Emerging issues on selection criteria of levodopa carbidopa infusion therapy: considerations on outcome of 28 consecutive patients.
Many studies confirmed the efficacy and safety of continuous infusion of intrajejunal levodopa/carbidopa gel (CIILG) for advanced Parkinson's disease (PD). Although this treatment is widely used, definite inclusion/exclusion criteria do not exist. In this prospective open-label study, we evaluated the long-term outcome in 28 consecutive patients and sought to detect any predictive factor to identify the best candidates for CIILG therapy. The assessment was carried out routinely at baseline, after 6 months and every year with UPDRS III-IV, FOG Questionnaire, non-motor symptoms scale, PD questionnaire (PDQ-8), cognitive and psychiatric status evaluation (MMSE, FAB, NPI) and caregiver's quality of life. 17/28 patients reached the 24-month follow-up. A statistically significant beneficial effect was shown on motor complications in short- and long-term follow-up, also on axial symptoms like gait disturbances. A concomitant improvement in PDQ8 score was observed, with a parallel mild amelioration, but not significant, on Caregivers QoL. When classified according to their outcome on QoL, the only predictive positive factor was less severe at Neuropsychiatric Inventory (NPI) score at baseline. Considering the improvement in motor scores (duration of "off" period), the more advanced age was associated with a poorer outcome. Our results confirmed a sustained efficacy and safety in long-term follow-up and suggest that younger age at operation and absence or mild presence of psychiatric/behavioural symptoms could be considered valid predicting factors in selecting the best candidates for this efficacious therapy.


[Prescriptions, access, and expenses on drugs among users of health services in Mexico].
To analyze the medical prescription, drug access and drug expenditure by patients based on the National Health Survey in Mexico, 1994. A descriptive analysis of drug access and expenditure was undertaken and predictive factors for medical prescription were identified by logistic regression for 3,324 patients. 78% of the patients received drug prescriptions. 92% of the Social Security patients and 35% of the Ministry of Health patients received drugs free of charge (p = 0.000). The region with the highest poverty index received the least amount of drugs free of charge. Regarding drug expenditure of patients who purchased drugs, median expenditure was 40.00 pesos (12.50 USD). Private health service patients spent significantly more than public health service patients. Drug access and drug expenditure are linked to socioeconomic factors and to the institutions attended by patients. The Mexican health system faces, among others, the challenge of increasing the equity of access to medical drugs.


The laser guidewire experience: 'crossing the Rubicon'.
Despite continued improvements in mechanical hardware for coronary angioplasty, chronic total occlusions (CTO) remain a true challenge in the field of interventional cardiology. Therefore, new guidewire technology, which made use of the unique forward debulking properties of excimer laser light, was designed and introduced into clinical practice in 1993. After an initial pilot-study phase, a European Multicenter Surveillance Study was initiated to evaluate the performance of the new laser guidewire. A short overview is given of the incidence of CTO. The limitations of the percutaneous treatment with various mechanical guidewires and the clinical and angiographic follow-up of CTO are discussed. Furthermore, the initial experience with the laser guidewire during the pilot-phase and preliminary results of the European Multicenter Surveillance Study are presented. At the introduction of yet another new (and costly) device, the key question is: 'Yes, but does it allow us to expand the battle field of interventional cardiology?'


Suppressed levels of growth hormone and insulin-like growth factor-1 during successful pregnancy in persistent acromegaly.
Pregnancy is a rather rare event in acromegaly because fertility is often reduced during active disease. Previous reports of pregnancy in acromegalic patients showed that the pituitary growth hormone (GH) level was unaffected and the insulin-like growth factor (IGF)-1 level was elevated during the second and third trimesters. We describe here a case of persistent acromegaly that showed suppressed levels of GH and IGF-1 during pregnancy. The suppression of GH secretion and IGF-1 may be due to increased estrogen or other factors circulating in mid- to late pregnancy.


Comparative epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia and South Korea.
MERS-CoV infection emerged in the Kingdom of Saudi Arabia (KSA) in 2012 and has spread to 26 countries. However, 80% of all cases have occurred in KSA. The largest outbreak outside KSA occurred in South Korea (SK) in 2015. In this report, we describe an epidemiological comparison of the two outbreaks. Data from 1299 cases in KSA (2012-2015) and 186 cases in SK (2015) were collected from publicly available resources, including FluTrackers, the World Health Organization (WHO) outbreak news and the Saudi MOH (MOH). Descriptive analysis, t-tests, Chi-square tests and binary logistic regression were conducted to compare demographic and other characteristics (comorbidity, contact history) of cases by nationality. Epidemic curves of the outbreaks were generated. The mean age of cases was 51 years in KSA and 54 years in SK. Older males (⩾70 years) were more likely to be infected or to die from MERS-CoV infection, and males exhibited increased rates of comorbidity in both countries. The epidemic pattern in KSA was more complex, with animal-to-human, human-to-human, nosocomial and unknown exposure, whereas the outbreak in SK was more clearly nosocomial. Of the 1186 MERS cases in KSA with reported risk factors, 158 (13.3%) cases were hospital associated compared with 175 (94.1%) in SK, and an increased proportion of cases with unknown exposure risk was found in KSA (710, 59.9%). In a globally connected world, travel is a risk factor for emerging infections, and health systems in all countries should implement better triage systems for potential imported cases of MERS-CoV to prevent large epidemics.


A test of the survival processing advantage in implicit and explicit memory tests.
The present study was designed to investigate the survival processing effect (Nairne, Thompson, & Pandeirada, Journal of Experimental Psychology: Learning, Memory, and Cognition, 33, 263-273, 2007) in cued implicit and explicit memory tests. The survival effect has been well established in explicit free recall and recognition tests, but has not been evident in implicit memory tests or in cued explicit tests. In Experiment 1 of the present study, we tested implicit and explicit memory for words studied in survival, moving, or pleasantness contexts in stem completion tests. In Experiment 2, we further tested these effects in implicit and explicit category production tests. Across the two experiments, with four separate memory tasks that included a total of 525 subjects, no survival processing advantage was found, replicating the results from implicit tests reported by Tse and Altarriba (Memory & Cognition, 38, 1110-1121, 2010). Thus, although the survival effect appears to be quite robust in free recall and recognition tests, it has not been replicated in cued implicit and explicit memory tests. The similar results found for the implicit and explicit tests in the present study do not support encoding elaboration explanations of the survival processing effect.


Does training improve compliance with hand hygiene and decrease infections in the neonatal intensive care unit? A prospective study.
The most important tool in any infection control program is good hand hygiene. Despite recognizing that hand hygiene is crucial in reducing infection rates, hand hygiene compliance remains suboptimal. This study was designed to determine hand hygiene compliance, before and after an educational intervention and its impact on hospital infection rates. The study was done in neonatal intensive care unit of an educational hospital. All healthcare providers working in the unit at the time of study were trained on importance of hand hygiene and methods of hand hygiene observation; after that hand washing compliance controlled by a physician during postintervention phase. Hand hygiene compliance, healthcare associated infection and mortality rates compared before and after educational intervention. Compliance of health-care workers for all hand hygiene opportunities combined was 30% before intervention and improved to 70% in postintervention. In postintervention phase, healthcare associated infection rates and mortality rates decreased significantly as the hand hygiene compliance improved. Good control of hand hygiene compliance by physician after an educational program may have good effect in healthcare associated infections control in neonatal intensive care unit.


Factor structure of PTSD in a community sample of sexual assault survivors.
Recent factor analytic research on posttraumatic stress disorder (PTSD) has questioned the 3-factor structure of the diagnosis as codified in the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV), proposing that a 4-factor model may more accurately reflect the phenomenology of the disorder. Confirmatory factor analyses of the Posttraumatic Stress Diagnostic Scale (E. B. Foa, 1995) were used to conduct model tests of the structure of PTSD in a large sample (N = 967) of adult female sexual assault survivors. A model specifying 4 correlated factors of reexperiencing, effortful avoidance, dysphoria, and hyperarousal provided the best fit to the data, although no model fits were excellent (including that of the traditional DSM-IV 3-factor model). Tests of measurement invariance across race and education suggest that differences may exist in the underlying factor structure of PTSD.


A new modified limited incision for superficial parotidectomy compared to modified Blair's incision.
Many incisions have been used to perform parotidectomy, but they result in a visible scar on the neck and may cause patient dissatisfaction by producing disfigurement sometimes. The aim of this study is to use a modified limited incision for superficial parotidectomy as an alternative to the classical incision, with no obvious scarring and without affecting the identification of the facial nerve, resulting in better cosmesis. A prospective comparative study on 100 patients has undergone superficial parotidectomy using a modified limited incision and another 100 patients who have undergone superficial parotidectomy using the modified Blair's incision (control group) for variant benign pathologies. The surgeries were conducted in four hospitals (three private and one public) in Baghdad, Iraq, from January 2016 to September 2022. In both groups, the patients were followed up through outpatient visits to assess the cosmetic result of the incision and detect postoperative complications. All tumors were removed with no need for extending the skin incision. The cosmetic result of the incision was very satisfactory and only a nominal scar could be seen 6 months after surgery. Five percent of patients only developed postoperative complications. A modified limited incision for superficial parotidectomy provides better patient satisfaction compared to a modified Blair's incision. The modified limited incision can be performed safely with a better cosmetic appearance of the surgical scar compared to the standard incision.


