Functional organization of human subgenual cortical areas: Relationship between architectonical segregation and connectional heterogeneity.
Human subgenual anterior cingulate cortex (sACC) is involved in affective experiences and fear processing. Functional neuroimaging studies view it as a homogeneous cortical entity. However, sACC comprises several distinct cyto- and receptorarchitectonical areas: 25, s24, s32, and the ventral portion of area 33. Thus, we hypothesized that the areas may also be connectionally and functionally distinct. We performed structural post mortem and functional in vivo analyses. We computed probabilistic maps of each area based on cytoarchitectonical analysis of ten post mortem brains. Maps, publicly available via the JuBrain atlas and the Anatomy Toolbox, were used to define seed regions of task-dependent functional connectivity profiles and quantitative functional decoding. sACC areas presented distinct co-activation patterns within widespread networks encompassing cortical and subcortical regions. They shared common functional domains related to emotion, perception and cognition. A more specific analysis of these domains revealed an association of s24 with sadness, and of s32 with fear processing. Both areas were activated during taste evaluation, and co-activated with the amygdala, a key node of the affective network. s32 co-activated with areas of the executive control network, and was associated with tasks probing cognition in which stimuli did not have an emotional component. Area 33 was activated by painful stimuli, and co-activated with areas of the sensorimotor network. These results support the concept of a connectional and functional specificity of the cyto- and receptorarchitectonically defined areas within the sACC, which can no longer be seen as a structurally and functionally homogeneous brain region.


[Extensive transbasal approach for removal of tumours in the nasal, sphenoid and clival regions].
To improve operative results of removal of the tumors in midline cranial base and the reconstruction of defect at frontal base through modification of the operative approach and techniques. Extensive transbasal approach was used in 15 patients with tumours in the nasal, sphenoid and clival regions. The tumor was removed in 10 patients, near totally removed in 4 and partial removed in 1. The operative results of all patients were excellent except an elderly patient with mild operative morbidity. The procedure we used expand the operative indications for the tumors situated at the midline cranial base and improve the operative results. The procedure has advantages such as wide operative space, reliable reconstruction of the frontal base, and no severe complications.


The Impact of Upper Limb Apraxia on General and Domain-Specific Self-Efficacy in Post-Stroke Patients.
Upper limb apraxia (ULA) is a neurological syndrome characterized by the inability to perform purposeful movements. ULA could impact individuals' perceptions, including perceived self-efficacy. The aim of this study is to investigate whether ULA is related to general self-efficacy and self-efficacy for managing symptoms in post-stroke patients. A cross-sectional study was conducted involving 82 post-stroke patients. Regression analyses were implemented using a stepwise model including seven dimensions of ULA: imitation (non-symbolic, intransitive, and transitive), pantomime (non-symbolic, intransitive, and transitive), and dimension of apraxic performance in activities of daily living. These dimensions were independent variables, while general self-efficacy and symptom management self-efficacy dimensions were dependent variables. The findings revealed that intransitive imitation accounted for 14% of the variance in general self-efficacy and 10% of self-efficacy for managing emotional symptoms. Transitive imitation explained 10% of the variance in self-efficacy for managing global symptoms and 5% for social-home integration symptoms. The combination of intransitive imitation, non-symbolic pantomime, and alterations in activities of daily living performance associated with ULA explained 24% of the variance in cognitive self-efficacy. Hence, ULA dimensions seem to be related to the levels of general perceived self-efficacy and self-efficacy for managing symptoms among post-stroke patients.


[Genetic polymorphism and drug interactions: their importance in the treatment of pain].
To evaluate the impact of certain genetic polymorphisms on variable responses to analgesics Systematic review, by means of a structured computerized search in the Medline database (1966-2004). Articles in English and French were selected. References in relevant articles were also retrieved. Most analgesics are metabolized by CYP isoenzymes subject to genetic polymorphism. NSAIDs are metabolized by CYP2C9; opioids described as "weak" (codeine, tramadol), anti-depressants and dextromethorphan are metabolized by CYP2D6 and some "potent" opioids (buprenorphine, methadone or fentanyl) by CYP3A4/5. After the usual doses have been administered, drug toxicity or, on the contrary, therapeutic ineffectiveness may occur, depending on polymorphism and the substance. Drug interactions mimicking genetic defects because of the existence of CYP inhibitors and inducers, also contribute to the variable response to analgesics. Some opioids are substrates of P-gp, a transmembrane transporter also subject to genetic polymorphism. However, P-gp could only play a minor modulating role in man on the central effects of morphine, methadone and fentanyl. In the near future, pharmacogenetics should enable us to optimize therapeutics by individualizing our approach to analgesic drugs and making numerous analgesics safer and more effective. The clinical usefulness of these individualized approaches will have to be demonstrated by appropriate pharmacoeconomic studies and analyses.


[Recommendations for the management of bone demineralization in cystic fibrosis].
A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.


Application of phase rotation to STRESS localization scheme at 3 T.
Application of phase rotation to the STRESS (=STEAM+PRESS) localization scheme, to shorten echo time, minimize J-coupling dephasing and estimate B1+ inhomogeneity. STRESS (=STEAM + PRESS) simultaneously refocuses and acquires the double spin echo (SE123 ) and stimulated echo (STE- ) pathways, combining PRESS-like signal with lower chemical shift displacement as in STEAM. Phase rotation effectively separates coherence pathways, allows reduction of spoiling gradients moments leading to reduction in echo time. Implementing it in STRESS allows one to individually phase-correct SE123 and STE- prior to combination. Moreover, B1+ inhomogeneity can be assessed by comparing the measured ratio of resonance intensities of SE123 and STE- pathways to the simulated one. In vivo spectra were acquired from a single voxel placed in the sensory-motor cortex of 10 healthy volunteers, using phase rotation-STRESS/PRESS/STEAM sequences at 3 T scanner. The phases of each slice-selective pulse were incremented by Δϕ1/2/3=22.5°/-45°/45°. Phase rotation-STRESS showed quantification accuracy (% Cramer Rao lower bounds) and reproducibility (% coefficients of variation) comparable to PRESS and STEAM, in both phantoms and in vivo study. Minimal echo time achieved was 13 ms. Phase rotation complements STRESS by reducing echo time, allowing processing of each pathway individually prior to addition and providing B1+ estimation in single voxel proton magnetic resonance spectroscopy. Magn Reson Med 79:2481-2490, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Effects of left atrial and airway pressures on airway blood flow.
The blood flow contributions of the pulmonary and systemic circulations to airway blood flow from the trachea down to the 5th generation airways when either 15 cmH2O positive end expiratory pressure (PEEP) or 20 mmHg left atrial pressure was applied were assessed in anesthetized dogs by injecting 15-microns radiolabeled microspheres into the right and left heart, respectively. After the microsphere injections, the animals were killed, and the tracheal cartilage, tracheal muscle-mucosa, main bronchi and the 2nd generation bronchi down to the 5th generation airways were excised and collected for radioactive counting. The results of this study showed that under normal conditions, tracheal blood flow was primarily systemic (> 95% of total tracheal blood flow) averaging 15-26 ml.min-1 x (100 g)-1, while both the pulmonary [10 ml.min-1 x (100 g)-1] and systemic circulations [15 ml.min-1 x (100 g)-1] contributed substantially to main bronchi blood flow. The systemic blood flow contribution to the lower airway generations (2nd to the 5th generation airways) stayed relatively constant, averaging 13-31 ml.min.(100 g)-1 while the pulmonary blood flow contribution increased significantly in these airway segments to a maximum of over 100 ml.min-1 x (100 g)-1 at the 5th generation. At 15 cmH2O PEEP, the systemic contribution to all of the airway segments (except the 5th generation, P < 0.09) and the pulmonary component to the main bronchi, significantly decreased (P < 0.05). In contrast, elevated left atrial pressure had little effect on the pulmonary and systemic contributions to airway blood flow. The results of this study suggest that elevated PEEP has a greater effect than elevated left atrial pressure on the systemic blood flow contribution to the airways, while the pulmonary blood flow contribution to the airways is affected very little by either of these perturbations.


Metastatic choroidal paraganglioma.
To describe a patient with metastatic choroidal paraganglioma that was locally controlled with radiotherapy. Interventional clinicopathologic case report. One patient with metastatic choroidal paraganglioma. Interventional clinicopathologic case report and systematic search of the literature. Description of clinicopathologic features, treatment methods, and outcome. A 50-year-old man had a nonpigmented atypical choroidal mass with secondary retinal detachment in the left eye. After incisional biopsy, the diagnosis of paraganglioma was established. Metastatic work-up revealed vertebral, mediastinal, and pulmonary metastases of a nonsecretory, malignant paraganglioma without tracer uptake. The primary tumor was not identified. The ocular tumor regressed after stereotaxic radiotherapy. Two years later, recurrent lesions developed in the contralateral eye, which also was irradiated. Malignant paraganglioma can metastasize in the choroid and should be included in the differential diagnosis of a nonpigmented choroidal mass. Stereotaxic radiation therapy is an effective treatment method. To the authors' knowledge, this is the first report of a patient with choroidal paraganglioma. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Bioremediation of Neonicotinoid Pesticide, Imidacloprid, Mediated by Bacillus cereus.
Imidacloprid, a toxic pesticide of the chloronicotinyl category, is employed extensively in agricultural fields, and its exposure causes serious health issues. Biodegradation is considered to be a green and economical approach to remediate pesticides. Herein, imidacloprid degradation efficiency of Bacillus sp. is highlighted, among which Bacillus cereus exhibited the greatest degradation; optimization of experimental variables (pH, imidacloprid and agitation time) via Box-Behnken factorial design and analysis of variance (ANOVA) revealed 92% biodegradation at the initial substrate concentration of 0.03 mM, aerobically in 11 days under favorable pH 7. The subsequent metabolites, identified through liquid chromatography-mass spectrometry, were 5-hydroxy imidacloprid, imidacloprid-guanidine and 6-chloronicotinic acid.


