Hydrogen sulfide is an oxygen sensor in the carotid body.
There is considerable controversy surrounding the initial step that transduces a fall in [Formula: see text] into a physiological signal, i.e., the "oxygen sensor" in chemoreceptors. Initial studies on systemic and respiratory vessels suggested that the metabolism of hydrogen sulfide (H(2)S) could serve as the oxygen sensor. This model was subsequently extended to chemoreceptors in fish and tissues of other animals. In this model, constitutive production of biologically active H(2)S is offset by H(2)S oxidation; when oxygen availability falls, production of H(2)S exceeds metabolism, and the resultant increase in intracellular H(2)S initiates the appropriate physiological responses. This model is supported by observations that the effects of hypoxia and H(2)S are similar, if not identical in many tissues: hypoxic responses are inhibited by inhibitors of H(2)S biosynthesis and augmented by sulfur donating molecules, and the tipping point between H(2)S production and oxidation occurs at physiologically relevant [Formula: see text] . Recent studies from other laboratories support this mechanism of O(2) sensing in the carotid body. This review summarizes information that supports the H(2)S metabolic hypothesis in these tissues with emphasis on the carotid chemoreceptors. Evidence suggesting that H(2)S is not involved in oxygen sensing in the carotid body is also critically evaluated.


Factors associated with improved MCH epidemiology functioning in state health agencies.
This paper discusses characteristics that are associated with enhanced maternal and child health (MCH) epidemiology functioning in state health agencies. The concept of the "MCH Epidemiology Effort" is introduced as "the epidemiologic work carried out by multiple units and agencies aimed at informing program planning and policy development on behalf of women, children and families." This concept focuses attention on MCH epidemiology functioning at the organizational level rather than on individual MCH epidemiologists. The analysis used data from all 50 states and the District of Columbia. Each state participated in a telephone interview and submitted material that demonstrated the breadth, depth, and capacity of its MCH Epidemiology Effort. Several organizations, including the Council for State and Territorial Epidemiologists, the Health Resources and Services Administration/Maternal and Child Health Bureau, and the Centers for Disease Control and Prevention provided additional secondary data. The outcome for analysis was a three-category measure of MCH epidemiology functioning. The findings are consistent with, and add specificity to, those from prior assessments. In a multivariable model, agenda-setting by consensus, involvement of external stakeholders, the total of doctorally trained staff, and accessing CDC assignees or other staff were all significantly related to higher level MCH epidemiology functioning (ORs of 6.1, 6.6, 2.5, and 6.4, respectively; P<0.05). Organizational visibility of the MCH Epidemiology Effort and a data environment marked by routine data-sharing and data integration were marginally related. We provide recommendations for action at the state and federal level for advancing evidence-based decision-making in maternal and child health.


Substance P: A neuropeptide involved in the psychopathology of anxiety disorders.
Substance P (SP) is the most widely distributed neuropeptide in central nervous system (CNS) where it participates in numerous physiological and pathophysiological processes including stress and anxiety related behaviors. In line with this notion, brain areas that are thought to be involved in anxiety regulation contains SP and its specific NK1 receptors. SP concentration in different brain regions alters with the exposure of stressful stimulus and affected NK1 receptor binding is observed. SP is released in response to a stressor, which produces anxiogenic effects via activation of hypothalamic-pituitary-adrenal (HPA) axis, resulting in the liberation of cortisol. Moreover, SP is also involved in the activation of the sympathetic nervous system via stimulation of locus coeruleus (LC). This sympathetic surge initiates cortisol discharge by activation of HPA axis, representing the indirect anxiogenic effect of SP. Besides the aforementioned regions, SP also has an impact on other brain regions known to be involved in stress and anxiety mechanisms, including amygdala, lateral septum (LS), periaqueductal gray (PAG), ventromedial nucleus of the hypothalamus (VMH), and bed nucleus of stria terminalis (BNST). Thus, SP acts as an important neuromodulator in various brain regions in stress and anxiety response. Consistent with the above statement, SP makes a robust link in the psychopathology of anxiety disorders. As SP concentration is found elevated in stressed conditions, several studies have reported that the pharmacological antagonism or genetic depletion of NK-1 receptors results in the anxiolytic response making them a suitable therapeutic target for the treatment of stress and anxiety related disorders.


APP2: automatic tracing of 3D neuron morphology based on hierarchical pruning of a gray-weighted image distance-tree.
Tracing of neuron morphology is an essential technique in computational neuroscience. However, despite a number of existing methods, few open-source techniques are completely or sufficiently automated and at the same time are able to generate robust results for real 3D microscopy images. We developed all-path-pruning 2.0 (APP2) for 3D neuron tracing. The most important idea is to prune an initial reconstruction tree of a neuron's morphology using a long-segment-first hierarchical procedure instead of the original termini-first-search process in APP. To further enhance the robustness of APP2, we compute the distance transform of all image voxels directly for a gray-scale image, without the need to binarize the image before invoking the conventional distance transform. We also design a fast-marching algorithm-based method to compute the initial reconstruction trees without pre-computing a large graph. This method allows us to trace large images. We bench-tested APP2 on ~700 3D microscopic images and found that APP2 can generate more satisfactory results in most cases than several previous methods. The software has been implemented as an open-source Vaa3D plugin. The source code is available in the Vaa3D code repository http://vaa3d.org. Supplementary data are available at Bioinformatics online.


Magnetic resonance imaging in naso-oropharyngeal carcinoma: role of texture analysis in the assessment of response to radiochemotherapy, a preliminary study.
Identifying MRI texture parameters able to distinguish inflammation, fibrosis, and residual cancer in patients with naso-oropharynx carcinoma after radiochemotherapy (RT-CHT). In this single-centre, observational, retrospective study, texture analysis was performed on ADC maps and post-gadolinium T1 images of patients with histological diagnosis of naso-oropharyngeal carcinoma treated with RT-CHT. An initial cohort of 99 patients was selected; 57 of them were later excluded. The final cohort of 42 patients was divided into 3 groups (inflammation, fibrosis, and residual cancer) according to MRI, 18F-FDG-PET/CT performed 3-4 months after RT-CHT, and biopsy. Pre-RT-CHT lesions and the corresponding anatomic area post-RT-CHT were segmented with 3D slicer software from which 107 textural features were derived. T-Student and Wilcoxon signed-rank tests were performed, and features with p-value < 0.01 were considered statistically significant. Cut-off values-obtained by ROC curves-to discriminate post-RT-CHT non-tumoural changes from residual cancer were calculated for the parameters statistically associated to the diseased status at follow-up. Two features-Energy and Grey Level Non-Uniformity-were statistically significant on T1 images in the comparison between 'positive' (residual cancer) and 'negative' patients (inflammation and fibrosis). Energy was also found to be statistically significant in both patients with fibrosis and residual cancer. Grey Level Non-Uniformity was significant in the differentiation between residual cancer and inflammation. Five features were statistically significant on ADC maps in the differentiation between 'positive' and 'negative' patients. The reduction in values of such features between pre- and post-RT-CHT was correlated with a good response to therapy. Texture analysis on post-gadolinium T1 images and ADC maps can differentiate residual cancer from fibrosis and inflammation in early follow-up of naso-oropharyngeal carcinoma treated with RT-CHT.


Knowledge, legitimacy and economic practice in informal markets for medicine: a critical review of research.
Current debates and market based interventions in international public health seek to bring about explicit improvements in the quality of care offered by informal providers. In this paper we examine how informal providers are framed as problematic and question assumptions about what constitutes appropriate knowledge and expectations of how economic actors in the medical marketplace will behave. We argue that existing portraits of informal providers tend to establish clear cut distinctions between different kinds of practitioner; 'dis-embed' biomedical transactions from the broader relationships within which they take place; freeze or anatomise what are dynamic economic relationships between stakeholders, and obscure or ignore the position of informal providers in a global pharmaceutical supply chain.


Interferon-alpha (IFN-alpha)-conditioned DC preferentially stimulate type-1 and limit Treg-type in vitro T-cell responses from RCC patients.
Dendritic cells (DCs) are potent antigen presenting cells and represent attractive candidates for use in novel immunotherapies for patients with renal cell carcinoma (RCC), a disease that has proven refractory to conventional treatment modalities, such as chemotherapy and radiotherapy. Given the perceived need to augment antitumor type-1 immunity (TC1 and Th1) as a therapeutic end point, and the known functional plasticity of DC populations that may display heterogeneous capacity to promote T-cell responses, we sought to identify a preferred DC preparation with this capacity. We compared 2 different preparations of monocyte-derived DC using interferon-alpha (IFN-alpha) (IFN-DC and alphaDC1) with classic DCs "matured" (mDCs) using interleukin-1beta/interleukin-6/tumor necrosis factor-alpha/prostaglandin E2, for their ability to promote autologous TC1 antitumor responses from RCC patients in vitro. IFN-alpha-conditioned DC promoted significantly higher numbers of RCC-specific CD8+ T cells exhibiting a cytotoxic phenotype after in vitro stimulation (IVS) than cytokine cocktail-mDCs. Furthermore, IVS using IFN-DCs was able to diminish regulatory-type T cells among CD4+ T-cell responder populations versus IVS using conventional mDC-based vaccines. These data emphasize an important role for IFN-alpha in modulating the immunologic functions of DCs toward a polarized DC1-type capable of coordinately promoting TH1-type and TC1-type T-cell mediated immunity and supports the translational development of patient-derived IFN-alpha-conditioned DC for use in novel immunotherapies for patients with RCC, and in whom, endogenous tumor-specific TC1 effector cells may be dysfunctional, anergic, or prone to undergo apoptosis.


Effect of Chinese herbs on immunoglobulin A nephropathy: a randomized controlled trial.
The accumulation of extracellular matrix (ECM) is one of the main causes of renal fibrosis. Emerging evidence suggests that the metabolic enzyme of ECM is associated with renal fibrosis. In this study, we applied randomly controlled trial to check the curative effect of Chinese herbs on patients with immunoglobulin A nephropathy (IgAN). Twenty-six patients were randomly divided into group A (control group) treated with Western Medicine and group B (treatment group) treated with combination of Traditional Chinese Medicine (TCM) and Western Medicine. Blood and urine tests were done before treatment and after 8-week treatment. The levels of the main composition of extracellular matrix (MC-ECM), the metabolic enzyme of ECM (ME-ECM) and some cytokines in group B decreased more obviously than those in group A after 8-week treatment. So did the level of 24-hour urine protein. However, Metal matrix protease (MMP)-2 and vascular endothelial growth factor in group B increased more obviously than those in group A after 8-week treatment. No effects on the renal function were found in both groups. Our study provided important information on using the combination of TCM with Western Medicine to inhibit the progression of renal fibrosis in patients with IgAN.