[Multi-factorial analysis on the flap thickness influenced by laser operation in situ keratomileusis].
To investigate the various factors that influencing the flap thickness after laser operation in situ keratomileusis (LASIK). 369 LASIK eyes (192 cases; among them, 15 patients for surgery monocular) with M2 130 microkeratome heads, grouped by left or right eye were analyzed by Chi-square test and logistic regression analysis based on age, sex, occupation, family history of myopia and ophthalmologic examination results before and after LASIK. The result of analysis of one-way variance which P < 0.05 as the variance to described with logistic regression analysis. Results from logistic regression analysis showed that the flap thickness after LASIK of right eye group was related to two factors: the preoperative refractive power (P = 0.017, OR = 0.832,95% CI: 0.715-0.968), and the corneal thickness (P = 0.000, OR = 1.023, 95% CI: 1.011-1.036) while left eye group was related to three factors: the preoperative astigmatism power (P = 0.044, OR = 2.094, 95% CI: 1.021-4.294), negative pressure suction time (P = 0.019, OR = 1.418, 95% CI: 1.059-1.898) and the corneal thickness (P = 0.000, OR = 1.049, 95% CI: 1.025-1.073). Corneal thickness, the preoperative astigmatism power and the negative pressure suction time tended to make the flap thicker while the preoperative refractive power tended to make the flap thinner. Results showed that the flap thickness performed at the first time was more obvious than at the second time.


Small brains predisposed Late Quaternary mammals to extinction.
The Late Quaternary witnessed a dramatic wave of large mammal extinctions, that are usually attributed to either human hunting or climatic change. We hypothesized that the large mammals that survived the extinctions might have been endowed with larger brain sizes than their relatives, which could have conferred enhanced behavioral plasticity and the ability to cope with the rapidly changing Late Quaternary environmental conditions. We assembled data on brain sizes of 291 extant mammal species plus 50 more that went extinct during the Late Quaternary. Using logistic, and mixed effect models, and controlling for phylogeny and body mass, we found that large brains were associated with higher probability to survive the Late Quaternary extinctions, and that extant species have brains that are, on average, 53% larger when accounting for order as a random effect, and 83% when fitting a single regression line. Moreover, we found that models that used brain size in addition to body size predicted extinction status better than models that used only body size. We propose that possessing a large brain was an important, yet so far neglected characteristic of surviving megafauna species.


A novel robot visual homing method based on SIFT features.
Warping is an effective visual homing method for robot local navigation. However, the performance of the warping method can be greatly influenced by the changes of the environment in a real scene, thus resulting in lower accuracy. In order to solve the above problem and to get higher homing precision, a novel robot visual homing algorithm is proposed by combining SIFT (scale-invariant feature transform) features with the warping method. The algorithm is novel in using SIFT features as landmarks instead of the pixels in the horizon region of the panoramic image. In addition, to further improve the matching accuracy of landmarks in the homing algorithm, a novel mismatching elimination algorithm, based on the distribution characteristics of landmarks in the catadioptric panoramic image, is proposed. Experiments on image databases and on a real scene confirm the effectiveness of the proposed method.


Foam separation of microbial cells.
Batch foam separation has been employed to separate Saccharomyces carlsbergensis cells from their broth without the use of any external surface-active agent. A model has been developed to predict the foamate cell concentration as well as the variation of cell concentration in the bulk liquid in the foam column as a function of time. The model assumes a linear equilibrium relation between the cell concentrations at the interface and the bulk. The foam has interface as well as interstitial liquid. The interface is assumed to be in equilibrium with the interstitial liquid, which in turn is assumed to have the same concentration as the bulk. The interfacial area is calculated by assuming the foam bubbles to be pentagonal dodecahedral in shape. The model has been found to explain the results of foam separation of cells quite well, particularly with respect to the effect of bubble size and aeration rate.


Near-ultraviolet evanescent-wave absorption sensor based on a multimode optical fiber.
Fiber-optic near-ultraviolet evanescent-wave sensors have been constructed, and their feasibility for practical applications has been demonstrated. The sensors, used for the detection of ozone near the 254-nm peak of the Hartley absorption band, were fabricated from coiled segments of low-cost multimode plastic-clad silica optical fibers. The sensing sections were produced alternatively by stripping only the protective jacket from the fiber to expose the gas-permeable silicone cladding or by stripping the jacket and the cladding to expose the bare-silica fiber core. Response characteristics are given, including sensitivity to ozone, reversibility, and aging effects. The useful lifetime was unacceptably short for the sensor that employed the bare-silica core, whereas the exposed-cladding sensor demonstrated good stability over the entire two-month period of investigation. The latter, more useful sensor demonstrated a linear response to ozone over the range 0.02-0.35 vol% and a reversible response with a time constant on the order of 1 min. Differences in ozone absorption spectra obtained in the transmission and evanescent-wave modes are discussed. Projected applications of the new exposed-cladding sensor include ozone determination in water-treatment processes and ozone production plants.


Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies.
Many neurodegenerative diseases, such as Huntington's disease, are hallmarked by the formation of intracellular inclusion bodies (IBs) that are decorated with ubiquitin, proteasomes and chaperones. The apparent enrichment of ubiquitin and components involved in protein quality control at IBs suggests local ubiquitin-dependent enzymatic activity. In this study, we examine recruitment of ubiquitin to IBs of polyglutamine-expanded huntingtin fragments (mHtt) by using synthesized TAMRA-labeled ubiquitin moieties. We show that intracellular TAMRA-ubiquitin is dynamic at mHtt IBs and is incorporated into poly-ubiquitin chains of intracellular substrates, such as mHtt, in a conjugation-dependent manner. Furthermore, we report that mHtt IBs recruit catalytically active enzymes involved in (de)-ubiquitination processes based on novel activity-based probes. However, we also find that the overexpression of the GFP-ubiquitin reporter, unlike the endogenous ubiquitin and TAMRA-ubiquitin, becomes irreversibly sequestered as a ring-like structure around the mHtt IBs, suggesting a methodical disadvantage of GFP-tagged ubiquitin. Our data provide supportive evidence for dynamic recruitment of ubiquitin and ubiquitin (de)-conjugating activity at mHtt initiated IBs.


A randomized prospective study of music therapy for reducing anxiety during cast room procedures.
Cast room procedures, such as cast application and removal, pin removal, and suture removal can cause significant anxiety in young children. The use of music therapy in the cast room to decrease anxiety has not been previously reported. We performed a randomized, prospective study of soft lullaby music compared with no music in 69 children 10 years or younger undergoing cast room procedures. Heart rates (beats per minute) were recorded in the waiting room and cast room using a pulse oximeter. A total of 28 children were randomized to music and 41 children to no music. The mean rise in heart rate between the waiting room and entering the cast room was -2.7 beats/min in the music group and 4.7 beats/min in the no music group (P = 0.001). The mean difference in heart rate between the waiting room and during the procedure was 15.3 beats/min in the music group and 22.5 beats/min in the no music group (P = 0.05). There were 7 patients in the no music group with heart rate increases of greater than 40 beats/min. No patient in the music group had an increase of this magnitude. Playing soft music in the cast room is a simple and inexpensive option for decreasing anxiety in young children during cast room procedures. Randomized Clinical Trial, Level II.


New approaches for determining apoptotic volume decrease in cells.
The loss of cell volume or cell shrinkage, termed apoptotic volume decrease (AVD), is a classical characteristic of apoptosis. Microscopy, Coulter electronic sizing, and/or flow cytometry has traditionally been the means to measure this characteristic of apoptosis. Although electronic cell sizing allows for precise determination of changes in cell size, these measurements provide data on the entire population of apoptotic cells. In contrast, flow cytometry examines and separates unique populations of apoptotic cells based on the light-scattering properties of the cells to determine alterations in cellular dimensions. However, this technique does not provide exact measurements of cell size and volume. The Cell Lab Quanta SC flow cytometer combines the power of electronic sizing with the ability to isolate and examine unique populations of apoptotic cells to determine exact changes in cell size as they undergo cell death. This chapter describes several methods for using the Cell Lab Quanta SC to study AVD during apoptosis.


Real-world experience of secukinumab in moderate to severe psoriasis patients in Thailand: Characteristics, effectiveness, and safety.
Secukinumab demonstrated high efficacy and favorable safety profile in patients with moderate-to-severe plaque psoriasis (PsO) in clinical trials. However, understanding of patient characteristics and clinical outcomes in real world in Thailand is still limited. To describe patient characteristics, effectiveness and safety of secukinumab in Thai PsO patients. This retrospective study analyzed data from medical records of adult PsO patients who initiated secukinumab at 7 dermatology centers from September 2017 to April 2021. Study outcomes included patient characteristics and changes in Psoriasis Area and Severity Index (PASI) score from baseline at weeks 4 and 16 after secukinumab initiation. Adverse events were recorded. Subgroup analyses by adherence rate and completeness of loading dose were performed. Of 163 patients, the mean (SD) age was 44.0 (14.0) years. Most patients (84.7%) were previously treated with topical therapy while 62.0% and 21.5% of patients had received systemic and biologic therapy, respectively. The mean baseline PASI score was 15.4 (9.3). Overall, the mean PASI score improved by 58.0% at week 4 and 78.4% at week 16. Statistically significant differences in PASI approvement were revealed among subgroups of patients with different loading dose and adherence rate. Adverse effects were reported in 8.0% of patients. The characteristics of patients in this study were slightly different from clinical trials in terms of demographic and clinical characteristics, as well as PsO treatment. Secukinumab was effective and safe in Thai patients with PsO, especially among those with complete loading dose and a higher adherence rate.


A 1 kA-class cryogen-free critical current characterization system for superconducting coated conductors.
A cryogenic electrical transport measurement system is described that is particularly designed to meet the requirements for routine and effective characterization of commercial second generation high-temperature superconducting (HTS) wires in the form of coated conductors based on YBa2Cu3O7. Specific design parameters include a base temperature of 20 K, an applied magnetic field capability of 8 T (provided by a HTS split-coil magnet), and a measurement current capacity approaching 1 kA. The system accommodates samples up to 12 mm in width (the widest conductor size presently commercially available) and 40 mm long, although this is not a limiting size. The sample is able to be rotated freely with respect to the magnetic field direction about an axis parallel to the current flow, producing field angle variations in the standard maximum Lorentz force configuration. The system is completely free of liquid cryogens for both sample cooling and magnet cool-down and operation. Software enables the system to conduct a full characterization of the temperature, magnetic field, and field angle dependence of the critical current of a sample without any user interaction. The system has successfully been used to measure a wide range of experimental and commercially-available superconducting wire samples sourced from different manufacturers across the full range of operating conditions. The system encapsulates significant advances in HTS magnet design and efficient cryogen-free cooling technologies together with the capability for routine and automated high-current electrical transport measurements at cryogenic temperatures. It will be of interest to both research scientists investigating superconductor behavior and commercial wire manufacturers seeking to accurately characterize the performance of their product under all desired operating conditions.