Clinical profile and long term follow up of children and adolescents with prolactinomas.
We report clinical presentation, response to medical treatment, and long-term follow-up of 39 children and adolescents with prolactinoma (F:M; 30:9) (30 macro and 9 microadenoma) diagnosed at the age of 9-20 years. Mean duration of follow up was 56 months. All patients were treated with bromocriptine (BC) at doses ranging from 2.5 to 20 mg/day or by cabergoline at doses ranging from 0.5 to 2 mg/week orally. Two patients received external conventional radiotherapy after surgery. In patients with macroprolactinoma (F:M; 21:9), headache and/or visual defects were the first symptoms. All females had primary or secondary amenorrhea. Growth arrest was not observed in any patient and pubertal development was appropriate for their age. Spontaneous or provocative galactorrhea was observed in 23 patients (all females) and none of male patient had gynecomastia. Mean serum prolactin (PRL) concentration at the time of diagnosis was 322.50 ng/ml in patients with microadenoma, 522.38 ng/ml in patients with macroadenoma and 2,294.86 ng/ml in patients with macroadenoma with suprasellar extension. In 25 patients, BC normalized PRL levels and caused variable, but significant, tumor shrinkage. Cabergoline normalized PRL concentrations in 14 patients. Pregnancy occurred in 6 patients while on treatment. Pregnancies were uncomplicated, and the patients delivered normal newborns at term. Impairment of other pituitary hormone secretion was documented at the time of diagnosis in only one patient. Postoperatively six patients had other pituitary hormone deficiencies. In conclusion, the medical treatment with dopaminergic compounds is effective and safe in patients with prolactinoma with onset in childhood, allowing preservation of the anterior pituitary function.


Maternal-fetal surgery for structural malformations.
Although most prenatally diagnosed correctable anatomic abnormalities are best addressed by surgical interventions after birth, the outcomes of a small number of severe structural malformations with predicted fetal demise or devastating sequelae postnatally may be improved by correction before birth. Consideration of maternal-fetal surgical intervention is restricted to those anatomic malformations that interfere with normal organ development and which, if alleviated, may permit normal development to proceed. Advances in prenatal diagnosis and technical innovations in the surgical approach to the fetus have resulted in an increase in the successful clinical application of fetal intervention over the past 3 decades. The purpose of this review is to describe the current status of maternal-fetal surgery, with a focus on the congenital anomalies most commonly treated by intervention before birth, and to highlight the key areas for further research in this evolving surgical specialty.


PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.


The preoperative triglyceride-glucose index has a positive effect on predicting the risk of short-term restenosis after carotid artery stenting: a retrospective cohort study.
Increasing evidence suggests that insulin resistance is linked to cardiovascular disease and atherosclerosis. The triglyceride-glucose (TyG) index has proven to be a convincing marker to quantitatively evaluate insulin resistance. However, there is no relevant information about the relationship between the TyG index and restenosis after carotid artery stenting. A total of 218 patients were enrolled. Carotid ultrasound and computed tomography angiography were used to evaluate in-stent restenosis. A Kaplan-Meier analysis and Cox regression method were performed to analyze the correlation between TyG index and restenosis. Schoenfeld residuals were used to determine the proportional-hazards assumption. A restricted cubic spline method was used to model and visualize the dose-response relationship between the TyG index and the risk of in-stent restenosis. Subgroup analysis was also performed. Thirty-one participants (14.2%) developed restenosis. The preoperative TyG index had a time-varying effect on restenosis. Within 29 months post-surgery, an increasing preoperative TyG index was linked to a significant increased risk of restenosis (hazard ratio: 4.347; 95% confidence interval 1.886-10.023). However, after 29 months, the effect was decreased, although not statistically significant. The subgroup analysis showed that the hazard ratios tended to be higher in the age ≤ 71 years subgroup (p < 0.001) and participants with hypertension (p < 0.001). The preoperative TyG index was significantly associated with the risk of short-term restenosis after CAS within 29 months post-surgery. The TyG index may be employed to stratify patients based on their risk of restenosis after carotid artery stenting.


Mediastinal computed tomography in myasthenia gravis.
Thirty-six of 119 patients with myasthenia gravis examined by computed tomography for possible thymic mass had a thymectomy. The computed tomographic findings were compared to the findings of chest x-ray and linear tomography and then correlated with the surgical histopathologic results. Computed tomography detected all cases of thymoma or thymic enlargement due to hyperplasia. Chest x-ray correctly demonstrated 50% of thymomas present while linear tomography demonstrated 88%. Computed tomography was not able to distinguish between enlargement due to thymoma or hyperplasia unless calcification was present. The role of computed tomography is detailed and discussed in relationship to the other diagnostic modalities.


Update of the WHO global air quality guidelines: Systematic reviews - An introduction.
This paper aims to serve as an introduction to the Special Issue in Environment International entitled "Update of the WHO Global Air Quality Guidelines: Systematic Reviews". The article has two main objectives. One is to provide the context to this Special Issue, related to (a) policy context, overall exposure to air pollution, and burden of disease attributable to air pollution, and the other is to describe (b) the WHO guideline development process, with special emphasis on the systematic reviews. In particular, this paper presents the systematic reviews and other supporting evidence that was used and discussed during the process and summarizes important methodological information about the approaches taken to conduct the systematic reviews. These approaches include the definition of population, exposure, comparator, outcomes and study design (PECOS) questions, the assessment of the risk of bias in individual studies and the assessment of the overall certainty of the evidence. In summary, the new WHO global air quality guidelines are informed by the best available scientific evidence covering a vast number of research papers published until September 2018, and appraised by experts and stakeholders in the field of air quality. However, research gaps remain and, therefore, further research is warranted.


Metastatic Colonization: Escaping Immune Surveillance.
Cancer immunotherapy has shifted the paradigm in cancer therapy by revitalizing immune responses against tumor cells. Specifically, in primary tumors cancer cells evolve in an immunosuppressive microenvironment, which protects them from immune attack. However, during tumor progression, some cancer cells leave the protective tumor mass, disseminating and seeding secondary organs. These initial disseminated tumor cells (DTCs) should potentially be susceptible to recognition by the immune system in the new host tissues. Although Natural Killer or T cells eliminate some of these DTCs, a fraction escape anti-tumor immunity and survive, thus giving rise to metastatic colonization. How DTCs interact with immune cells and the underpinnings that regulate imperfect immune responses during tumor dissemination remain poorly understood. Uncovering such mechanisms of immune evasion may contribute to the development of immunotherapy specifically targeting DTCs. Here we review current knowledge about systemic and site-specific immune-cancer crosstalk in the early steps of metastasis formation. Moreover, we highlight how conventional cancer therapies can shape the pre-metastatic niche enabling immune escape of newly arrived DTCs.


The role of halofuginone in fibrosis: more to be explored?
Fibrosis, which can be defined as an abnormal or excessive accumulation of extracellular matrix (ECM), particularly fibrillar collagens, is a key driver of progressive organ dysfunction in many inflammatory and metabolic diseases, including idiopathic pulmonary fibrosis (IPF), cirrhosis, nephropathy, and oral submucous fibrosis (OSF). It has been estimated to contribute to ∼45% of deaths in the developed world. Therefore, agents that target specific fibrotic pathways, with the consequence of slowing, arresting, or even reversing the progression of tissue fibrogenesis, are urgently needed. 7-Bromo-6-chloro-3-[3-(3-hydroxy-2-piperidinyl)-2-oxopropyl]-4(3H)-quinazolinone (halofuginone), an analog of febrifugine, which specifically targets the pathogenesis of ECM proteins, inhibits tissue fibrosis and regeneration and even affects the development of tumors in various tissues. Four modes of actions of halofuginone against fibrosis have been presented: 1) Inhibition of mothers against decapentaplegic homolog 3 (Smad3) phosphorylation downstream of the TGF-β signaling pathway, 2) reduction of collagen amounts, 3) decreases in ECM protein, and 4) selective prevention of Th17 cell differentiation. In this review, we will mainly focus on the rationale for halofuginone against fibrosis.


Initial safety analysis of a randomized phase II trial of nelipepimut-S + GM-CSF and trastuzumab compared to trastuzumab alone to prevent recurrence in breast cancer patients with HER2 low-expressing tumors.
The development of HER2-targeted therapy has decreased recurrence rates and improved survival, transforming the natural history of HER2-positive breast cancer. However only a minority of breast cancer patients benefit as these agents are not used in patients with tumors expressing low levels of HER2. Preclinical data suggests a synergistic action of HER2-targeted vaccination with trastuzumab. We report the initial safety interim analysis of a phase II trial that enrolled patients with HER2 low-expressing (IHC 1+/2+) breast cancer who were clinically disease-free after standard therapy. Patients were randomized to receive the HER2-peptide vaccine nelipepimut-S + GM-CSF with trastuzumab (vaccine arm) or trastuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analysis that occurred after enrollment of 150 patients showed no significant differences in toxicity between the two arms, including cardiac toxicity. The clinical efficacy of this combination will be reported 6 months after the final patient was enrolled.


Lysophosphatidic acid activates TGFBIp expression in human corneal fibroblasts through a TGF-β1-dependent pathway.
Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease caused by a R124H point mutation in the transforming growth factor-β-induced gene (TGFBI). However, the cellular role of TGFBI and the regulatory mechanisms underlying corneal dystrophy pathogenesis are still poorly understood. Lysophosphatidic acid (LPA) refers to a small bioactive phospholipid mediator produced in various cell types, and binds G protein-coupled receptors to enhance numerous biological responses, including cell growth, inflammation, and differentiation. LPA levels are elevated in injured cornea and LPA is involved in proliferation and wound healing of cornea epithelial cells. Accumulating evidence has indicated a crucial role for LPA-induced expression of TGFBI protein (TGFBIp) through secretion of transforming growth factor-beta1 (TGF-β1). In the current study, we demonstrate that LPA induces TGFBIp expression in corneal fibroblasts derived from normal or GCD2 patients. LPA-induced TGFBIp expression was completely inhibited upon pretreatment with the LPA(1/3) receptor antagonists, VPC32183 and Ki16425, as well as by silencing LPA(1) receptor expression with small hairpin RNA (shRNA) in corneal fibroblasts. LPA induced secretion of TGF-β1 in corneal fibroblasts, and pretreatment with the TGF-β type I receptor kinase inhibitor SB431542 or an anti-TGF-β1 neutralizing antibody also inhibited LPA-induced TGFBIp expression. Furthermore, we show that LPA requires Smad2/3 proteins for the induction of TGFBIp expression. LPA elicited phosphorylation of Smad2/3, and Smad3 specific inhibitor SIS3 or siRNA-mediated depletion of endogenous Smad2/3 abrogates LPA-induced TGFBIp expression. Finally, we demonstrate that LPA-mediated TGFBIp induction requires JNK activation, but not ERK signaling pathways. These results suggest that LPA stimulates TGFBIp expression through JNK-dependent activation of autocrine TGF-β1 signaling pathways and provide important information for understanding the role of phospholipids involved in cornea related diseases.