The inhibitory effects of nicotinic antagonists on currents elicited by GABA in rat hippocampal neurons.
The nicotinic antagonists d-tubocurarine and trimethaphan camsylate competitively inhibit GABA-induced currents. Hexamethonium, mecamylamine and dihydro-beta-erythroidine, other nicotinic antagonists, do not affect GABA-elicited currents. The trimethaphan effect is completely reversed by a putative convulsant receptor antagonist, alpha-isopropyl-alpha-methyl-gamma-butyrolactone, which implies that the trimethaphan binding site may be closely associated with the convulsant site. However, nicotine was ineffective in competing for either the d-tubocurarine or trimethaphan effect at the GABAA receptor. From these observations, we propose that the nicotinic and GABAA receptor ionophore complexes share similar configurational patterns that accommodate some of the same molecules. Possible mechanisms for the trimethaphan and d-tubocurarine blockades are discussed.


Epididymal metastases as the first sign of a colon cancer recurrence.
Metastastic tumours involving the epididymis are rare and most often found in patients with disseminated disease. It is even more unusual when the metastasis of the epididymis is the first sign of tumour recurrence. We report a case of an asymptomatic recurrent colon carcinoma presenting as metastasis in the epididymis. Although metastatic cancer presenting as an intra-scrotal mass is extremely rare, it should be considered as a possibility in patients who present with a mass involving the testicle or epididymis.


[Pelizaeus-Merzbacher disease].
Two cases of Pelizaeus-Merzbacher disease are described, one with the classical and one with the connatal form, both in the same family. It is an X-linked disease affecting the myelinisation of the brain. Pelizaeus-Merzbacher manifests itself within a few months after birth and has a progressive character. The disease is caused by a point mutation in the PLP gene coding for the myelin-protein proteolipid protein. MRI imaging has improved the possibility for diagnosis especially in families with cases of Pelizaeus-Merzbacher disease and PLP gene detection has brought antenatal diagnosis in focus.


The monitoring of ascorbate and monoamine transmitter metabolites in the striatum of unanaesthetised rats using microprocessor-based voltammetry.
Voltammetry in vivo has suffered from the limitation that electrodes which give high resolution of the various electroactive compounds present in brain tissue have a short life span, and, conversely, that stable electrodes give poor resolution. Carbon paste electrodes and linear sweep voltammetry with semidifferentiation can resolve changes in the concentration of ascorbate, deaminated and methylated metabolites of catecholamines, and the 5-hydroxyindoles in vivo and give stable recordings over many weeks. However, these changes in concentration are difficult to quantify. We have now developed the method further with the application of microprocessor technology. Microprocessor-based voltammetry and data analysis enable one to quantify changes in the concentration of electroactive species in complex mixtures where there are no separate oxidation peaks for the components; this has been achieved both in vitro and in vivo. Changes in dopamine release from the striatum have been monitored continuously over 48 h in unanaesthetised rats after the intraperitoneal administration of haloperidol. Carbon paste electrodes and microprocessor-controlled linear sweep voltammetry facilitates the quantitative, continuous monitoring of the extracellular concentration of ascorbate, the deaminated and methylated metabolites of catecholamines, and the 5-hydroxyindoles in the brain of unrestrained animals.


[Risk of infection and preventative strategies in the domestic environment of immunosuppressed hematologic oncology patients].
To date, the problem of infectious risks in the domestic environment has not been focused as intensively as that in the clinical environment. Due to increasing costs in health care, there are considerations to intensify outpatient treatment models, e.g., for hematology-oncology patients, enhancing the importance of this problem. Based on a review of the relevant literature, this article summarizes the potential infectious risks for immunosuppressed patients in the domestic environment and gives recommendations for control measures. The topics of daily life are considered in detail including special risks of leisure activities. For most of the risks, evidence-based recommendations cannot be given. The scope of these recommendations is to support the attending physician when advising the immunocompromised patient and to give suggestions for possible control measures to the patient.


Socio-economic impact of first 21 days nationwide lockdown- 1 on the spread of SARS-COV-2 in India in relation to health.
On March 11, 2020 World Health Organization (WHO) declared corona virus disease (COVID-19) to be a pandemic disease, which is caused by a novel coronavirus "severe acute respiratory syndrome coronavirus-2 (SARS CoV- 2)" and till now it has affected about 213 countries. A nationwide lockdown was announced by the Honorable Prime Minister of India on 24th March 2020 for 21 days to prevent the spread of the COVID-19. Our nation, being a developing nation and emerging market, there was a vast socio-economic consequence of this lockdown. Our health care services were at the war front. Due to this step, there was a reduction in the rate of the spread of COVID- 19. Other health hazards due to pollution, road traffic accidents, crimes including robberies, rapes, murders, thefts, etc., were decreased substantially. People learned good hygiene and family bonding, which was further strengthened. Negatively affected sectors were trading companies, schools, and education, economy, stock markets, ongoing events in sports, politics, entertainment industry, transportation, and activities related to religious places, tourists, and hotels. Due to starvation, poor people were worst affected as they were daily bread earners though, the government tried to provide money and food. Finally, it was the primary care physician, termed "corona warriors," who suffered socially, economically, mentally, and physically. Despite all these hardships, the primary care physician learned the innovative way to help patients and ease their suffering with proper advice and awareness.


Is it ethical for journals to request self-citation?
By following the recently published paper in Science titled "Coercive Citation in Academic Publishing", in this paper, we aim to discuss the demand of some journals that request authors to cite recently published papers in that journal to increase the impact factor of that journal. It will be mentioned that some of these demands are not ethical and consequently will diminish the reputation of the journal.


Anthropogenic aerosols in precipitation over the Indo-Gangetic basin.
This study investigated the concentration of heavy metals in rainwater (RW) at a semi-arid region of the Indo-Gangetic basin to understand the influence of local, regional, or long-range transport of air pollutants during the monsoon and non-monsoonal rain. The concentration of heavy metals in RW was determined using Atomic Absorption Spectrophotometer with Graphite Furnace, the scavenging ratio was estimated, and source interpretation was carried out using Principle Component Analysis (PCA) and HYSPLIT model. Ca was the highest contributor in RW followed by Na, Fe, Mg, and Al whereas Ba, Cr, Cu, Mn, Ni, Pb, and Zn were found in trace quantity. During the non-monsoon period, the crustal component (Ca) was the highest; however, during the monsoon, sea salt components (Na and Fe) were found higher. The scavenging ratio for metals was estimated and was found many times higher than those reported over European sites. The moderate concentration of heavy metal in RW was found with higher wind from South (S), South-West (SW), and North-West (NW) directions. Air mass back trajectory shows a significant contribution of metals from the Arabian Sea (South-Westerly wind) during active monsoon, whereas, in the non-monsoon season, the air masses mainly originated from the north-west indicating a contribution from wind-blown dust. The correlation analysis has shown the positive correlations between Ca and Mg, Mg and Na, Na and Cu, Al and Zn, Zn and Ba, Ba and Cr, and Cr and Zn. Principal Component Analysis (PCA) indicated loading of Ca, Na, Mg, Cu, Mn, and Ni in the first factor suggesting their crustal origin, whereas the second factor showed high loading of Al, Ba, Zn, Cr, and Ni indicating vehicular exhaust and industrial emission as their major sources, and loading for Ba and Mg in the third factor indicates the mixed contribution from both natural and anthropogenic sources in rainwater during the monsoon and non-monsoon periods. The data of this study can be used in the air pollution transport model. This study will help in source interpretation over the Indo-Gangetic basin and will help in planning for National Clean Air Program (NCAP) and deriving critical load.


Real-world evidence on health resource use among patients with haemophilia and inhibitor exhibiting severe bleeding episodes.
This study aimed to explore real-world evidence on health resource use (HRU) spending on patients with haemophilia and inhibitor. Medical records from 1990 to 2019 of patients with haemophilia and inhibitor from three comprehensive haemophilia treatment centres were retrospectively retrieved. In all, 31 patients with haemophilia (A = 30, B = 1) and inhibitor ≥5 BU were included. The mean initial inhibitor of 95.4 BU was detected at the mean age of 6.7 years. The mean number of annual hospitalisations was 3.9. A total of 795 bleeding episodes (major =125, minor =670) were evaluated. The treatment included bypassing agents or plasma exchange before administering high-dose factor VIII concentrate and intervention or surgery. Six patients succumbed to bleeding at the mean age of 17.2 years. Nineteen surviving patients experienced multiple morbidity except six patients with successful and partially successful immune tolerance induction (ITI). The mean (SD) annual total medical consumption for episodic treatment and successful ITI per patient with haemophilia A were 30,804 (81,332) USD and 55,531 (100,566) USD, respectively. Only episodic treatment was paid by the government budget for limited amounts of bypassing agents. Management for patients with haemophilia and inhibitor exhibiting severe bleeding is challenging for medical personnel in countries having limited resources over decades. The real-world data will be used to negotiate with the government to increase budget for adequate bypassing agents or nonreplacement therapy and to include ITI in the national haemophilia treatment.


The role of childhood trauma and stress reactivity for increased alcohol craving after induced psychological trauma: an experimental analogue study.
Traumatic events are associated with alcohol use problems with increased alcohol craving as a potential mediator. There is still a lack of knowledge regarding the causal nature of this association and its underlying mechanisms. This study investigated the effects of acute trauma exposure on alcohol craving in healthy individuals considering the role of stress reactivity and childhood trauma (CT) using a laboratory randomized controlled design. Ninety-five healthy participants were randomly exposed to a trauma or a neutral film. History of CT, and pre- to post-film changes in craving (craving reactivity, CR), anxiety, skin conductance, heart rate, and saliva cortisol levels were assessed. Moreover, associations between trauma film exposure and CR, the moderating role of CT, and associations between CT, stress reactivity, and trauma-induced CR were analyzed. Relative to the neutral film, the trauma film elicited an increase in CR in females but not in males. In males but not in females, the association between trauma film exposure and CR was moderated by CT, with trauma-induced CR increasing with the number of CT. In males, CT was related to decreased cortisol reactivity and increased heart rate and skin conductance response of which skin conductance was also associated with CR. These findings provide further evidence for a causal link between traumatic experiences and CR. While this association seems to be stronger in females, males might still be at risk in case of other vulnerability factors such as CT, with altered sympathetic stress reactivity as a potential contributing mechanism.