Teratogenicity of cytochalasin D in the mouse.
Cytochalasin D, a mold metabolite identified in food, was injected intraperitoneally in doses of 0.4 to 0.9 mg per kilogram on gestational days 7 through 11 and produced evidence of teratogenicity in two out of three strains of mice. Exencephaly, hypognathia and axial skeletal defects were found in strains C57BL/6J and BALB/c while no increase in defects was observed in the Swiss Webster strain. In all three strains, a significantly increased resorption rate was found. Oral doses of approximately 7.0 mg per kg on days 7 through 11 in the BALB/c produced exencephaly in the offspring. Autoclaved cytochalasin D retained its teratogenic potential.


Biosurfactants production potential of native strains of Bacillus cereus and their antimicrobial, cytotoxic and antioxidant activities.
Present study was designed to evaluate the biosurfactant production potential by native strains of Bacillus cereus as well as determine their antimicrobial and antioxidant activities. The strains isolated from garden soil were characterized as B. cereus MMIC 1, MMIC 2 and MMIC 3. Biosurfactants were extracted as grey white precipitates. Optimum conditions for biosurfactant production were 37°C, the 7th day of incubation, 0.5% NaCl, pH 7.0. Moreover, corn steep liquor was the best carbon source. Biuret test, Thin Layer Chromatography (TLC), agar double diffusion and Fourier Transform Infrared Spectroscopy (FTIR) characterized the biosurfactants as cationic lipopeptides. Biosurfactants exhibited significant antibacterial and antifungal activity against S. aureus, E. coli, P. aeruginosa, K. pneumoniae, A. niger and C. albicans at 30 mg/ml. Moreover, they also possessed antiviral activity against NDV at 10 mg/ml. Cytotoxicity assay in BHK-21 cell lines revealed 63% cell survival at 10 mg/ml of biosurfactants and thus considered as safe. They also showed very good antioxidant activity by ferric-reducing activity and DPPH scavenging activity at 2 mg/ml. Consequently, the study offers an insight for the exploration of new bioactive molecules from the soil. It was concluded that lipopeptide biosurfactants produced from native strains of B. cereus may be recommended as safe antimicrobial, emulsifier and antioxidant agent.


Effects of parathyroidectomy on renal allograft survival.
Hyperparathyroidism is a common problem secondary to renal insufficiency and is often not entirely resolved after renal transplantation (TX). In this retrospective analysis, the effects of parathyroidectomy (PTX) on allograft function were evaluated and the risk factors involved in allograft deterioration in patients after PTX will be discussed. The rise in creatinine was steeper 1 year after PTX compared to 2 years before PTX in the majority (13 of 22) of patients. Compared to a cohort without PTX, graft survival was significantly decreased by 60% in 6 years (p < 0.0001). After multivariate adjustment, risk factors attributed to graft function included baseline creatinine (p = 0.02), baseline systolic blood pressure (p = 0.04) and time between TX and PTX, but not PTX itself. The peri-PTX drop in serum calcium was significantly more accentuated in patients exhibiting a worsening of graft function after PTX (p = 0.04). In patients requiring PTX, graft function is in danger of worsening. Since many factors contribute to this negative correlation and no association with parathyroid hormone (PTH) levels before PTX has been observed, we do not recommend prophylactic PTX on the basis of PTH levels only. However, appropriate management of peri-PTX risk factors is highly important. If the clinical situation, e.g. progressive renal osteodystrophy, requires removal of parathyroid glands, the procedure should be performed, if possible, in the presence of stable graft function.


Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors.
The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR-625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFß1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers.


Carbon monoxide-reacting pigment from Desulfotomaculum nigrificans and its possible relevance to sulfite reduction.
The separation of an autoxidizable brown pigment, P582, from Desulfotomaculum nigrificans is described. It reacted with Na(2)S(2)O(4) and was characterized by absorption maxima in the oxidized state at 392, 582, and 700 nm. In the presence of Na(2)S(2)O(4), P582 formed complexes with CO and, under alkaline conditions, pyridine. There was no reaction with cyanide. The molecular weight of P582 was approximately 145,000, and the purest preparations contained Fe, Zn, and acid-labile sulfide but not Cu, Mo, or Mn. Preparations of P582 catalyzed the reduced methyl viologen (MVH)-linked reduction of sulfite, hydroxylamine, and nitrite but not of sulfate, thiosulfate, or nitrate. Reduced pyridine nucleotides did not substitute for MVH. A major product of the MVH-sulfite reaction was sulfide. CO partially inhibited the enzymatic activities. Sulfite, hydroxylamine, and nitrite and CO caused changes in the spectrum of Na(2)S(2)O(4)-reduced P582. Fe(2+)-chelating reagents reacted with part of the Fe of P582 and caused partial losses of labile sulfide and enzymatic activity. The spectral and CO-reacting properties of P582 were, however, unaffected by chelating agents. The reaction between P582 and chelating agents was stimulated by reducing agents.


Defense mechanisms against cadmium toxicity. III. Effects of pretreatment with a small oral dose of cadmium on metallothionein synthesis after a large oral dose of cadmium in mice.
Pretreatment of female mice with a small oral dose of Cd2+ (15 mg Cd2+/kg) decreased Cd2+ uptake by the liver and kidney and increased that by the small intestinal mucosa at 4 or 24 hr after challenge with a large oral dose of Cd2+ (100 mg Cd2+/kg). By 4 hr after the challenge dose, more Cd2+ taken up by the liver was bound to metallothionein (MT) in the Cd2+-pretreated mice than the water-pretreated controls (10 ml H2O/kg); but at 24 hr, the amount of Cd2+ bound to MT in the liver and kidney were lower in the former than the latter. The amount of Cd2+ not bound to MT in the liver at 4 and 24 hr after the challenge dose and that in the kidney at 24 hr were lower in the Cd2+-pretreated mice than the water-pretreated controls. These results suggested that the factor directly related to the toxic action of Cd2+ was the amount of Cd2+ not associated with MT in the liver and other organs. More Cd2+ taken up by the small intestinal mucosa at 24 hr after the challenge dose was associated with MT in the Cd2+-pretreated mice than the water-pretreated controls. The present study indicates that MT induced in the small intestinal mucosa by pretreatment prevents Cd2+ absorption by sequestering subsequently administered Cd2+, and Cd2+ taken up by the liver and kidney is bound to MT in an inert form, thus the decrease in the amount of Cd2+ not bound to MT, giving protection from the acute oral toxicity of the cation. Pretreatment 24 hr prior to the challenge dose was found to be the most effective.


Double atrial septum with interatrial chamber formation and recurrent paradoxical embolism.
Paradoxical embolism is a common cause of cryptogenic stroke. Cardiogenic origin is often the real culprit of unexplained stroke. We report a rare case of double atrial septum with an interatrial chamber and stenosis of the inferior vena cava orifice, which lead to recurrent paradoxical embolism, and then highlight the clinical importance of this rare type of congenital heart disease.


Dissociation of the IPSP and response to GABA during spreading depression-like depolarizations in hippocampal slices.
We have compared the sensitivity of CA1 and CA3 hippocampal pyramidal cells, in mature and immature tissue, to spreading depression-like depolarization episodes. Using hippocampal slices from rabbit, we have found that mature and immature tissue, and CA1 and CA3 neurons, were differentially prone to depolarization episodes, depending on the method used to produce the depolarization. CA1 region was generally more sensitive than CA3. Spontaneous and stimulus-evoked depolarizations were seen more frequently in immature tissue than in mature slices, but anoxia-induced depolarizations were much more likely to occur in mature tissue. Synaptic transmission and responses to somatic gamma-aminobutyric acid (GABA) ejection were compared during anoxia-induced depolarizations in mature slices. The early component of the inhibitory postsynaptic potential (IPSP) normally had the same reversal potential as the GABA response. During anoxia-induced depolarization, both the drug response and the PSPs were lost. Synaptic transmission generally disappeared before the response to exogenous GABA application; the GABA response reappeared before synaptic function was restored. During the recovery of resting potential (RMP) following depolarization, the reversal potential of the early IPSP differed significantly from that of the GABA response; when the cell had recovered to RMP, the IPSP was depolarizing, whereas GABA application produced a 'normal' cell hyperpolarization. IPSPs and GABA-mediated responses attained their pre-depolarization form within a few minutes of RMP recovery. These observations suggest that, at least under special circumstances, the early component of the IPSP and GABA-mediated hyperpolarizations can be dissociated. Therefore, the early IPSP may be mediated by more complex mechanisms than a simple alteration in chloride conductance due to GABA-receptor interactions.


Electron-rich diferrous-phosphane-thiolates relevant to Fe-only hydrogenase: is cyanide "nature's trimethylphosphane"?
The two-step one-pot oxidative decarbonylation of [Fe2(S2C2H4)(CO)4(PMe3)2] (1) with [FeCp2]PF6, followed by addition of phosphane ligands, led to a series of diferrous dithiolato carbonyls 2-6, containing three or four phosphane ligands. In situ measurements indicate efficient formation of 1(2+) as the initial intermediate of the oxidation of 1, even when a deficiency of the oxidant was employed. Subsequent addition of PR3 gave rise to [Fe2(S2C2H4)(mu-CO)(CO)3(PMe3)3]2+ (2) and [Fe2(S2C2H4)(mu-CO)(CO)2(PMe3)2(PR3)2]2+ (R = Me 3, OMe 4) as principal products. One terminal CO ligand in these complexes was readily substituted by MeCN, and [Fe2(S2C2H4)(mu-CO)(CO)2(PMe3)3(MeCN)]2+ (5) and [Fe2(S2C2H4)(mu-CO)(CO)(PMe3)4(MeCN)]2+ (6) were fully characterized. Relevant to the H(red) state of the active site of Fe-only hydrogenases, the unsymmetrical derivatives 5 and 6 feature a semibridging CO ligand trans to a labile coordination site.


