Unveiling the angiogenic effects of cannabinoids: Enhancers or inhibitors?
Cannabinoids are compounds found in the cannabis sativa plant. Cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have potential therapeutic benefits in various medical conditions. Some can activate the cannabinoid receptors type-1 and -2 (CB1 and CB2), that are part of the endocannabinoid system (ECS), alongside the endocannabinoids and their metabolic enzymes. The ECS regulates physiological and cognitive processes and is a potential therapeutic target for a wide range of health conditions like chronic pain, anxiety, and neurodegenerative diseases. Synthetic cannabinoids, are associated with serious health risks, including addiction, psychosis, and death. Nonetheless, some of these molecules are also being explored for pharmacological applications. Angiogenesis is the process of forming new blood vessels from existing ones, crucial for growth, repair, and tissue maintenance. Dysregulation of this process is associated with several diseases, including cancer, diabetic retinopathy and reproductive pathologies, such as preeclampsia. Recent data suggests that cannabinoids may affect angiogenesis. Here, we reviewed their impact on pro-angiogenic factors, extracellular matrix enzymes and inhibitors, immune-inflammatory responses, angiogenic pathways and functional assays, focusing on the main compounds for each cannabinoid class: THC and CBD for phytocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) for endocannabinoids and WIN-55, JWH-133, XLR-11, LYR-7 and LYR-8, for the synthetic cannabinoids. Despite conflicting reports about the actions of phytocannabinoids and endocannabinoids on angiogenesis, the ability to modulate the angiogenic process is undoubtedly confirmed. This may open a new therapeutical route for angiogenesis-related pathologies. In addition, synthetic cannabinoids present anti-angiogenic actions in several cell models, hinting their potential as anti-angiogenic drugs.


Non-host Plant Resistance against Phytophthora capsici Is Mediated in Part by Members of the I2 R Gene Family in Nicotiana spp.
The identification of host genes associated with resistance to Phytophthora capsici is crucial to developing strategies of control against this oomycete pathogen. Since there are few sources of resistance to P. capsici in crop plants, non-host plants represent a promising source of resistance genes as well as excellent models to study P. capsici - plant interactions. We have previously shown that non-host resistance to P. capsici in Nicotiana spp. is mediated by the recognition of a specific P. capsici effector protein, PcAvr3a1 in a manner that suggests the involvement of a cognate disease resistance (R) genes. Here, we have used virus-induced gene silencing (VIGS) and transgenic tobacco plants expressing dsRNA in Nicotiana spp. to identify candidate R genes that mediate non-host resistance to P. capsici. Silencing of members of the I2 multigene family in the partially resistant plant N. edwardsonii and in the resistant N. tabacum resulted in compromised resistance to P. capsici. VIGS of two other components required for R gene-mediated resistance, EDS1 and SGT1, also enhanced susceptibility to P. capsici in N. edwardsonii, as well as in the susceptible plants N. benthamiana and N. clevelandii. The silencing of I2 family members in N. tabacum also compromised the recognition of PcAvr3a1. These results indicate that in this case, non-host resistance is mediated by the same components normally associated with race-specific resistance.


Statistical mechanics of double-helical polymers.
We introduce a simple geometric model for a double-stranded and double-helical polymer. We study the statistical mechanics of such polymers using both analytical techniques and simulations. Our model has a single energy scale which determines both the bending and twisting rigidity of the polymer. The helix melts at a particular temperature T(c) below which the chain has a helical structure and above which this structure is disordered. Under extension we find that for small forces, the behavior is very similar to wormlike chain behavior but becomes very different at higher forces.


Factors associated with the stability of titanium screws placed in the posterior region for orthodontic anchorage.
Recently, implant anchors such as titanium screws have been used for absolute anchorage during edgewise treatment. However, there have been few human studies reporting on the stability of implant anchors placed in the posterior region. The purpose of this study was to examine the success rates and to find the factors associated with the stability of titanium screws placed into the buccal alveolar bone of the posterior region. Fifty-one patients with malocclusions, 134 titanium screws of 3 types, and 17 miniplates were retrospectively examined in relation to clinical characteristics. The 1-year success rate of screws with 1.0-mm diameter was significantly less than that of other screws with 1.5-mm or 2.3-mm diameter or than that of miniplates. Flap surgery was associated with the patient's discomfort. A high mandibular plane angle and inflammation of peri-implant tissue after implantation were risk factors for mobility of screws. However, we could not detect a significant association between the success rate and the following variables: screw length, kind of placement surgery, immediate loading, location of implantation, age, gender, crowding of teeth, anteroposterior jaw base relationship, controlled periodontitis, and temporomandibular disorder symptoms. We concluded that the diameter of a screw of 1.0 mm or less, inflammation of the peri-implant tissue, and a high mandibular plane angle (ie, thin cortical bone), were associated with the mobility (ie, failure) of the titanium screw placed into the buccal alveolar bone of the posterior region for orthodontic anchorage.


The short-term dynamics of social organization in preschool triads.
Sequential dependencies in solitary and interactive states of social organization were examined as a function of age, sex, and type of toy in 12 triads of 3 1/2- and 5-year-old children. Each triad was observed during 2 30-min sessions, one in which objects with highly specific functions (e.g., dolls, trucks) were available, and one in which objects with relatively ambiguous functions (e.g., pipe cleaners, cardboard cylinders) were present. The results indicated that, while old and young triads did not differ in the tendency to initiate triadic interaction when the preceding state was solitary, old triads were more likely than young triads to maintain the triadic state and to shift to that state from the dyadic state. Boy triads were more likely than girl triads to remain in a solitary state and less likely to shift to and remain in a dyadic state, though no sex difference was found in the transition probabilities when the preceding state was triadic. Triads were more likely to remain in a solitary state in the presence of high-specificity toys than in the presence of low-specificity toys. Verbal metacommunication was more frequent among old triads than young triads, and it facilitated maintenance, but not initiation, of interactive states. The distinction between initiation and maintenance tendencies was formalized in a Markov model of the dynamics of social organization, and the parameter estimates yielded by the model were used to provide a simplified description of the "main" effects of age, sex, and type of toy. It is argued that models such as this one are useful in circumventing certain restrictions on the possible interpretations of raw sequential statistics.


Efficacy of Green Synthesized Nanoparticles in Photodynamic Therapy: A Therapeutic Approach.
Cancer is a complex and diverse disease characterized by the uncontrolled growth of abnormal cells in the body. It poses a significant global public health challenge and remains a leading cause of death. The rise in cancer cases and deaths is a significant worry, emphasizing the immediate need for increased awareness, prevention, and treatment measures. Photodynamic therapy (PDT) has emerged as a potential treatment for various types of cancer, including skin, lung, bladder, and oesophageal cancer. A key advantage of PDT is its ability to selectively target cancer cells while sparing normal cells. This is achieved by preferentially accumulating photosensitizing agents (PS) in cancer cells and precisely directing light activation to the tumour site. Consequently, PDT reduces the risk of harming surrounding healthy cells, which is a common drawback of conventional therapies such as chemotherapy and radiation therapy. The use of medicinal plants for therapeutic purposes has a long history dating back thousands of years and continues to be an integral part of healthcare in many cultures worldwide. Plant extracts and phytochemicals have demonstrated the ability to enhance the effectiveness of PDT by increasing the production of reactive oxygen species (ROS) and promoting apoptosis (cell death) in cancer cells. This natural approach capitalizes on the eco-friendly nature of plant-based photoactive compounds, offering valuable insights for future research. Nanotechnology has also played a pivotal role in medical advancements, particularly in the development of targeted drug delivery systems. Therefore, this review explores the potential of utilizing photosensitizing phytochemicals derived from medicinal plants as a viable source for PDT in the treatment of cancer. The integration of green photodynamic therapy with plant-based compounds holds promise for novel treatment alternatives for various chronic illnesses. By harnessing the scientific potential of plant-based compounds for PDT, we can pave the way for innovative and sustainable treatment strategies.


Development of a Fluorescent Immunochromatographic Assay Based on Quantum Dot-Functionalized Two-Dimensional Monolayer Ti3C2 MXene Nanoprobes for the Simultaneous Detection of Influenza A Virus and SARS-CoV-2.
Accurate and rapid detection of the influenza A virus (FluA) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can effectively control their spread. We developed a colorimetric and fluorescent dual-functional two-channel immunochromatographic assay (ICA) biosensor to simultaneously detect the above-mentioned viruses. A unique two-dimensional Ti3C2-QD immunoprobe was established by adsorbing dense quantum dots (QDs) onto the light green monostromatic Ti3C2 MXene surface, resulting in light green colorimetric and superior fluorescence signals and guaranteeing high sensitivity, stability, and excellent liquidity for ICA detection. Rapid visual screening for FluA and SARS-CoV-2 infections was applicable via a green colorimetric signal. Sensitive and quantitative detection of viruses in their early stages of infection was performed by using the fluorescence signal. Our proposed Ti3C2-QD-ICA biosensor can simultaneously detect 1 ng/mL or 2.4 pg/mL FluA and 1 ng/mL or 6.2 pg/mL SARS-CoV-2 via its colorimetric or fluorescence signals, respectively, with a short testing time (20 min), good reproducibility, specificity, and accuracy. In addition, this method demonstrated sensitivity higher than that of the conventional AuNP-based ICA method in throat swab samples. Hence, our proposed Ti3C2-QD-ICA method can be potentially applied for the rapid, ultrasensitive, and multiplex detection of respiratory viruses.


Myeloperoxidase produces nitrating oxidants in vivo.
Despite intense interest in pathways that generate reactive nitrogen species, the physiologically relevant mechanisms for inflammatory tissue injury remain poorly understood. One possible mediator is myeloperoxidase, a major constituent of neutrophils, monocytes, and some populations of macrophages. The enzyme uses hydrogen peroxide and nitrite to generate 3-nitrotyrosine in vitro. To determine whether myeloperoxidase produces nitrating intermediates in vivo, we used isotope dilution gas chromatography/mass spectrometry to quantify 3-nitrotyrosine in two models of peritoneal inflammation: mice infected with Klebsiella pneumoniae and mice subjected to cecal ligation and puncture. Both models developed an intense neutrophil inflammatory response, and the inflammatory fluid contained markedly elevated levels of 3-chlorotyrosine, a marker of myeloperoxidase action. In striking contrast, 3-nitrotyrosine levels rose only in the mice infected with K. pneumoniae. Levels of total nitrite and nitrate were 20-fold higher in mice injected with K. pneumoniae than in mice subjected to cecal ligation and puncture. Levels of 3-nitrotyrosine failed to increase in mice infected with K. pneumoniae that lacked functional myeloperoxidase. Our observations provide strong evidence that myeloperoxidase generates reactive nitrogen species in vivo and that it operates in this fashion only when nitrite and nitrate become available. This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.