The clinical significance of vascular endothelial growth factor in malignant ascites.
Ascites can be caused by many kinds of diseases. Patients with undetermined ascites represent a diagnostic challenge. The aims of this study were to determine the diagnostic value of vascular endothelial growth factor (VEGF) in differentiation of malignant ascites from benign ascites and to investigate the clinical value of ascitic VEGF as an independent prognostic parameter. The study included 462 consecutive patients with malignant ascites and 550 patients with benign ascites, VEGF level in ascites were determined by a sandwich enzyme-linked immunosorbent assay. The survival rate was calculated by the Kaplan-Meier method and the log-rank test. Multivariate survival analysis was performed using the Cox hazards model. In our study, we found VEGF levels in malignant ascites (676.59 ± 303.86 pg/ml) were significantly higher than those in benign ascites (218.37 ± 98.15 pg/ml) (P < 0.001). Meanwhile, we also found that VEGF levels in malignant ascites from patients with ovarian cancer were higher than those with other cancers. Areas under the receiver operating characteristic (ROC) curves of ascitic VEGF was 0.940. At a cutoff value of 319.5 pg/ml, VEGF yielded a sensitivity of 89.2 % and a specificity of 88.4 %. Patients associated with the high-level VEGF value (≥613.38 pg/ml) in malignant ascites exhibited poor mean survival rates (8.3 ± 0.52 vs 15.11 ± 0.66 months, P < 0.001). In a multivariate Cox regression model, higher ascitic VEGF was an independent prognostic factor for overall survival. Planned subgroup analysis was performed for patients with tumor node metastasis (TNM) stage I. In the univariate analysis, only ascitic VEGF was associated with overall survival. VEGF was found to have a highly accurate sensitivity and specificity, suggesting that it could be considered as a new biomarker to differentiate malignant ascites from the benign one. The high level of VEGF value in malignant ascites may be used as an independent prognostic factor in patients with all stages of cancer.


Different Mesorhizobium species sharing the same symbiotic genes nodulate the shrub legume Anagyris latifolia.
The isolation and characterization of six rhizobial strains isolated from Anagyris latifolia, a shrub legume endemic to the Canary Islands, is reported in this study. The isolates were characterized by 16S-ARDRA, and sequencing of the ribosomal 16SrRNA gene, the 16S-23SrDNA intergenic spacer region, and the housekeeping gene for glutamine synthetase II (glnII). The phylogenies based on the three types of sequences matched, showing that the isolates belonged to three distinct lineages within the genus Mesorhizobium that could represent different species. However, the ribosomal and glnII phylogenies revealed some discrepancies in the relationships between the isolates and the named species in this genus. Despite their different taxonomic affiliation, all the isolates showed identical nodC sequences which were closely related (95% similarity) to that of the Mesorhizobium tianshanense type strain, indicating that they must have acquired the nodulation genes by a phenomenon of lateral gene transfer.


Changes of allergic inflammation and immunological parameters after Alt a 1 and A. alternata immunotherapy in mice.
The efficacy of allergen-specific subcutaneousimmunotherapy (SCIT) with Alt a 1 of the fungus A. alternata is still unknown. Yet, few studies compare the therapeutic effects and immunological mechanisms of Alt a 1 and A. alternata extracts. We aim to explore and compare the changes in allergic inflammation and immunological mechanisms of Alt a 1 and A. alternata in mice. Female BALB/c mice administrated recombinant Alt a 1 (rAlt a 1), native Alt a 1 (nAlt a 1), and A. alternata. Lung histology, airway hyper-reactivity (AHR), bronchoalveolar lavage fluid (BALF) cytokine levels, serum immunoglobulin responses, the expression of Bcl-6, the percentages of T follicular helper cells (Tfh), cytokine-related Tfh subtypes, regulatory B cells (Breg), and IL-10+ Breg cells were detected. High-purity nAlt 1 protein was obtained. SCIT with Alt a 1 and Alternaria decreased airway and lung inflammation, including improvement of lung pathology, lower levels of AHR, reduction of total cell numbers, and IL-4 and IL-13 levels in BALF. Furthermore, Alt a 1-SCIT effectively suppressed the IgE responses, elevated IgG titers, and was superior in decreasing the expression of Bcl-6. Additionally, Alternaria-SCIT significantly decreased the expression of Tfh cells, L-4+ Tfh, and IL-5+ Tfh cells in the spleen, whereas Alt a 1 showed superior therapeutic effects in the lymph node. IL-13+ Tfh cells in these two treatment groups not being significant. IL-17A+ Tfh cells were alleviated most effectively after A. alternata-SCIT in both the spleen and lymph node. Intriguingly, IL-10+ Breg cells decreased remarkably in response to SCIT with rAlt a 1. Treatments with Alt a 1 and A. alternata extracts had beneficial effects on allergic inflammation. Alt a 1-SCIT resulted in prominent improvement in the immunoglobulin responses, Bcl-6, and IL-10+ Breg cells. Alternaria-SCIT was more likely to suppress the expression of Tfh and cytokine-related Tfh subtypes.


Strategies for the prevention of continuous positive airway pressure failure.
Progress in neonatal intensive care is closely linked to improvements in the management of respiratory failure in preterm infants. Current modalities of respiratory support range from the more benign continuous positive airway pressure (CPAP) to various modes of mechanical ventilation. Data from recent randomized control trials suggest that the use of nasal (n)CPAP as the initial mode of respiratory support in critically ill very low birth weight infants is associated with a lower incidence of chronic lung disease. The practice of early initiation of nasal-prong CPAP in all spontaneously breathing infants at Columbia University has resulted in very low rates of chronic lung disease for decades. Many institutions have attempted to replicate the practices and results at Columbia University. However, success rates with nCPAP are highly variable, which may in part be attributable to how well it is utilized. With recent renewed interest in non-invasive respiratory support, particularly bubble nCPAP, it is essential to evaluate strategies for the prevention of CPAP failure. This review discusses strategies that address these issues and shares the practical aspects for replicating success with bubble nCPAP. In addition, it reviews desirable features, major components, and physiological consequences of various bubble CPAP systems along with clinical experience of CPAP use.


Evidence of a limited intra-individual diversity of nevi: intuitive perception of dominant clusters is a crucial step in the analysis of nevi by dermatologists.
Although nevi are highly polymorphous, it has been suggested that each individual is characterized by only a few dominant patterns of nevi. Therefore, a nevus that does not fit in with these patterns, the "ugly duckling" nevus, is suspicious. Our objective was to study the intra-individual diversity of nevi, using human ability to build "perceived similarity clusters" (PSCs). Nine dermatologists had to cluster all the nevi of 80 patients into PSCs, at the clinical scale (CS) and at the dermoscopic scale (DS) (subset of 30 patients). Nine novices did the same in a subset of 11 patients. The experts identified a mean of 2.8 PSCs/patient at CS. Concordance was higher between experts than between novices at CS and at DS. Despite a trend for more PSCs at DS than at CS, the number of nevus patterns per patient remained low, regardless of the number of nevi. Inter-expert concordance permits a consensus representation of nevus diversity in each individual. Nevus diversity is limited in each patient and constitutes an individual reference system, which we can intuitively perceive. This reference is probably crucial for nevus analysis and melanoma detection and opens perspectives for computer-aided diagnostics.


Publisher Correction: Idiosyncratic choice bias naturally emerges from intrinsic stochasticity in neuronal dynamics.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Sex-Related Differences in Inflammatory and Immune Activation Markers Before and After Combined Antiretroviral Therapy Initiation.
Women progress to death at the same rate as men despite lower plasma HIV RNA (viral load). We investigated sex-specific differences in immune activation and inflammation as a potential explanation. Inflammatory and immune activation markers [interferon γ, tumor necrosis factor (TNF) α, IL-6, IL-18, IFN-γ-induced protein 10, C-reactive protein (CRP), lipopolysaccharide, and sCD14] were measured at weeks 0, 24, and 48 after combination antiretroviral therapy (cART) in a random subcohort (n = 215) who achieved virologic suppression in ACTG A5175 (Prospective Evaluation of Antiretrovirals in Resource-Limited Settings). Association between sex and changes in markers post-cART was examined using random effects models. Average marker differences and 95% confidence intervals were estimated using multivariable models. At baseline, women had lower median log10 viral load (4.93 vs 5.18 copies per milliliter, P = 0.01), CRP (2.32 vs 4.62 mg/L, P = 0.01), detectable lipopolysaccharide (39% vs 55%, P = 0.04), and sCD14 (1.9 vs 2.3 µg/mL, P = 0.06) vs men. By week 48, women had higher interferon γ (22.4 vs 14.9 pg/mL, P = 0.05), TNF-α (11.5 vs 9.5 pg/mL, P = 0.02), and CD4 (373 vs 323 cells per cubic millimeter, P = 0.02). In multivariate analysis, women had greater increases in CD4 and TNF-α but less of a decrease in CRP and sCD14 compared with men. With cART-induced viral suppression, women have less reduction in key markers of inflammation and immune activation compared with men. Future studies should investigate the impact of these sex-specific differences on morbidity and mortality.


Open surgical and endovascular treatment of superior vena cava syndrome caused by nonmalignant disease.
The purpose of this study was to evaluate the role of endovascular and open surgical reconstructions in patients with superior vena cava (SVC) syndrome caused by nonmalignant disease. Clinical data from 32 consecutive patients who underwent endovascular or open surgical reconstruction of central veins because of symptomatic benign SVC syndrome between November 1983 and June 2001 were retrospectively reviewed. The study included 17 male and 15 female patients (mean age, 38 years; range, 5-69 years). Presenting symptoms were head fullness (n = 26), dyspnea or orthopnea (n = 23), headache (n = 17), or dizziness (n = 11); physical signs were head swelling (n = 31), chest wall collateral vessels (n = 29), facial cyanosis (n = 18), or arm swelling (n = 17). Etiologic factors included mediastinal fibrosis (n = 19), indwelling catheter (n = 8), idiopathic thrombosis (n = 4), or post-surgery (n = 1). Two patients were heterozygous for factor V Leiden; 1 patient had antithrombin III deficiency. Twenty-nine patients underwent surgical reconstruction with 31 bypass grafts: spiral saphenous vein (n = 20), superficial femoral vein (n = 4), human allograft (n = 1), or expanded polytetrafluoroethylene (ePTFE, n = 6). Eleven patients underwent percutaneous transluminal angioplasty or stenting; 3 primary and 8 secondary endovascular procedures were performed to treat graft stenosis (n = 7) or occlusion (n = 1). There were no early deaths. Five early graft failures in 3 ePTFE grafts and 2 bifurcated vein grafts (thrombosis, n = 4; stenosis, n = 1) were successfully treated with open surgical revision. Over a mean follow-up of 5.6 years (range, 0.4-16.6 years) in surgical patients, 17 additional secondary interventions were performed in 8 patients, 14 endovascular and 3 surgical. Primary, assisted primary, and secondary patency rates of surgical bypass grafts were 63%, 79%, and 85%, respectively, at 1 year, and 53%, 68%, and 80%, respectively, at 5 years. Graft patency was significantly higher in vein grafts compared with ePTFE grafts (P =.02). Mean follow-up after percutaneous transluminal angioplasty or stenting was 3.1 years (range, 1 day-11.7 years). Twelve secondary endovascular interventions were performed in 6 patients (primary group, 3 of 3; secondary group, 3 of 9 grafts in 8 patients) to maintain patency in 11 of 12 reconstructions. Mean follow-up in the entire patient cohort was 5.3 years (range, 0.4-16.6 years). In 79% of patients symptoms had resolved or were significantly improved at last follow-up. Surgical treatment of benign SVC syndrome is effective over the long term, with secondary endovascular interventions to maintain graft patency. Straight spiral saphenous vein graft remains the conduit of choice for surgical reconstruction, with results superior to those with bifurcated vein and ePTFE. Endovascular treatment is effective over the short term, with frequent need for repeat interventions. It does not adversely affect future open surgical reconstruction and may prove to be a reasonable primary intervention in selected patients. Patients who are not suitable for or who fail endovascular intervention merit open surgical reconstruction.