Preretinopic changes in the colour vision of juvenile diabetics.
To examine the colour vision of juvenile patients suffering from diabetes mellitus without retinopathy in relation to metabolic and ophthalmic state. Metameric matches, both Rayleigh (red/green) and Moreland (blue/green) were used to test the colour vision yearly of 10 juvenile patients. The patients were monitored over 4 years, and during the final year, their blood glucose level was determined directly after testing colour vision. An ophthalmic examination was performed on the day of colour vision testing and blood and urine were analysed regularly throughout the 4 years. Their results are compared with an aged matched control group of 20 subjects, seven of whom were retested after 9-16 months. After 4 years, the colour vision results show an enlarged matching range for the Moreland match, as well as a smaller increase in the matching range for the Rayleigh match. No significant correlation was found between blood glucose at the time of testing and any of the variables measured. The pattern of colour vision deficits in metameric matching shown by juvenile diabetics is consistent with postreceptoral alterations of the inner retina, at this preretinopic stage of disease. Duration of diabetes is correlated with both colour vision changes and morphological alteration of the retina.


The short-term effects of reducing elevated blood pressure in elderly patients with propranolol and dyazide.
Propranolol and Dyazide (25 mg hydrochlorothiazide and 50 mg triamterene) were used singly to reduce the elevated blood pressure (systolic ranging from 170 to 271 mmHg and diastolic ranging from 100 to 141 mmHg) of 38 elderly hypertensive patients whose ages ranged from 69 to 91 years. Each compound was administered for a period of four weeks with a wash-out period of four weeks in between. The following parameters were assessed before and after each treatment period: cerebral blood flow (CBF), mental functions, cardiac output (CO), electrocardiogram, glomerular filtration rate (GFR) and serum biochemistry. Both systolic and diastolic blood pressure were significantly reduced following the administration of either compound. No significant change in CBF and CO could be observed after reducing the blood pressure whether Propranolol or Dyazide was used. The GFR was, however, significantly reduced and the plasma creatinine significantly increased following Dyazide but not Propranolol administration. As expected the administration of the latter compound was associated with a significant bradycardia. No significant change could be observed in the other parameters studied.


A high throughput screen identifies Nefopam as targeting cell proliferation in β-catenin driven neoplastic and reactive fibroproliferative disorders.
Fibroproliferative disorders include neoplastic and reactive processes (e.g. desmoid tumor and hypertrophic scars). They are characterized by activation of β-catenin signaling, and effective pharmacologic approaches are lacking. Here we undertook a high throughput screen using human desmoid tumor cell cultures to identify agents that would inhibit cell viability in tumor cells but not normal fibroblasts. Agents were then tested in additional cell cultures for an effect on cell proliferation, apoptosis, and β-catenin protein level. Ultimately they were tested in Apc1638N mice, which develop desmoid tumors, as well as in wild type mice subjected to full thickness skin wounds. The screen identified Neofopam, as an agent that inhibited cell numbers to 42% of baseline in cell cultures from β-catenin driven fibroproliferative disorders. Nefopam decreased cell proliferation and β-catenin protein level to 50% of baseline in these same cell cultures. The half maximal effective concentration in-vitro was 0.5 uM and there was a plateau in the effect after 48 hours of treatment. Nefopam caused a 45% decline in tumor number, 33% decline in tumor volume, and a 40% decline in scar size when tested in mice. There was also a 50% decline in β-catenin level in-vivo. Nefopam targets β-catenin protein level in mesenchymal cells in-vitro and in-vivo, and may be an effective therapy for neoplastic and reactive processes driven by β-catenin mediated signaling.


The premise, promise, and perils of the prevention of lethal ventricular tachyarrhythmias.
Sudden cardiac death caused by ventricular tachyarrhythmias claims about 360,000 lives a year in the United States. The premature ventricular complex (PVC) hypothesis has been the cornerstone for understanding this problem, but it is now recognized as an incomplete explanation for this catastrophy. The recognition of the importance of structural heart disease in this process has led to the development of the Substrate Hypothesis as an alternative explanation. In this construct, PVCs may trigger lethal arrhythmias but only if an abnormal electrophysiologic substrate is present. This hypothesis more completely describes the pathophysiology of the process, provides the basis for understanding the value and limitations of the techniques used for risk assessment and management, and helps clarify the potential endpoints and potential adverse effects of therapy to prevent arrhythmias. Since no single diagnostic technique is ideal and no therapeutic modality is universally effective, an approach to the management of this problem must be multidimensional and based on a firm understanding of the actual risk of a life threatening arrhythmia, the potential but unproven benefits and uncertain endpoints of drug therapy, the cost, and the potential for arrhythmia exacerbation or significant side effect.


The Days Add Up: Daily Marital Discord and Depressive Reactivity Linked to Past-Month Depressed Mood and Marital Risk across 10 Years.
Marital discord fuels depression, according to decades of research. Most prior studies in this area have focused on macro-longitudinal change in depression over the course of years, and on global ratings of marital satisfaction. Less work has examined fluctuations in depressed mood and marital discord in daily life, and none has investigated associations of short-term patterns with longer-term depressed mood and marital outcomes. Using data from participants in the Midlife in the U.S. (MIDUS) project, the current study examined daily associations between marital discord and depressed mood, as well as their links to concurrent and prospective patterns of past-month depressed mood and marital risk. Results showed that, on average, depressed mood rose on days when individuals had an argument or tension with their spouse (i.e., marital discord). More frequent daily marital discord was also associated with greater past-month depressed mood and marital risk, above and beyond prior levels. Those with larger depressive mood responses to discord in daily life (i.e., greater reactivity) exhibited higher concurrent past-month depressed mood and greater 10-year increases in depressed mood. As the first study to link daily marital patterns to concurrent and prospective changes in depressed mood and marital outcomes, this investigation uncovered two novel processes-daily marital discord and depressive reactivity-as important for understanding long-term patterns of marital risk and depression.


Magnetic resonance imaging of Chiari malformations.
The authors describe the features of magnetic resonance (MR) images of Chiari type I and II malformations and present four illustrative cases. Downward displacement of the posterior fossa was more pronounced with type II than type I. A variety of intracranial anomalies were associated with the Chiari type II malformation, whereas type I was mainly associated with syringomyelia and craniovertebral changes. MR imaging is useful in the diagnosis of intracranial anomalies and those situated at the craniovertebral junction, including Chiari malformations.


Insight into the uptake, accumulation, and metabolism of the fungicide phenamacril in lettuce (Lactuca sativa L.) and radish (Raphanus sativus L.).
The fungal species Fusarium can cause devastating disease in agricultural crops. Phenamacril is an extremely specific cyanoacrylate fungicide and a strobilurine analog that has excellent efficacy against Fusarium. To date, information on the mechanisms involved in the uptake, accumulation, and metabolism of phenamacril in plants is scarce. In this study, lettuce and radish were chosen as model plants for a comparative analysis of the absorption, accumulation, and metabolic characteristics of phenamacril from a polluted environment. We determined the total amount of phenamacril in the plant-water system by measuring the concentrations in the solution and plant tissues at frequent intervals over the exposure period. Phenamacril was readily taken up by the plant roots with average root concentration factor ranges of 60.8-172.7 and 16.4-26.9 mL/g for lettuce and radish, respectively. However, it showed limited root-to-shoot translocation. The lettuce roots had a 2.8-12.4-fold higher phenamacril content than the shoots; whereas the radish plants demonstrated the opposite, with the shoots having 1.5 to 10.0 times more phenamacril than the roots. By the end of the exposure period, the mass losses from the plant-water systems reached 72.0% and 66.3% for phenamacril in lettuce and radish, respectively, suggesting evidence of phenamacril biotransformation. Further analysis confirmed that phenamacril was metabolized via hydroxylation, hydrolysis of esters, demethylation, and desaturation reactions, and formed multiple transformation products. This study furthers our understanding of the fate of phenamacril when it passes from the environment to plants and provides an important reference for its scientific use and risk assessment.


Genomic and pharmacogenetic studies of childhood acute lymphoblastic leukemia.
With the cure rate of childhood acute lymphoblastic leukemia (ALL) approaching 90%, further improvement in the treatment outcome and quality of life of patients will require better understanding of the mechanisms of drug resistance, identifying new leukemic cell genetic lesions that are amendable to available target therapy, and optimizing treatment based on host pharmacodynamics and pharmacogenomics. Deeper characterization of leukemic cell genetic abnormalities has discovered new subtypes of leukemia such as early T-cell precursor ALL and Philadelphia chromosome-like ALL, and identified many genomic alterations that have diagnostic, prognostic, or therapeutic implications. In this regard, several novel fusion transcripts are responsive to ABL tyrosine kinase inhibitors and potentially to JAK inhibitors. Genome-wide analyses have also unraveled the role of inherited cancer predisposing genes and small nucleotide polymorphisms of several genes in the development of childhood ALL. These advances promise to lead to more sophisticated personalized treatment strategies in the near future.


Reactions on cell membranes: comparison of continuum theory and Brownian dynamics simulations.
Biochemical transduction of signals received by living cells typically involves molecular interactions and enzyme-mediated reactions at the cell membrane, a problem that is analogous to reacting species on a catalyst surface or interface. We have developed an efficient Brownian dynamics algorithm that is especially suited for such systems and have compared the simulation results with various continuum theories through prediction of effective enzymatic rate constant values. We specifically consider reaction versus diffusion limitation, the effect of increasing enzyme density, and the spontaneous membrane association/dissociation of enzyme molecules. In all cases, we find the theory and simulations to be in quantitative agreement. This algorithm may be readily adapted for the stochastic simulation of more complex cell signaling systems.