A Low-Molecular-Weight Compound Derived from Human Leukocytes Determines a Bactericidal Activity of the Interferon Preparation.
The aim of this study was to characterize the structure and mode of action of antimicrobials derived from a commercial preparation of alfa-interferon. By combination of semi-preparative/analytical reversed-phase high-performance liquid chromatography, we isolated and purified a novel active substance based on carbohydrate with a complex of amino acids, which determines antimicrobial property of commercial preparation of interferon. A size-exclusion chromatography was performed and LC/ESI-MS revealed molecular masses of active substance were in the range of 180-249 Da. Edman sequencing identified phenylthiohydantoin (PTH) derivatives which consisted a set of preliminary (Asp, Glu, Gly, and Ala) and minor amino acids (Leu and Thr) at equimolar ratio. Thus, the purified active substance is a compound containing the complex of amino acids connected with carbohydrate background and called leucidin. Leucidin demonstrated antimicrobial activity against the model Escherichia coli (E. coli) K12 strain at a minimal inhibitory concentration of 20 μg mL-1. The revealed antimicrobial mechanism of action is associated with violation of the bacterial cell wall leading to a SOS response and bacterial autolysis. Despite the preliminary nature of the results, obtained data allowed us to discover the previously unknown leukocyte-derived antimicrobial molecules.


Revamping Biopharmaceutics-Pharmacokinetics with Scientific and Regulatory Implications for Oral Drug Absorption.
The Wagner-Nelson and Loo-Riegelman methods developed in the 1960s and used since for the construction of percent of drug absorbed as a function of time as well as in in vitro in vivo correlations are re-considered in the light of the physiologically sound Finite Absorption Time (F.A.T.) concept developed recently. The classical equations for the percentage of drug absorption as a function of time were modified by taking into account the termination of drug absorption at F.A.T., replacing the parameters associated with the assumption of infinite drug absorption. Mathematical analysis using the relevant Physiologically Based Pharmacokinetic Finite Time (PBFTK) models assuming one- or two-compartment drug disposition, revealed that the modified %absorbed versus time curves are of bilinear type with an ascending limb intersecting the horizontal line at F.A.T. A computer-based methodology is described for the estimation of F.A.T. from experimental data. More than one linear ascending limb is found when more than one absorption phase is operating. Experimental data were analyzed and the estimates for F.A.T were found to be similar to those derived from nonlinear regression analysis using PBFTPK models. These results place an end to the routinely reported exponential %absorbed versus time curves prevailing in biopharmaceutics-pharmacokinetics since their inception in the'60 s. These findings point to the use of the F.A.T. concept in drug absorption research and regulatory guidelines such as deconvolution techniques for the assessment of drug input rate, stochastic mean absorption time calculations, population analyses, in vitro in vivo correlations and bioequivalence guidelines.


Measuring the activity of leucine-rich repeat kinase 2: a kinase involved in Parkinson's disease.
Mutations in the LRRK2 (Leucine-Rich Repeat Kinase 2) gene are the most common cause of autosomal dominant Parkinson's disease. LRRK2 has multiple functional domains including a kinase domain. The kinase activity of LRRK2 is implicated in the pathogenesis of Parkinson's disease. Developing an assay to understand the mechanisms of LRRK2 kinase activity is important for the development of pharmacologic and therapeutic applications. Here, we describe how to measure in vitro LRRK2 kinase activity and its inhibition.


Licofelone: the answer to unmet needs in osteoarthritis therapy?
Licofelone, a competitive inhibitor of cyclooxygenases 1 and 2 and 5-lipoxygenase enzyme, is under clinical evaluation for its effectiveness in the treatment of osteoarthritis (OA). Licofelone decreases the production of both prostaglandins and leukotrienes and has been shown to possess a combination of analgesic or anti-inflammatory effects with a promising gastrotolerability profile. Available clinical data have shown that licofelone is at least as effective as the conventional nonsteroidal anti-inflammatory drugs or coxibs in ameliorating the symptoms of OA, but it may offer the advantage of improved gastrotolerability and fewer or no incidences of worsened peripheral edema. Last, further evidence suggests that it could be a suitable alternative for the long-term treatment of a wide population of patients with OA. The preset review describes the status of licofelone in the treatment of OA.


Auditory hallucinations and reduced language lateralization in schizophrenia: a meta-analysis of dichotic listening studies.
Reduced left-hemispheric language lateralization has been proposed to be a trait marker for schizophrenia, but the empirical evidence is ambiguous. Recent studies suggest that auditory hallucinations are critical for whether a patient shows reduced language lateralization. Therefore, the aim of the study was to statistically integrate studies investigating language lateralization in schizophrenia patients using dichotic listening. To this end, two meta-analyses were conducted, one comparing schizophrenia patients with healthy controls (n = 1407), the other comparing schizophrenia patients experiencing auditory hallucinations with non-hallucinating controls (n = 407). Schizophrenia patients showed weaker language lateralization than healthy controls but the effect size was small (g = -0.26). When patients with auditory hallucinations were compared to non-hallucinating controls, the effect size was substantially larger (g = -0.45). These effect sizes suggest that reduced language lateralization is a weak trait marker for schizophrenia as such and a strong trait marker for the experience of auditory hallucinations within the schizophrenia population.


Sex allocation in a field population of an autoparasitoid.
Autoparasitoid wasps lay fertilized eggs in homopteran nymphs, and these eggs develop into female primary parasitoids. Unfertilized, male-producing eggs are laid in immatures of the wasps' own or another primary parasitoid species; males then develop as secondary or hyperparasitoids. In the population of Encarsia pergandiella studied in Ithaca, NY, fertilized eggs were laid in the nymphs of the whitefly Trialeurodes packardi (primary hosts) and unfertilized eggs were laid almost exclusively in pupal females of their own species (secondary hosts). In the two years the population was studied, secondary hosts were always much less abundant than primary hosts at both sites. However, secondary hosts were parasitized at a significantly greater rate than primary hosts. In a laboratory experiment, the encounter rate of females with primary and secondary hosts was not significantly different. Moreover, there was no evidence from the field that wasps found leaves bearing secondary hosts more frequently than leaves without secondary hosts. Dissections of field-collected females showed them to be mated, and thus capable of laying both unfertilized and fertilized eggs. These results suggest that wasps did not encounter secondary hosts at a greater rate, nor were they constrained to lay unfertilized eggs, but rather secondary hosts were preferred. The oviposition sex ratios were influenced by the proportion of secondary hosts, but were less female-biased than would be predicted from the proportion of secondary hosts alone. The results do not support the predictions of Godray and Waage (1990) for either strictly host-limited autoparasitoids (sex ratio should reflect the proportion of secondary hosts) or for egg-limited autoparasitoids (sex ratio should be equal, and independent of the proportion of secondary hosts).


Flexible nano- and microliter injections on a single liquid chromatography-mass spectrometry system: Minimizing sample preparation and maximizing linear dynamic range.
Lack of knowledge on the expected concentration range or insufficient linear dynamic range of the analytical method applied are common challenges for the analytical scientist. Samples that are above the upper limit of quantification are typically diluted and reanalyzed. The analysis of undiluted highly concentrated samples can cause contamination of the system, while the dilution step is time consuming and as the case for any sample preparation step, also potentially leads to precipitation, adsorption or degradation of the analytes.


Comparative study of small-incision lenticule extraction and phakic intraocular lens implantation for the correction of high myopia: 6-year results.
To compare the long-term safety, efficacy, and complications of small-incision lenticule extraction (SMILE) and flexible iris-fixated anterior chamber phakic intraocular lens (pIOL) implantation for the treatment of high myopia. University of Health Science Turkey, Beyoğlu Eye Training and Research Hospital, İstanbul, Turkey. Retrospective comparative case series. Data of patients who underwent SMILE or pIOL (Artiflex) implantation for myopia were retrospectively reviewed. Only patients with preoperative manifest refraction spherical equivalent from -6.00 to -10.00 diopters (D) were included in the study. There were 47 eyes of 32 patients in the SMILE group and 52 eyes of 29 patients in the pIOL group. The mean postoperative follow-up was 63.75 ± 18.40 months in the SMILE group and 65.38 ± 16.22 months in the p-IOL group (P = .71). At 6 years postoperatively, refractive predictability was slightly better in the pIOL group, and the percentages of eyes within ±0.50 D of the attempted correction were 77% and 83% in the SMILE and pIOL groups, respectively. Although mean uncorrected distance visual acuity was comparable (SMILE, 0.12 ± 0.06 logarithm of the minimum angle of resolution [logMAR]; p-IOL, 0.09 ± 0.05 logMAR), the safety indices (1.08 ± 0.22 vs 1.11 ± 0.20; P = .02) and the efficacy indices (0.92 ± 0.24 vs 1.11 ± 0.22; P = .03) were statistically significantly higher after pIOL implantation. Despite a mean of 11.09% of the endothelial cell being lost at 6 years after pIOL implantation, no pIOL was explanted due to endothelial cell loss. In this comparative and long-term study, iris-fixated anterior chamber pIOL implantation for high myopic correction showed slightly better safety and efficacy profiles but with statistically significant endothelial cell loss.


Immunochemical observations of antigen 5, a major venom allergen of hornets, yellowjackets and wasps.
Antigen 5 is a venom protein of hornets, yellowjackets and wasps, and it is an important allergen for insect-sensitive patients. Antigen 5s from these insects are found to have similar amino-terminal sequences for their first 20 residues, and to have similar cyanogen bromide cleavage patterns. A partial sequence homology of antigen 5s and scorpion neurotoxins is observed. Antigen 5s from these insects show varying extents of cross reactivity when tested with mouse polyclonal antibodies by enzyme immunoassay and they show limited or no cross reactivity with mouse monoclonal antibodies. Chemically modified antigen 5s shown greatly decreased binding of antigen 5-specific mouse polyclonal antibodies. The modified antigen 5s include its reduced and carboxymethylated


The effects of late turnout on the epidemiology and control of ostertagiasis in calves.
The main purpose of this experiment was to study the importance of time of turnout on the epidemiology and impact of ostertagiasis in calves pastured for the first time. When time of turnout onto permanent pasture was postponed from mid-May to mid-June, fewer overwintered larvae were picked up and re-contamination of pastures was markedly diminished. Consequently, the acquisition of loss-producing parasite burdens in the late part of the season was significantly reduced. Late turnout as a control strategy is discussed in relation to other preventive measures.