Application of GQSAR for Scaffold Hopping and Lead Optimization in Multitarget Inhibitors.
Many literature reports suggest that drugs against multiple targets may overcome many limitations of single targets and achieve a more effective and safer control of the disease. However, design of multitarget drugs presents a great challenge. The present study demonstrates application of a novel Group based QSAR (GQSAR) method to assist in lead optimization of multikinase (PDGFR-beta, FGFR-1 and SRC) and scaffold hopping of multiserotonin target (serotonin receptor 1A and serotonin transporter) inhibitors. For GQSAR analysis, a wide variety of structurally diverse multikinase inhibitors (225 molecules) and multiserotonin target inhibitors (162 molecules) were collected from various literature reports. Each molecule in the data set was divided into four fragments (kinase inhibitors) and three fragments (serotonin target inhibitors) and their corresponding two-dimensional fragment descriptors were calculated. The multiresponse regression GQSAR models were developed for both the datasets. The developed GQSAR models were found to be useful for scaffold hopping and lead optimization of multitarget inhibitors. In addition, the developed GQSAR models provide important fragment based features that can form the building blocks to guide combinatorial library design in the search for optimally potent multitarget inhibitors.


Resiliency in the Face of Adversity: A Short Longitudinal Test of the Trait Hypothesis.
Resilience represents coping with adversity and is in line with a more positive paradigm for viewing responses to adversity. Most research has focused on resilience as coping-a state-based response to adversity. However, a competing hypothesis views resilience or resiliency as a trait that exists across time and types of adversity. We tested undergraduates enrolled in social work classes at a large southern university at two time periods during a single semester using measures of adversity, positive and negative affect, and trait-based resiliency. Consistent with the trait-based resiliency, and in contrast to state-based resilience, resiliency scores were not strongly correlated with adversity at both testing points but were with positive affect, and resiliency scores remained the same over time despite adversity variations. There was no gender or ethnic group difference in resilience scores. Black/African Americans reported significantly less negative affect and more positive affect than White/Caucasians.


Patterns of motor recovery and structural neuroplasticity after basal ganglia infarcts.
To elucidate the timeframe and spatial patterns of cortical reorganization after different stroke-induced basal ganglia lesions, we measured cortical thickness at 5 time points over a 6-month period. We hypothesized that cortical reorganization would occur very early and that, along with motor recovery, it would vary based on the stroke lesion site. Thirty-three patients with unilateral basal ganglia stroke and 23 healthy control participants underwent MRI scanning and behavioral testing. To further decrease heterogeneity, we split patients into 2 groups according to whether or not the lesions mainly affect the striatal motor network as defined by resting-state functional connectivity. A priori measures included cortical thickness and motor outcome, as assessed with the Fugl-Meyer scale. Within 14 days poststroke, cortical thickness already increased in widespread brain areas (p = 0.001), mostly in the frontal and temporal cortices rather than in the motor cortex. Critically, the 2 groups differed in the severity of motor symptoms (p = 0.03) as well as in the cerebral reorganization they exhibited over a period of 6 months (Dice overlap index = 0.16). Specifically, the frontal and temporal regions demonstrating cortical thickening showed minimal overlap between these 2 groups, indicating different patterns of reorganization. Our findings underline the importance of assessing patients early and of considering individual differences, as patterns of cortical reorganization differ substantially depending on the precise location of damage and occur very soon after stroke. A better understanding of the macrostructural brain changes following stroke and their relationship with recovery may inform individualized treatment strategies.


The Reciprocal Relationship Between Handwriting Fluency and Spelling Accuracy in Chinese: A Longitudinal Study.
Mastering transcription skills is an important goal in the development of children's written language abilities, and handwriting fluency and spelling accuracy are crucial indicators of transcription ability. The current study was a two-year longitudinal study to investigate the reciprocal relationship of handwriting fluency and spelling accuracy. Participants included 123 students living in mainland China, who were tracked from third to fifth grade, and were administered a comprehensive battery of tests including assessments for non-verbal intelligence, phonological awareness, rapid automatized naming, and copying and dictation of Chinese characters. The results showed that: (1) previous handwriting fluency predicted subsequent spelling accuracy; and (2) previous spelling accuracy predicted subsequent handwriting fluency. These findings indicated there is a bidirectional relationship between handwriting fluency and spelling accuracy in Chinese. This implies spelling accuracy should not be unilaterally emphasized when teaching children new vocabulary, but attention should also be given to the cultivation of handwriting fluency in daily pedagogical practice.


A case of hepatoid carcinoma of the ovary.
A 50-year-old female was admitted with abdominal distention. Her serum CA125 level was elevated. Ultrasonography and computerized tomography showed adnexal tumoral masses with intraperitoneal metastases but no hepatic parenchymal involvement. She was operated on and histopathological and immunohistochemistry findings indicated ovarian hepatoid tumor. We present this case of ovarian hepatoid tumor and discuss the two-year disease progression from diagnosis to death.


Hypoplastic enamel treatment in permanent anterior teeth of a child.
In some patients with labial white stains involving the enamel and dentin, bleaching associated with a restorative procedure using composites may be an appropriate treatment alternative. Although bleaching makes the teeth and the stain whiter, the staining is less evident and easier to restore. Restorative procedures using adequate composites may then recover the natural optical properties while also providing appropriate mechanical properties, thereby ensuring the longevity of the treatment. In this article, the clinical case of a 9-year-old patient who reported dissatisfaction with her smile because of the presence of hypoplastic enamel staining at the central superior and inferior incisors is reported. The treatment consisted of a bleaching protocol followed by composite resin restorations using the stratification technique. The final esthetic result demonstrated the possibility of obtaining a natural smile with an adequate color and natural-looking restorations, thereby ensuring the esthetics and the patient's functional satisfaction.


Pulmonary endothelial cell signaling and function.
RhoA is an important modulator of endothelial monolayer permeability. Posttranslational carboxyl methylation of small GTPases, such as RhoA and Ras, regulates subcellular localization and GTPase activity, resulting in altered cellular function. In this study, we investigated the role of RhoA carboxyl methylation in modulating endothelial monolayer permeability. We found that inhibition of isoprenylcysteine-O-carboxyl methyltransferase (ICMT) with adenosine plus homocysteine (Ado/HC) or N-acetyl-S-geranylgeranyl-L-cysteine (AGGC) decreased RhoA carboxyl methylation and activation, which correlated with decreased monolayer permeability of bovine pulmonary artery endothelial cells (BPAEC). Conversely, BPAEC stably overexpressing ICMT had enhanced endothelial monolayer permeability, associated with elevated RhoA carboxyl methylation and activation. These results suggest that ICMT modulates endothelial monolayer permeability by altering RhoA carboxyl methylation and activation. In addition, we demonstrated that adenosine deaminase inhibitor not only attenuated, but also rescued, lung edema induced by a non-inflammatory edemagenic agent. Our data suggest that increasing intracellular adenosine is a useful therapeutic strategy against diseases characterized by increased vascular permeability.


Survival and Thermal Resistance of Salmonella Enteritidis PT 30 on Almonds after Long-Term Storage.
Salmonella survival and thermal resistance on the surface of almond kernels were evaluated after periods of storage. Almond kernels were inoculated with Salmonella Enteritidis PT 30 and equilibrated to 0.45 water activity. Samples were separated into two groups (I and II) and stored in sealed metal cans at room temperature. Group I samples (stored 7, 15, 27, and 68 weeks) were re-equilibrated in controlled humidity chambers to 0.45 water activity before performing the thermal treatments after each storage period, but group II samples (stored 70 and 103 weeks) were thermally treated immediately after the cans were opened. For thermal treatments, individual almond kernels were vacuum sealed in thin plastic bags, heated isothermally in a water bath (80°C) for nine intervals, immediately cooled in an ice bath, and assayed for surviving Salmonella. Log-linear and Weibull models were fit to the inactivation data. Salmonella population decreased ( P < 0.05) more than 2 log CFU/g during the long-term storage. Salmonella survival in group II at 70 weeks (7.3 log CFU/g) was higher ( P < 0.05) than in group I (which had been re-equilibrated multiple times) at 68 weeks (6.2 log CFU/g). However, the thermal resistance of Salmonella Enteritidis PT 30 did not decrease ( P > 0.05) for up to 68 weeks of storage, and the log-linear model best described the thermal inactivation data. Overall, the results suggest that re-equilibrating almonds (group I) multiple times may have increased the rate of reduction of Salmonella populations during long-term storage. However, Salmonella thermal resistance on almonds appears to be essentially unaffected by long-term storage, which is important information for designing and conducting validation studies for pathogen control processes.


Consistency of Use and Effectiveness of Household Water Treatment among Indian Households Claiming to Treat Their Water.
Household water treatment (HWT) can improve drinking water quality and prevent disease if used correctly and consistently by populations at risk. Current international monitoring estimates by the Joint Monitoring Programme for water and sanitation suggest that at least 1.1 billion people practice HWT. These estimates, however, are based on surveys that may overstate the level of consistent use and do not address microbial effectiveness. We sought to assess how HWT is practiced among households identified as HWT users according to these monitoring standards. After a baseline survey (urban: 189 households, rural: 210 households) to identify HWT users, 83 urban and 90 rural households were followed up for 6 weeks. Consistency of reported HWT practices was high in both urban (100%) and rural (93.3%) settings, as was availability of treated water (based on self-report) in all three sampling points (urban: 98.8%, rural: 76.0%). Nevertheless, only 13.7% of urban and 25.8% of rural households identified at baseline as users of adequate HWT had water free of thermotolerant coliforms at all three water sampling points. Our findings raise questions about the value of the data gathered through the international monitoring of HWT as predictors of water quality in the home, as well as questioning the ability of HWT, as actually practiced by vulnerable populations, to reduce exposure to waterborne diseases.