Quantitative modeling of the transduction of electromagnetic acoustic transducers operating on ferromagnetic media.
The noncontact nature of electromagnetic acoustic transducers (EMATs) offers a series of advantages over traditional piezoelectric transducers, but these features are counter-balanced by their relatively low signal-to-noise ratio and their strong dependence on material properties such as electric conductivity, magnetic permeability, and magnetostriction. The implication is that full exploitation of EMATs needs detailed modeling of their operation. A finite element model, accounting for the main transduction mechanisms, has been developed to allow the optimization of the transducers. Magnetostriction is included and described through an analogy with piezoelectricity. The model is used to predict the performance of a simple EMAT: a single current-carrying wire, parallel to a bias magnetic field generating shear horizontal waves in a nickel plate close to it. The results are validated against experiments. The model is able to successfully predict the wave amplitude dependence on significant parameters: the static bias field, the driving current amplitude, and the excitation frequency. The comparison does not employ any arbitrary adjustable parameter; for the first time an absolute validation of a magnetostrictive EMAT model has been achieved. The results are satisfactory: the discrepancy between the numerical predictions and the measured values of wave amplitude per unit current is less than 20% over a 200 kHz frequency range. The study has also shown that magnetostrictive EMAT sensitivity is not only a function of the magnetostrictive properties, because the magnetic permeability also plays a significant role in the transduction mechanism, partly counterbalancing the magnetostrictive effects.


An Atypical Case of Autochthonous Cutaneous Leishmaniasis Associated with Naturally Infected Phlebotomine Sand Flies in Texas, United States.
In the United States, phlebotomine sand flies carrying Leishmania (Leishmania) mexicana are endemic along the southern border. However, relatively little is known about the enzootic and zoonotic transmission of L. (L.) mexicana within the United States, and autochthonous cases of the consequent disease are rarely reported. We investigated an atypical case of cutaneous leishmaniasis (CL) caused by L. (L.) mexicana in a patient from central Texas which did not respond to a typical antileishmanial chemotherapy. We also investigated sand fly vectors around the patient's residence. PCR followed by DNA sequencing was used for determination of Leishmania spp., sand fly species, and host blood meal source. The L. (L.) mexicana genotype from the patient was identical to one found in a positive sand fly. Moreover, this genotype presented the same single-nucleotide polymorphisms as other historical CL cases acquired in Texas over the last 10 years, but distinct from those originating in Mexico and Central America. Three sand fly species were identified among the samples analyzed (n = 194), the majority of which were Lutzomyia (Dampfomyia) anthophora (n = 190), of which four specimens tested positive for Leishmania and two blood-fed specimens showed the presence of a human blood meal. This study highlights the complexity of clinical management of CL in a setting where the disease is infrequently encountered. The detection of human blood in Lu. (D.) anthophora is the first documentation of anthropophagy in this species. This is the first report of wild-caught, naturally infected sand flies found in association with an autochthonous case of human leishmaniasis and the specific strain of Leishmania (Leishmania) mexicana in the United States.


Multiseptate gallbladder as a cause of biliary pain.
A 45-yr-old Japanese woman with multiseptate gallbladder, a quite rare congenital anomaly, is presented. Her epigastric pain, with a 35-yr history, was relieved by cholecystectomy. The septa were present only at the neck portion of the gallbladder and were lined by mucosal epithelium containing a muscular layer continuous to the gallbladder wall. A review of 26 patients (including the present case) reported in the world literature revealed that only two of them had such partial involvement at the infundibulum of the gallbladder.


Folding of a single domain protein entering the endoplasmic reticulum precedes disulfide formation.
The relationship between protein synthesis, folding, and disulfide formation within the endoplasmic reticulum (ER) is poorly understood. Previous studies have suggested that pre-existing disulfide links are absolutely required to allow protein folding and, conversely, that protein folding occurs prior to disulfide formation. To address the question of what happens first within the ER, that is, protein folding or disulfide formation, we studied folding events at the early stages of polypeptide chain translocation into the mammalian ER using stalled translation intermediates. Our results demonstrate that polypeptide folding can occur without complete domain translocation. Protein disulfide isomerase (PDI) interacts with these early intermediates, but disulfide formation does not occur unless the entire sequence of the protein domain is translocated. This is the first evidence that folding of the polypeptide chain precedes disulfide formation within a cellular context and highlights key differences between protein folding in the ER and refolding of purified proteins.


Discovery of Novel Gq-Biased LPA1 Negative Allosteric Modulators.
Lysophosphatidic acid (LPA) activates the G-protein-coupled receptor LPA1, which regulates various cellular processes, including cell proliferation and migration. Although LPA1 transduces cellular responses via Gq, Gi, and G12/13, associations between these signaling molecules and cellular phenotypes remain poorly characterized due to the lack of signal-specific pharmacological tools. Here, we characterized novel signal-biased modulators using multiple assays, including label-free impedance assays. LPA caused dramatic changes in cellular impedance in LPA1-expressing recombinant cells, which were susceptible to G-protein and protein kinase inhibitors. Subsequently, Gq-biased LPA1 negative allosteric modulators (NAMs) were identified using high-throughput screening, and a nonbiased antagonist differently affected the LPA-induced cellular impedance. These NAMs provide pharmacological tools for further investigations of the biology of LPA1.


Treatment of coronary bifurcation lesions: current knowledge and future perspectives.
Coronary lesions at bifurcation sites are frequent and still remain a challenging subset for the interventional cardiologist. Although in the last years the provisional stenting technique has shown more consistent results, coronary bifurcation interventions still share a worse procedural success rate and increased rates of mid- and long-term cardiac events. Most of the dedicated devices proposed in the last few years have failed to show improved results when compared with standard devices. The broader use of imaging techniques, such as intravascular ultrasound and optical coherence tomography, lead to a better understanding of the real anatomy of bifurcations and has shown to be a great tool for percutaneous coronary intervention optimization. Preliminary results come from drug-coated balloons and bioresorbable vascular scaffolds, especially for the 'leave nothing behind' concept, particularly interesting in this setting of lesions.


Role of toll-like receptor signalling in Abeta uptake and clearance.
Deposits of amyloid beta-protein (Abeta) in neuritic plaques and cerebral vessels are a pathological hallmark of Alzheimer's disease. Fibrillar Abeta deposits are closely associated with inflammatory responses such as activated microglia in brain with this disease. Increasing lines of evidence support the hypothesis that activated microglia, innate immune cells in the CNS, play a pivotal role in the progression of the disease: either clearing Abeta deposits by phagocytic activity or releasing cytotoxic substances and pro-inflammatory cytokines. Toll-like receptors (TLRs) are a family of pattern-recognition receptors in the innate immune system. Exogenous and endogenous TLR ligands activate microglia. To investigate the role of TLR4 in the amyloidogenesis in vivo, we determined the amounts of cerebral Abeta in Alzheimer's disease mouse models with different genotypes of TLR4 using three distinct methods. We show that mouse models (Mo/Hu APPswe PS1dE9 mice) homozygous for a destructive mutation of TLR4 (Tlr(Lps-d)/Tlr(Lps-d)) had increases in diffuse and fibrillar Abeta deposits by immunocytochemistry, fibrillar Abeta deposits by thioflavine-S staining and buffer-soluble and insoluble Abeta by ELISA in the cerebrum, as compared with TLR4 wild-type mouse models. Although the differences in these parameters were less significant, mouse models heterozygous for the mutation (Tlr(Lps-d)/) showed co-dominant phenotypes. Consistent with these observations in vivo, cultured microglia derived from Tlr(Lps-d)/Tlr(Lps-d) mice failed to show an increase in Abeta uptake after stimulation with a TLR4 ligand but not with a TLR9 ligand in vitro. Furthermore, activation of microglia (BV-2 cell) with a TLR2, TLR4 or TLR9 ligand, markedly boosted ingestion of Abeta in vitro. These results suggest that TLR signalling pathway(s) may be involved in clearance of Abeta-deposits in the brain and that TLRs can be a therapeutic target for Alzheimer's disease.


Gratitude, self-efficacy, and health-related quality of life in individuals with Parkinson's Disease.
Parkinson's Disease (PD) is a chronic disease that can affect the physical, psychological, and social functioning of an individual. Minimal research has examined the relationship among positive psychological variables such as gratitude and self-efficacy and their relationship with health-related quality of life (HRQOL) in this population. Gender analyses have also been limited. The aim of this exploratory, cross-sectional study was to examine the relationship among gratitude, self-efficacy, and HRQOL by gender in individuals with Parkinson's Disease (PD). Participants included 102 individuals with PD (55 women; 42 men; 5 did not report gender) who completed questionnaires on gratitude (Gratitude Questionnaire-6), self-efficacy (General Self-Efficacy Scale), and HRQOL problems (Parkinson's Disease Questionnaire-39). Although there were no gender differences between gratitude, self-efficacy, or health-related quality of life problems, there were key gender differences in how those variables were related. Gratitude was associated with more HRQOL problems for women than men, whereas self-efficacy was associated with more HRQOL problems for men than women. In addition, self-efficacy emerged as a more important predictor of HRQOL problems for women and men than gratitude. This research could lead to targeted interventions by gender aimed at improving HRQOL in individuals with PD, particularly in building self-efficacy.


Ultrasound-based multimodal molecular imaging and functional ultrasound contrast agents.
Ultrasound-based multimodal molecular imaging and functional ultrasound contrast agents (UCAs) have garnered great interest in biomedical imaging over the past few years. With the rapid development of molecular imaging technique, UCAs with single-function and single imaging modality can no longer satisfy increasingly growing medical diversification and hominization demand. The device of functional UCAs including multimodality and multifunction is of great value for disease diagnosis, treatment and research, and greatly accelerate the development of ultrasound-based multimodal molecular imaging. Functional UCAs can not only be applied for multimodality imaging to compensate for the disadvantages of each imaging modality whilst taking advantage of their individual strengths to acquire more biological information, but also can act as a vector carrying drugs or therapeutic genes to accomplish the combination of diagnosis and treatment, which is an existing study hotspot and has achieved initiatory success. In this paper, we reviewed the advances of ultrasound-based multimodal imaging, multimodal and multifunctional UCAs.