Mastectomy without radiotherapy: outcome analysis after 10 years of follow-up in a single institution.
The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10 years. Overall survival was 89.8 % at 5 years and 76.6 % at 10 years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1-3, 4-9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences (n = 16, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67 ≥ 20 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for recurrences in the regional LNs. Moreover, within each category of positive LNs, high values of Ki-67 and extensive PVI were associated with the highest risk of LRR while low values of Ki-67 and absence of extensive PVI were associated with the lowest risk of LRR. Women with node-negative tumors have the lowest risk of LRR and represent the group of patients that might benefit the least from radiotherapy. PVI and Ki-67 might help tailoring PMRT indications among patients with positive LNs. Finally, the very low incidence of recurrences in the axillary LNs raises questions about the inclusion of the axilla in the radiation field.


Dielectrophoretic ultra-high-frequency characterization and in silico sorting on uptake of rare earth elements by Cupriavidus necator.
Rare earth elements (REEs) are widely used across different industries due to their exceptional magnetic and electrical properties. In this work, Cupriavidus necator is characterized using dielectrophoretic ultra-high-frequency measurements, typically in MHz range to quantify the properties of cytoplasm in C. necator for its metal uptake/bioaccumulation capacity. Cupriavidus necator, a Gram-negative bacteria strain is exposed to REEs like europium, samarium, and neodymium in this study. Dielectrophoretic crossover frequency experiments were performed on the native C. necator species pre- and post-exposure to the REEs at MHz frequency range. The net conductivity of native C. necator, Cupriavidus europium, Cupriavidus samarium, and Cupriavidus neodymium are 15.95 ± 0.029 μS/cm, 16.15 ± 0.028 μS/cm, 16.05 ± 0.029 μS/cm, 15.61 ± 0.005 μS/cm respectively. The estimated properties of the membrane published by our group are used to develop a microfluidic sorter by modeling and simulation to separate REE absorbed C. necator from the unabsorbed native C. necator species using COMSOL Multiphysics commercial software package v5.5.


Overexpression of SlMBP22 in Tomato Affects Plant Growth and Enhances Tolerance to Drought Stress.
MADS-box transcription factors play crucial and diverse roles in plant growth and development, and the responses to biotic and abiotic stresses. However, the implementation of MADS-box transcription factors in regulating plant architecture and stress responses has not been fully explored in tomato. Here, we found that a novel MADS-box transcription factor, SlMBP22, participated in the control of agronomical traits, tolerance to abiotic stress, and regulation of auxin and gibberellin signalling. Transgenic plants overexpressing SlMBP22 (SlMBP22-OE) displayed pleiotropic phenotypes, including reduced plant height and leaf size, by affecting auxin and/or gibberellin signalling. SlMBP22 was induced by dehydration treatment, and SlMBP22-OE plants were more tolerant to drought stress than wild-type (WT). Furthermore, SlMBP22 overexpression plants accumulated more chlorophyll, starch and soluble sugar than WT, indicating that the darker green leaves might be attributed to increased chlorophyll levels in the transgenic plants. RNA-Seq results showed that the transcript levels of a series of genes related to chloroplast development, chlorophyll metabolism, starch and sucrose metabolism, hormone signalling, and stress responses were altered. Collectively, our data demonstrate that SlMBP22 plays an important role in both regulating tomato growth and resisting drought stress.


Dataset on in-vitro study of chitosan-graphene oxide films for regenerative medicine.
Chitosan (CS) is well-known for its biological properties, especially its ability to induce tissue cicatrization. However, considerable research proved that CS presents a high inflammatory response and poor mechanical properties. For these reasons, we decided to use chitosan (CS) functionalized GO by a covalent bond (CS-GO). Due to the resistant structure of the GO and the high presence of oxygen functional groups on it, it will enhance the biocompatibility of the material. The data obtained in this investigation aimed to prove the possible application of CS-GO in regenerative medicine. For this reason, it was performed an In vitro analysis using brine shrimp to prove materials biocompatibility and gingival fibroblasts for a cell growth test.


Characterization of a distinct low-grade oncocytic renal tumor (CD117-negative and cytokeratin 7-positive) based on a tertiary oncology center experience: the new evidence from China.
To examine the clinicopathologic and immunohistochemical features of a group of newly defined low-grade oncocytic renal tumors (LOT) that have the "CD117 negative/cytokeratin (CK)7 positive" immunoprofile. We have queried our hospital database and found 4456 consecutive renal tumors between 2016 and 2019. Among these renal tumors, eight (8) cases meet the morphologic and immunohistochemical characterization for low-grade oncocytic renal tumor (LOT). The eight (8) patients' mean age is 56.6 years (range 39-70 years old), and the male to female ratio is 1:1. Macroscopically, these LOTs generally present with tan-brown and solid cut surfaces and demonstrate similar solid, compact nested growth pattern microscopically. Tumor cells exhibit oncocytic cytoplasm and uniformly rounded to oval nuclei. There are areas of edematous stroma containing dispersed single or small clustered tumor cells. All tumors are negative for CD117 and positive for CK7. Uniform reactivity is also found for BerEP4, cyclin D1, and SDHB. Besides, CD10, vimentin, and AMACR are either negative or only focally positive. All of the tumors are negative for CA9 and TFE. The Ki-67 index is less than 5% in the seven (7) internal cases. Seven (7) of the eight (8) patients who are available for follow-up are alive and without disease recurrence (mean follow-up period of 21.6 months, ranging from 6 to 43 months). We described a group of low-grade oncocytic renal tumors identified retrospectively in a large tertiary cancer center, which was probably the first report originated from China or even Asia in the English literature so far. These tumors demonstrated eosinophilic cytoplasm and low-grade appearing nuclei with a "CD117 negative/CK7 positive" immunoprofile. The incidence rate was about 3.7% of the oncocytic renal tumors and 0.18% of all the renal tumors that were received in our lab during the four-year period. It is necessary to separate this group of tumors by its characteristic morphologic and immunophenotypic features.


Parathyroidectomy leads to decreased blood lead levels in patients with refractory secondary hyperparathyroidism.
Secondary hyperparathyroidism (SHPT) is characterized by high bone turnover and may result in increased release of lead (Pb) from bone stores. Parathyroidectomy (PTX) drastically changes bone remodeling. This study investigated the effects of PTX on the levels of blood lead (blood Pb) in patients with refractory SHPT. The study included 30 patients on long-term hemodialysis (HD) who underwent PTX in the nephrology units of two Taiwanese hospitals. Changes in serum levels of intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BAP), type 5b tartrate-resistant acid phosphatase (TRAP), total calcium (tCa), and blood Pb were analyzed. After PTX, serum iPTH was markedly decreased while serum BAP was progressively increased and peaked 2weeks after PTX. Serum TRAP levels were progressively decreased during the 4week follow-up period. Serum tCa and blood Pb levels decreased sharply immediately after PTX. There was a positive correlation between the percentage of decrease in tCa and blood Pb at one day after PTX. Further analysis indicated a significant positive correlation between levels of blood Pb and serum iPTH (r=0.378, p<0.001), blood Pb and serum TRAP (r=0.180, p<0.05), and a negative correlation between blood Pb and serum BAP (r=-0.205, p<0.05). PTX effectively suppressed the elevated levels of blood Pb and serum bone remodeling markers, which are common features of SHPT. In addition to decreased Pb release from bone, an increased store of Pb in bone may play a role in decreasing serum blood Pb levels. These findings suggest that patients undergoing PTX for refractory SHPT should strictly avoid environmental exposure to Pb.


Effect of flosequinan upon isoenzymes of phosphodiesterase from guinea-pig cardiac and vascular smooth muscle.
The effect of flosequinan and its sulphone metabolite BTS 53,554, on phosphodiesterase isoenzymes isolated from guinea-pig cardiac and vascular smooth muscle using DEAE-cellulose chromatography was investigated. Zaprinast and milrinone showed peak I and peak III selectivity, and IBMX non-selective activity respectively, against both cardiac and vascular smooth muscle isoenzymes, as expected for these reference inhibitors. Flosequinan and BTS 53,554 demonstrated non-selective inhibition with similar potency against both cardiac and vascular smooth muscle isoenzymes and, overall, were the least potent compounds tested. The high inhibitory concentrations observed (IC50 peak III 660 microM for cardiac tissue and 230 microM for vascular smooth muscle with flosequinan) relative to its clinically effective plasma concentration (10 microM) questions the relevance of phosphodiesterase inhibition to the efficacy of flosequinan in heart failure.


A monoclonal antibody specific for immunoglobulin A receptor triggers polymorphonuclear neutrophil superoxide release.
An immunoglobulin M (IgM) monoclonal antibody, My43, specific for IgA Fc receptor (Fc alpha R) on human monocytes, bound to human polymorphonuclear neutrophils (PMNs) and inhibited their ability to bind IgA but not IgG. It was observed that the PMN oxidative burst was induced by both polymeric IgA and aggregated IgG, whereas IgM was without effect. The IgG-mediated oxidative burst was inhibited by anti-Fc gamma RII Fab and anti-Fc gamma RIII F(ab')2 but not by My43. Conversely, the IgA-mediated oxidative burst was inhibited by My43 but not by anti-Fc gamma RII or anti-Fc gamma RIII. When anti-Fc receptor monoclonal antibodies (mAbs) were used directly as ligands, it was observed that both anti-Fc gamma RII Fab and anti-Fc gamma RII F(ab')2 promoted the oxidative burst when cross-linked. Moreover, My43, when cross-linked with F(ab')2 antimouse IgM, also triggered the oxidative burst, whereas an IgM anti-CD15 mAb, PM81, did not stimulate function. This demonstrates that IgA receptors on PMNs are function-triggering molecules and that an anti-IgA receptor mAb may be substituted as a ligand.