The development of genetic and molecular markers to register and commercialize Penicillium rubens (formerly Penicillium oxalicum) strain 212 as a biocontrol agent.
Penicillium oxalicum strain 212 (PO212) is an effective biocontrol agent (BCA) against a large number of economically important fungal plant pathogens. For successful registration as a BCA in Europe, PO212 must be accurately identified. In this report, we describe the use of classical genetic and molecular markers to characterize and identify PO212 in order to understand its ecological role in the environment or host. We successfully generated pyrimidine (pyr-) auxotrophic mutants. In addition we also designed specific oligonucleotides for the pyrF gene at their untranslated regions for rapid and reliable identification and classification of strains of P. oxalicum and P. rubens, formerly P. chrysogenum. Using these DNA-based technologies, we found that PO212 is a strain of P. rubens, and is not a strain of P. oxalicum. This work presents PO212 as the unique P. rubens strain to be described as a BCA and the information contained here serves for its registration and commercialization in Europe.


Borderline personality disorder features and mate retention tactics.
The purpose of the present study was to examine the association between features of borderline personality disorder (BPD) and mate retention tactics as a means of examining an evolutionary perspective on the association between BPD features and interpersonal problems and violence in romantic relationships. Two-hundred twenty-five college student participants completed the Personality Assessment Inventory for Borderlines (PAI-BOR; Morey, 1991) and the Mate Retention Inventory-Short Form (MRI-SF; Buss, Shackelford, & McKibbin, 2008) embedded within other measures. There was a strong association between BPD features and cost-inflicting mate retention tactics, including the specific tactics of vigilance, punishing mate's infidelity threat, intrasexual threats, and sexual inducements for both men and women. There were also gender-specific associations for additional tactics. These results contribute to our understanding of problems in romantic relationships among men and women with BPD features, including violence, and to our understanding of impulsive sexual behavior among individuals with BPD features by showing how these behaviors are used as extreme, maladaptive attempts at mate retention.


Development and Application of Medicine-Engineering Integration in the Rehabilitation of Traumatic Brain Injury.
The rapid progress of the combination of medicine and engineering provides better chances for the clinical treatment and healthcare engineering. Traumatic brain injury (TBI) and its related symptoms have become a major global health problem. At present, these techniques has been widely used in the rehabilitation of TBI. In this review article, we summarizes the progress of the combination of medicine and industry in the rehabilitation of traumatic brain injury in recent years, mainly from the following aspects: artificial intelligence (AI), brain-computer interfaces (BCI), noninvasive brain stimulation (NIBS), and wearable-assisted devices. We believe the summary of this article can improve insight into the combination of medicine and industry in the rehabilitation of traumatic brain injury.


[Effects of post length on the dislocation of post and core crown].
To evaluate the effects of the length of post on the dislocation of cast post and core crown. Forty simulated tooth roots made of polymethyl methacrylate were divided into five groups according to different length of post. These cast post and core were bonded with zinc phosphate cement. Then these specimens were strectched on the INSTRON-4302 by the speed of 10 mm/min. The maximum of load was recorded. The loads of 7 mm, 7.5 mm, 8 mm, 8.5 mm, 9 mm were (203.25 +/- 57.19) N, (213.63 +/- 45.06) N, (234.44 +/- 59.27) N, (317.75 +/- 60.94) N, (334.25 +/- 58.00) N respectively. Linear regression analysis revealed the linear relationship of post length with dislocation, bonding, and mechanical interlocking; the values of r being 0.676, 1.000, 0.949; the regression equations being D = 73.225L - 325.776, B = 0.442L + 9.951, M = 72. 676L-334. 338. Mechanical interlocking is the main factor in dislocation of post and core crown. The length of post should be increased from 2/3 to 3/4 of the length of tooth root when prepared in clinic.


Combination Adjuvants Enhance Recombinant Protein Vaccine Protection against Fungal Infection.
The development of effective vaccines against fungal infections requires the induction of protective, pathogen-specific cell-mediated immune responses. Here, we asked whether combination adjuvants based on delta inulin (Advax) formulated with Toll-like receptor (TLR) agonists could improve vaccine protection mediated by a fungal recombinant protein, Bl-Eng2 (i.e., Blastomyces endoglucanase 2), which itself harbors an immunodominant antigen and dectin-2 agonist/adjuvant. We found that Bl-Eng2 formulated with Advax3 containing TLR9 agonist or Advax8 containing TLR4 agonist provided the best protection against pulmonary infection with Blastomyces dermatitidis, being more effective than complete Freund's adjuvant or Adjuplex. Advax3 was most efficient in inducing gamma interferon (IFN-γ)- and interleukin-17 (IL-17)-producing antigen-specific T cells that migrated to the lung upon Blastomyces dermatitidis infection. Mechanistic studies revealed Bl-Eng2/Advax3 protection was tempered by neutralization of IL-17 and particularly IFN-γ. Likewise, greater numbers of lung-resident T cells producing IFN-γ, IL-17, or both IFN-γ and IL-17 correlated with fewer fungi recovered from lung. Protection was maintained after depletion of CD4+ T cells, partially reduced by depletion of CD8+ T cells, and completely eliminated after depletion of both CD4+ and CD8+ T cells. We conclude that Bl-Eng2 formulated with Advax3 is promising for eliciting vaccine-induced antifungal immunity, through a previously uncharacterized mechanism involving CD8+ and also CD4+ T cells producing IFN-γ and/or IL-17. Although no licensed vaccine exists as yet against any fungal disease, these findings indicate the importance of adjuvant selection for the development of effective fungal vaccines. IMPORTANCE Fungal disease remains a challenging clinical and public health problem. Despite medical advances, invasive fungal infections have skyrocketed over the last decade and pose a mounting health threat in immunocompetent and -deficient hosts, with worldwide mortality rates ranking 7th, even ahead of tuberculosis. The development of safe, effective vaccines remains a major hurdle for fungi. Critical barriers to progress include the lack of defined fungal antigens and suitable adjuvants. Our research is significant in identifying adjuvant combinations that elicit optimal vaccine-induced protection when formulated with a recombinant protective antigen and uncovering the mechanistic bases of the underlaying vaccine protection, which will foster the strategic development of antifungal vaccines.


PEG10 promotes the migration of human Burkitt's lymphoma cells by up-regulating the expression of matrix metalloproteinase-2 and -9.
Paternally expressed gene 10 (PEG10) is important for apoptosis resistance in cancer cells; however, the effect of PEG10 on tumor cell migration remains poorly understood. In this study, we investigated the effects of PEG10 on proliferation, apoptosis, adhesion and migration in the Burkitt's lymphoma cell line, Raji. Apoptosis was induced by 5-fluorouracil (5-FU) in pcDNA3.0/PEG10 transiently transfected HEK293T cells and PEG10-suppressed Raji cells. siRNAPEG10 was used to inhibit PEG10 expression. Fluorescence-activated cell sorting (FACS) were performed to analyze the effect of PEG10 on apoptosis. CCK-8 were performed to detect cell proliferation and adhesion. Matrigel invasion were performed using PEG10-suppressed Raji cells to investigate cell migration. The expression levels of matrix metalloproteinases -2and -9 (MMP-2 and MMP-9) were analyzed in PEG10-suppressed Raji cells using both real-time RT-PCR and Western blot analysis. HEK293T cells that overexpressed PEG10 exhibited greater viability 48 h following treatment with 5-FU, relative to control cells. Specific inhibition of PEG10 expression by siRNA resulted in inhibition of growth and apoptosis in Raji cells. Adherence and invasion capabilities were downregulated and expression levels of MMP-2 and MMP-9 were reduced in PEG10-suppressed Raji cells. Our findings demonstrated that PEG10 enhances the apoptotic resistance and viability of Raji cells. The migration and adherence invasion capacity of Raji cells could potentially be affected by regulation of the expression of MMP-2 and MMP-9. Our research provides a promising strategy for cancer immunotherapy of lymphoma.


Differential effects of three acute stressors on the serotonin 5-HT1A receptor system in rat brain.
The effects of different acute stressors on circulating corticosterone levels, 5-HT1A receptors and 5-HT1A mRNA levels were measured in male Sprague-Dawley rats. Two hours restraint stress, short swim stress (15 min) and long swim stress (30 min) increased circulating corticosterone levels 10-, 13- and 18-fold, respectively, when measured immediately after termination of the stress. Each stressor produced a unique profile of changes in 5-HT1A receptors measured in coronal sections 24 h after the termination of stress with the antagonist [125I]-4-(2'-methoxyphenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido ] ethylpiperazine and the agonist [3H]-8-hydroxy-2-(di-n-propylamino)tetralin. Restraint stress produced decreases in antagonist binding in the CA3 region and dentate gyrus: agonist binding was decreased only in the dentate gyrus. Despite the larger elevation in circulating corticosterone level measured after short swim stress, no changes in agonist or antagonist binding were detected after this stressor. In contrast, the long swim stress increased antagonist binding in the CA2 region and in layers IV-VI of the cortex: agonist binding was also increased in all regions of the hippocampus and in layers I-VI of the cortex. Thus, restraint and long swim stress produce opposite effects on 5-HT1A receptor expression in different subregions of the hippocampus. Analysis of presynaptic 5-HT1A receptors in the raphe nuclei revealed an increase in antagonist binding in the dorsal raphe following long swim stress. No change in the level of 5-HT1A mRNA measured in adjacent sections was detected following any of the stressors. The role of corticosteroid receptors in these stress-induced alterations of 5-HT1A receptors and the potential significance of these alterations in the context of affective disorders are discussed.


Size matters: Erythromelalgia mutation S241T in Nav1.7 alters channel gating.
The Nav1.7 sodium channel is preferentially expressed in most nociceptive dorsal root ganglion neurons and in sympathetic neurons. Inherited erythromelalgia (IEM, also known as erythermalgia), an autosomal dominant neuropathy characterized by burning pain in the extremities in response to mild warmth, has been linked to mutations in Nav1.7. Recently, a substitution of Ser-241 by threonine (S241T) in the domain I S4-S5 linker of Nav1.7 was identified in a family with IEM. To investigate the possible causative role of this mutation in the pathophysiology of IEM, we used whole-cell voltage-clamp analysis to study the effects of S241T on Nav1.7 gating in HEK293 cells. We found a hyperpolarizing shift of activation midpoint by 8.4 mV, an accelerated time to peak, slowing of deactivation, and an increase in the current in response to small, slow depolarizations. Additionally, S241T produced an enhancement of slow inactivation, shifting the midpoint by -12.3 mV. Because serine and threonine have similar biochemical properties, the S241T substitution suggested that the size of the side chain at this position affected channel gating. To test this hypothesis, we investigated the effect of S241A and S241L substitutions on the gating properties of Nav1.7. Although S241A did not alter the properties of the channel, S241L mimicked the effects of S241T. We conclude that the linker between S4 and S5 in domain I of Nav1.7 modulates gating of this channel, and that a larger side chain at position 241 interferes with its gating mechanisms.