Rx and its downstream factor, Musashi1, is required for establishment of the apical organ in sea urchin larvae.
Acetylcholine, a vital neurotransmitter, plays a multifarious role in the brain and peripheral nervous system of various organisms. Previous research has demonstrated the proximity of cholinergic neurons to serotonergic neurons in the apical organ of sea urchin embryos. While several transcription factors have been identified as playing a role in the development of serotonergic neurons in this region of a sea urchin, Hemicentrotus pulcherrimus, comparatively little is known about the specific transcription factors and their spatiotemporal expression patterns that regulate the development of cholinergic neurons. In this study, we establish the requirement of the transcription factor Rx for the development of cholinergic neurons in the apical organ of the species. Furthermore, we investigate the role of the RNA-binding protein Musashi1, known to be involved in neurogenesis, including cholinergic neurons in other organisms, and demonstrate that it is a downstream factor of Rx, and that choline acetyltransferase expression is suppressed in Musashi1 downregulated embryos. Our research also highlights the intricate network formed by neurons and other cells in and around the apical organ of sea urchin larvae through axons and dendrites, providing possibility for a systematic and complexed neural pattern like those of the brain in other organisms.


Efficacy of intravenous granisetron in suppressing the bradycardia and hypotension associated with a rabbit model of the Bezold-Jarisch reflex.
This study investigated whether granisetron, a 5-HT3 receptor antagonist, can alter the Bezold-Jarisch reflex (i.e., hypotension and inappropriate heart rate slowing). A hemorrhagic rabbit model that has been shown to induce the Bezold-Jarisch reflex was used. In 11 rabbits (3.8 kg), catheters were placed in the carotid arteries one day before experimental hemorrhage. On the day of the study, the rabbits were given intravenous granisetron (50 micrograms/kg) or an equal volume of saline. Five minutes after administration of granisetron or saline, hemorrhage was induced by continuous blood withdrawal at 5 mL/min and blood pressure (BP) and heart rates were obtained at frequent intervals until systolic BP declined to 80 mmHg. Six rabbits received saline and five granisetron. An average of 77.6 mL +/- 16.4 mL of blood was removed in the group receiving granisetron (compared with 56.5 mL +/- 13.1 mL for the saline group) before achieving the target systolic BP of 80 mmHg. The group receiving granisetron demonstrated the same ability to increase their heart rate from baseline as the saline group. However, the granisetron group had a final heart rate that was closer to their maximal heart rate than the saline group. In this animal model, granisetron was significantly more effective at preventing inappropriate heart rate slowing and allowed significantly more blood to be removed before reaching the target blood pressure. This implies that granisetron may be effective in preventing vasovagal syncope, although further study should be carried out to verify these potentially interesting findings.


Tracheostomy for COVID-19 respiratory failure: timing, ventilatory characteristics, and outcomes.
Whereas data from the pre-pandemic era have demonstrated that tracheostomy can accelerate liberation from the ventilator, reduce need for sedation, and facilitate rehabilitation, concerns for healthcare worker safety have led to disagreement on tracheostomy placement in COVID-19 patients. Data on COVID-19 patients undergoing tracheostomy may inform best practices. Thus, we report a retrospective institutional cohort experience with tracheostomy in ventilated patients with COVID-19, examining associations between time to tracheostomy and duration of mechanical ventilation in relation to patient characteristics, clinical course, and survival. Clinical data were extracted for all COVID-19 tracheostomies performed at a quaternary referral center from April-July 2020. Outcomes studied included mortality, adverse events, duration of mechanical ventilation, and time to decannulation. Among 64 COVID-19 tracheostomies (13% of COVID-19 hospitalizations), patients were 64% male and 42% African American, with a median age of 54 (range, 20-89). Median time to tracheostomy was 22 (range, 7-60) days and median duration of mechanical ventilation was 39.4 (range, 20-113) days. Earlier tracheostomy was associated with shortened mechanical ventilation (R2=0.4, P<0.01). Median decannulation time was 35.3 (range, 7-79) days. There was 19% mortality and adverse events in 45%, mostly from bleeding in therapeutically anticoagulated patients. Tracheostomy was associated with swifter liberation from the ventilator and acceptable safety for physicians in this series of critically ill COVID-19 patients. Patient mortality was not increased relative to historical data on acute respiratory distress syndrome (ARDS). Future studies are required to establish conclusions of causality regarding tracheostomy timing with mechanical ventilation, complications, or mortality in COVID-19 patients.


Curvature and ionization-induced reversible hydrogen storage in metalized hexagonal B36.
The synthesis of quasiplanar boron clusters (B36) with a central hexagonal hole provides the first experimental evidence that a single-atomic-layer borophene with hexagonal vacancies is potentially viable [Z. Piazza, H. Hu, W. Li, Y. Zhao, J. Li, and L. S. Wang, Nat. Commun. 5, 3113 (2014)]. However, owing to the hexagonal holes, tunning the electronic and physical properties of B36 through chemical modifications is not fully understood. Based on (van der Waals corrected-) density functional theory, we show that Li adsorbed on B36 and B36 (-) clusters can serve as reversible hydrogen storage media. The present results indicate that the curvature and ionization of substrates can enhance the bond strength of Li due to the energetically favorable B 2p-Li 2p orbitals hybridization. Both the polarization mechanism and the orbital hybridization between H-s orbitals and Li-2s2p orbitals contribute to the adsorption of H2 molecules and the resulting adsorption energy lies between the physisorbed and chemisorbed states. Interestingly, the number of H2 in the hydrogen storage medium can be measured by the appearance of the negative differential resistance behavior at different bias voltage regions. Furthermore, the cluster-assembled hydrogen storage materials constructed by metalized B36 clusters do not cause a decrease in the number of adsorbed hydrogen molecules per Li. The system reported here is favorable for the reversible hydrogen adsorption/desorption at ambient conditions.


Microencapsulation of Theobroma cacao L. waste extract: optimization using response surface methodology.
The cocoa extract (Theobroma cacao L.) has a significant amount of polyphenols (TP) with potent antioxidant activity (AA). This study aims to optimise microencapsulation of the extract of cocoa waste using chitosan and maltodextrin. Microencapsulation tests were performed according to a Box-Behnken factorial design, and the results were evaluated by response surface methodology with temperature, maltodextrin concentration (MD) and extract flowrate (EF) as independent variables, and the fraction of encapsulated TP, TP encapsulation yield, AA, yield of drying and solubility index as responses. The optimum conditions were: inlet temperature of 170 °C, MD of 5% and EF of 2.5 mL/min. HPLC analysis identified epicatechin as the major component of both the extract and microparticles. TP release was faster at pH 3.5 than in water. These results as a whole suggest that microencapsulation was successful and the final product can be used as a nutrient source for aquatic animal feed. Highlights Microencapsulation is optimised according to a factorial design of the Box-Behnken type. Epicatechin is the major component of both the extract and microcapsules. The release of polyphenols from microcapsules is faster at pH 3.5 than in water.


Integration of scRNA-Seq and bulk RNA-Seq uncover perturbed immune cell types and pathways of Kawasaki disease.
Kawasaki disease (KD) is an acute febrile illness primarily affecting children and characterized by systemic inflammation and vasculitis that can lead to coronary artery complications. The aim of this study was to gain a comprehensive understanding of immune dysregulation in KD. To this end, we employed integration of single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing (bulk RNA-Seq) data. Furthermore, we conducted flow cytometry analysis for a cohort of 82 KD patients. Our analysis revealed significant heterogeneity within immune cell populations in KD patients, with distinct clusters of T cells, B cells, and natural killer (NK) cells. Importantly, CD4+ naïve T cells in KD patients were found to predominantly differentiate into Treg cells and Th2 cells, potentially playing a role in the excessive inflammation and vascular damage characteristic of the disease. Dysregulated signaling pathways were also identified, including the mTOR signaling pathway, cardiomyopathy pathway, COVID-19 signaling pathway, and pathways involved in bacterial or viral infection. These findings provide insights into the immunopathogenesis of KD, emphasizing the importance of immune cell dysregulation and dysregulated signaling pathways. Integration of scRNA-Seq and bulk RNA-Seq data offers a comprehensive view of the molecular and cellular alterations in KD and highlights potential therapeutic targets for further investigation. Validation and functional studies are warranted to elucidate the roles of the identified immune cell types and pathways in KD pathogenesis and to develop targeted interventions to improve patient outcomes.


The efficacy of homemade tolcapone in the treatment of patients with Parkinsons disease.
The aim of the study was to investigate the efficacy of homemade tolcapone in treatment of patients with Parkinson's disease (PD). Eighty patients with PD were subjected to randomized, double-blind, placebo-controlled and parallel-group study. PD patients were randomly divided into the tolcapone treatment group (41 cases) and placebo group (39 cases). Each patient received 1 pill of tolcapone or placebo, 3 times per day for 26 weeks. Efficacy was evaluated using the internationally used unified Parkinson's disease rating scale (UPDRS) scoring system for PD symptoms. After the treatment for 26 weeks, the cognitive function, tremor, muscle stiffness, voluntary movement and autonomic nerve symptoms were compared between the two groups using UPDRS scores. Compared with the placebo group, cognitive function, muscle stiffness and voluntary movement reduction were significantly improved in patients of the tolcapone group (P<0.05). However, no significant differences in UPDRS scores of autonomic nerve symptoms and tremor were found between two groups after treatment (P>0.05). Tolcapone, a catechol-O-methyl transferase (COMT) inhibitor, can improve the motor function of patients with PD, especially exercise and muscle stiffness. Tolcapone can also improve the cognitive function of patients.