Our PDT experience in the treatment of non-melanoma skin cancer over the last 7 years.
Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) was first described by Kennedy et al. in 1990; currently, accumulated evidence shows that topical PDT is effective in the treatment of actinic keratoses, Bowen's disease and superficial basal cell carcinoma, being potentially advantageous where size, anatomical location or number of lesions limit the efficacy and/or the acceptability of conventional therapies. It involves the use of photosensitizing drugs and the administration of an appropriate light source to activate the sensitizing agent, which leads to the production of activated oxygen species for tissue destruction. The topically administered prodrug 5-ALA is converted within cells into the active photosensitizer protoporphyrin IX, via haem cycle, with preferential accumulation in tumour cells. The authors describe their experience with topical PDT, using 20% 5-ALA and two different incoherent light sources, 'Waldman 1200 L' and 'VersaLight', in the treatment of non-melanoma skin cancer and precursor lesions. More than 100 patients were treated since 1997, with up to a 7-year follow-up period. Cases are illustrated and results are presented and discussed in the light of the relevant Literature. The study suggests that 5-ALA PDT is effective in the treatment of superficial skin cancer and premalignant lesions.


Cardiac troponin T determination by a highly sensitive assay in postmortem serum and pericardial fluid.
The main objective of this study was to test, for the first time, a highly sensitive cardiac troponin T (cTnThs) assay in postmortem serum and pericardial fluid and to evaluate cardiac troponin T (cTnT) levels and their stability after death at different postmortem intervals, in an attempt to determine the viability of the cTnThs assay in the postmortem diagnosis of the cause of death. cTnT levels were determined in serum and pericardial fluid samples taken from 58 cadavers at known postmortem intervals, whose causes of death were categorized into the following groups: (1) sudden cardiac deaths, (2) multiple trauma, (3) mechanical asphyxia, and (4) other natural deaths. cTnT was determined by inmunoassay, using the Troponin T highly sensitive STAT assay (Roche(®)). Average cTnT levels measured by a highly sensitive assay in postmortem serum were markedly higher than clinical serum levels. Moreover, similar results, higher cTnT levels in postmortem pericardial fluid, were obtained when compared to levels found in pericardial fluid taken from two living patients during coronary artery bypass surgery. cTnT levels in both postmortem fluids remained stable for up to 34 h after death. No differences in cTnT levels in either postmortem fluid by sex and age were detected. Levels of cTnT found in pericardial fluid in the other natural deaths group were significantly lower than the cTnT levels found in that postmortem fluid from any of the other causes of death groups. It is therefore reasonable to conclude that determination of cTnT by a highly sensitive assay in pericardial fluid can provide forensic pathologists with a complementary test to the diagnosis of cause of death.


[Danazol in the treatment of menometrorrhagia in patients with mitral prosthesis treated with warfarin].
The difficulty in the treatment of patients undergoing Warfarin therapy for mitral stenosis, is underlined and cases treated with Danazol in sideropenic anaemia caused by menometrorrhagia are reported.


Quantitative analysis of ovarian cysts and tumors by using T2 star mapping.
The aim of this study was to investigate the efficacy of T2 star (T2*) mapping in diagnosing ovarian cysts/ tumors. Pelvic magnetic resonance examinations including T2*WI were performed before surgery in 35 patients. The region of interest, consisted of a 10 mm2 diameter circle, was set as much as possible inside ovarian tumors/cysts to measure T2*values, and mean T2* values were compared in ovarian cyst/tumor types, retrospectively. Diagnoses of 40 ovarian cysts/tumors were determined by pathological reports, in which 17 were endometriomas, 13 were mature cystic teratomas, 6 were mucinous cystadenomas and 4 were serous cystadenomas. The average T2* values of endometrioma was 56.8 ± 8.7 ms (mean ± SEM), which was significantly lower than that of mucinous cystadenoma (334.2 ± 58.5 ms, mean ± SEM) or serous cystadenoma (237.0 ± 45.4 ms, mean ± SEM). There was no difference in T2* values between endometrioma and mature cystic teratoma (64.1 ± 22.6 ms, mean ± SEM). Receiver operating characteristics curve analysis revealed that optimal cut-off value for differential diagnosis of endometrioma and mucinous or serous cystadenoma was 149.2 ms as T2* value, which has an area under the curve of 0.95 (sensitivity = 92.4%, specificity = 78.6%). T2* values were useful to diagnose various types of ovarian cyst/tumor.


Generation and agglomeration behaviour of size-selected sub-nm iron clusters as catalysts for the growth of carbon nanotubes.
Mass-selected, ligand-free Fe(N) clusters with N = 10-30 atoms (cluster diameter: 0.6-0.9 nm) were implanted into [Al@SiO(x)] surfaces at a low surface coverage corresponding to a few thousandths up to a few hundredths of a monolayer in order to avoid initial cluster agglomeration. These studies are aimed towards gaining an insight into the lower limit of the size regime of carbon nanotube (CNT) growth by employing size-selected sub-nm iron clusters as catalyst or precatalyst precursors for CNT growth. Agglomeration of sub-nm iron clusters to iron nanoparticles with a median size range between three and six nanometres and the CNT formation hence can be observed at CVD growth temperatures of 750 °C. Below 600 °C, no CNT growth is observed.


Mutations in the lipoprotein lipase gene as a cause of hypertriglyceridemia and pancreatitis in Taiwan.
Familial lipoprotein lipase (LPL) deficiency is inherited as an autosomal recessive trait and is characterized by chylomicronemia, eruptive xanthoma, hepatosplenomegaly, and recurrent pancreatitis. Two unrelated Chinese of Han descent with hypertriglyceridemia were enrolled in this study, and another six Han Chinese with no family history of hypertriglyceridemia and diabetes were recruited as normal controls. LPL activity was determined with use of an artificial substrate of 14C-trioleine and Arabic gum, and release of 14C free fatty acid was determined by the liquid-liquid partitioning system. LPL mass was measured by enzyme immunoassay. Genomic DNA was extracted from EDTA-preserved whole blood, and PCR was used to amplify the nine coding exons and the minimal promoter of the LPL gene. DNA sequence analysis revealed that mutations were identified in both patients; one patient had compound heterozygous mutations in codon 252 [CTG(Leu) --> GTG(Val)] and in codon 264 [TGC(Cys) --> TGa(Ter)] of exon 6, and the other patient had homozygous L252V mutation. These subjects had > or =90% reduction in LPL mass and > or =60% reduction in LPL activity. The mutated and truncated LPLs caused hypertriglyceridemia in these patients in Taiwan with hypertriglyceridemia and pancreatitis.


Successful transplant outcomes using pediatric en bloc kidneys into adult recipients.
En bloc pediatric kidneys have been used in adult renal transplantation for over 30 years. Despite the duration of this experience, issues such as increased technical difficulties and associated complications, hyperfiltration injury, and ultimately a limited allograft half-life have limited the use of these organs at many centers. To date, however, the collected experience suggests that these organs may in fact be an excellent source of allografts for adult transplantation. The present paper was a retrospective review of the experience using en bloc kidneys for adult transplantation from two institutions. These results support the use of these kidneys. Actual patient and graft survival at 2 years was 97% and 94% respectively.


Determination of metoprolol and two major metabolites in plasma and urine by column liquid chromatography and fluorometric detection.
Metoprolol and its alpha-hydroxy metabolite were determined in plasma down to 2 nmol/l (S.D. 10-15%) after solvent extraction and bonded-phase liquid chromatography with fluorometric detection. The major metabolite with a carboxylic function was also measured in plasma when liquid-solid extraction on a column activated with dodecyl sulphate was applied. In urine the three components were assayed by direct injection of a diluted sample.


Inhibitory effects of apple peel polyphenol extract on the formation of heterocyclic amines in pan fried beef patties.
The efficacy of polyphenol-rich dried apple peel extract (DAPP) to inhibit the formation of heterocyclic aromatic amines (HCAs) during frying of beef patties was assessed after DAPP was applied at 0.1, 0.15 and 0.3% (w/w) either on the surface of the patties or mixed inside the patty prior to frying. 2-Amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx), 2-amino-1-ethyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were quantified after frying. HCA concentrations decreased (p<0.05) upon both surface and mixed applications of DAPP at all of the tested doses. Surface application of 0.3% DAPP showed greater (p<0.05) inhibitory effects on HCA formation by 68% for MeIQx, 56% for 4,8-DiMeIQx and 83% for PhIP as opposed to 41%, 21% and 60% respectively, for the mixed DAPP application of 0.3%. The present study results indicate that surface application of DAPP in meat preparation prior to pan-frying can be a useful approach to minimize the formation of genotoxic HCAs in fried beef patties.


Association between activity restriction due to fear of falling and mortality: Results from the Korean longitudinal study of aging.
To analyze the correlation between activity restriction due to fear of falling and mortality among Koreans aged ≥45 years. After excluding missing values, the data of 411 participants from the first to sixth waves of the Korean Longitudinal Study of Aging were analyzed using the χ2 -test, log-rank tests and Cox proportional hazards model. In model 1, which did not include activity restriction due to fear of falling as an independent variable, the death rate increased by 1.024-fold (hazard ratio 1.024, 95% confidence interval 1.000-1.050, P = 0.0498) as the number of falls increased by one. In model 2, which included activity restriction due to fear of falling as an independent variable, participants with experience of activity restriction showed 1.993-fold higher mortality (hazard ratio 1.993, 95% confidence interval 1.112-3.572, P = 0.0205) than those without such experience. In addition, as the number of falls in the group with chronic diseases increased by one, the mortality rate increased by 1.028-fold (hazard ratio 1.028, 95% confidence interval 1.001-1.057, P = 0.043). There was a close relationship between activity restriction due to fear of falling and mortality. Therefore, this study can serve as the foundation for policies and institutional measures to reduce the mortality rate of groups with activity restrictions due to fear of falling. Geriatr Gerontol Int 2022; 22: 168-174.