Prevalence of cough throughout childhood: A cohort study.
Cough in children is a common reason for medical consultations and affects quality of life. There are little population-based data on the epidemiology of recurrent cough in children and how this varies by age and sex, or between children with and without wheeze. We determined the prevalence of cough throughout childhood, comparing several standardised cough questions. We did this for the entire population and separately for girls and boys, and for children with and without wheeze. In a population-based prospective cohort from Leicestershire, UK, we assessed prevalence of cough with repeated questionnaires from early childhood to adolescence. We asked whether the child usually coughed more than other children, with or without colds, had night-time cough or cough triggered by various factors (triggers, related to increased breathing effort, allergic or food triggers). We calculated prevalence from age 1 to 18 years using generalised estimating equations for all children, and for children with and without wheeze. Of 7670 children, 10% (95% CI 10-11%) coughed more than other children, 69% (69-70%) coughed usually with a cold, 34% to 55% age-dependently coughed without colds, and 25% (25-26%) had night-time cough. Prevalence of coughing more than peers, with colds, at night, and triggered by laughter varied little throughout childhood, while cough without colds and cough triggered by exercise, house dust or pollen became more frequent with age. Cough was more common in boys than in girls in the first decade of life, differences got smaller in early teens and reversed after the age of 14 years. All symptoms were more frequent in children with wheeze. Prevalence of cough in children varies with age, sex and with the questions used to assess it, suggesting that comparisons between studies are only valid for similar questions and age groups.


General strategy for fabricating thoroughly mesoporous nanofibers.
Recently, preparation of mesoporous fibers has attracted extensive attentions because of their unique and broad applications in photocatalysis, optoelectronics, and biomaterials. However, it remains a great challenge to fabricate thoroughly mesoporous nanofibers with high purity and uniformity. Here, we report a general, simple and cost-effective strategy, namely, foaming-assisted electrospinning, for producing mesoporous nanofibers with high purity and enhanced specific surface areas. As a proof of concept, the as-fabricated mesoporous TiO2 fibers exhibit much higher photocatalytic activity and stability than both the conventional solid counterparts and the commercially available P25. The abundant vapors released from the introduced foaming agents are responsible for the creation of pores with uniform spatial distribution in the spun precursor fibers. The present work represents a critically important step in advancing the electrospinning technique for generating mesoporous fibers in a facile and universal manner.


Constrictive Pericarditis: A Challenging Diagnosis in Paediatrics.
Constrictive pericarditis is an uncommon disease in children, usually difficult to diagnose. We present the case of a 14-year-old boy with a previous history of tuberculosis and right heart failure, in whom constrictive pericarditis was diagnosed. The case highlights the need to integrate all information, including clinical data, noninvasive cardiac imaging, and even invasive hemodynamic evaluation when required, in order to establish the correct diagnosis and proceed to surgical treatment.


Combination of Synovial Fluid IL-4 and Polymorphonuclear Cell Percentage Improves the Diagnostic Accuracy of Chronic Periprosthetic Joint Infection.
Synovial fluid biomarkers have been found to improve the diagnosis of chronic periprosthetic joint infection (PJI); however, no "gold standard" exists yet. Interleukin-4 (IL-4) and polymorphonuclear cell (neutrophil) count in the synovial fluid are crucial in mediating local inflammation during bacterial infections and could be valuable biomarkers for PJI. This prospective study was conducted to investigate the diagnostic potential of synovial fluid IL-4 (SF-IL4) and polymorphonuclear cell percentage (SF-PMN%) for chronic PJI. A total of 110 patients who underwent revision arthroplasty between January 2019 and October 2020 were enrolled, and 11 patients were excluded. Of 99 patients, 43 were classified as having PJI and 56 as having aseptic failures according to the 2013 Musculoskeletal Infections Society criteria. In all patients, SF-IL4, SF-PMN%, serum C-reactive protein (CRP), and serum erythrocyte sedimentation rate (ESR) were quantified preoperatively. The diagnostic value for each biomarker was analyzed, and optimal cutoff values were calculated. The patient demographics did not significantly vary. The area under the curve of SF-IL4 and SF-PMN% was 0.97 and 0.89, respectively, higher than that for serum ESR (0.72) and serum CRP (0.83). The combination of SF-IL4 and SF-PMN% provided higher specificity (97.0%) and accuracy (96.0%) when the cut-off values were 1.7 pg/mL and 75%, respectively. SF-IL4 is a valuable biomarker for chronic PJI detection, and the combination of SF-IL4 and SF-PMN% improved the diagnostic value of chronic PJI, and further studies are needed until its clinical application.


Two-dimensional NMR spectroscopy of urinary glycosaminoglycans from patients with different mucopolysaccharidoses.
Patients with different types of mucopolysaccharidoses (MPS) lack specific lysosomal enzymes, which leads to tissue accumulation and urinary excretion of glycosaminoglycans (GAGs). Since little is known about the molecular composition of the excreted GAG fragments, we used two-dimensional [1H,13C]-correlation nuclear magnetic resonance (NMR) spectroscopy for a detailed analysis of the urinary GAGs of patients with MPS types I, II, IIIA, IVA and VI. The method revealed that the molecular structures of the excreted GAGs, i.e. heparan sulfate (HS), dermatan sulfate (DS), chondroitin sulfate (CS), and keratan sulfate (KS) are clearly distinct for the different MPS types. The chain terminal residues that are the normal substrates for the defective enzymes constitute characteristic sets of signals for each MPS type. The GAG chains show variations in carbohydrate composition and sulfation patterns that can be related to the different MPS types and clinical features. For example, two patients with MPS IIIA (M. Sanfilippo) with signs of CNS degeneration but only mild somatic features excrete a highly sulfated variant of HS, resembling HS in porcine brain, whereas a patient with MPS I (M. Scheie) and two patients with MPS II (M. Hunter), who present primarily with coarse facial features, joint contractures and skeletal deformities excrete a different type of HS with lower sulfation. In another case study, a patient with MPS IVA (M. Morquio), who presented mainly with skeletal dysplasia, excreted not only excessive amounts of KS but also a highly sulfated CS variant, resembling CS in articular cartilage. The high-resolution NMR analysis of urinary GAGs presented here for the first time provides a solid basis for future studies with a larger number of patients to further explore pathogenesis and course of the MPS diseases.


Involvement of perivascular sensory fibers in the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage.
The involvement of perivascular sensory fibers containing substance P (SP) and calcitonin gene-related peptide (CGRP) in the events occurring in conjunction with subarachnoid hemorrhage (SAH) has been studied in a rat model. Two days after blood injection, the time point at which maximum vasoconstriction is occurring in this model, immunocytochemistry and radioimmunoassay showed a reduction in SP- and CGRP-like immunoreactivity (LI). The quantitative measurements revealed a significant 50% reduction of CGRP-LI and a slight reduction of SP-LI in SAH as compared to controls. This partial reduction in neurotransmitter content (denervation) caused no change in the sensitivity of the rat basilar artery to SP or CGRP as studied using a sensitive in vitro method. However, the maximum relaxant response to CGRP was increased from 52 to 81% (p less than 0.05), while there was no change in the maximum SP-induced relaxations. It is suggested that not only a pre-, but also a postsynaptic modulation of perivascular sensory fibers may occur in experimental SAH.


In vitro and in vivo effects of reovirus on HPV16-transformed mice cells.
Oncolytic viruses are examined to serve as anticancer therapeutics. It is expected that in addition to direct oncolytic effect their action will also help eliciting a solid antitumor immunity. In presented series of experiments we have employed two HPV16-transformed mouse (strain C57/B6) cell lines, TC-1 and MK16/III/ABC (MK16), and reovirus type 3, strain Dearing (RV). Both cell lines are highly susceptible to RV and produce large amounts of infectious virus in vitro while normal human are not susceptible to RV. Still, some differences were encountered. TC-1 cells produced moderately lesser amounts of infectious virus, but, paradoxically, were more efficient producers of delta1 antigen of RV and as a consequence of virus infection died more rapidly than simultaneously infected MK16 cells. Minor differences between the cell lines were observed in the percentage of cells arrested in theG2/M phase of the cell cycle and in some markers of apoptosis. When inoculating high doses (5x106) of infected cells (MOI 10 PFU/cell) into syngeneic animals their oncogenic activity was strongly suppressed, nearly completely in the case of MK16 cells and somewhat less efficiently in the case of more oncogenic TC-1 cells. Immunizing experiments in which non-oncogenic doses (106) of RV infected TC-1 cells were tested in parallel with the same doses of irradiated cells brought surprising results. When immunized animals were challenged with TC-1 cells, the irradiated cells proved to be a much better immunogen that the infected cells. However, when challenged with MK16 cells the opposite was true. It is believed that this difference was associated with the different biological properties of the cell lines tested. reovirus type 3, HPV16-transformed mouse cell lines, apoptosis, cell cycle, immunization/challenge experiments.


Tunable Magnetic Domain Patterns in Thickness-Gradient Nickel Films on Flexible PDMS Substrates.
Flexible magnetoelectronic devices (based on magnetic films) have great application prospects in the fields of information storages, bionic robotics, and electronic skins. The intrinsic stress and external loading are very important to modulate the structures and properties of flexible magnetic films due to the magnetoelastic coupling effect. Here, we report on tunable magnetic domain patterns in thickness-gradient nickel (Ni) films deposited on flexible polydimethylsiloxane substrates. It is found that stripe magnetic domains spontaneously form in the Ni films and their sizes increase with the film thickness. The internal stress evolves from tensile to compressive states with decreasing film thickness, leading to the formation of cracks in thicker regions and wrinkles in thinner regions. Meanwhile, the orientations of stripe magnetic domains change from the gradient direction to the orthogonal direction. The structural features, evolution behaviors, and physical mechanisms of the cracks, wrinkles, and magnetic domains are analyzed based on the stress theory and magnetoelastic coupling. Periodic gradient Ni films with large-scale regulations of stripe magnetic domains are also realized by masking of copper grids. This study helps to better understand the magnetoelastic coupling effect in gradient flexible magnetic films and provides a technique to modulate anisotropic magnetic properties by designing specific film systems.


