyanidins from black soybeans: isolation and characterisation of proanthocyanidin oligomers from black soybean seed coats.
Proanthocyanidin oligomers (dimers to tetramers) were isolated from black soybean seed coats, using Sephadex LH-20 column chromatography and reversed-phase preparative HPLC. The isolated oligomers consisted of only (-)-epicatechin units, which were linked through either 4β→8 or 4β→6 (B-type) bonds. Procyanidin B2, procyanidin C1, and cinnamtannin A2 were identified as the main compounds of the proanthocyanidin dimers, trimers, and tetramers, respectively.


Partial replacement of chicken semen by turkey semen in artificial insemination of chickens.
Chicken semen undiluted, diluted with a diluent containing fructose and/or mixed with turkey semen was used to inseminate Leghorn hens. In two of three experiments there was an improvement in fertility from insemination by mixed semen as compared to semen diluted to the same extent with the diluent.


Differential Cognitive Functioning and Benefit From Surgery in Patients Undergoing Coronary Artery Bypass Grafting and Carotid Endarterectomy.
Stenosing atherosclerosis in both coronary and carotid arteries can adversely affect cognition. Also their surgical treatments, coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA), are associated with cognitive changes, but the mechanisms of cognitive decline or improvement may not be the same. This study was designed to compare the cognitive profile and outcome in patients undergoing surgical treatment for coronary or carotid disease. A total of 100 CABG patients and 44 CEA patients were recruited in two previously reported studies. They were subjected to a comprehensive neuropsychological examination prior to surgery and in the acute (3-8 days) and stable (3 months) phase after operation. A group of 17 matched healthy controls were assessed with similar intervals. We used linear mixed models to compare cognitive trajectories within six functional domains between the CABG, CEA and control groups. Postoperative cognitive dysfunction (POCD) and improvement (POCI) were determined with the reliable change index method in comparison with healthy controls. Before surgery, the CEA patients performed worse than CABG patients or healthy controls in the domains of executive functioning and processing speed. The CABG patients exhibited postoperative cognitive dysfunction more often than the CEA patients in most cognitive domains in the acute phase but had regained their performance in the stable phase. The CEA patients showed more marked postoperative improvement in executive functioning than the CABG group in the acute phase, but the difference did not reach significance in the stable phase. Our findings suggest that anterior cerebral dysfunction in CEA patients impairs preoperative cognition more severely than global brain dysfunction in CABG patients. However, CEA may have more beneficial effects on cognition than CABG, specifically in executive functions mainly operated by the prefrontal lobes. In addition, the results underline that POCD is a heterogeneous condition and dependent on type of revascularization surgery.


Glucagon-like peptide-1 gene therapy.
Glucagon-like peptide 1 (GLP-1) is a small peptide component of the prohormone, proglucagon, that is produced in the gut. Exendin-4, a GLP-1 receptor agonist originally isolated from the saliva of H. suspectum or Gila monster, is a peptide that shares sequence and functional homology with GLP-1. Both peptides have been demonstrated to stimulate insulin secretion, inhibit glucagon secretion, promote satiety and slow gastric emptying. As such, GLP-1 and Exendin-4 have become attractive pharmaceutical targets as an adjunctive therapy for individuals with type II diabetes mellitus, with several products currently available clinically. Herein we summarize the cell biology leading to GLP-1 production and secretion from intestinal L-cells and the endocrine functions of this peptide and Exendin-4 in humans. Additionally, gene therapeutic applications of GLP-1 and Exendin-4 are discussed with a focus on recent work using the salivary gland as a gene therapy target organ for the treatment of diabetes mellitus.


First encounters--deployment of defence-related natural products by plants.
Plant-derived natural products have important functions in ecological interactions. In some cases these compounds are deployed to sites of pathogen challenge by vesicle-mediated trafficking. Polar vesicle trafficking of natural products, proteins and other, as yet uncharacterized, cargo is emerging as a common theme in investigations of diverse disease resistance mechanisms in plants. Root-derived natural products can have marked effects on interactions between plants and soilborne organisms, for example by serving as signals for initiation of symbioses with rhizobia and mycorrhizal fungi. They may also contribute to competitiveness of invasive plant species by inhibiting the growth of neighbouring plants (allelopathy). Very little is known about the mechanisms of release of natural products from aerial plant parts or from roots, although there are likely to be commonalities in these processes. There is increasing evidence to indicate that pathogens and symbionts can manipulate plant endomembrane systems to suppress host defence responses and facilitate accommodation within plant cells. The relationship between secretory processes and plant interactions forms the focus of this review, which brings together different aspects of the deployment of defence-related natural products by plants.


Effect of isosmotic removal of extracellular Na+ on cell volume and membrane potential in muscle cells.
Isosmotic removal of extracellular Na+ (Nao) is a frequently performed manipulation. With the use of isolated voltage-clamped barnacle muscle cells, the effect of this manipulation on isosmotic cell volume was studied. Replacement of Nao by tris(hydroxymethyl)aminomethane produced membrane depolarization (approximately 20 mV) and cell volume loss (approximately 14%). The membrane depolarization was verapamil insensitive but depended on extracellular Ca2+ (Cao) and was probably due to activation of intracellular Ca2+ (Cai)-dependent nonselective cation channels. The cell volume loss did not require membrane depolarization but depended on Cao. This was probably due to an increase in Cai, mediated by activation of Ca2+ influx via Na+/Ca2+ exchange. Nao replacement by Li+ also promoted membrane depolarization (approximately 20 mV) and cell volume loss (20%). Both effects were reduced (approximately 73%) but were not abolished by Cao removal. Under this condition, the remaining membrane depolarization was probably due to a higher membrane permeability of Li+ over Na+. The remaining cell volume loss was due to membrane depolarization, which probably induced Ca2+ release from intracellular stores.