Pelvic floor electrical stimulation for genuine stress incontinence: who will benefit and when?
This study sought to determine the characteristics of women in whom pelvic floor electrical stimulation will reduce stress urinary incontinence. It also evaluates how long electrical stimulation should be used before significant improvements are seen in clinical outcomes. Subjects with genuine stress incontinence were enrolled into a multicenter non-randomized trial. They used electrical stimulation for 15 minutes twice daily or every other day for 20 weeks. At the end of 20 weeks, those with a 50% reduction in leakage episodes on voiding diary ('responders') were compared with those who did not show a 50% reduction ('non-responders'). Thirty-one subjects were enrolled and 28 completed the study. After the treatment period, 19 subjects were defined as responders and 9 as non-responders. There were no significant differences between the two groups in baseline demographics (e.g. age, parity, largest birth weight etc.) other than body mass index (greater in nonresponders). Significant subjective and objective improvements were noted among responders by 10 and 14 weeks, respectively. Compliance was higher in responders during weeks 12-15 of the study (P=0.05). It was concluded that a minimum of 14 weeks of pelvic floor stimulation was necessary before significant objective improvements were seen. Body mass index and patient compliance may affect success.


Two distinct epitopes on the ovalbumin 323-339 peptide differentiating CD4⁺T cells into the Th2 or Th1 phenotype.
The epitopes for OVA323-339-specific CD4⁺T cells from OVA23-3 food allergy model and DO11.10 tolerant induction model mice were analyzed. We found that OVA23-3 CD4⁺T cells recognized the N-terminal region, showing strong proliferation and the Th2-phenotype, and that DO11.10 CD4⁺T cells recognized the C-terminal region, showing milder proliferation and a Th1-skewed response. These differences may regulate the responses of those mice to OVA-feeding, inflammation and tolerance.


Comparison of compressed sensing and conventional coronary magnetic resonance angiography for detection of coronary artery stenosis.
This study aimed to compare the efficacy of compressed sensing (CS) and conventional coronary magnetic resonance angiography (CMRA) in detecting coronary artery stenosis. Twenty-eight patients underwent 3 T contrast-enhanced CS and conventional CMRA; for late gadolinium enhancement (LGE) imaging, 0.1 mmol/kg gadolinium medium was infused. CS CMRA was scanned within the LGE waiting time. After the LGE image acquisition, conventional CMRA was performed. The diagnostic performance of both CMRA for the detection of significant stenosis was evaluated using coronary angiography as a reference. The analysis was conducted to examine the three main coronary artery vessels: left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). These arteries were subdivided into 8 segments (LAD; main, proximal, and middle, LCX; proximal and distal, RCA; proximal, middle, and distal). Of these, hypoplastic segments and vessels after coronary stent implantation were excluded. The acquisition time of CS CMRA was compared with that of conventional CMRA. The coronary arteries were evaluated in 197 segments. The sensitivity, specificity, and accuracy of CS CMRA in detecting significant stenosis were 85.2 %, 82.5 %, and 83.2 %, respectively, on a per-segment basis. Those of conventional CMRA were 85.2 %, 86.7 %, and 86.3 %, respectively. The acquisition time was 207 s (range, 144-258 s) for CS and 975 s (range, 787-1226s) for conventional CMRA (p < 0.001). Similar to conventional CMRA, CS CMRA has shown potential for the detection of significant coronary artery stenosis.


Sulfated polysaccharides from Undaria pinnatifida improved high fat diet-induced metabolic syndrome, gut microbiota dysbiosis and inflammation in BALB/c mice.
Undaria pinnatifida was shown to reduce serum lipids and fat accumulation and produce beneficial effect on type 2 diabetes, but its effect on intestinal micro-ecology remains unclear. This study showed that sulfated polysaccharides from U. pinnatifida (UPSP) reduced weight gain, fat accumulation and metabolic disorders in mice fed with high fat diet (HFD). UPSP not only alleviated HFD-induced microbiota dysbiosis indicated as increased abundances of some Bacteroidales members that had positive correlations with the improvement of physiological indexes, but also maintained gut barrier integrity and reduced metabolic endotoxemia. A dose-effect relationship was observed between the dose of UPSP and its effect on some physiological indexes, gut microbiota community and nutrient utilization. The in vitro result showed that the use of Bacteroides species within Bacteroidales on UPSP was species-dependent, and the dose of UPSP affected the growth properties of some Bacteroides species. It implied that UPSP can be considered as prebiotic agent to prevent gut dysbiosis and obesity-related diseases in obese individuals.


[A clinical study on memory function in climacteric and periclimacteric women].
This study was designed to investigate memory function in climacteric and periclimacteric women who lived a normal, ordinary life. Two hundred women treated at the gynecological outpatient clinic of Koshigaya Hospital were divided into 7 groups: groups A(31-35 yr), B(36-40 yr), C(41-45 yr), D(46-50 yr), E(51-55 yr), F(56-60 yr) and G(61-65 yr). Each group consisted of 30 women except group G(n = 20). The memory function of each group was determined and the mean scores for 10 paired hard-associates after three trials of presentation were compared. The mean scores (+/- SD) for groups A and B were 8.0 +/- 2.0 and 8.2 +/- 1.7, respectively, which were not statistically different. The scores for both groups were significantly higher than those for the other groups (p < 0.01). The mean scores for groups C and D were 5.9 +/- 2.1 and 5.6 +/- 2.4, respectively, which were not statistically different. The score for group C was significantly higher than those for groups E(4.5 +/- 2.4), F(4.2 +/- 2.2), and G(3.3 +/- 1.6) (p < 0.05). The score for group D was significantly higher than those for groups F and G(p < 0.05). The score for group E was significantly higher than that for group G(p < 0.01). The decrease in memory function was the greatest in group C. In the climacterium, memory impairment was also observed in group E. The former corresponds to the climacteric commencement age group where cyclic changes in serum estrogen levels decrease or cease, and the latter corresponds to the age group for menopause.(ABSTRACT TRUNCATED AT 250 WORDS)


Cold-inducible PPA1 is critical for the adipocyte browning in mice.
Promoting the thermogenic capacity of brown/beige adipocytes is becoming a promising strategy to counteract obesity and related metabolic diseases. Inorganic pyrophosphatase 1 (PPA1) is an enzyme that catalyzes the hydrolysis of PPi to Pi, and its presence is required for anabolism to take place in cells. Our previous study demonstrated the importance of PPA1 in maintaining adipose tissue function and whole-body metabolic homeostasis. In this study, we found that the expression of PPA1 was positively associated with the thermogenic capacity of brown/beige adipocytes. PPA1+/- mice exhibited less browning capacity in subcutaneous white adipose tissue compared to wild-type mice and also showed apparent cold intolerance. We found that decreased PPA1 abundance may lead to mitochondrial dysfunction and inhibited adipocyte browning both in vivo and in vitro. Furthermore, our study also revealed that PPA1 worked as a new target gene of nuclear respiratory factor 1 (NRF1), a major transcription regulator of mitochondrial biogenesis. Together, our findings indicated an essential role of PPA1 in mitochondrial function and browning in adipocytes and suggested PPA1 as a new therapeutic target for increasing thermogenesis to combat obesity and metabolic diseases.


Ornamental plants adapted to urban ecosystem pollution: lawn grasses and painted daisy tolerating copper.
Lawns and flower are major aesthetical and environmental elements of the urban ecosystem. However, harsh urban conditions such as pollution by heavy metals are unfavorable for plants. For example, copper is toxic for ornamental plants, limiting the spread of lawn grass and flowering plants. Therefore, here we hypothesized that plants could be adapted to urban conditions by breeding. We first showed the possibility of using environmental biotechnology in urban greening to obtain, tolerating copper flowering plants and lawn grasses. We tested the adaptation of creeping bentgrass (Agrostis stolonifera L.) and painted daisy (Chrysanthemum carinatum Schousb.) to сopper. We measured Cu resistance in the next generations of those plant species. Results show that some next generations of plant regenerants have increased resistance up to 100 mg/kg Cu for Agrostis stolonifera, and up to 30 mg/kg for Chrysanthemum carinatum. Our findings thus imply that city plants may be adapted and improved by сell selection. Our approach thus represents a novel biotechnology consisting of adapting plants to pollution by сell selection.


Correction to Boosting the Oxygen Evolution Reaction Activity of NiFe2O4 Nanosheets by Phosphate Ion Functionalization.
[This corrects the article DOI: 10.1021/acsomega.8b03081.].


Iminyl radicals from alpha-azido o-iodoanilides via 1,5-H transfer reactions of aryl radicals: new transformation of alpha-azido acids to decarboxylated nitriles.
The radical reaction of tributyltin hydride with o-iodo- N-methylanilides derived from alpha-azido acids provides an excellent access to alpha-(aminocarbonyl)iminyl radicals through 1,5-hydrogen transfer reaction of initially formed aryl radicals followed by beta-elimination of dinitrogen from ensuing alpha-azido-alpha-(aminocarbonyl)alkyl radicals. The outcoming iminyls display a peculiar tendency to form corresponding nitriles by beta-elimination of aminocarbonyl radicals.


Kluyveromyces lactis and Saccharomyces cerevisiae, two potent deacidifying and volatile-sulphur-aroma-producing microorganisms of the cheese ecosystem.
Cheese flavour is the result of complex biochemical transformations attributed to bacteria and yeasts grown on the curd of smear-ripened cheeses. Volatile sulphur compounds (VSCs) are responsible for the characteristic aromatic notes of several cheeses. In the present study, we have assessed the ability of Kluyveromyces lactis, Kluyveromyces marxianus and Saccharomyces cerevisiae strains, which are frequently isolated from smear-ripened cheeses, to grow and deacidify a cheese medium and generate VSCs resulting from L-methionine degradation. The Kluyveromyces strains produced a wider variety and higher amounts of VSCs than the S. cerevisiae ones. We have shown that the pathway is likely to be proceeding differently in these two yeast genera. The VSCs are mainly generated through the degradation of 4-methylthio-oxobutyric acid in the Kluyveromyces strains, in contrast to the S. cerevisiae ones which have higher L-methionine demethiolating activity, resulting in a direct conversion of L-methionine to methanethiol. The deacidification activity which is of major importance in the early stages of cheese-ripening was also compared in S. cerevisiae and Kluyveromyces strains.