Factors associated with late-stage presentation of cervical cancer in Ghana.
To explore factors associated with late clinical presentation among Ghanaian women with cervical cancer. This is a cross-sectional survey using a paper questionnaire. Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. Participants were women presenting for cervical cancer care at KATH. Inclusion criteria were histologically diagnosed cervical cancer and age ≥18 years. The exclusion criteria was age <18. All women presenting from August 2018-August 2019 were recruited. The primary outcome was the proportion of participants presenting with late-stage cervical cancer, defined as stage II or higher. Of 351 total participants, 33.6% were unemployed, 35.3% had no formal education, and 96.6% had an average monthly income of less than five hundred Ghana cedis ($86 USD). Time from symptoms to seeing a doctor ranged from fewer than two weeks (16.0%) to more than twelve months (8.6%). Participants' most common barrier in seeking healthcare was financial constraints (50.0%). Most participants presented at late-stage cervical cancer (95.2%, n=334), with only 4.8% (n=17) presenting at stage I. Of participants presenting with late-stage cervical cancer, the vast majority had never had a Papanicolaou (Pap) smear (99.1%) nor a recent gynecologic exam (99.3%). After adjusting for age, parity, and distance to a healthcare facility, a late-stage presentation was associated with lower income and living in a rural area. In Ghana, 95% of women with cervical cancer seek care at a late clinical stage, defined as stage II or greater, when the cancer is inoperable. None declared.


Recurrent fractures in an elderly patient with systemic lupus erythematosus.
Glucocorticoid-induced osteoporosis (GIO) is an important problem that remains undertreated, even by rheumatologists. We present a case of an elderly patient with systemic lupus erythematosus diagnosed more than 40 years ago, who suffered from recurrent fractures and attendant complications despite a bone mineral density (BMD) score in the osteopenic range and treatment with bisphosphonates. With improved treatment and outcome of lupus, an increasing number of elderly patients who are susceptible to osteoporotic fractures are expected. This case serves to highlight that rheumatic disease patients on steroids should be screened for GIO, as effective treatment and preventive measures are available. Teriparatide is a promising treatment for patients who have failed bisphosphonate treatment or who are at high risk for fracture. We should also bear in mind that BMD scores alone are not indicative of fracture risk, and other tools such as the WHO-FRAX (Fracture risk assessment tool), serum vitamin D3 levels and bone turnover markers should be used where appropriate. Other measures including attention to factors that contribute to falls should also be considered, necessitating a multi-disciplinary approach.


Cyclosporine, FK506, and rapamycin. Some effects on early activation events in serum-free, mitogen-stimulated mouse spleen cells.
Both cyclosporine and FK506 (FK) inhibit Con A-stimulated mouse spleen cells from entering the cell division cycle at the G0/G1 interface. Rapamycin, a fungal metabolite structurally related to FK, acts later and blocks progress through the cell division cycle at some point in G1. The effect of CsA, FK, and rapamycin drug combinations appeared additive, while certain concentrations of FK and rapamycin appeared to be antagonistic. The early blockade of lymphocyte activation caused by CsA and by FK was not due to altered membrane transport kinetics, nor to perturbation of the dynamic behavior of actin. However, both drugs showed the same specific effects on gene activation over a profile of genes encoding oncoproteins, putative transcription factors, cyclophilin, heat-shock proteins, IL-2, and IL-2-R. Of note was the drug-associated super-induction of krox-24 and reduced induction of krox-20. Both krox-24 and krox-20 encode proteins containing zinc-binding fingers, and are likely to regulate gene transcription, and this is the first report of gene control mechanisms being specifically affected by CsA and by FK.


Demographic History of the Brown Bear (Ursus arctos) on Hokkaido Island, Japan, Based on Whole-Genomic Sequence Analysis.
Previous studies of the brown bear (Ursus arctos) on Hokkaido Island, Japan, have detected three geographically distinct subpopulations representing different mitochondrial lineages and shown that gene flow between subpopulations has occurred due to male-biased dispersal. In this study, we determined whole-genomic sequences for six Hokkaido brown bears and analyzed these data along with previously published genomic sequences of 17 brown bears from other parts of the world. We found that the Hokkaido population is genetically distinct from the other populations, keeping genetic diversity higher than the endangered populations in western Europe but lower than most populations on the continents. A reconstruction of historical demography showed no increase in population size for the Hokkaido population during the Eemian interglacial period (130,000-114,000 years ago). In a phylogenetic analysis of the autosomal data, the Hokkaido population formed a clade distinct from North American and European populations, showing that it has maintained genetic diversity independently from continental populations following geographical isolation on the island. This autosomal genetic similarity contrasts with the geographically separate mitochondrial lineages on Hokkaido and indicates the occurrence of male-driven gene flow between subpopulations.


Ultrasound assisted engineering of lactose crystals.
To engineer lactose crystals of desired size, shape, surface and particle size distribution (PSD) as a carrier for dry powder inhalers (DPI) by ultrasound assisted in-situ seeding. Lactose crystals were obtained from solution by ultrasound assisted in-situ seeding, followed by growth in viscous glycerin solution. The crystals were characterized for physical properties and 63-90 mum size fractions of different batches were mixed with salbutamol sulphate (SS) and compared for in-vitro deposition. Cooling crystallization with stirring for 10-20 h resulted in crystals with wide PSD and varied shape. Application of ultrasound resulted in rapid and complete crystallization in 5 min with rod-shaped fine crystals (15-30 microm) and narrow PSD. In-situ seeded batches yielded micro-fine rod-shaped seed crystals. Seeding followed by growth in glycerin showed desirable size, high elongation ratio, smooth surface and narrow PSD, while growth under stirring showed high elongation ratio with rough surface. Crystals grown in glycerin showed highest dispersibility and fine particle fraction (FPF) of SS. Ultrasound assisted in-situ seeding, followed by ordered growth in glycerin offers rapid technique for separation of nuclei induction from crystal growth yielding desirable characteristics for better dispersion and in-vitro deposition when employed as DPI carrier.


[CHANGES IN COLON MICROBIOCENOSIS COMPOSITION AND ANTIOXIDANT PROPERTIES OF COLONOCYTES UNDER THE CONDITION OF EXPERIMENTAL DYSBIOSIS AND EMOXIPIN PROPHYLAXIS].
Study the composition of colon microbiocenosis and antioxidant properties of colonocytes under the conditions of experimental dysbiosis and prophylaxis application of emoxipin. With the aim of prophylaxis, antioxidant emoxipin was administered to mice, in which medicinal dysbiosis was formed by intraperitoneal administration of gentamicin. Quantitative and qualitative study of mucous microflora of the mice colon was carried out by a bacteriological method. The state of lipid peroxidation system was judged by the content of acylhydroperoxides and malonic dialdehyde, system of antioxidant protection--by enzyme activity (catalase and superoxide dismutase). Experimental dysbiosis of the colon manifested by changes in the composition of mucous microflora of the animals and antioxidant properties of colonocytes. Dysbiosis prophylaxis by emoxipin resulted in normalization of the activity of antioxidant protection enzymes and products of lipid peroxidation in intestine tissue. The study results allow to consider, that use of emoxipin results in an increase of adaptive-compensatory capabilities of the macroorganism during experimental dysbiosis.


Circulating calcitonin levels in healthy children and subjects with congenital hypothyroidism from birth to adolescence.
Using an extraction-concentration technique of circulating calcitonin (exCT) that permits a sensitive and specific assessment of circulating CT monomer levels, we measured exCT levels in 115 healthy children (59 girls and 56 boys), aged 0-16 yr, and 25 patients (15 girls and 10 boys), aged 2 months to 22 yr, with congenital hypothyroidism (CH), a condition characterized by a marked CT deficiency in adults. We found a significant negative correlation between CT levels and age in healthy children (girls, r = -0.83; boys, r = -0.63; P < 0.001). There was a 5-fold decrease in CT levels from the neonatal period to adolescence. The fall in CT levels was particularly marked in early infancy (e.g. for the age category 1 day to 1 yr, 19.0 +/- 1.9 vs. 7.3 +/- 1.2 ng/L for the group 1-5 yr, P < 0.01), but less pronounced thereafter (for the group 5-10 yr, 4.7 +/- 0.8 ng/L; P < 0.001 vs. the group 1 day to 1 yr). The well established sex difference in CT levels in adults was significant only for the age category above 10 yr (2.7 +/- 0.4 ng/L for girls vs. 4.5 +/- 0.7 ng/L for boys, P < 0.05). In patients with CH, the mean exCT level was 2.0 +/- 0.3 ng/L under 3 yr of age (n = 9), whereas all CT values were undetectable after the age of 3 yr, which could contribute to the lower bone mass of adult CH patients. CT values were normal in 3 children with metabolic goiter. In healthy children, our results demonstrate the existence of an age-related decrease in circulating CT levels, which was particularly marked in infancy. The sex difference in CT levels progressively appeared in childhood, but was significant only after 10 yr of age. Such changes in CT levels could be important for neonatal calcium metabolism and contribute to the lower bone mass in females.


Prognostic Role of Examined and Positive Lymph Nodes after Distal Pancreatectomy for Non-Functioning Neuroendocrine Neoplasms.
The most appropriate nodal staging system for non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) remains unclear. Despite some evidence is available for pancreaticoduodenectomy, the adequate nodal staging is still unknown for distal pancreatectomy (DP). The aim of the present study was to evaluate the prognostic impact of the number of positive lymph nodes (PLNs) after DP for NF-PanNETs and to define the minimal number of lymph nodes to be harvested for an appropriate nodal staging. Data were retrospectively collected from patients who underwent DP with curative intent (R0-R1) for sporadic well-differentiated NF-PanNETs in 4 European high-volume centres. NF-PanNETs with nodal involvement (N+) were subclassified into N1 (1-3 PLNs) and N2 (4 or more PLNs). Univariate and multivariate analyses of disease-free survival (DFS) were performed. Of 271 patients in the study, 62 (23%) had nodal involvement (N+). A higher probability of N+ was associated with the following factors: grading, resection margin status, perineural and microvascular invasion, and the number of examined lymph nodes. Three-year DFS rate for N0, N1, and N2 patients was 92, 72, and 50%, respectively (p < 0.001). At multivariate analysis, independent predictors of DFS were grading, T stage, presence of necrosis, and nodal status. For patients with ≥12 examined/resected lymph nodes, the N status remained a significant predictor of disease recurrence (p < 0.001), while it failed to predict recurrence in patients with <12 lymph nodes examined/resected (p = 0.116). A minimal number of 12 nodes should be harvested in case of DP for NF-PanNET for an appropriate nodal staging. The number of positive lymph nodes is an independent predictor of DFS after DP for NF-PanNET, and the N0/N1/N2 nodal classification seems to be more relevant than the current N0/N+ staging.