Cord blood neutrophils display a galectin-3 responsive phenotype accentuated by vaginal delivery.
Term neonates are at increased risk of infections due to undeveloped immune mechanisms, and proper neutrophil function is important for perinatal immune defence. Galectin-3, an endogenous β-galactoside-binding lectin, is emerging as an inflammatory mediator and we have previously shown that primed/activated, but not resting, adult neutrophils respond to this lectin by production of reactive oxygen species (ROS). We investigated if galectin-3 is of importance in perinatal immune defence, focusing on plasma levels and neutrophil responsiveness. Neutrophils were isolated from peripheral blood of healthy adults and cord blood (CB) after elective Caesarean section (CSCB) and vaginal delivery (VDCB). ROS production was measured by chemiluminescence, L-selectin expression by flow cytometry, and interleukin-8 (IL-8) and galectin-3 concentrations by ELISA. Statistical evaluations were performed using the Mann-Whitney test. In response to galectin-3, CSCB neutrophils showed a small but clear ROS production not evident in adult cells, signifying that neonatal neutrophils exist in a primed state. IL-8 production was elevated in CSCB cells while L-selectin exposure was equal to adult cells. Comparing CSCB to VDCB neutrophils, the latter showed an extensive galectin-3 responsiveness, indicating that the degree of priming is dependent on mode of delivery. VDCB neutrophils were increasingly prone to shed L-selectin, while the amount of IL-8 was similar to CSCB cells. The endogenous galectin-3 levels were higher in neonatal as compared to adult plasma, unaffected by mode of delivery. Neutrophils enter a pre-primed state already in the fetus. Upon exposure to the inflammatory stimuli that are associated with labor, the neutrophils develop a reactive phenotype with extensive priming features.


Modified use of a 4-branched frozen elephant trunk prosthesis for treatment of a right-sided aortic arch aneurysm with an aberrant left subclavian artery.
Right aortic arch aneurysm originating from a Kommerell's diverticulum associated with an aberrant left subclavian artery is a rare congenital entity. We report a case of an asymptomatic 60-year-old female with right aortic arch aneurysm with an aberrant left subclavian artery, treated with a modified frozen elephant trunk technique using a 4-branched prosthesis, with the perfusion branch as an extra-anatomical bypass to the aberrant left subclavian artery. This case demonstrates short-term safety and efficacy of this technique.


Presumed vestibular hemorrhage secondary to warfarin.
Hemorrhage secondary to anticoagulant therapy is well documented. We report a patient who presented with acute vertigo and unilateral deafness while on warfarin and was found to have a probable hemorrhage in the labyrinth, identified on MRI.


Unusual presentation of basilar artery stroke secondary to patent foramen ovale: a case report.
We report a case of a patient presenting with neuropsychiatric manifestations secondary to paradoxical embolism Unexplained rapid onset of confusion with amnesia and minimal neurological deficits can be a manifestation of various systemic causes of which stroke, either ischemic or hemorrhagic, is one. Thorough and systematic evaluation of these patients can be highly rewarding in terms of optimizing patient outcome. We report the case of a 45-year-old woman whose initial presentation was with acute onset of confusion, memory loss with personality change and headaches. A differential diagnosis of systemic illness and cerebral pathology was entertained. She was empirically treated for neurological infection. Brain imaging revealed bilateral thalamic and cerebellar infarction. Further evaluation with an aim to define the etiology, revealed the diagnosis of Patent Foramen Ovale with paradoxical embolism. The differential diagnosis of unexplained rapid onset of confusion, amnesia with minimal motor neurological deficits and relevant appropriate investigations are discussed in this case report. This case highlights the importance of recognising the atypical manifestations of posterior fossa stroke. In young patients presenting with non-focal neuropsychiatric manifestations, paradoxical embolism, secondary to patent foramen ovale is a possible cause.


Comparison of thymic and peripheral T cell Ly-2/3 antigens.
Major structural differences occur between the thymic and peripheral T cell forms of the Ly-2/3 antigen. Thymus Ly-2/3 consists of similar amounts of two types of disulfide-linked heterodimer, alpha beta and alpha' beta (Mr alpha = 38000, Mr alpha' = 35000, Mr beta = 30000). In contrast material from peripheral T cells consists almost exclusively of alpha beta dimers. The alpha chains of thymus and peripheral T cells differ also in isoelectric point with the thymic alpha chain being the more acidic. Based on peptide mapping experiments the alpha and alpha' chains of thymus are likely to be alternatively modified forms of the same polypeptide backbone. Individual T cell clones or T cell tumors propagated in vitro exhibit either a typical thymus or a typical peripheral T cell Ly-2/3 polypeptide pattern indicating that the synthesis of both alpha and alpha' chains can occur in the same cell. The heterogeneity of thymic Ly-2/3 can be considerably reduced by removal of sialic acid residues, and after desialylation the alpha chains of thymus and a cloned cytotoxic T lymphocyte (CTL) line cannot be electrophoretically distinguished. If Ly-2 structures affected the antigen specificity of CTL, a different structural variant would be expected in individual clones. The electrophoretic identity of desialylated thymus and CTL alpha chains suggests that Ly-2 does not exhibit clonal variation in polypeptide structure and, therefore, cannot contribute to antigen specificity.


The Impact of Pepsin on Human Nasal Epithelial Cells In Vitro: A Potential Mechanism for Extraesophageal Reflux Induced Chronic Rhinosinusitis.
To describe potential mechanisms by which pepsin induces inflammation in refractive chronic rhinosinusitis (CRS). Our hypothesis was that pepsin induces mitochondrial damage and cytokine expression in human nasal epithelial cells (HNEpC) in vitro. Western blot was used to detect pepsin in sinus lavages from patients with CRS and controls. The HNEpC cells were treated with pepsin (pH 7; 0.1 mg/mL) for 1 or 16 hours and routine electron microscopy (EM) and MTT assay were performed. Cytokine ELISA was performed on media collected from HNEpC cells 16 hours following a 1-hour pepsin treatment. Pepsin was detected in sinus lavages from 4 out of 6 CRS patients and 0 out of 3 controls. The EM showed mitochondrial damage in pepsin-treated HNEpC cells but not in control cells. The MTT assay demonstrated reduced mitochondrial activity in pepsin-treated HNEpC cells compared to controls (P < .001). Pepsin increased IL-1A (P = .003) and IL-6 (P = .04) expression in HNEpC cells. Pepsin in sinus lavages from patients with CRS is consistent with previous studies. This study reveals the damaging effect of pepsin on mitochondria in nasal epithelial cells in vitro. Cytokines previously associated with CRS were elevated following pepsin treatment of HNEpC cells in vitro. These results demonstrate mechanisms by which pepsin may potentiate CRS.


[Realization of the modern educational concept for the organization of the teaching and learning activities at the Department of Forensic Medicine of I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation].
The modern educational concept for the organization of the teaching and learning activities (continuous, free, and open education) implies the necessity for its implementation the development and introduction of the new approaches to the work with the students. This problem should be addressed based on the use of the up-to-date technologies for education of the adult subjects. Such technologies find the increasingly wider application at the Department of Forensic Medicine of the I.M. Sechenov First Moscow State Medical University. It markedly contributes to the improvement of the quality of education.


Synthesis, Antioxidant and Antiproliferative Evaluation, Molecular Docking and DFT Studies of Some Novel Coumarin and Fused Coumarin Derivatives.
N'-[(4-Chloro-2-oxo-2H-chromen-3-yl)methylene]-2-cyanoacetohydrazide (3) was synthesized in excellent yield from the condensation of 4-Chloro-2-oxo-2H-chromene-3-carbaldehyde with cyanoacetohydrazide. Compound 3 was utilized as a building block to synthesize novel coumarin and heterocycle-fused coumarin derivatives. The chemical structures of all the new coumarin compounds were identified by spectral analyses. Some of the new coumarins compounds were screened in human cancer cell lines (HEPG-2, MCF-7, HCT-116 and PC-3) to learn about their cytotoxic effects in addition to the study of their DNA damage and antioxidant activity. Three of these compounds exhibited remarkable antioxidant and anti-proliferative activities. Moreover, they have the capability to protect DNA from damage induced by bleomycin. Molecular docking, DFT and molecular electrostatic potential studies were performed on the compounds in vitro.


Sudden unexpected death due to coronary thrombosis associated with isolated necrotizing vasculitis in the coronary arteries of a young adult.
Coronary arteritis is an uncommon cause of sudden death in non-atherosclerotic coronary diseases, and is mostly associated with systemic vasculitis or systemic autoimmune diseases; therefore, sudden death due to isolated coronary arteritis rarely occurs. The case described in this report is that of a 34-year-old man with no significant personal medical history who died suddenly after presenting with nausea. Postmortem examination revealed a significant infiltration of lymphocytes predominantly on the adventitia and periadventitial tissues of the coronary arteries in the epicardium. The lymphocytic infiltrate partially extended to the thickened intima with fibrosis, destructing the media and internal elastic lamina, and the lumen was occluded by a thrombus in the left main stem and left anterior descending branch. The arterial walls exhibited focal fibrinoid necrosis with regression in the intima and fibrous scars with angiogenesis in the media and adventitia. Focal myocardial infarction was detected in the left ventricle as a fibrotic change of the myocardium. No findings associated with vasculitis were discerned in the aorta, other peripheral arteries, or major organs. Laboratory tests of postmortem blood samples returned negative results for antinuclear antibodies, cryoglobulin, immunoglobulin G4, and cytoplasmic anti-neutrophil cytoplasmic antibodies for myeloperoxidase and proteinase 3. These autopsy findings suggest that the sudden death was caused by isolated necrotizing vasculitis that is assumed to be polyarteritis nodosa localized at the coronary arteries. However, pathological characteristics may not be exactly the same between isolated necrotizing vasculitis in the coronary arteries and polyarteritis nodosa.