Diabetes structured self-management education programmes: a narrative review and current innovations.
Both type 1 and type 2 diabetes are associated with long-term complications that can be prevented or delayed by intensive glycaemic management. People who are empowered and skilled to self-manage their diabetes have improved health outcomes. Over the past 20 years, diabetes self-management education programmes have been shown to be efficacious and cost-effective in promotion and facilitation of self-management, with improvements in patients' knowledge, skills, and motivation leading to improved biomedical, behavioural, and psychosocial outcomes. Diabetes self-management education programmes, developed robustly with an evidence-based structured curriculum, vary in their method of delivery, content, and use of technology, person-centred philosophy, and specific aims. They are delivered by trained educators, and monitored for quality by independent assessors and routine audit. Self-management education should be tailored to specific populations, taking into consideration the type of diabetes, and ethnic, social, cognitive, literacy, and cultural factors. Ways to improve access to and uptake of diabetes self-management programmes are needed globally.


Theory of Planned Behavior and Mindfulness Intentions in Chronic Low Back Pain.
Theory of planned of behavior (TPB) constructs have been linked to health behavior intentions. Intentions to try mindfulness-based stress reduction (MBSR), a first-line therapy for chronic low back pain (cLBP), have been less studied. This study aimed to identify which TPB constructs could inform strategies to improve adoption of MBSR. People with cLBP (n = 457) read a description of MBSR then completed survey items assessing TPB constructs: attitudes, norms, self-efficacy, perceived control, and intentions to try MBSR training. Structural equation modeling showed self-efficacy/control (coefficient: 0.564), norms (0.245), and attitudes (0.131) were all positively associated with intentions to try mindfulness trainings. Results suggest self-efficacy/control may be the most strongly related TPB construct with intentions to try MBSR. Dissemination of MBSR for cLBP could focus on adapting the intervention to increase accessibility and improving available resources to overcome logistical barriers (online formats, drop-in classes). The online version contains supplementary material available at 10.1007/s12671-022-02022-2.


Population-based analysis of the impact of trauma on longer-term functional outcomes.
Functional outcome measures are important as most patients survive trauma. The aim of this study was to describe the long-term impact of trauma within a healthcare region from a social perspective. People active in work or education and admitted to hospitals in Central Norway in the interval 1 June 2007 to 31 May 2010 after sustaining trauma were included in the study. Clinical data were linked to Norwegian national registers of cause of death, sickness and disability benefits, employment and education. Primary outcome measures were receipt of medical benefits and time to return to preinjury work level. Secondary outcome measures were mortality within 30 days or during follow-up. Some 1191 patients were included in the study, of whom 193 (16·2 per cent) were severely injured (Injury Severity Score greater than 15). Five years after injury, the prevalence of medical benefits was 15·6 per cent among workers with minor injuries, 22·3 per cent in those with moderate injuries and 40·5 per cent among workers with severe injuries. The median time after injury until return to work was 1, 4 and 11 months for patients with minor, moderate and severe injuries respectively. Twelve patients died within 30 days and an additional 17 (1·4 per cent) during follow-up. Patients experiencing minor or major trauma received high levels of medical benefits; however, most recovered within the first year and resumed preinjury work activity. Patients with severe trauma were more likely to receive medical benefits and have a delayed return to work. Registration number: NCT02602405 (http://www.clinicaltrials.gov).


Glycine and GABA(A) receptor subunits on Renshaw cells: relationship with presynaptic neurotransmitters and postsynaptic gephyrin clusters.
Inhibitory synapses with large and gephyrin-rich postsynaptic receptor areas are likely indicative of higher synaptic strength. We investigated the presynaptic inhibitory neurotransmitter content (GABA, glycine, or both) and the presence and subunit composition of GABA(A) and glycine postsynaptic receptors in one example of gephyrin-rich synapses to determine neurochemical characteristics that could also contribute to enhance synaptic strength. Hence, we analyzed subunit receptor expression in gephyrin patches located on Renshaw cells, a type of spinal interneuron that receives powerful excitatory and inhibitory inputs and displays many large gephyrin patches on its surface. GABA(A) and glycine receptors were almost always colocalized inside Renshaw cell gephyrin clusters. According to the subunit-immunoreactivities detected, the composition of GABA(A) receptors was inferred to be either alpha(3)beta((2or3))gamma(2), alpha(5)beta((2or3))gamma(2), alpha(3)alpha(5)beta((2or3))gamma(2) or a combination of these. The types of neurotransmitters contained inside boutons presynaptic to Renshaw cell gephyrin patches were also investigated. The majority (60-75%) of terminals presynaptic to Renshaw cell gephyrin patches contained immunocytochemical markers for GABA as well as glycine, but a proportion contained markers only for glycine. Significantly, 40% of GABA(A) receptor clusters were opposed to presynaptic boutons that contained only glycinergic markers. We postulate that GABA and glycine corelease, and the presence of alpha3-containing GABA(A) receptors can enhance the postsynaptic current and contribute to strengthen inhibitory input on Renshaw cells. In addition, a certain degree of imprecision in the localization of postsynaptic GABA(A) receptors in regard to GABA release sites onto adult Renshaw cells was also found.


Using Multiple Control Groups and Matching to Address Unobserved Biases in Comparative Effectiveness Research: An Observational Study of the Effectiveness of Mental Health Parity.
Studies of large policy interventions typically do not involve randomization. Adjustments, such as matching, can remove the bias due to observed covariates, but residual confounding remains a concern. In this paper we introduce two analytical strategies to bolster inferences of the effectiveness of policy interventions based on observational data. First, we identify how study groups may differ and then select a second comparison group on this source of difference. Second, we match subjects using a strategy that finely balances the distributions of key categorical covariates and stochastically balances on other covariates. An observational study of the effect of parity on the severely ill subjects enrolled in the Federal Employees Health Benefits (FEHB) Program illustrates our methods.


Occipital-posterior cerebral artery bypass via the occipital interhemispheric approach.
The unavailability of the superficial temporal artery (STA) and the location of lesions pose a more technically demanding challenge when compared with conventional STA-superior cerebellar or posterior cerebral artery (PCA) bypass in vascular reconstruction procedures. To describe a case series of patients with cerebrovascular lesions who were treated using an occipital artery (OA) to PCA bypass via the occipital interhemispheric approach. We retrospectively reviewed three consecutive cases of patients with cerebrovascular lesions who were treated using OA-PCA bypass. OA-PCA bypass was performed via the occipital interhemispheric approach. This procedure included: (1) OA-PCA bypass (n = 1), and combined OA-posterior inferior cerebellar artery and OA-PCA saphenous vein interposition graft bypass (n = 1) in patients with vertebrobasilar ischemia; (2) OA-PCA radial artery interposition graft bypass in one patient with residual PCA aneurysm. OA-PCA bypass represents a useful alternative to conventional STA-SCA or PCA bypass.


mAPKL: R/ Bioconductor package for detecting gene exemplars and revealing their characteristics.
So far many algorithms have been proposed towards the detection of significant genes in microarray analysis problems. Several of those approaches are freely available as R-packages though their engagement in gene expression analysis by non-bioinformaticians is usually a frustrating task. Besides, only some of those packages offer a complete suite of tools starting from initial data import and ending to analysis report. Here we present an R/Bioconductor package that implements a hybrid gene selection method along with a bunch of functions to facilitate a thorough and convenient gene expression profiling analysis. mAPKL is an open-source R/Bioconductor package that implements the mAP-KL hybrid gene selection method. The advantage of this method is that selects a small number of gene exemplars while achieving comparable classification results to other well established algorithms on a variety of datasets and dataset sizes. The mAPKL package is accompanied with extra functionalities including (i) solid data import; (ii) data sampling following a user-defined proportion; (iii) preprocessing through several normalization and transformation alternatives; (iv) classification with the aid of SVM and performance evaluation; (v) network analysis of the significant genes (exemplars), including degree of centrality, closeness, betweeness, clustering coefficient as well as the construction of an edge list table; (vi) gene annotation analysis, (vii) pathway analysis and (viii) auto-generated analysis reporting. Users are able to run a thorough gene expression analysis in a timely manner starting from raw data and concluding to network characteristics of the selected gene exemplars. Detailed instructions and example data are provided in the R package, which is freely available at Bioconductor under the GPL-2 or later license http://www.bioconductor.org/packages/3.1/bioc/html/mAPKL.html.


[Diagnosis and therapy of esophageal webs (author's transl)].
Esophageal webs are thin, eccentric stenoses of the lumen, which are easily detected and treated by endoscopy. This is illustrated by a case report of a lower esophageal web.


Experiments on the influence of an aromatic retinoid on the chemical carcinogenesis in rats by butyl-butanol-nitrosamine and 1,2-dimethylhydrazine.
In male Sprague-Dawley rats it was tested whether the induction of carcinomas of the bladder by butyl-butanol-nitrosamine (BBN) and the induction of carcinomas of the colon by 1,2-dimethylhydrazine (DMH) could be influenced by an aromatic retinoid ethyl-allyl-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate (RO 10-9359). Neither an inhibitory nor an enhancing effect of the retinoid on carcinogenesis was observed.


The protein synthesis inhibitors from wheat, barley, and rye have identical antigenic determinants.
We have purified the protein synthesis inhibitors from wheat (tritin) and investigated their antigenic relationship to inhibitors from other grains and more distantly related plants. Three forms of tritin (tritin 1, 2, and 3) indistinguishable with regards to their molecular weight and enzymatic properties were found. Antiserum against the most abundant tritin, tritin 2, cross reacted with tritin 1, tritin 3, and with the translation inhibitors from barley and rye, but not with other plant-derived translational inhibitors. The results indicate that only closely related plants contain antigenically similar protein synthesis inhibitors.


First purification of the antiquitin protein and demonstration of its enzymatic activity.
Antiquitin is an evolutionarily conserved protein believed to play a role in the regulation of cellular turgor. Based on sequence analysis, this protein is classified as a member of the aldehyde dehydrogenase superfamily. All previous studies on antiquitin have been confined to the nucleotide level, and the protein has never been purified and characterized. In the present investigation, the antiquitin protein was purified for the first time. An acetaldehyde-oxidizing protein was isolated from the liver of black seabream (Mylio macrocephalus) by chromatographies on alpha-cyanocinnamate Sepharose and Affi-gel Blue agarose, followed by ammonium sulfate precipitation. The purified protein was identified as antiquitin by the first 18 N-terminal amino acid residues which showed 83.3% identity with the deduced sequence of human antiquitin. Electrophoretic mobility studies indicated that black seabream antiquitin is a tetramer with a subunit molecular mass of 57.5 kDa. Kinetic analysis of the purified protein indicated that it catalyzes the oxidation of acetaldehyde with K(m) and V(max) values of 2.0 mM and 1.3 U/mg, respectively. The longer aliphatic propionaldehyde and the aromatic benzaldehyde are also substrates of the purified enzyme. The enzyme is highly specific towards NAD+ as the coenzyme and is totally inactive towards NADP+. Maximal enzymatic activity was found at about pH 9-10.