TRAF3IP2-IL-17 Axis Strengthens the Gingival Defense against Pathogens.
Recent genome-wide association studies have suggested novel risk loci associated with periodontitis, which is initiated by dysbiosis in subgingival plaque and leads to destruction of teeth-supporting structures. One such genetic locus was the tumor necrosis factor receptor-associated factor 3 interacting protein 2 (TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)-17 receptor adaptor. In this study, we first determined that carriers of the lead exonic variant rs13190932 within the TRAF3IP2 locus combined with a high plaque microbial burden was associated with more severe periodontitis than noncarriers. We then demonstrated that TRAF3IP2 is essential in the IL-17-mediated CCL2 and IL-8 chemokine production in primary gingival epithelial cells. Further analysis suggested that rs13190932 may serve a surrogate variant for a genuine loss-of-function variant rs33980500 within the same gene. Traf3ip2 null mice (Traf3ip2-/-) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis-induced periodontal alveolar bone loss. Such bone loss was associated with a delayed P. gingivalis clearance and an attenuated neutrophil recruitment in the gingiva of Traf3ip2-/- mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2-/- mouse gingiva in comparison to WT mice prior to or upon P. gingivalis oral challenge. Further 16S ribosomal RNA sequencing analysis identified a distinct microbial community in the Traf3ip2-/- mouse oral plaque, which was featured by a reduced microbial diversity and an overabundance of Streptococcus genus bacteria. More P. gingivalis was observed in the Traf3ip2-/- mouse gingiva than WT control animals in a ligature-promoted P. gingivalis invasion model. In agreement, neutrophil depletion resulted in more local gingival tissue invasion by P. gingivalis. Thus, we identified a homeostatic IL-17-TRAF3IP2-neutrophil axis underpinning host defense against a keystone periodontal pathogen.


Absence of Bax switched MG132-induced apoptosis to non-apoptotic cell death that could be suppressed by transcriptional or translational inhibition.
Targeting to the ubiquitin proteasome degradation pathway has become a promising approach for treating cancer. Previous studies showed that inhibition of the proteasome can induce apoptosis in various cancer cells. However, whether and how the inhibition of the proteasome induces other forms of cell death is not quite known. We previously showed that proteasome inhibitors including MG132 and Bortezomib could induce apoptosis in a Bax- and caspase-dependent way. In the present study, we found that in the absence of Bax and caspase activation, inhibition of the proteasome could also kill cancer cells by an alternative, non-apoptotic form of cell death. We further demonstrated that proteasome inhibitors, such as MG132, could induce intracellular accumulation of polyubiquitinated proteins and extensive cellular vacuolization likely due to ER stress. Translational or transcriptional inhibitors suppressed MG132-induced polyubiquitinated protein accumulation, and in turn inhibited MG132-induced ER stress, cellular vacuolization and cell death. These findings thus suggested that non-apoptotic cell death was resulted from misfolded protein accumulation and ER stress. Furthermore, our study indicated that proteasome inhibitors could be favorable chemotherapeutic agents because they could induce non-apoptotic cell death in addition to apoptosis, which could overcome resistance due to compromised apoptotic machinery.


Does change in readiness influence retention among African American women and men in substance abuse treatment?
African Americans are less likely than other racial groups to engage in and complete outpatient substance abuse treatment. The current study, conducted as a secondary analysis of a multisite randomized clinical trial, examined whether readiness to change (RTC) over time influences retention and whether gender moderates the relationship between changes in RTC and retention among 194 African American women and men. Participants completed the University of Rhode Island Change Assessment at baseline and at the end of the 16-week study. Findings revealed a significant relationship between RTC over time and retention. Specifically, the more RTC increased throughout the 16-week study, the longer participants remained in treatment. In addition, gender moderated the relationship between changes in RTC and retention, with a stronger association between changes in RTC and retention among men relative to women. One approach to improving substance abuse treatment retention rates is to focus on increasing RTC during treatment, especially among African American men.


The pediatric surgeon and palliative care.
Palliative care is now a core component of pediatric care for children and families who are confronting serious illness with a low likelihood of survival. Pediatric surgeons, in partnership with pediatric palliative care teams, can play a pivotal role in assuring that these patients receive the highest possible quality of care. This article outlines a variety of definitions and conceptual frameworks, describes decision-making strategies and communication techniques, addresses issues of interdisciplinary collaboration and personal self-awareness, and illustrates these points through a series of case vignettes, all of which can help the pediatric surgeon perform the core tasks of pediatric palliative care.


Structure of the gene of tum- transplantation antigen P198: a point mutation generates a new antigenic peptide.
Mutagen treatment of mouse tumor cell line P815 produces tum- variants that are rejected by syngeneic mice because they express new transplantation antigens. These tum- antigens are recognized by cytotoxic T lymphocytes (CTL) but induce no detectable antibody response. By transfecting P815 cell line P1.HTR with DNA of tum- variant P198, we obtained transfectants expressing tum- antigen P198 that could be identified on the basis of their ability to stimulate anti-P198 CTL. This was repeated with DNA of a cosmid library derived from variant P198, and a cosmid carrying the sequence encoding antigen P198 was recovered from a transfectant. Gene P198 is 3 kb long and contains eight exons. It shows no homology with previously identified tum- gene P91A, nor with any gene presently recorded in the data banks. The long open reading frame codes for a 23.5-kD protein. The antigenic allele of gene P198 differs from the normal allele by a point mutation located in exon 7. This mutation causes an Ala to Thr change, and was shown by site-directed mutagenesis to be responsible for the expression of the antigen. An 11-amino acid synthetic peptide covering the sequence surrounding the tum- mutation rendered P815 cells sensitive to lysis by anti-P198 CTL. The homologous peptide corresponding to the normal sequence of the gene did not, but it was able to compete for binding to major histocompatibility complex molecule Kd. We conclude that tum- mutation P198 generates a new epitope recognized by syngeneic T cells. As observed with gene P91A, we found that a fragment of gene P198 that contained only exons 3-7, cloned in nonexpression vectors, transferred efficiently the expression of the antigen.


Oncogene abnormalities in astrocytomas: EGF-R gene alone appears to be more frequently amplified and rearranged compared with other protooncogenes.
Ten astrocytomas were tested for gene amplification or rearrangement utilizing distinct probes to nine different oncogenes by Southern hybridization. The probes spanned the four major protein-coding classes of oncogenes; growth factor proteins (csis); growth factor receptor/tyrosine kinase-related proteins [erbB1 (epidermal growth factor receptor, EGF-R), neu (HER2/neu, erbB2), mos, yes]; nuclear binding proteins (c-myc, c-fos); and guanosine 5'-triphosphate binding proteins (N-ras, H-ras). Three astrocytomas, all glioblastomas, showed amplification of EGF-R-related sequences, and two of these amplifications were rearranged. Both rearrangements appeared similar by two different restriction endonucleases. Our findings suggest that it is primarily the EGF-R protooncogene (erbB1) that is amplified or rearranged in astrocytic neoplasms. No other oncogenes were amplified or rearranged, although EGF-R and neu cross-hybridization produced a "pseudo-rearranged" pattern for neu in EGF-R-amplified cases. The similar EGF-R restriction endonuclease abnormalities seen in two patients warrant further study.


[Puerarin alleviates insulin resistance in type 2 diabetic mice by modulating fetuin B-AMPK/ACC signaling pathway in the liver].
To explore the role of fetuin B-AMPK/ACC signaling pathway in mediating the effect of puerarin on hepatic insulin resistance in mice with type 2 diabetes mellitus (T2DM). Forty C57BL/6J mouse models of T2DM induced by high-fat diet and intraperitoneal injection of streptozotocin were randomized into diabetic model (HFD) group and 3 puerarin groups for treatment with low-, moderate- and high- dose puerarin (50, 100 and 200 mg/kg, respectively), with another 10 mice fed a normal diet as the control group. After treatment for 8 weeks, the mice were examined for fasting blood glucose (FBG), fasting insulin (FINS), liver triglycerides (TG), cholesterol (TC) and free fatty acids (FFA) levels. The expression of fetuin B in the liver was detected by immunohistochemistry. RT-qPCR was used to detect the expressions of fetuin B, AMPK, and ACC mRNA in the liver, and the protein expressions of fetuin B, AMPKα1, ACC, P-AMPKαT183/T172, and P-ACC S79 were determined with Western blotting. Treatment with moderate- and high-dose puerarin significantly lowered TG, TC, FFA and FBG levels in diabetic mice (P < 0.01). Puerarin at all the 3 doses significantly lowered FINS and HOMA-IR of the mice (P < 0.01). In diabetic mice, hepatic expressions of fetuin B and ACC mRNA increased and AMPK mRNA decreased significantly (P < 0.01); the protein expressions of fetuin B and ACC increased while those of AMPKα1, P-AMPKαT183/T172 and P-ACC S79 decreased significantly (P < 0.01). Puerarin dose-dependently inhibited the mRNA and protein expressions of fetuin B and ACC, increased AMPK mRNA and protein expressions of AMPKα1, P-AMPKαT183/ T172, and P-ACC S79, and lowered fetuin B content in the liver of diabetic mice (P < 0.01). Puerarin alleviates insulin resistance and improves glucolipid metabolism in T2DM mice by modulating hepatic fetuin B-AMPK/ACC signaling pathway.


Emerging ideas: prevention of posttraumatic arthritis through interleukin-1 and tumor necrosis factor-alpha inhibition.
Despite surgical and mechanical stabilization of an acutely injured joint through ligament reconstruction, meniscus repair, or labral repair, the risk of posttraumatic arthritis remains high. Joint injury triggers three phases of pathogenic events: the early (acute) phase involves joint swelling, hemarthrosis, expression of inflammatory cytokines (especially interleukin-1 [IL-1] and tumor necrosis factor-α [TNF-α]), and biomarkers of cartilage catabolism; an intermediate phase is characterized by reduction of joint inflammation, ongoing joint catabolism, but no evidence yet for typical features of radiographic osteoarthritis (OA); and a late phase characterized by radiographic OA. We hypothesize that the early phase of acute knee injury represents a window of opportunity for providing biologic treatment to promote healing and to slow or prevent a subsequent cascade of destructive joint processes leading to OA. We propose a phase II, randomized, placebo-controlled, double-blinded, clinical trial to treat acute knee injuries with intraarticular injection of an IL-1 inhibitor. Patient-centered outcomes will include pain reduction and improvement of knee function. MR imaging and measurement of biochemical markers will be monitored during the subsequent 2 years to determine if the structural response to injury can be reversed. If this model is validated, modulation of the molecular pathways responsible for articular cartilage breakdown will augment current reconstructive procedures in the treatment of acute joint injuries and prevent the development of injury-related arthritis.