Human norovirus exhibits strain-specific sensitivity to host interferon pathways in human intestinal enteroids.
Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis worldwide; yet currently, no vaccines or FDA-approved antiviral drugs are available to counter these pathogens. To understand HuNoV biology and the epithelial response to infection, we performed transcriptomic analyses, RT-qPCR, CRISPR-Cas9 modification of human intestinal enteroid (HIE) cultures, and functional studies with two virus strains (a pandemic GII.4 and a bile acid-dependent GII.3 strain). We identified a predominant type III interferon (IFN)-mediated innate response to HuNoV infection. Replication of both strains is sensitive to exogenous addition of IFNs, suggesting the potential of IFNs as therapeutics. To obtain insight into IFN pathway genes that play a role in the antiviral response to HuNoVs, we developed knockout (KO) HIE lines for IFN alpha and lambda receptors and the signaling molecules, MAVS, STAT1, and STAT2 An unexpected differential response of enhanced replication and virus spread was observed for GII.3, but not the globally dominant GII.4 HuNoV in STAT1-knockout HIEs compared to parental HIEs. These results indicate cellular IFN responses restrict GII.3 but not GII.4 replication. The strain-specific sensitivities of innate responses against HuNoV replication provide one explanation for why GII.4 infections are more widespread and highlight strain specificity as an important factor in HuNoV biology. Genetically modified HIEs for innate immune genes are useful tools for studying immune responses to viral or microbial pathogens.


Long-Term Patency and Final Structure After Superficial Temporal Artery-Middle Cerebral Artery Bypass Surgery: A Retrospective Study.
To investigate long-term bypass patency and final structure for patients who underwent superficial temporal artery (STA)-middle cerebral artery (MCA) bypass. This study retrospectively evaluated 20 patients who underwent STA-MCA bypass and had 2-year follow-up with cerebral angiography. Patients were divided into internal carotid artery occlusion (n = 11) and MCA occlusion or stenosis (n = 9) groups, and diagnosis was either arteriosclerotic (n = 14) or nonarteriosclerotic (n = 6) disease. Final bypass formation was examined with cerebral angiography at 2 years postoperatively. Diameters of the STA, middle meningeal artery (MMA), and deep temporal artery (DTA) were measured at preoperative angiography and at 2-year follow-up. No significant differences in STA, MMA, and DTA diameters were reported between the internal carotid artery versus MCA group. For patients with arteriosclerotic disease, thicker STA diameters were noted on preoperative angiography. For patients with nonarteriosclerotic disease, MMA and DTA dilatation was noted on 2-year follow-up imaging. For patients with arteriosclerotic disease, all direct bypasses were patent at 2 years. For patients with nonarteriosclerotic disease, remarkable angiogenesis was demonstrated. Long-term patency of a direct bypass may be correlated with arteriosclerotic or nonarteriosclerotic etiology. An indirect bypass route may develop in patients with nonarteriosclerotic disease; therefore, it is important to create a foundation for an indirect bypass with MMA and DTA preservation during craniotomy. In 2 patients with nonarteriosclerotic disease, STA remained the primary bypass foundation; however, the technique resembled novel angiogenesis after encephaloduroarteriosynangiosis and not direct STA-MCA bypass. Therefore, final bypass structure might be affected by disease etiology.


A comparison of two dosage regimens of oral misoprostol for labor induction at term.
251 women with indications for labor induction at term were randomised to receive either 50 or 100 microgs of oral misoprostol, repeated every 4 h to a maximum of 5 doses. Parous women in the higher dose group received 50 microgs as their first dose, subsequent doses being 100 microgs. Women who failed to respond to the 5 doses of misoprostol had the option of having vaginal PGE2 gel. The primary outcome measure was the induction to delivery interval in those who delivered vaginally. Patient satisfaction was assessed by postnatal questionnaire. The induction to vaginal delivery interval, although shorter in the 100 microgs group was not statistically significant (26.8 versus 33.7 h, mean difference 6.9 h, 95% CI 0.4-13). There were, however, more failed inductions with misoprostol in the 50 microgs group (12.7% Vs 4.8%, RR 2.6, 95% CI 1.07-6.5). There were no differences in the modes of delivery, number of caesarean sections for fetal distress or in the neonatal outcomes in the two groups. Most patients, 83% and 92% in the 50 and 100 microgs, respectively, were satisfied with their inductions, and 64% of patients would prefer to have the inducing agent given orally if they were to have another induction. Oral misoprostol is effective in inducing labor and seems acceptable to patients. Both the 50 and 100 microgs dose regimens have a reasonable safety profile, but in view of the higher incidence of failed inductions with the 50 microgs dosage, the 100 microgs dose regimen may be the preferred dose regimen.


Cardiac myofibrillogenesis inside intact embryonic hearts.
How proteins assemble into sarcomeric arrays to form myofibrils is controversial. Immunostaining and transfections of cultures of cardiomyocytes from 10-day avian embryos led us to propose that assembly proceeded in three stages beginning with the formation of premyofibrils followed by nascent myofibrils and culminating in mature myofibrils. However, premyofibril and nascent myofibril arrays have not been detected in early cardiomyocytes examined in situ in the forming avian heart suggesting that the mechanism for myofibrillogenesis differs in cultured and uncultured cells. To address this question of in situ myofibrillogenesis, we applied non-enzymatic procedures and deconvolution imaging techniques to examine early heart forming regions in situ at 2- to 13-somite stages (beating begins at the 9-somite stage), a time span of about 23 h. These approaches enabled us to detect the three myofibril stages in developing hearts supporting a three-step model of myofibrillogenesis in cardiomyocytes, whether they are present in situ, in organ cultures or in tissue culture. We have also discovered that before titin is organized the first muscle myosin filaments are about half the length of the 1.6 mum filaments present in mature A-bands. This supports the proposal that titin may play a role in length determination of myosin filaments.


Acquired immunity against Cooperia spp. and Ostertagia spp. in calves: effect of level of exposure and timing of the midsummer increase.
In two experiments, groups of calves were exposed to different levels and patterns of infection with Ostertagia spp. and Cooperia spp. The experimental design simulated the stereotypic pattern of herbage infestation, including both as normal and a delayed midsummer increase, under conditions of set-stocking. After this simulated 'first grazing season', calves were followed during the subsequent winter housing. At the end of that housing period some calves were challenged with 100,000 L3 Cooperia spp. and 40,000 L3 Ostertagia spp. and slaughtered 23 days later. All previously infected calves were protected against the establishment of the challenge infection with Cooperia spp., but not against Ostertagia spp. For the latter a significant negative correlation was found between worm count and previous level of exposure to infection. During the simulated first grazing season, changes in the ratio of Cooperia to Ostertagia eggs in the faecal egg output and the genus-specific egg count were influenced by both the level of exposure and the timing of the midsummer increase. It is concluded that acquired immunity against both parasite genera develops depending on the level of exposure to infection during a first grazing season, and that delaying the midsummer increase results in a delay of the acquisition of an effective immunity as measured by faecal egg counts and the ratio of Cooperia to Ostertagia egg output.


Isolation of human immunodeficiency virus type 1 from peripheral blood monocytes.
Human immunodeficiency virus type 1 (HIV-1) can infect circulating peripheral blood monocytes and resting CD4+ T lymphocytes despite sustained suppression of plasma viremia to undetectable levels. These persistently infected cell populations pose a barrier for virus eradication by highly active antiretroviral therapy (HAART), and are a significant reservoir of HIV-1 contributing to viral rebound following cessation or failure of HAART. This chapter provides a protocol for isolating replication-competent HIV-1 from peripheral blood monocytes of HIV-1-infected individuals, including those with sustained plasma HIV-1 RNA levels below 50 copies/mL, by co-culture with CD8-depleted, phytohemagglutinin-activated donor peripheral blood mononuclear cells. In our laboratory, this protocol has the sensitivity to achieve a success rate of positive HIV-1 isolation in approx 70% of cases. The study of HIV-1 strains harbored by peripheral blood monocytes of patients undergoing HAART will contribute to the understanding of viral persistence in cellular reservoirs that impede effective HAART.


Histidine-tryptophan-ketoglutarate versus University of Wisconsin solution in living donor liver transplantation: results of a prospective study.
The grafts obtained from a living donor hepatectomy are perfused on the back table with either University of Wisconsin solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK). The efficacy and safety of these solutions have been studied in cadaveric liver transplantation, however, there is no study comparing the two solutions in adult-to-adult living donor liver transplantation. In this study, UW and HTK were used in the perfusion of right living donor grafts. The grafts were perfused with a predetermined sequence and volume of one of the solutions. Liver biochemistries, complications, and graft and patient survival were analyzed. From January 2001 to September 2002, 30 grafts were alternately perfused with either UW (UW group) or HTK (HTK group). The perfusion was performed first via the artery and then via the portal vein with a predetermined volume. At a mean follow-up of 13 +/- 7 months, no significant statistical difference between groups UW and HTK in posttransplantation liver biochemistries, complications, or patient and graft survival (84% and 80%, respectively) was observed. In conclusion, UW and HTK are equally effective and safe in the perfusion of the living donor liver grafts. HTK has a slight practical advantage over UW because it does not need to be flushed away before reperfusion of the graft and is less expensive.


Actinic lichen planus mimicking melasma. A clinical and histopathologic study of three cases.
Three cases of actinic lichen planus mimicking melasma are presented. Although the clinical similarity to melasma is striking, the histopathologic picture is distinctive. It is suggested that actinic lichen planus be considered in the differential diagnosis of melasma.