A third-generation hydrogen peroxide biosensor based on horseradish peroxidase immobilized in a tetrathiafulvalene-tetracyanoquinodimethane/multiwalled carbon nanotubes film.
A new third-generation biosensor for H(2)O(2) assay was developed on the basis of the immobilization of horseradish peroxidase (HRP) in a nanocomposite film of tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ)/multiwalled carbon nanotubes (MWCNTs) modified gold electrode. The prepared HRP/TTF-TCNQ/MWCNTs/Au electrode was used for the bioelectrocatalytic reduction of H(2)O(2), with a linear range from 0.005 to 1.05 mM and a detection limit of 0.5 microM for amperometric sensing of H(2)O(2). In addition, a novel method on the basis of electrochemical quartz crystal microbalance (EQCM) measurements was proposed to determine the effective enzymatic specific activity (ESA) of the immobilized HRP for the first time, and the ESA was found to be greater at the TTF-TCNQ/MWCNTs/Au electrode than that at the MWCNTs/Au or TTF-TCNQ/Au electrode, indicating that the TTF-TCNQ/MWCNTs film is a good HRP-immobilization matrix to achieve the direct electron transfer between the enzyme and the electrode.


Plasma magnesium in chronic schizophrenia. A preliminary report.
A group of 36 subjects, 20 chronic schizophrenic patients and 16 nonpsychotic mentally retarded patients were chosen at random from the chronic care wards of the Douglas Hospital to assess levels of magnesium, calcium and phosphorus. No significant differences were found between the two groups in calcium and phosphorus. However, the magnesium level was significantly lower (p less than 0.01) in the schizophrenic group than in the mentally retarded group. This difference reached a level of 0.001 significance when chronic female schizophrenic patients were compared to the female mentally retarded group. Hospitalization, diet and medication were excluded as possible etiological factors.


Babesia divergens: identification and characterization of BdHSP-20, a small heat shock protein.
This study describes the identification and characterization of the Babesia divergens alpha-crystallin/small heat shock protein 20 (BdHSP-20). BdHSP-20 was recognized by the DG7 monoclonal antibody (DG7 mAb) originally produced by Precigout et al. [Precigout, E., Valentin, A., Carcy, B., Gorenflot, A., Nakamura, K., Aikawa, M., Schrevel, J. 1993. Babesia divergens: characterization of a 17-kDa merozoite membrane protein. Experimental Parasitology 77, 425-434] against B. divergens merozoites. We used DG7 mAb to immunoscreen a B. divergens cDNA library to clone the gene encoding the small heat shock protein. Bdhsp-20 is a single copy gene interrupted by one intron. The deduced gene product (BdHSP-20) clearly belongs to the alpha-crystallin family and shows significant homology to Babesia bovis, Plasmodium falciparum and Toxoplasma gondii sHSPs, with the highest degree of sequence identity around the catalytic domain. Nutritient stress (serum depletion) treatment of the parasites induced the upregulation of BdHSP-20 gene expression observed by semi-quantitative PCR and immunoprecipitation. This regulation pattern suggests that BdHSP-20 could probably be of importance for parasite survival in the case of environmental stress. BdHSP-20 has previously been shown to be highly conserved among different strains and antibodies against the protein drastically reduce parasitemia in vitro.


Video Coaching: A National Survey of Surgical Residency Program Directors.
Video coaching has been demonstrated to improve resident and attending skills and is overwhelmingly well received by the participants. However, misperceptions about its utility among those who do not use video coaching may be a barrier to widespread implementation. Cross-sectional web-based survey SETTING: National survey PARTICIPANTS: Surgical program director members of the Association of Program Directors of Surgery STUDY DESIGN: The survey was developed via a deductive approach after a literature review and was piloted with surgical attendings and residents. All Likert scale were averaged and comparisons between groups was performed via independent t-tests. There were 52 responses from PDs. 27/52(51.9%) PDs reported their program supported video coaching of residents. PDs from residences with video coaching programs were more likely to believe that video coaching was useful in identifying their own strengths and weakness (p = 0.005), was a useful adjunct for resident feedback (p = 0.024), and a personal library of video recordings would be helpful (p = 0.015) when compared to PDs from residencies without video coaching. Programs without video coaching were more likely to believe barriers to implementation included it being ineffective (p = 0.024) and that the technology was unavailable (p = 0.006). Over 50% of respondents from both groups believed expense, difficulty with set up, time required, and patient privacy were "Very" or "Extremely" likely to be barriers to implementation. This is the first national survey of PDs regarding the use of video coaching. Residency programs without video coaching may underestimate the utility of video coaching in training surgical residents.


Associated risk factors and their interactions with type 2 diabetes among the elderly with prediabetes in rural areas of Yiyang City: A nested case-control study.
To explore associated risk factors and their interactions with type 2 diabetes (T2DM) among the elderly with prediabetes in rural areas in China.A nested case-control study was conducted in a fixed cohort to identify the risk factors for T2DM among the elderly with prediabetes in rural areas of Yiyang City in China. A total of 37 elderly with T2DM were included in the cases group and 111 elderly subjects with prediabetes were matched in the control group. Data related to sociodemographic characteristics, lifestyle behavior, and anthropometric variables were collected by trained staff using standard tools. The risk factors for T2DM were determined using conditional logistic regression analysis, and their additive interactions were also explored.Multivariable conditional logistic regression analysis results showed that overweight/obesity (odds ratio [OR] = 4.80, 95% confidence interval [CI]: 1.20-12.28), family history of diabetes (OR = 3.63, 95% CI: 1.03-12.81), physically inactive (OR = 3.08, 95% CI: 1.14-8.30), high waist-to-hip ratio (WHR) (OR = 3.15, 95% CI: 1.27-7.80), and inadequate diabetes-specific health literacy (DSHL) (OR = 3.92, 95% CI: 1.14-13.48) increased the risk for T2DM. Additive interactions for T2DM were observed between a family history of diabetes and high WHR with a relative excess risk of interaction (RERI) of 10.02 (95% CI: 4.25, 15.78), and between high WHR and overweight or obesity, with an RERI of 3.90 (95% CI: 0.36, 7.44).The independent risk factors for T2DM are overweight or obesity, high WHR, family history of diabetes, physically inactive, and inadequate DSHL. High WHR as a risk factor for T2DM has additive interactions with family history of diabetes and overweight or obesity.


Impact of infant feeding practices on the risk of mother to child transmission of HIV-1 in Zimbabwe.
To determine the magnitude of the contribution of infant feeding practices on the risk of mother to child transmission (MTCT) of the HIV-1 infection. Prospective data from birth until 24 months of age on 236 infants born to HIV-positive mothers in Harare, Zimbabwe was analysed for this study. However, because only a small proportion of infants (2.1%) were HIV-1 polymerase chain reaction (PCR) tested shortly after birth, the PCR results for infants at birth were not incorporated into our analyses. The contribution of infant feeding practices on the risk of MTCT of HIV-1 was assessed using Cox Proportional Hazards Regression Models. The incidence of HIV-1 through MTCT was greatest among breastfed (8.33 per 100 child-months) and mixed fed (8.64 per 100 child-months) infants by 3 months. After adjustment for maternal age, marital status, education and infant antibody HIV-1 status, the cumulative relative risk of MTCT of HIV-1 was 4.19 (95% confidence interval (CI) 3.44, 5.09) among breastfed and 1.10 (95% CI 0.97, 1. 25) among mixed fed infants. The overall MTCT rate of HIV-1 in this study was 40.3%. Breastfed infants had the greatest cumulative relative risk of MTCT of HIV-1, followed by mixed fed infants, with the highest incidences occurring within the first 3 months.


Group B streptococci in milk and late neonatal infections: an analysis of cases in the literature.
The source for late-onset neonatal infections (LONI) due to group B Streptococcus (GBS) has not been fully explored. We reviewed GBS LONI cases associated with contaminated breast milk to determine whether breast milk was a possible route for neonatal infection. A PubMed search from January 1977 to March 2013 was performed with MeSH words "Streptococcus agalactiae", "group B Streptococcus", "infection", "milk", "human", "late-onset infection" and/or "neonate"; relevant cross references were also reviewed. Forty-eight documented cases of GBS LONI matched our search criteria and were retrieved from the literature. When performed, molecular typing identified clonal isolates in the neonate and milk samples taken after LONI in all cases, with the hypervirulent sequence type 17 (ST-17) clone identified in two of these cases. Caesarean delivery combined with the absence of GBS recovery from maternal samples other than milk was noted for four cases. The rate of recurrent infections was high (35%) and, together with the data reviewed, points to a potential role of breast milk in GBS LONI. The cases reviewed here, together with the evidence of breast milk transmission for other pathogens, suggest that breast milk, which would account for repeated GBS transmission to the neonate, may favour gut translocation and subsequent LONI. Further investigations are nevertheless needed to study the relative importance of this contamination route compared with persistent postnatal gut colonisation and the dynamics of milk and neonatal gut colonisation.


Interfacial synthesis of dendritic platinum nanoshells templated on benzene nanodroplets stabilized in water by a photocatalytic lipoporphyrin.
Nanoscale metal shells have many potential uses and in some applications offer significant advantages over nanoparticles. The synthesis of platinum nanoshells using stabilized nanodroplets of benzene in water as growth templates is described; the nanodroplets are stabilized by a surfactant-like tin(IV)-porphyrin complex localized at the benzene-water interface. The porphyrin also acts as a photocatalyst that reduces the platinum complex and deposits metal onto the nanodroplets to form dendritic metal nanoshells. Below the solubility limit of benzene in water, the lipoporphyrin-stabilized nanodroplets have a reproducible number, size distribution, and surface area, which allows the thickness of the platinum shell walls to be controlled by changing the amount of platinum complex. Nanoscale platinum shells with magnetic interiors can be made by dispersing Fe3O4 nanoparticles in the benzene nanodroplets.