Sequential FDG PET and MRI findings in a case of human herpes virus 6 limbic encephalitis.
A 50-year-old woman developed a human herpes virus 6 limbic encephalitis characterized by memory loss and somnolence, 3 weeks after a cord blood-derived stem cell transplantation. Sequential scalp electroencephalogram failed to detect seizure activity. Cerebrospinal fluid polymerase chain reaction assay demonstrated human herpes virus 6 deoxyribonucleic acid (positive, 3.74 log). Acute phase FDG PET imaging showed bilateral intense FDG uptake in both hippocampi and amygdalae. After antiviral treatment (gancyclovir followed by foscarnet), neurologic symptoms disappear gradually. Late phase FDG PET imaging showed a regression in FDG uptake representing hippocampal hypometabolism because of hippocampal sclerosis.


Increase in Operator's Sympathetic Nerve Activity during Complicated Hepatobiliary Surgery: Evidence for Surgeons' Mental Stress.
Surgeons often experience stress during operations. The heart rate variability (HRV) is the variability in the beat-to-beat interval, which has been used as parameters of stress. The purpose of this study was to evaluate mental stress of surgeons before, during and after operations, especially during pancreaticoduodenectomy (PD) and living donor liver transplantation (LDLT). Additionally, the parameters were compared in various procedures during the operations. By frequency domain method using electrocardiograph, we measured the high frequency (HF) component, representing the parasympathetic activity, and the low frequency (LF)/HF ratio, representing the sympathetic activity. In all 5 cases of PD, the surgeon showed significantly lower HF component and higher LF/HF during operation, indicating predominance of sympathetic nervous system and increased stress, than those before the operation (p < 0.01) and these did not return to the baseline level one hour after the operation. Out of the 4 LDLT cases, the value of HF was decreased in two and the LF/HF increased in three cases (p < 0.01) during the operation compared to those before the operation. In all cases, the value of HF was decreased and/or the LF/HF increased significantly during the reconstruction of the vessels or bile ducts than during the removal of the liver. Thus, sympathetic nerve activity increased during hepatobiliary surgery compared with the level before the operation, and various procedures during the operations induced diverse changes in the autonomic nervous activities. The HRV analysis could assess the chronological changes of mental stress by measuring the autonomic nervous balances.


[Pedicled pectoralis major musculocutaneous flaps].
A retrospective series of 76 pedicled pectoralis major musculocutaneus flaps is presented. We used this technique in reconstruction after head and neck tumours resections and in complications of oncological surgery such as pharyngostomes or orostomes. Most of these flaps were used in reconstruction of oral cavity and in postradiotherapy salvaje surgery cases. We also analyse the presence of complications at the donor and receiver sites and its correlation with different parameters like protein levels, haemoglobin, administration of radiotherapy and its dose, previous quimiotherapy and the influence of systemic diseases.


1D ultrafine SnO2 nanorods anchored on 3D graphene aerogels with hierarchical porous structures for high-performance lithium/sodium storage.
SnO2 is considered as one of the most promising alternative anode materials for lithium ion batteries (LIBs) and sodium ion batteries (SIBs) due to high specific capacity, low discharge voltage plateau and environmental friendliness. In this work, 1D ultrafine SnO2 nanorods anchored on 3D graphene aerogel (SnO2 NRs/GA) composite is prepared through a simple reduction-induced self-assembly method in the solution of graphene oxide (GO), Vitamin C and SnO2 nanoparticles. Vitamin C plays an important role in the reduction of GO. The structural and morphological characterizations demonstrate that 1D ultrafine SnO2 nanorods are uniformly and tightly anchored on the surface of 3D graphene nanosheet aerogels. The unique 3D network structure as well as the synergistic effect between 3D graphene nanoshhet and 1D SnO2 nanorods endows the as-prepared SnO2 NRs/GA composite with the good electrochemical lithium/sodium storage performance. It delivers the high initial discharge capacity (1713 mA h g-1 at 0.1 A g-1 for LIBs and 539 mA h g-1 at 0.05 A g-1 for SIBs) and good cycle stability (869 mA h g-1 at 0.1 A g-1 after 50 cycles for LIBs and 232 mA h g-1 at 0.05 A g-1 after 100 cycles for SIBs). Moreover, the SnO2 NRs/GA composite exhibits excellent cycle stability for SIBs with a high reversible capacity of 96 mA h g-1 at as high as 1 A g-1 for 500 cycles. This work provides a simple method to fabricate the electro-active materials-graphene aerogel composites for high-performance LIBs and SIBs.


Acquired motility disorders in childhood.
Acquired motility disorders in childhood cause a number of gastrointestinal symptoms - principally, recurrent vomiting, abdominal pain and distension, constipation and loose stools. Gastrointestinal motility disorders result from disturbances of the control mechanisms of gut motor activity, which may be produced by organic disease involving enteric nerves and muscle, perturbation of the humoral environment of the nerves and muscle, and altered central nervous system input. In children, both congenital and acquired disease processes may produce these pathogenetic mechanisms, resulting in syndromes that vary in severity from chronic intestinal pseudo-obstruction to the irritable bowel syndrome.


Vibrio cholerae MARTX toxin heterologous translocation of beta-lactamase and roles of individual effector domains on cytoskeleton dynamics.
The Vibrio cholerae MARTXVc toxin delivers three effector domains to eukaryotic cells. To study toxin delivery and function of individual domains, the rtxA gene was modified to encode toxin with an in-frame beta-lactamase (Bla) fusion. The hybrid RtxA::Bla toxin was Type I secreted from bacteria; and then Bla was translocated into eukaryotic cells and delivered by autoprocessing, demonstrating that the MARTXVc toxin is capable of heterologous protein transfer. Strains that produce hybrid RtxA::Bla toxins that carry one effector domain in addition to Bla were found to more efficiently translocate Bla. In cell biological assays, the actin cross-linking domain (ACD) and Rho-inactivation domain (RID) are found to cross-link actin and inactivate RhoA, respectively, when other effector domains are absent, with toxin autoprocessing required for high efficiency. The previously unstudied alpha-beta hydrolase domain (ABH) is shown here to activate CDC42, although the effect is ameliorated when RID is also present. Despite all effector domains acting on cytoskeleton assembly, the ACD was sufficient to rapidly inhibit macrophage phagocytosis. Both the ACD and RID independently disrupted polarized epithelial tight junction integrity. The sufficiency of ACD but strong selection for retention of RID and ABH suggests these two domains may primarily function by modulating cell signaling.


Phylogenetic analysis of apicomplexan parasites infecting commercially valuable species from the North-East Atlantic reveals high levels of diversity and insights into the evolution of the group.
The Apicomplexa from aquatic environments are understudied relative to their terrestrial counterparts, and the seminal work assessing the phylogenetic relations of fish-infecting lineages is mostly based on freshwater hosts. The taxonomic uncertainty of some apicomplexan groups, such as the coccidia, is high and many genera were recently shown to be paraphyletic, questioning the value of strict morphological and ecological traits for parasite classification. Here, we surveyed the genetic diversity of the Apicomplexa in several commercially valuable vertebrates from the North-East Atlantic, including farmed fish. Most of the sequences retrieved were closely related to common fish coccidia of Eimeria, Goussia and Calyptospora. However, some lineages from the shark Scyliorhinus canicula were placed as sister taxa to the Isospora, Caryospora and Schellakia group. Additionally, others from Pagrus caeruleostictus and Solea senegalensis belonged to an unknown apicomplexan group previously found in the Caribbean Sea, where it was sequenced from the water column, corals, and fish. Four distinct parasite lineages were found infecting farmed Dicentrarchus labrax or Sparus aurata. One of the lineages from farmed D. labrax was also found infecting wild counterparts, and another was also recovered from farmed S. aurata and farm-associated Diplodus sargus. Our results show that marine fish apicomplexans are diverse, and we highlight the need for a more extensive assessment of parasite diversity in this phylum. Additionally, parasites recovered from S. canicula were recovered as basal to their piscine counterparts reflecting hosts phylogeny.


[Biomechanical evaluation of the gliding nail in trochanteric fractures].
The purpose of the present study is to evaluate wether the gliding nail with it's double-t-shaped geometry is appropriate in the stabilization of unstable trochanteric fractures or not and if this evaluation can be performed with a static finite element simulation. Surface-Reconstruction with CT database of a proximal femur and reconstruction with CT based density data was done. After modelling of geometry, isotropic material behaviour and load application during one leg standing in slow walking was done with a limited dataset of relevant muscles. Two relevant fractures are modelled. FE-simulation shows a movement of the femoral head distally, medially and posteriorly. Maximum bending strain is in the femoral diaphysis medial compression and lateral tension strain. In the proximal part we find a nearly homogeneous strain distribution. The clinical effect of lateralization of the proximal main fragment is also result of the simulation. In the area of the modelled fractures there is much more compressive stress than shear stress. Elastomechanical behaviour of the gliding nail is demonstrated with correlation of clinical observed effects. In both simulated fracture areas there is a bone union supporting compressive stress. This means in the FE-simulation the gliding nail is appropriate in the stabilization in unstable trochanteric fractures.


Elevated plasma leptin levels are associated with vascular access dysfunction in patients on maintenance hemodialysis.
Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.