Ovarian remnant syndrome with paraintestinal ovarian serous cystadenofibroma arose 30 years after bilateral salpingo-oophorectomy: A case report.
Ovarian cystadenofibroma is a relatively rare benign ovarian tumor. Ovarian remnant syndrome (ORS) is a rare complication of bilateral salpingo-oophorectomy (BSO). We report a rare case of ORS with paraintestinal ovarian serous cystadenofibroma that developed 30 years after total abdominal hysterectomy and BSO in a 73-year-old woman. A 73-year-old woman complained of long-term lower abdominal discomfort. She was diagnosed with a cystic lesion in the lower abdomen on transabdominal ultrasonography. Further diagnostic imaging and laboratory tests could not exclude a diagnosis of malignancy. The patient underwent laparoendoscopic single-site surgery. We found one cystic lesion 5 cm in size with multiple septa that was adhered to the small bowel. We consulted a general surgeon for tumor resection. Dissection was performed and the specimen was then removed from the umbilical wound. Histopathological examination revealed an ovarian serous cystadenofibroma. The postoperative recovery was uneventful. Patients with lower abdominal pain after a previous hysterectomy and BSO should be examined with transabdominal sonography for ORS.


A brief history of tendon and ligament bioreactors: Impact and future prospects.
Bioreactors are powerful tools with the potential to model tissue development and disease in vitro. For nearly four decades, bioreactors have been used to create tendon and ligament tissue-engineered constructs in order to define basic mechanisms of cell function, extracellular matrix deposition, tissue organization, injury, and tissue remodeling. This review provides a historical perspective of tendon and ligament bioreactors and their contributions to this advancing field. First, we demonstrate the need for bioreactors to improve understanding of tendon and ligament function and dysfunction. Next, we detail the history and evolution of bioreactor development and design from simple stretching of explants to fabrication and stimulation of two- and three-dimensional constructs. Then, we demonstrate how research using tendon and ligament bioreactors has led to pivotal basic science and tissue-engineering discoveries. Finally, we provide guidance for new basic, applied, and clinical research utilizing these valuable systems, recognizing that fundamental knowledge of cell-cell and cell-matrix interactions combined with appropriate mechanical and chemical stimulation of constructs could ultimately lead to functional tendon and ligament repairs in the coming decades.


One-step purification of R-phycoerythrin from the red edible seaweed Grateloupia turuturu.
A one-step chromatographic method for the purification of R-phycoerythrin (R-PE) of Grateloupia turuturu Yamada is described. Native R-PE was obtained with a purity index of 2.89 and a recovery yield of 27% using DEAE-Sepharose Fast Flow chromatography with a three-step increase in ionic strength. The analysis by SDS electrophoresis showed a broad band between 18 and 21kDa in size corresponding to subunits α and β and a low intensity band of 29kDa corresponding to the γ subunit. Two forms of R-PE were identified by gel filtration chromatography: a native form with a molecular weight of 260±5kDa and a dissociated form with a molecular weight of 60±2kDa. The native form presented the characteristic absorption spectrum of R-PE with three absorbance maxima at 498, 540 and 565nm, whereas the dissociated form presented only the 498 and 540nm peaks. Moreover, the two forms displayed two different fluorescence maxima.


Solid-contact Hg(II)-selective electrode based on a carbon-epoxy composite containing a new dithiophosphate-based ionophore.
The experimental results herein concern a novel ion-selective electrode manufactured with an inner solid contact based on a new ligand O,O'-(2,2'-biphenylene)dithiophosphate pentyl (PenDTF). This electrode displays high selectivity toward the Hg(II) ion even in the presence of different divalent ions. The electrode also exhibited a good Nernstian response to Hg(II) (33.7±1.0 mV decade(-1)) over an ample concentration range (5.3×10(-7)-1.0×10(-2) mol L(-1)), with a detection limit of (6.1±1.7)×10(-7) mol L(-1). As a result of design, the electrode can be used for many experiments, simply renewing its contact surface with emery paper, without giving rise to a significant response deviation, exhibiting a variation coefficient of 3%, capable of being tested within the 0-5 pH interval. The electrode was used satisfactorily as indicating electrode during the potentiometric titration of Hg(II) ions with EDTA.


Rosiglitazone treatment enhances intracellular actin dynamics and glucose transport in hypertrophic adipocytes.
To accommodate surplus energy, adipose tissue expands by increasing both adipose cell size (hypertrophy) and cell number (hyperplasia). Enlarged, hypertrophic adipocytes are known to have reduced insulin response and impaired glucose transport, which negatively influence whole-body glucose homeostasis. Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, known to stimulate hyperplasia and to efficiently improve insulin sensitivity. Still, a limited amount of research has investigated the effects of rosiglitazone in mature, hypertrophic adipocytes. Therefore, the objective of this study was to examine rosiglitazone's effect on insulin-stimulated glucose uptake in hypertrophic adipocytes. C57BL/6J male mice were subjected to 2 weeks of high-fat diet (HFD) followed by 1 week of HFD combined with daily administration of rosiglitazone (10 mg/kg). Adipose cell-size distribution and gene expression were analysed in intact adipose tissue, and glucose uptake, insulin response, and protein expression were examined using primary adipocytes isolated from epididymal and inguinal adipose tissue. HFD-feeding induced an accumulation of hypertrophic adipocytes, which was not affected by rosiglitazone-treatment. Still, rosiglitazone efficiently improved insulin-stimulated glucose transport without restoring insulin signaling or GLUT4 expression in similar-sized adipocytes. This improvement occurred concurrently with extracellular matrix remodelling and restored intracellular levels of targets involved in actin turnover. These results demonstrate that rosiglitazone improves glucose transport in hypertrophic adipocytes, and highlights the importance of the cytoskeleton and extracellular matrix as potential therapeutic targets.


Bacteriophage T4 late promoters: mapping 5' ends of T4 gene 23 mRNAs.
More than thirty 5' ends of RNA molecules which transverse the bacteriophage T4 late gene, gene 23, have been mapped by nuclease protection and reverse transcription, to a 1.7 kilobase pair (kbp) region upstream of gene 23. Most of these 5' ends arise from RNA processing and degradation. Two sites at which RNA synthesis is initiated have been identified by guanylylation of diphosphate- or triphosphate-terminated RNA with vaccinia virion "capping" enzyme and are situated approximately 0.1 and 0.9 kbp upstream of gene 23. At least one other promoter lies more than 1.7 kbp upstream of gene 23, that is, outside of the mapped region.


Distribution and characterization of Clostridium difficile isolated from dogs in Japan.
We collected 204 nondiarrhoeic canine fecal samples and isolated 68 Clostridium difficile strains from 62 of these samples. Strains were grouped into 29 PCR ribotypes. Only 47% of the strains were toxigenic.


Production of rare isotope beams at the Texas A&M University Cyclotron Institute.
The Cyclotron Institute at Texas A&M is currently configuring a scheme for the production of radioactive-ion beams that incorporates a light-ion guide and a heavy-ion guide coupled with an electron-cyclotron-resonance ion source constructed for charge-breeding. This scheme is part of an upgrade to the facility and is intended to produce radioactive beams suitable for injection into the K500 superconducting cyclotron. The current status of the project and details on the ion sources used in the project is presented.


Bismuth staining of a nucleolar protein.
A major nucleolar protein in Chinese hamster ovary cells with a molecular weight (MW) of 100 kD has been found to stain selectively with the bismuth tartrate technique of Locke & Huie [19]. After glutaraldehyde fixation and bismuth staining of electrophoretic transfers of total nucleolar proteins separated by SDS-PAGE, a single band corresponding to the 100 kD protein is revealed. When the technique is applied to whole cells, small punctate regions of the nucleoli are strongly stained. At the ultrastructural level, bismuth selectively contrasts the fibrillar centers and the adjoining cords of the dense fibrillar component. The remainder of the dense fibrillar component is not stained. It is proposed that the high phosphorylation level of the 100 kD protein is responsible for its glutaraldehyde-insensitive bismuth staining. The concentration of this protein in certain localized regions of the nucleolus suggests that it plays a metabolic rather than a structural role.


Shifts in periphyton research themes over the past three decades.
It has been well documented that periphyton communities play a key role in primary productivity, nutrient cycling, and food web interactions. However, a worldwide overview of research on the key themes, current situation, and major trends within the field is lacking. In this study, we applied the machine learning technique (latent Dirichlet allocation, LDA) to analyze the abstracts of 6690 publications related to periphyton from 1991 to 2020 based on the Web of Science database. The relative frequency of classical and basic research on periphyton related to colonization, biomass, growth rate, and habitats has been clearly decreasing. The increasing trends of research on periphyton are embodied in the periphyton function in freshwater ecosystems (e.g., application as ecological indicators, function in the removal of nutrients, and application in paleolimnology), the research at macroscales (e.g., spatial-temporal variation, and functional and taxonomic diversity), and the anthropogenic themes (e.g., climate warming, response to multiple stressors, and land use type). The keyword and title analysis showed that the periphyton studies are concentrated mainly on diatom aspects, especially with respect to streams relative to lakes. The thematic space based on non-metric multidimensional scaling (NMDS) showed that the classical themes such as growth rate, colonization, and environmental factors (e.g., multiple stressors and climate warming) were most linked to other research themes. We proposed that future trends in the periphyton should focus on the function of periphyton in lakes and their response to multiple environmental pressures with the increasingly extensive eutrophication in lakes and the increasingly significant change in the climate.


Liquid-gel partitioning using Lipidex in the determination of polychlorinated biphenyls in cod liver oil.
A technique was developed for transfer of fat and polychlorinated biphenyls from cod liver oil into the lipophilic gel Lipidex 5000. Subsequent elution of the gel separated about 60% of the fat from the sample. Following further purification on aluminium oxide and silica gel, toxic non-ortho- and mono-ortho-PCB congeners were isolated in two separate fractions on charcoal. Recoveries were studied by addition of twelve different PCB congeners to 0.2 g of fat. The non-ortho-PCBs were labelled with 13C. The recoveries of 5-50 ng of the unlabelled compounds were 80-100% and those of 50-100 pg of the labelled compounds were 76-106%.


Fertigation to recover nitrate-polluted aquifer and improve a long time eutrophicated lake, Spain.
Use of nitrogen and phosphorus in agriculture increases agricultural production but also generates important environmental problems around the world, such as high nitrate levels in aquifers and an increase in eutrophication of waters. A set of tools and models are used, ENVIRO-GRO and PATRICAL models, to analyse the effect of large irrigation system modernization, 13,700 ha, from traditional flood irrigation to modernized drip irrigation, in the aquifer nitrate levels and in the phosphorus inputs to a 50-years eutrophicated RAMSAR lake, Albufera lake. Based on data collected from end users, modernized irrigation system reduces the amount of nitrogen applied from 25 % to 45 % and phosphorus applied around 90-95 %, so phosphorus content on soil, phosphorus legacy, is reducing by time. Obtained results indicate that nitrogen leaching as nitrate is reduced by 70 % to 83 % and surface runoff during irrigation events disappear, hence phosphorus contributions to surface waters are eliminated. Nitrate polluted aquifer will be recovered in 5-6 years after complete implement of measures and phosphorus inputs to the lake are reduced around 20 % contributing to improve the status of the eutrophicated Albufera lake. Results show great agreement with the European Strategy to reduce the use of fertilizers and how the fertilizers technical management in fertigation can contribute to greater efficiency in it use and improvement of the environment.