Social Network Structures of Breast Cancer Patients and the Contributing Role of Patient Navigators.
Minority women in the U.S. continue to experience inferior breast cancer outcomes compared with white women, in part due to delays in care delivery. Emerging cancer care delivery models like patient navigation focus on social barriers, but evidence demonstrating how these models increase social capital is lacking. This pilot study describes the social networks of newly diagnosed breast cancer patients and explores the contributing role of patient navigators. Twenty-five women completed a one hour interview about their social networks related to cancer care support. Network metrics identified important structural attributes and influential individuals. Bivariate associations between network metrics, type of network, and whether the network included a navigator were measured. Secondary analyses explored associations between network structures and clinical outcomes. We identified three types of networks: kin-based, role and/or affect-based, or heterogeneous. Network metrics did not vary significantly by network type. There was a low prevalence of navigators included in the support networks (25%). Network density scores were significantly higher in those networks without a navigator. Network metrics were not predictive of clinical outcomes in multivariate models. Patient navigators were not frequently included in support networks, but provided distinctive types of support. If navigators can identify patients with poorly integrated (less dense) social networks, or who have unmet tangible support needs, the intensity of navigation services could be tailored. Services and systems that address gaps and variations in patient social networks should be explored for their potential to reduce cancer health disparities. This study used a new method to identify the breadth and strength of social support following a diagnosis of breast cancer, especially examining the role of patient navigators in providing support. While navigators were only included in one quarter of patient support networks, they did provide essential supports to some individuals. Health care providers and systems need to better understand the contributions of social supports both within and outside of health care to design and tailor interventions that seek to reduce health care disparities and improve cancer outcomes.


Current Landscape of Various Techniques and Methods of Gene Therapy through CRISPR Cas9 along with its Pharmacological and Interventional Therapies in the Treatment of Type 2 Diabetes Mellitus.
Type 2 diabetes mellitus (T2DM) is frequently referred to as a "lifestyle illness". In 2000, India (31.7 million) had the greatest global prevalence of diabetes mellitus, followed by China (20.8 million), the United States (17.7 million), and other countries. In recent years, the treatment of gene therapy (T2DM) has attracted intensive interest. We aimed to critically review the literature on the various techniques and methods, which may be a possible novel approach through the gene therapy CRISPR Cas9 and some other gene editing techniques for T2DM. Interventional and pharmacological approaches for the treatment of T2DM were also included to identify novel therapies for its treatment. An extensive literature survey was done on databases like PubMed, Elsevier, Science Direct and Springer. It can be concluded from the study that recent advancements in gene-editing technologies, such as CRISPR Cas9, have opened new avenues for the development of novel therapeutic approaches for T2DM. CRISPR Cas9 is a powerful tool that enables precise and targeted modifications of the genome.


Quantitative and qualitative studies of red cell ferritin in refractory anemia of myelodysplastic syndrome.
The red cell ferritin (rFt) level in 10 patients with refractory anemia (RA) was measured and analyzed by column isoelectric focusing (IEF). The levels in 9 of the 10 patients (90.0%) were higher than the upper limit in healthy controls (MV +/- SD: male 14.3 +/- 10.3 ag/cell, female 7.5 +/- 3.6 ag/cell). The isoelectric point (pI) of rFt determined by IEF in healthy subjects ranged from 5.1 to 5.7. However, the pI ranges for RA patients varied widely; the pI value was thought to correlate with the severity of the morphological abnormalities of bone marrow (BM) erythroblasts. That is, the greater the proportion of morphologically abnormal erythroblasts with respect to all erythroid precursors, the lower the pI range for rFt. The rFt content was not related to serum iron, transferrin saturation, serum ferritin, reticulocyte count, red cell iron content, or BM erythroblast count. These data suggest that rFt synthesis in RA patients is influenced by factor(s) other than iron; this is considered an essential feature of erythropoiesis in myelodysplastic syndrome (MDS).


Epidemiological and clinical characteristics of 333 confirmed cases with coronavirus disease 2019 in Shanghai, China.
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease first identified in Wuhan City, Hubei Province, China. As of 19 February 2020, there had been 333 confirmed cases reported in Shanghai, China. This study elaborates on the epidemiological and clinical characteristics of COVID-19 based on a descriptive study of the 333 patients infected with COVID-19 in Shanghai for the purpose of probing into this new disease and providing reference. Among the 333 confirmed cases in Shanghai, 172 (51.7%) were males and 161 (48.3%) were females, with a median age of 50 years. 299 (89.8%) cases presented mild symptoms. 139 (41.7%) and 111 (33.3%) cases were infected in Wuhan and Shanghai, respectively. 148 (44.4%) cases once had contact with confirmed cases before onset, while 103 (30.9%) cases had never contacted confirmed cases but they had a sojourn history in Wuhan. The onset date of the first case in Shanghai was 28 December, with the peak appearing on 27 January. The median incubation period of COVID-19 was estimated to be 7.2 days. 207 (62.2%) cases had fever symptoms at the onset, whereas 273 (82.0%) cases experienced fever before hospitalization. 56 (18.6%) adults experienced a decrease in white blood cell and 84 (42.9%) had increased C-reactive protein after onset. Elderly, male and heart disease history were risk factors for severe or critical pneumonia. These findings suggest that most cases experienced fever symptoms and had mild pneumonia. Strengthening the health management of elderly men, especially those with underlying diseases, may help reduce the incidence of severe and critical pneumonia. Time intervals from onset to visit, hospitalization and diagnosis confirmed were all shortened after Shanghai's first-level public health emergency response. Shanghai's experience proves that COVID-19 can be controlled well in megacities.


An adolescent with abdominal pain taking isotretinoin for severe acne.
A 19-year-old female patient is presented who was taking isotretinoin for severe, nodulocystic acne. She subsequently developed abdominal pain during the course of treatment, thought to be related to an adverse reaction to the medication. A concerning side effect of isotretinoin is hypertriglyceridemia, which may be a cause of pancreatitis. A lipase level was determined to be elevated in this case. The patient was diagnosed with acute pancreatitis and the offending agent was discontinued. Clinicians need to be aware of the side effects when prescribing isotretinoin for recalcitrant acne.


Identification of dysregulated microRNAs involved in arachidonic acid metabolism regulation in dilated cardiomyopathy-mediated heart failure patients.
Heart failure (HF), a clinical syndrome with high morbidity and mortality, is becoming a growing public health problem. Dilated cardiomyopathy (DCM) is one of the major causes of HF, yet the molecular mechanisms underlying DCM-mediated HF are not completely understood. Previous studies have shown that dysregulation of arachidonic acid (AA) metabolism could contribute to the development of HF. To explore the roles of microRNAs (miRNAs) in regulating AA metabolism in HF, we used two public datasets to analyze the expression changes of miRNAs in the patients of DCM-mediated HF. A total of 101 and 88 miRNAs with significant abundance alterations in the two dataset were obtained, respectively. Around 1/3 of these miRNAs were predicted to target AA metabolic pathway genes. We also investigated the distribution of known single nucleotide polymorphisms (SNPs) within the sequences of miRNAs dysregulated in DCM-mediated HF patients, and identified miRNAs harboring high number of SNPs in either the seed regions or the entire sequences. These information could provide clues for further functional studies of miRNAs in the pathogeny of DCM-mediated HF.


The right way for nurses to prescribe, administer and critique digital therapies.
Nurses should be mindful that prescribing and administering digital therapies comes with patient safety responsibilities. Due diligence is required by nurses to ensure that they are prescribing and administering digital therapies to ensure they are safe practitioners in this new health field. Nurses without requisite digital literacy and critiquing skills should consider what actions they need to undertake to up-skill, if it is required, to maintain their safe practice standards [Wilson, 2017. E Mental Health. Mental Health: A perosn-centred Approach. N. Procter, H. Hamer, D. McGarry, Wilson R. L. and T. Frogatt. Port Melbourne: Cambridge University Press].


A retrotracheal right subclavian artery in association with a vertebral artery and thyroidea ima.
The retro-oesophageal right subclavian artery is an anatomical abnormality encountered by anatomists and pathologists and, more recently, interventional cardiologists and thoracic surgeons with an incidence of 0.2-2% in the population. We report a case of a retrotracheal right subclavian artery which originated distally along the left aortic arch and coursed between the trachea and the oesophagus. Additionally, the aortic arch gave rise to a common trunk, which subsequently bifurcated to yield to a right vertebral artery and a left thyroidea ima, replacing the left inferior thyroid artery. Consequently the right and the left recurrent laryngeal nerves were found to recur normally. The possible embryonic development of these branching patterns and their clinical significance is discussed.


Episodic cluster headache: NREM prevalence of nocturnal attacks. Time to look beyond macrostructural analysis?
A high prevalence of nocturnal sleep-related attacks is reported in patients with cluster headache (CH). Episodic CH is considered closely related to rapid eye movement (REM) sleep. The aim of this study was to analyze the relationships between episodic CH attacks and sleep macrostructure. Data were obtained by means of 24-hour continuous ambulatory polysomnography (PSG) capturing CH attacks in 4 out of 7 episodic CH patients (all males; mean age 38.4 +/- 9.2 years) studied. Eight CH attacks were captured during the PSG monitoring; 5 arose from sleep: 4 from non-rapid eye movement (NREM) sleep (stage 2 NREM), and 1 from REM sleep. One patient experienced CH attacks during both NREM and REM sleep in the same night. In the light of previous literature findings, the prevalence of NREM-related episodic CH attacks observed, and the finding of attacks arising during both REM and NREM sleep in the same subject, suggest that the relationship between CH and sleep stages is heterogeneous, and the existence of a specific macrostructural pattern associated with episodic CH attacks appears to be uncertain. A more comprehensive approach taking into account the microstructure of NREM and REM sleep is expected to provide more in depth information about the pathophysiology of CH, whose complexity might overcome the simplistic dichotomy of REM/NREM staging.