Establishment of human hair follicle mesenchymal stem cells with overexpressed human hepatocyte growth factor.
Chronic liver disease has become a major health problem that causes serious damage to human health. Since the existing treatment effect was not ideal, we need to seek new treatment methods. We utilized the gene recombination technology to obtain the human hair mesenchymal stem cells which overexpression of human hepatocyte growth factor (hHGF). Furthermore, we verified the property of transfected cells through detecting surface marker by flow cytometry. We show here establishment of the hHGF-overexpressing lentivirus vector, and successfully transfection to human hair follicle mesenchymal stem cells. The verified experiments could demonstrate the human hair follicle mesenchymal stem cells which have been transfected still have the properties of stem cells. We successfully constructed human hair follicle mesenchymal stem cells which overexpression hHGF, and maintain the same properties compared with pro-transfected cells.


Photocatalytic and Chemoselective Transfer Hydrogenation of Diarylimines in Batch and Continuous Flow.
A visible-light photocalytic method for the chemoselective transfer hydrogenation of imines in batch and continuous flow is described. The reaction utilizes Et3N as both hydrogen source and single-electron donor, enabling the selective reduction of imines derived from diarylketimines containing other reducible functional groups including nitriles, halides, esters, and ketones. The dual role of Et3N was confirmed by fluorescence quenching measurements, transient absorption spectroscopy, and deuterium-labeling studies. Continuous-flow processing facilitates straightforward scale-up of the reaction.


Acute Respiratory Distress Syndrome and Posterior Reversible Encephalopathy Syndrome following Rituximab Therapy.
The anti-CD20 monoclonal antibody rituximab is associated with rare but significant adverse events, notably posterior reversible encephalopathy syndrome (PRES) and acute respiratory distress syndrome (ARDS). We report a case of concomitant ARDS and PRES developing after rituximab therapy for treatment of cryoglobulinaemic vasculitis. There are 7 reported cases of PRES complicating rituximab use. PRES onset varied from immediate to 21 days after administration. All patients recovered completely, and rituximab was reintroduced in half of the cases. The occurrence of ARDS in association with rituximab is rarer. Only 3 confirmed cases exist, and ARDS may occur as a delayed reaction.


Treatment for calcium channel blocker poisoning: a systematic review.
Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.


Direct observation of the effective bending moduli of a fluid membrane: free-energy cost due to the reference-plane deformations.
Effective bending moduli of a fluid membrane are investigated by means of the transfer-matrix method developed in our preceding paper. This method allows us to survey various statistical measures for the partition sum. The role of the statistical measures is arousing much attention, since Pinnow and Helfrich claimed that under a suitable statistical measure, that is, the local mean curvature, the fluid membranes are stiffened, rather than softened, by thermal undulations. In this paper, we propose an efficient method to observe the effective bending moduli directly: We subjected a fluid membrane to a curved reference plane, and from the free-energy cost due to the reference-plane deformations, we read off the effective bending moduli. Accepting the mean-curvature measure, we found that the effective bending rigidity gains even in the case of very flexible membrane (small bare rigidity); it has been rather controversial that for such a nonperturbative regime, the analytical prediction does apply. We also incorporate the Gaussian-curvature modulus and calculated its effective rigidity. Thereby, we found that the effective Gaussian-curvature modulus stays almost scale invariant. All these features are contrasted with the results under the normal-displacement measure.


Developing NaviCanPlan: A Mobile Web Resource Locator for Cancer Providers and Survivors.
As of January, 2012, an estimated 13.7 million persons are living as cancer survivors. This population is expected to grow to nearly 18 million by 2022. While their treatment may be considered successful, many cancer survivors experience long-term physical, emotional, and psychosocial late effects of treatment. Our focus was on community-based cancer care-both rural and urban-as almost 90% of cancer care occurs in community settings, where a full complement of supportive healthcare professionals may not be available. This study describes the results of stakeholder engagement and the feedback processes used to create NaviCanPlan, a mobile web resource locator designed to educate and inform both providers and survivors in finding health-related services, often in noncancer center settings. Individual interviews with survivors and providers regarding resource needs to address a variety of physical and psychosocial late effects were supplemented with site visits, web-based polling, and webinars discussions. Overall, the results indicated a need for a programmatic approach to providing education about community, medical, and nonmedical resources for providers and survivors. Design and content criteria for a web-based mobile resource locator were defined, articulated, and implemented.


Aqueous phase behavior of polyelectrolytes with amphiphilic counterions modulated by cyclodextrin: the role of polyion flexibility.
Polyelectrolytes with amphiphilic counterions, PEACs, are water insoluble because the amphiphiles self-assemble into highly charged micelles that strongly associate with the equally highly charged polyions. However, in the presence of water soluble cyclodextrins (CDs) that form inclusion complexes with the amphiphiles and prevent micellization, PEACs become soluble as the dispersed amphiphiles behave essentially as simple monovalent counterions. In this paper, we illustrate, by example, how strongly the ternary phase behavior of PEAC:CD:water depends on the polyion flexibility; for a highly flexible polyion (polyacrylate) the amphiphilic aggregates dictate the phase behavior, whereas a much stiffer polyion (DNA) itself dictates liquid crystalline ordering.