Bisphenol A(BPA), BPS and BPB-induced oxidative stress and apoptosis mediated by mitochondria in human neuroblastoma cell lines.
The analogues of biphenol A (BPA), including bisphenol S (BPS) and bisphenol B (BPB), are commonly used to replace the application of BPA in containers and wrappers of daily life. However, their safeties are questioned due to their similar chemical structure and possible physiological effects as BPA. To investigate the neurotoxic effects of BPA, BPS, and BPB as well as their underlying mechanism, IMR-32 cell line from male and SK-N-SH cell line from female were exposed respectively to BPA, BPS and BPB with concentrations of 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, and 100 μM for 24 h. Additionally, 24 h exposure of BPA combining epigallocatechin gallate (EGCG) (4 μM and 8 μM for IMR-32 and SK-N-SH respectively) were conducted. Results demonstrated that BPs exposure could promote reactive oxygen species production and increase level of malondialdehyde (MDA) while decrease levels of superoxide dismutase (SOD). Intensive study revealed that after exposure to BPA mitochondrial membrane potential (MMP) dropped down and the protein expression levels of Bak-1, Bax, cytochrome c and Caspase-3 were up-regulated but Bcl-2 were down-regulated significantly. Moreover, apoptosis rate was raised and cell activity declined remarkably in the neuroblastoma cells. All the effects induced by BPA could be alleviated by the adding of EGCG, which similar alleviations could be inferred in IMR-32 and SK-N-SH cells induced by BPS and BPB. Furthermore, BPS showed lower neurotoxic effects compared to BPA and BPB. Interestingly, the neurotoxic effects of BPA on IMR-32 cells were significantly higher than those on SK-N-SH cells. In conclusion, the results suggested that BPA, BPS and BPB could induce oxidative stress and apoptosis via mitochondrial pathway in the neuroblastoma cells and male is more susceptible to BPs than female.


Microelectrode of the Thomas type using a liquid membrane electrode.
By replacing the glass-based pH electrode (L. R. Pucacco, S. K. Corona, H. R. Jacobson, and N. W. Carter (1986) Anal. Biochem. 153, 251-261) with a liquid membrane-based pH electrode, a relatively easy-to-manufacture modified Thomas electrode has been developed. The liquid membrane-based modified Thomas electrode can be manufactured without the special equipment (forge) and materials (glass) required to make the glass membrane pH microelectrode (L. R. Pucacco and N. W. Carter (1976) Anal. Biochem. 73, 501-512). The sensitivity (57.4 +/- 0.22 mV/pH unit), response time (20.0 +/- 2.67 s), and electrical resistance (3.48 +/- 0.67 X 10(11) ohm) of this electrode are similar to those of the glass-based version.


A partially functional 245-amino-acid internal deletion derivative of Escherichia coli sigma 70.
Two hundred forty-five consecutive amino acids of the sigma 70 subunit of Escherichia coli RNA polymerase are not conserved in the homologous protein of Bacillus subtilis. We show that their deletion from a sigma 70-32 hybrid protein caused no severe loss of function in vivo, while sigma 70 itself retained considerable function in vitro.


Experience-dependent plasticity modulates ongoing activity in the antennal lobe and enhances odor representations.
Ongoing neural activity has been observed across several brain regions and is thought to reflect the internal state of the brain. Yet, it is important to understand how ongoing neural activity interacts with sensory experience and shapes sensory representations. Here, we show that the projection neurons of the fruit fly antennal lobe exhibit spatiotemporally organized ongoing activity. After repeated exposure to odors, we observe a gradual and cumulative decrease in the amplitude and number of calcium events occurring in the absence of odor stimulation, as well as a reorganization of correlations between olfactory glomeruli. Accompanying these plastic changes, we find that repeated odor experience decreases trial-to-trial variability and enhances the specificity of odor representations. Our results reveal an odor-experience-dependent modulation of ongoing and sensory-evoked activity at peripheral levels of the fruit fly olfactory system.


Aroma improvement of dealcoholized Merlot red wine using edible flowers.
There is an increasing market share of dealcoholized wines due to rise in patronage by wine consumers. However, the aroma of such wines deteriorates the more the alcohol content is reduced. Improving the aroma with edible flowers may curb this problem. To improve the aroma of a dealcoholized Merlot red wine, extracts of peach, rose, and lily flowers (FEs) were added to develop three reconstituted dealcoholized wines (RDWS). RDWS were compared with the original wine and the dealcoholized wine (DW) based on chemical properties, aroma compounds, and sensory characteristics. The FEs had no effect on the chemical parameters of RDWS. The FEs improved the volatile composition of RDWS, especially ethyl octanoate, isoamyl octanoate, linalool, and geraniol. Sensory analysis showed that aroma intensity and fruity and floral notes improved in RDWS compared to DW. Among the FEs, rose was the best and can improve the aroma of dealcoholized Merlot red wine.


Oncolytic virotherapy: molecular targets in tumor-selective replication and carrier cell-mediated delivery of oncolytic viruses.
Tremendous advances have been made in developing oncolytic viruses (OVs) in the last few years. By taking advantage of current knowledge in cancer biology and virology, specific OVs have been genetically engineered to target specific molecules or signal transduction pathways in cancer cells in order to achieve efficient and selective replication. The viral infection and amplification eventually induce cancer cells into cell death pathways and elicit host antitumor immune responses to further help eliminate cancer cells. Specifically targeted molecules or signaling pathways (such as RB/E2F/p16, p53, IFN, PKR, EGFR, Ras, Wnt, anti-apoptosis or hypoxia) in cancer cells or tumor microenvironment have been studied and dissected with a variety of OVs such as adenovirus, herpes simplex virus, poxvirus, vesicular stomatitis virus, measles virus, Newcastle disease virus, influenza virus and reovirus, setting the molecular basis for further improvements in the near future. Another exciting new area of research has been the harnessing of naturally tumor-homing cells as carrier cells (or cellular vehicles) to deliver OVs to tumors. The trafficking of these tumor-homing cells (stem cells, immune cells and cancer cells), which support proliferation of the viruses, is mediated by specific chemokines and cell adhesion molecules and we are just beginning to understand the roles of these molecules. Finally, we will highlight some avenues deserving further study in order to achieve the ultimate goals of utilizing various OVs for effective cancer treatment.


Investigation of isoflavone constituents from tuber of Apios americana Medik and its protective effect against oxidative damage on RIN-m5F cells.
In our previous study, AI-3, a mixture of isoflavones, was obtained from Apios Americana Medik tuber and showed strong protective ability on oxidative damaged RIN-m5F cells. This study aimed to identify the main compounds of AI-3 and elucidate their activities and underlying mechanism. In results, eleven compounds were purified from AI-3. Among them, Compound 8 (2'-Hydroxy, 5-methoxy genistein-7-O-glucoside, HMG) was the most effective compound against H2O2-induced injury in RIN-m5F cells (stronger than positive control α-LA). Further RNA-seq analysis found that compared with H2O2 group, 388 differentially expressed genes (DEGs) were identified in HMG group. The enrichment analyses revealed fluid shear stress and atherosclerosis pathway and hepatocellular carcinoma pathway enriched the most DEGs, in which HOX-1, GST, NQO1, SQSTM, TrxR1 were significantly up-regulated. The finding indicated Keap1-Nrf2-ARE signaling pathway may play essential role in the protective effect of HMG on oxidative damaged RIN-m5F cells.


Coordination properties of 3-functionalized beta-cyclodextrins. Thermodynamic stereoselectivity of copper(II) complexes of the A,B-diamino derivative and its exploitation in LECE.
The bis-amino AB derivative of beta-cyclodextrin on the secondary rim was synthesised and spectroscopically characterised by different techniques. Its binary systems both with protons and copper(II) were thermodynamically characterised by pH-metric potentiometry. In addition the ternary systems with each of the enantiomers of tryptophan and alanine were investigated. A thermodynamic stereoselectivity was observed for the tryptophan enantiomers and this was exploited to separate them by capillary electrophoresis through a ligand exchange mechanism (LECE). LECE separation of racemates of phenylalanine and tyrosine was also obtained.


Breeding population fluctuations in some raptors.
We investigated differences in annual breeding population stability and its relationship to diversity in food habits for several species of raptors. Chi-square tests showed no significant differences between observed and expected (based on logistic growth equation) breeding population sizes for Peregrine Falcons (Falco peregrinus) during recovery from pesticide induced declines in 4 Alaskan populations. This indicates that no major Peregrine Falcon population fluctuations occurred aside from the recovery itself. On the Colville River, Alaska, Rough-legged Hawk (Buteo lagopus) and Gyrfalcon (F. rusticolus) breeding populations experienced several declines and increases during the Peregrine Falcon recovery. Serial correlation analysis does not indicate consistent regularity in fluctuation for either the Rough-legged Hawk or Gyrfalcon on the Colville River during 1967-1985. Possible occurrence of regular fluctuations in sub-populations or over shorter time periods, however, could not be investigated. Population fluctuations for the Rough-legged Hawk and Gyrfalcon are significantly correlated during 1971-1985, with largest declines for both occurring synchronously. This correlation is consistent with the possibility that shared environmental stresses, among other factors, are responsible for population limitation. Regularity, with a 3 year interval, is indicated, however, for extremely small fluctuations in an Idaho, USA population of the Red-tailed Hawk (Buteo jamaicensis), suggesting that investigations of raptor population fluctuation and regelarity should not be limited to arctic or subarctic environments. Low diversity in food habits is not a good predictor of degree of annual population fluctuation in the study groups, while greater diversity in food habits is associated with relatively stable annual populations. An association was found in the Rought-legged Hawk between reduced annual population variability and reduced climatic severity. Neither food habits diversity nor annual population variability is constant across species ranges. Food habits diversity was also variable between years in local populations of Peregrine Falcon, Rough-legged Hawk and Gyrfalcon.