[Construction and identification of recombinant avian adeno-associated virus expressing GFP reporter gene].
To generate recombinant avian adeno-associated virus (rAAAV) for gene transfer studies in avian cells, the recombinant plasmid containing the whole genome of AAAV was digested with restriction enzymes to remove the Rep and Cap genes, resulting in AAAV transfer vector pAITR. GFP-expressing cassette was amplified by PCR and inserted into the AAAV transfer vector. The Rep-Cap gene of AAAV amplified by high fidelity PCR was subcloned into eukaryotic expression vector pcDNA3, resulting in an AAAV helper vector pcDNA-ARC. The Rep and Cap genes amplified by high fidelity PCR were subcloned separately into the co-expression vector pVITRO2-mcs, resulting in another AAAV helper vector pVITRO2-ARC. Using calcium phosphate precipitation method, rAAAV-GFP was generated by co-transfecting AAV-293 cells with a cocktail of pAITR-GFP, pcDNA-ARC or pVITRO2-ARC, and adenovirus helper vector pHelper. The three structural proteins VP1, VP2 and VP3 of correct molecular masses were detected by SDS-PAGE and the GFP reporter gene was detected by PCR in purified rAAAV-GFP virions. Chicken embryonic fibroblast (CEF) cells and CEL cell line were transduced with the recombinant virus, the GFP-positive cells were easily observed under fluorescent microscope, expression of which lasted for at least two weeks. These data demonstrate that an efficient helper virus-free packaging system has been established for generating recombinant AAAV particles for gene transfer studies in avian cells and for development of recombinant vaccines against avian diseases.


Toxic epidemic syndrome: musculoskeletal manifestations.
The musculoskeletal manifestations of a new systemic disease that developed after toxic oil consumption are described. Clinically, it was characterized by the presence of arthralgias, sometimes arthritis, extensive muscle atrophy, severe neuropathy and a scleroderma-like skin involvement. Radiologically, different types of osteopenia could be seen in the absence of joint space narrowing or erosions. Neither hypertrophy, nor hyperplasia of synoviocytes were seen on microscopic examination. A non-necrotizing vasculitis and increase in fibrous tissue were observed at different levels.


Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1.
Endoglin (ENG)/CD105 is an essential endothelial cell co-receptor of the transforming growth factor β (TGF-β) superfamily, mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1) and involved in tumor angiogenesis and preeclampsia. Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9). BMP9 interacts with a hydrophobic surface of the N-terminal orphan domain of ENG, which adopts a new duplicated fold generated by circular permutation. The interface involves residues mutated in HHT1 and overlaps with the epitope of tumor-suppressing anti-ENG monoclonal TRC105. The structure of the C-terminal zona pellucida module suggests how two copies of ENG embrace homodimeric BMP9, whose binding is compatible with ligand recognition by type I but not type II receptors. These findings shed light on the molecular basis of the BMP signaling cascade, with implications for future therapeutic interventions in this fundamental pathway.


Efficacy of Colloidal Silver-Hydrogen Peroxide and 2-Bromo-2-nitroporopane-1,3-diol Compounds Against Different Serogroups of Legionella pneumophila Strains.
Cooling towers are considered as amplifier and disseminator sources for Legionella spp. despite preventive treatments. Information which was obtained from biocidal tests could improve the effectiveness of treatments. Therefore, the choice of appropriate biocides and the applying of biocides in correct dosages and contact times are important. Various oxidizing and non-oxidizing biocides have been investigated in vitro for their effectiveness against legionellae. Colloidal silver-hydrogen peroxide (CSHP) and 2-bromo-2-nitroporopane-1,3-diol (BNPD) biocides were selected as an example for oxidizing and non-oxidizing agents, respectively, in view of bactericidal action against different serogroups of L. pneumophila strains [serogroup 1 (S1) and serogroup 2-14 (S2)] which are isolated different cooling towers in the vicinity of Istanbul, Turkey and reference strain. In the current study, oxidizing biocide was found more effective than non-oxidizing biocide in terms of contact times, log reductions and recommended dosages. At the recommended concentrations for cooling towers (100 ppm), while CSHP compound killed all strains in 3 h contact time, BNPD compound killed S2 and reference strain in the same contact time, S1 strain after 6 h contact time. The results of the present study showed that effective biocide applications can be achieved by pre-determining minimum inhibitory concentration (MIC) and minimum contact time of different biocides to kill target bacteria.


Removal of the protein-bound solute p-cresol by convective transport: a randomized crossover study.
Middle molecules (MMs) and protein-bound solutes are poorly removed by conventional hemodialysis (HD). Hemodiafiltration (HDF) combines convection and diffusion in a single therapy and has been shown to be superior for the elimination of several small and larger retention molecules. Information on the elimination of protein-bound solutes during convective strategies is scarce. The primary aim of this randomized crossover study is to evaluate the influence of internal filtration, postdilution HDF, and predilution HDF on removal of the protein-bound solute p-cresol. Fourteen stable patients on regular thrice-weekly medium-flux HD therapy were assigned to 5 treatment periods of 2 weeks each for: HD with HF80(S); HD with FX80; postdilution HDF, 20 L, with FX80; predilution HDF, 20 L, with FX80; and predilution HDF, 60 L, with FX80 (all dialyzers from Fresenius Medical Care, Bad Homburg, Germany). As for the water-soluble solutes, elimination of p-cresol was better during HDF and increased with greater filtration volumes. Removal of beta2-microglobulin (beta2m) also was enhanced during HDF. However, the positive effect of convection was offset when high predilution substitution volumes were applied, probably as a result of dilution. Within each dialytic approach, removal of the MM beta2m and the protein-bound solute p-cresol was significantly less than that of the water-soluble molecules urea nitrogen and creatinine. Our data indicate that convection can provide superior protein-bound solute removal compared with high-flux HD. Our findings also suggest that better elimination of the unbound fraction is the most plausible underlying mechanism.


País de gordos/país de muertos: Obesity, death and nation in biomedical and forensic genetics in Mexico.
This article provides a comparison between genomic medicine and forensic genetics in Mexico, in light of recent depictions of the nation as a 'país de gordos' (country of the fat) and a 'país de muertos' (country of the dead). We examine the continuities and ruptures in the public image of genetics in these two areas of attention, health and security, focusing especially on how the relevant publics of genetic science are assembled in each case. Publics of biomedical and forensic genetics are assembled through processes of recruitment and interpellation, in ways that modulate current theorizations of co-production. The comparison also provides a vista onto discussions regarding the involvement of genetics in regimes of governance and citizenship and about the relationship between the state and biopower in a context of perceived health crisis and war-like violence.


Is there a relationship between eating disorder and affective disorder? New evidence from sleep recordings.
There is evidence that patients with anorexia nervosa (particularly those who also have bulimia) and patients with affective disorder share many features. The authors present sleep polygraph data from 20 young women with anorexia nervosa (17 also bulimic) and 10 age-matched normal women. Their urinary free cortisol levels were determined, and the subjects with eating disorders were also rated for depression. The findings suggest the existence of a subgroup of patients who show sleep abnormalities, in addition to clinical and possibly endocrine abnormalities, that indicate concurrent affective disorder. The authors present several models that could account for this relationship.


Trends of ankyloglossia and lingual frenotomy in hospital settings among children in Denmark.
It has been proposed that ankyloglossia and lingual frenotomy have increased. The aim of this study was to analyse the trends of ankyloglossia and lingual frenotomy among children treated in hospitals in Denmark in the 1996-2015 period. We included children aged 0-17 years registered with the diagnosis ankyloglossia (DQ381) or the procedure frenotomy (KEJC20) using nationwide hospital-based data from the Danish National Patient Registry in 1996-2015. The incidence during the study period and the average annual percentage change (AAPC) and age-specific incidences were calculated. A total of 1,608 children were diagnosed with ankyloglossia (67% boys). The overall incidence of ankyloglossia increased from 3.2 per 100,000 in 1996 to 13.6 per 100,000 in 2015, corresponding to an AAPC of 7.1%. The age-specific incidence revealed a more than ten times higher incidence of ankyloglossia among patients less than one year old compared with those aged one year or above. In all, 3,625 frenotomy procedures were carried out (66% boys). The frequency of frenotomy increased from 5.1 per 100,000 in 1996 to 38.5 per 100,000 in 2015, corresponding to an AAPC of 11.1%. The age-specific incidence of frenotomy showed a more than thirty times higher frequency among children less than one year of age. Ankyloglossia and frenotomy increased significantly during the period 1996-2015 among children in Denmark according to nationwide hospital data. Rates of both ankyloglossia and frenotomy were highest in children less than one year of age and among boys. none. not relevant.


Low expression of cyclin D2 in G2/M-arrested and transformed proliferating Balb/3T3 cells.
At present, the effect of cyclin D2 implicated in cell cycle regulation, differentiation, and oncogenic transformation is not fully confirmed. To better elucidate the role of cyclin D2 in controling the cell proliferation, cyclin D2 expression level was determined at the early initiation and promotion stages during the in vitro two-stage transformation process of Balb/3T3 A31 cells. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced G2/M-arrested cells expressed low level of cyclin D2 mRNA, while the contact-inhibited nonproliferating cells expressed high level of cyclin D2 mRNA. In the transformed proliferating cells at the promotion stage, cyclin D2 mRNA was not expressed. These data suggest that cyclin D2 expression may be associated with the type of growth arrest and nonproliferating state, but not with the cell proliferation and transformation.