Cataract progression after prophylactic laser peripheral iridotomy: potential implications for the prevention of glaucoma blindness.
To evaluate changes in lens opacity in the first year after prophylactic laser peripheral iridotomy (LPI) performed in fellow eyes of subjects with acute primary angle closure (APAC). Prospective observational case series. Sixty Asian subjects with unilateral APAC. All fellow eyes underwent prophylactic LPI within the first week of presentation, followed by 1 week of topical steroids. The degree of lens opacity was graded at the slit-lamp examination using the Lens Opacity Classification System III (LOCS III) with standard color photographs as the reference for grading of lens opacity. This was performed 2 weeks, 4 months, and 12 months after LPI. Progression in lens opacity was defined as an increase in LOCS III grade by 2 or more units in any lens region. Lens Opacity Classification Sytem III grades in nuclear, cortical, and posterior subcapsular (PSC) regions. Most patients were Chinese (85%) and female (63.3%), with an average age of 61.5 +/- 10.6 years. The mean baseline LOCS grades in the nuclear, cortical, and PSC regions were 3.58 +/- 0.74, 0.57 +/- 1.08, and 0.23 +/- 0.72, respectively. With 12 months of follow-up, 14 of the 60 eyes (23.3%; 95% confidence interval, 16.9-29.7%) showed significant progression in any lens region. Progression in the nuclear, cortical, and PSC regions was documented in 5%, 6.7%, and 16.7% of cases, respectively. By use of logistic regression, the following factors were not found to be significant for cataract progression in any lens region: age, race, gender, history of hypertension or diabetes, presence of peripheral anterior synechiae or angle width at baseline, and total laser energy delivered. In fellow eyes of APAC, prophylactic LPI is complicated by significant cataract progression, mainly in the posterior subcapsular region. These findings may have implications for the role of prophylactic LPI in the prevention of angle-closure blindness.


High-field magnetic resonance imaging for epilepsy.
Epileptogenic lesions are often subtle, do not change during life, and are easily overlooked, if spatial resolution and signal to noise ratio are inappropriate. 2D or more recently 3D-FLAIR sequences are best suited to detect small cortical dysplasias which are often located at the bottom of a sulcus. 3D-T1-weighted gradient echo sequences are used for multiplanar, curved surface reformations, and voxel-based analyses. 3 T MR imaging is currently the state-of-the-art imaging modality for patients with suspected structural epilepsies in which an epileptogenic lesion has not yet been found.


[Psychological findings in alleged phlebologic disorders of the leg].
Twenty-six female patients with restless legs underwent psychiatric investigation as part of a pilot study. Most exhibited a depressive-anxious-hypochondric syndrome. The development of physical symptoms in connection with psychic disturbances and the treatment of patients with restless legs are discussed.


Cardiovascular effects and changes in midbrain periaqueductal gray neuronal activity induced by electrical stimulation of the hypothalamus in the rat.
The effects of low-intensity electrical stimulation of sites in the hypothalamus and zona incerta (ZI) on mean blood pressure (MBP), heart rate (HR), and neuronal activity in the midbrain periaqueductal gray (PAG) were investigated in rats. Long-lasting depressor responses were elicited from 67 sites in the hypothalamus and ZI. Effects on HR were variable, except for the ZI where bradycardiac responses were evoked. The amplitude of the depressor responses was significantly correlated with baseline MBP on stimulation of the dorsomedial hypothalamic nucleus (DMH) or the dorsal hypothalamic area. Extracellular single-unit recordings were made from 94 PAG neurons. Most units were located in the ventral half of the PAG (62/94), where spontaneous firing rates were significantly higher than in the dorsal half: 12.5 +/- 1.4 spikes/s as compared to 6.0 +/- 0.9 spikes/s. Changes in PAG neuronal activity to both ipsi- and contralateral hypothalamic stimulation were observed. Most neurons were inhibited or unresponsive. There was no site specificity: responsive and unresponsive neurons were scattered throughout the PAG. Inhibition was most effectively evoked by stimulation of the DMH (25 out of 39 neurons) and the ZI (9 out of 15 neurons). In most neurons, the inhibition strictly followed the time course of hypothalamic stimulation. The results suggest that PAG as well as nonPAG pathways participate in the hypothalamic control of cardiovascular function.


A group-administered lag task as a measure of working memory.
The purpose of the present studies was to evaluate the utility of a group-administered version of the n-back, or lag task. Experiments 1 and 2 describe the construction of the task and reveal that the modified lag task (MLT) produces the same performance trends as have been observed in individually administered versions of the lag task; performance decreased significantly as lag conditions increased in difficulty. Experiments 3 and 4 established convergent validity by comparing the MLT to another common working memory task, the operation-word span task, as well as the updated version of this task, the automatic operation span task. The results showed that MLT performance was significantly correlated to scores on both measures. These experiments provide important details about the MLT as a measure of working memory, in a group- or individual-administration setting.


Infundibular spasm in Fallot's tetralogy - an account and its management in anaesthesia.
The value of propranolol in relieving infundibular spasm is illustrated. The pathophysiology of infundibular spasm in Fallot's tetralogy and its management in anaesthesia is reviewed.


Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma.
Xp11 translocation renal cell carcinoma (TRCC) is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor-targeted therapy in case of recurrence.


Effective removal of cationic dyes from aqueous solution using gum ghatti-based biodegradable hydrogel.
Biodegradable hydrogels of gum ghatti (Gg) with a co-polymer mixture of acrylamide (AAm) and methacrylic acid (MAA) (termed as Gg-cl-P(AAm-co-MAA)) were synthesised by microwave-assisted free radical graft co-polymerisation technique. The hydrogel polymer was characterized by FTIR, SEM, and Brunauer-Emmett-Teller techniques. The Gg-cl-P(AAm-co-MAA) hydrogel was studied as an adsorbent for the removal of methylene blue (MB) and methyl violet (MV) from aqueous solutions. Adsorption of both the dyes followed pseudo-second-order kinetics and Langmuir adsorption isotherm models. The hydrogel polymer adsorbed 98% of MB and 95% of MV from aqueous solution. The Gg-cl-P(AAm-co-MAA) maintained its original sorption capacity for three cycles of adsorption-desorption. Furthermore, the hydrogel polymer degraded fully within 50 days in soil compost. In summary, the Gg-cl-P(AAm-co-MAA) hydrogel could be a potential adsorbent for the remediation of dyes from industrial wastewater.


Aptamers to the sigma factor mimic promoter recognition and inhibit transcription initiation by bacterial RNA polymerase.
Promoter recognition by bacterial RNA polymerase (RNAP) is a multi-step process involving multiple protein-DNA interactions and several structural and kinetic intermediates which remain only partially characterized. We used single-stranded DNA aptamers containing specific promoter motifs to probe the interactions of the Thermus aquaticus RNAP σ(A) subunit with the -10 promoter element in the absence of other parts of the promoter complex. The aptamer binding decreased intrinsic fluorescence of the σ subunit, likely as a result of interactions between the -10 element and conserved tryptophan residues of the σ DNA-binding region 2. By monitoring these changes, we demonstrated that DNA binding proceeds through a single rate-limiting step resulting in formation of very stable complexes. Deletion of the N-terminal domain of the σ(A) subunit increased the rate of aptamer binding while replacement of this domain with an unrelated N-terminal region 1.1 from the Escherichia coli σ(70) subunit restored the original kinetics of σ-aptamer interactions. The results demonstrate that the key step in promoter recognition can be modelled in a simple σ-aptamer system and reveal that highly divergent N-terminal domains similarly modulate the DNA-binding properties of the σ subunit. The aptamers efficiently suppressed promoter-dependent transcription initiation by the holoenzyme of RNA polymerase, suggesting that they may be used for development of novel transcription inhibitors.


Intramural esophageal location of a portosystemic shunt in a dog with two congenital portosystemic shunts on CT angiography.
A 5-year-old male neutered pug with hematuria was presented to a referral hospital after identification of an extrahepatic portosystemic shunt (EHPSS) during abdominal ultrasonography. Computed tomographic-angiography revealed two anomalous blood vessels (left gastroazygous and left gastrophrenic). The left gastroazygous vessel followed an atypical path within the dorsolateral esophageal wall before entering the azygous vein. The morphology of this highly unusual vessel has not, based on the authors' review of the literature, been previously reported. In combination with a second anomalous vessel, this resulted in a unique presentation of an EHPSS. Computed tomography-angiography was essential for diagnosis and surgical planning in this case.


A model for metal selenide formation under biological conditions.
The essential trace element selenium is known to be capable of reducing the toxicity of heavy metals like cadmium(II), mercury(II) and silver(I). One mechanism by which this occurs is through the formation of an inert metal selenide like silver selenide. It is not clear why selenide should react in the body preferentially with silver(I) over other metals such as zinc(II), an ion which is capable of forming zinc selenide, and which is present at relatively high levels. A reaction is discussed which can account for the ability of mercury(II) and silver(I) to lead to metal selenide formation in preference to zinc(II). Metal ions which have a sufficiently large formation constant for the metal selenide can induce the disproportionation of elemental selenium to produce the metal selenide; both mercury(II) and silver(I) can induce such reactions, whereas zinc(II) cannot. If this model is accurate, it should provide a basis to predict which metal ions can produce metal selenides in the body, and which ions are unlikely to result in metal selenide formation.


Cell- and gene-based approaches to tendon regeneration.
Repair of rotator cuff tears in experimental models has been significantly improved by the use of enhanced biologic approaches, including platelet-rich plasma, bone marrow aspirate, growth factor supplements, and cell- and gene-modified cell therapy. Despite added complexity, cell-based therapies form an important part of enhanced repair, and combinations of carrier vehicles, growth factors, and implanted cells provide the best opportunity for robust repair. Bone marrow-derived mesenchymal stem cells provide a stimulus for repair in flexor tendons, but application in rotator cuff repair has not shown universally positive results. The use of scaffolds such as platelet-rich plasma, fibrin, and synthetic vehicles and the use of gene priming for stem cell differentiation and local anabolic and anti-inflammatory impact have both provided essential components for enhanced tendon and tendon-to-bone repair in rotator cuff disruption. Application of these research techniques in human rotator cuff injury has generally been limited to autologous platelet-rich plasma, bone marrow concentrate, or bone marrow aspirates combined with scaffold materials. Cultured mesenchymal progenitor therapy and gene-enhanced function have not yet reached clinical trials in humans. Research in several animal species indicates that the concept of gene-primed stem cells, particularly embryonic stem cells, combined with effective culture conditions, transduction with long-term integrating vectors carrying anabolic growth factors, and development of cells conditioned by use of RNA interference gene therapy to resist matrix metalloproteinase degradation, may constitute potential advances in rotator cuff repair. This review summarizes cell- and gene-enhanced cell research for tendon repair and provides future directions for rotator cuff repair using biologic composites.