Encapsulation of Tea Polyphenol in Zein through Complex Coacervation Technique to Control the Release of the Phenolic Compound from Gelatin-Zein Composite Film.
Green tea polyphenol (TP) was encapsulated in zein and fabricated into a gelatin-zein composite film by complex coacervation. Transglutaminase (TG) crosslinking was employed to obtain a compact structural orientation of the film to prolong the release of bioactive compounds. The encapsulation efficiency of zein and the TP release rate from the composite film were investigated. The retention rate was over 30% and 80% after film fabrication and storage, respectively. Crosslinking decreased the diffusion coefficient by half, thus improving the release of TP from the film. The antioxidant properties were satisfactory after discharge from the film detected by DPPH/ABTS scavenging. The value of crosslinking degree (~60%) and increased molecular weight of the protein were investigated by SDS-PAGE, indicating the compatibility of TP and TG treatment. According to physicomechanical findings, the TG2TP1 film exhibited the best characteristics. Tensile strength and water solubility properties were ameliorated by the TG treatment of TP-encapsulated films compared to the control film. TG and TP-loaded gelatin-zein composite film had better thermal stability than the control film. Moreover, the TP loading reduced the transparency value and improved the light-barrier properties of the film. The films showed significant antimicrobial activities against two food-borne bacteria, including Staphylococcus aureus BCTC13962 and Escherichia coli BCRC10675. The result obtained shows that the encapsulation of TP and TG treatment may be used to fabricate gelatin-zein composite film with controlled release of phenolic compounds for active packaging applications.


The clinical, neuropsychological, and brain functional characteristics of the ADHD restrictive inattentive presentation.
There is an ongoing debate about the restrictive inattentive (RI) presentation of attention deficit hyperactivity disorder (ADHD). The current study aimed to systematically investigate the clinical, neuropsychological, and brain functional characteristics of children with ADHD restrictive inattentive presentation. A clinical sample of 789 children with or without ADHD participated in the current study and finished clinical interviews, questionnaires, and neuropsychological tests. Those individuals with a diagnosis of ADHD were further divided into three subgroups according to the presentation of inattentive and/or hyperactive/impulsive symptoms, the ADHD-RI, the ADHD-I (inattentive), and the ADHD-C (combined) groups. Between-group comparisons were carried out on each clinical and neuropsychological measure using ANCOVA, with age and sex as covariates. Bonferroni corrections were applied to correct for multiple comparisons. Two hundred twenty-seven of the subjects also went through resting-state functional magnetic resonance imaging scans. Five ADHD-related brain functional networks, including the default mode network (DMN), the dorsal attention network (DAN), the ventral attention network, the executive control network, and the salience network, were built using predefined regions of interest (ROIs). Voxel-based group-wise comparisons were performed. Compared with healthy controls, all ADHD groups presented more clinical problems and weaker cognitive function. Among the ADHD groups, the ADHD-C group had the most clinical problems, especially delinquent and aggressive behaviors. Regarding cognitive function, the ADHD-RI group displayed the most impaired sustained attention, and the ADHD-C group had the worst response inhibition function. In terms of brain functional connectivity (FC), reduced FC in the DMN was identified in the ADHD-C and the ADHD-I groups but not the ADHD-RI group, compared to the healthy controls. Subjects with ADHD-I also presented decreased FC in the DAN in contrast to the control group. The ADHD-RI displayed marginally significantly lower FC in the salience network compared to the ADHD-I and the control groups. The ADHD-RI group is distinguishable from the ADHD-I and the ADHD-C groups. It is characterized by fewer externalizing behaviors, worse sustained attention, and better response inhibition function. The absence of abnormally high hyperactive/impulsive symptoms in ADHD-RI might be related to less impaired brain function in DMN, but potentially more impairment in the salience network.


Impaired potassium-stimulated aldosterone production: a possible explanation for normokalemic glucocorticoid-remediable aldosteronism.
Unlike other forms of primary aldosteronism, recent prospective studies have paradoxically revealed that glucocorticoid-remediable aldosteronism (GRA) is usually characterized by normal potassium (K+) levels. To evaluate this paradox we studied 10 GRA subjects and 14 healthy controls in two protocols: 1) the renal K+ excretory response to acute oral administration of 50 mmol K+ chloride and to fludrocortisone, 0.2 mg p.o. q12 h x 4 doses; and 2) the aldosterone response to administration of 50 mmol K+ chloride. The K+ excretion rate (KER) in GRA subjects (n = 6) at baseline (45.6 +/- 8.3 microEq/min), after K+ (134 +/- 34.2 microEq/min), and after fludrocortisone (100 +/- 35.0 microEq/min) was not significantly different than that seen in the control (n = 8) subjects (54.9 +/- 19.0, 154 +/- 35.5, 112 +/- 45.8 microEq/min, respectively). Thus the renal kaliuretic response to K+ ingestion and exogenous mineralocorticoid is normal in GRA. Serum aldosterone increased from 5.0 +/- 3.8 at baseline to a maximum of 13.1 +/- 6.6 ng/dL 60 min after K+ ingestion in control subjects (n = 7), but failed to increase in GRA subjects (n = 14), going from 8.7 +/- 3.8 (baseline) to 8.8 +/- 5.4 ng/dL at 60 min (P = 0.004 vs. control). The blunted aldosterone response to K+ in GRA in association with the sharp diurnal decline in aldosterone in this ACTH-regulated syndrome probably results in a milder degree of hyperaldosteronism compared with other forms of primary aldosteronism, thereby producing volume expansion with minimal renal K+ wasting.


[Protection of Transcutaneous Acupoint Electrical Stimulation for Brain Injury Undergoing Intervention: a Clinical Observation].
To observe the effect of transcutaneous acupoint electrical stimulation (TAES) combined dexmedetomidine on hemodynamic of intracranial aneurysmal subarachnoid hemorrhage patients undergoing intervention, and their protection for brain Injury. Totally 108 intracranial aneurysmal subarachnoid hemorrhage patients undergoing intervention were randomly assigned to the electroacupuncture (EA) group and the control group according to random digit table, 54 in each group. All patients were anesthetized with dexmedetomidine. Patients in the EA group were needled at bilateral Neiguan (PC6), Lieque (LU7), and Yunmen (LU2). Parameter setting was as follows: The dilatational wave at 1. 5 Hz, strength 2 - 4 mA, 30 min. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were compared between the two groups immediately after entry into the room (T0), after administration (T1), intubating (T2), resuscitation (T3), extubation (T4), and leaving the operating room (T5). Levels of S100β protein (S100β) and neuron specific enolase (NSE) were compared between the two groups at T0, immediately after surgery (T6), 6 h after operation (T7), 12 h after operation (T8), and 24 h after operation (T9). Compared with the same group at T0, SBP, DBP, MAP, and HR were significantly reduced in the two groups at T1-T5(P <0. 05), serum levels of S100β and NSE in the two groups were significantly increased at T6-T9 (P<0. 05). Compared with the control group at T1 - T5, SBP, DBP, MAP, and HR decreased in the EA group (P <0. 05). Compared with the control group at T6-T9, serum levels of S100β and NSE decreased in the EA group (P <0. 05). TAES combined dexmedetomidine could effectively maintain stable hemodynamics of intracranial aneurysmal subarachnoid hemorrhage patients undergoing intervention, and regulate their serum levels of S100β and NSE.


Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection.
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection, claiming millions of lives annually. The virus infects various cells of the respiratory tract as well as resident inflammatory cells such as macrophages. Infection activates a variety of cellular factors such as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of which are important players in the respiratory disease. However, the exact natural route of RSV infection and its etiology remain relatively unknown. In this paper, we test the hypothesis that human corneal epithelial cells, which constitute the outermost layer of the cornea, can be infected with RSV, and that the infection leads to the activation of proinflammatory macromolecules. Corneal swabs obtained from pediatric patients with acute respiratory disease were found to contain RSV at a high frequency (43 positive out of 72 samples, i.e., 60%). Primary corneal epithelial cells in tissue culture supported robust infection and productive growth of RSV. Infection resulted in the activation of TNF-alpha, IL-6 and sixteen chemokines as well as NF-kappa B. Three proinflammatory CXC chemokines (MIG, I-TAC, IP-10) underwent the greatest activation. The ocular epithelium is readily infected by RSV. The pro-inflammatory cytokines are likely to play critical roles in the etiology of inflammation and conjunctivitis commonly seen in pediatric patients with respiratory infections. RSV-eye interactions have important implications in RSV transmission, immunopathology of RSV disease, and in the management of conjunctivitis.


Is anti-doping analysis so far from clinical, legal or forensic targets?: The added value of close relationships between related disciplines.
There are many areas of common interest between anti-doping laboratories and those working in the clinical, legal and forensic fields. In addition to methodological similarities, there are aspects of the findings in sport drug testing that overlap with other fields in such a way that sport drug testing and clinical, legal or forensic work may benefit from mutual interaction. Three recent examples are presented from the author's experience. Case report 1 concerns the clinical relevance of hCG findings in sport drug testing as potential indicators of the presence of a (testicular) tumour in athletes. Case report 2 refers to difficulties that accredited laboratories can encounter due to differences between national legal systems and the administrative regulation systems of sport authorities. The example involves a network of blood collection for further autologous transfusion. Case report 3 relates to additional forensic-type investigations needed to interpret a situation where intoxication of a whole delegation was responsible for apparent doping cases. Clinical, legal and forensic fields must recognize the added value that some results and developments coming from anti-doping laboratories may have. At the same time anti-doping analysts should be aware of new issues, methodologies and problems appearing in related fields.


Hydration and hydrogen bond network of water around hydrophobic surface investigated by terahertz spectroscopy.
Water conformation around hydrophobic side chains of four amino acids (glycine, L-alanine, L-aminobutyric acid, and L-norvaline) was investigated via changes in complex dielectric constant in the terahertz (THz) region. Each of these amino acids has the same hydrophilic backbone, with successive additions of hydrophobic straight methylene groups (-CH2-) to the side chain. Changes in the degree of hydration (number of dynamically retarded water molecules relative to bulk water) and the structural conformation of the water hydrogen bond (HB) network related to the number of methylene groups were quantitatively measured. Since dielectric responses in the THz region represent water relaxations and water HB vibrations at a sub-picosecond and picosecond timescale, these measurements characterized the water relaxations and HB vibrations perturbed by the methylene apolar groups. We found each successive straight -CH2- group on the side chain restrained approximately two hydrophobic hydration water molecules. Additionally, the number of non-hydrogen-bonded (NHB) water molecules increased slightly around these hydrophobic side chains. The latter result seems to contradict the iceberg model proposed by Frank and Evans, where water molecules are said to be more ordered around apolar surfaces. Furthermore, we compared the water-hydrophilic interactions of the hydrophilic amino acid backbone with those with the water-hydrophobic interactions around the side chains. As the hydrophobicity of the side chain increased, the ordering of the surrounding water HB network was altered from that surrounding the hydrophilic amino acid backbone, thereby diminishing the fraction of NHB water and ordering the surrounding tetrahedral water HB network.