The toxicity of the monoterpenes from lemongrass is mitigated by the detoxifying symbiosis of bacteria and fungi in the tick Haemaphysalis longicornis.
The entry mode of terpenes into the atmosphere is via volatilization of hydrocarbons from foliage over heavily forested areas besides entering the environment through surface water runoff. Some monoterpenes in essential oils are phytotoxins, acting as plant chemical defenses against bacteria or fungi infections and plant-eating insects. For organisms to survive, their enzymatic systems are activated in response to an assault by potentially harmful compounds. Certain bacterial and fungal genera have developed special abilities to transform toxic terpenes into less toxic derivatives. Here, we investigated the response of the bacterial and fungal community in Haemaphysalis longicornis exposed to Cymbopogon citratus (lemongrass) essential oil (EO) and citronellal. Sequencing of bacterial 16S rRNA and fungal ITS1 regions on an Illumina NovaSeq PE250 sequencing platform was performed for H. longicornis tick samples treated with 15 and 20 mg/mL of lemongrass essential oil and citronellal. The diversity recorded in samples treated with C. citratus EO was higher in comparison to those treated with citronellal but significantly lower in the control samples as reflected by the Shannon diversity index. All major H. longicornis bacterial phyla, including Proteobacteria (93.81 %), Firmicutes (2.58 %), and Bacteroidota (0.99 %) were detected. A switch of dominance from Coxiella to Pseudomonas, which has high biotransformation capacity, was observed in the bacterial community, whereas the phylum Ascomycota (Genera: Aspergillus, Archaeorhizomyces, Alternaria, and Candida) dominated in the fungal community indicating detoxifying symbiosis. Other significantly abundant bacterial genera include Ralstonia, Acinetobacter, Vibrio, and Pseudoalteromonas, while Ganoderma and Trichosporon (yeasts) spp. represented the fungi Basidiomycota. This study expanded the understanding of enzymatic modification of phytotoxic substances by microorganisms, which could provide deeper insights into the mitigation of harmful phytotoxins and the synthesis of eco-friendly derivatives for the control of ticks.


Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery.
The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.


Synthesis of Ultrathin Topological Insulator β-Ag2 Te and Ag2 Te/WSe2 -Based High-Performance Photodetector.
β-Ag2 Te has attracted considerable attention in the application of electronics and optoelectronics due to its narrow bandgap, high mobility, and topological insulator properties. However, it remains a significant challenge to synthesize 2D Ag2 Te because of the non-layered structure of Ag2 Te. Herein, the synthesis of large-size, ultrathin single crystal topological insulator 2D Ag2 Te via the van der Waals epitaxial method for the first time is reported. The 2D Ag2 Te crystal exhibits p-type conduction behavior with high carrier mobility of 3336 cm2 V-1 s-1 at room temperature. Taking advantage of the high mobility and perfect electron structure of Ag2 Te, the Ag2 Te/WSe2 heterojunctions are fabricated via mechanical stacking and show an ultrahigh rectification ratio of 2 × 105 . Ag2 Te/WSe2 photodetector also exhibits self-driven properties with a fast response speed (40 µs/60 µs) in the near-infrared region. High responsivity (219 mA W-1 ) and light ON/OFF ratio of 6 × 105 are obtained under the photovoltaic mode. The overall performance of the Ag2 Te/WSe2 photodetector is significantly competitive among all reported 2D photodetectors. These results indicate that 2D Ag2 Te is a promising candidate for future electronic and optoelectronic applications.


Functional gait asymmetry of unilateral transfemoral amputees.
The aim of prosthetic devices is to mimic the function of biological systems. Numerous investigations have demonstrated significant asymmetries in unilateral amputee gait. The underlying interactions of prosthetic and intact leg are not widely discussed, so far. To get more insight into the functionality of asymmetries, we investigated temporal and kinetic parameters of walking transfemoral amputees wearing the computerized C-Leg and the non-computerized 3R80. Experiments were conducted on an instrumented treadmill at four different walking speeds (0.5, 0.8, 1.1, 1.4m/s) measuring vertical and horizontal ground reaction forces. Single support, double support and contact times, vertical and horizontal impulses as well as their asymmetry factors were calculated. Gait patterns were similar for both prosthetic knee joints, manifesting in (i) reduced stance times of the prosthetic leg, (ii) prolonged load transfer during double support from intact to prosthetic leg at lower speeds, (iii) reduced vertical and horizontal impulses of the prosthetic leg, (iv) net accelerating horizontal impulses during contact of the prosthetic leg, (v) missing impacts at touch-down of the prosthetic leg. Our results suggest that deficits of the prosthetic leg like missing active knee extension and ankle push-off are compensated by the intact leg. The altered touch-down configuration for the prosthetic leg enables it to provide forward propulsion while load bearing is largely shifted to the intact leg.


A brief report: Cerebrospinal fluid rhinorrhea after repetitive nasal swab testing for coronavirus disease 2019(COVID-19).
For the past year, COVID-19 Pandemic has been the biggest focal point of medicine. Due to its novelty and its highly infectious nature, the impact of Sars-Cov-2 on society has been growing rapidly. The primary route for prevention of this highly infectious virus is detection. The detection methods for Sars-Cov-2 include nasal swab tests, saliva samplings and antibody tests. The main preferred method has been the RT-PCR with Nasal Swab sampling which is performed on the nasopharyngeal region. However, the nasal swab testing may come with its own iatrogenic outcomes due to its invasiveness. In this report, we describe a rare case of iatrogenic unilateral cerebrospinal fluid rhinorrhea which occurred due to repetitive nasal swab testing for COVID-19.


Uterine rupture successfully treated with a damage-control strategy of hysterectomy and resuscitative endovascular balloon occlusion of the aorta-assisted cardiopulmonary resuscitation.
Uterine rupture is a major cause of postpartum hemorrhage (PPH) that requires surgery. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is also helpful for PPH. However, the effectiveness of REBOA in PPH with cardiac arrest is unknown. A 40-year-old woman developed hemorrhagic shock due to uterine rupture after an induced delivery. She developed cardiac arrest, but was rescued by cardiopulmonary resuscitation (CPR), REBOA, a hysterectomy, and pelvic gauze packing. The hemodynamics were too unstable to move to the operating room. Then we initiated the CPR assisted with REBOA and decided to activate massive transfusion and perform laparotomy in the emergency room. She was finally discharged home without neurological sequelae. Our damage control strategy, including REBOA-assisted CPR, contributed to saving the life of a patient with a life-threatening PPH.


Erinacine C: A novel approach to produce the secondary metabolite by submerged cultivation of Hericium erinaceus.
Erinacine C is a cyathane scaffold-based secondary metabolite, which is naturally produced by the filamentous fungus Hericium erinaceus and has a high potential to treat nervous diseases such as Alzheimer's disease. The investigated approach consists of combining an optimised precultivation of H. erinaceus with an enhanced erinacine C production by developing a suitable main cultivation medium enabling the utilisation of high biomass contents. The final erinacine C production medium is buffered by 100 mM HEPES to ensure a stable pH value of 7.5 during main cultivation at inoculation ratios of up to 5:10 (v/v). The medium components, such as 5.0 g L(-1) oatmeal, 1.5 g L(-1) calcium carbonate, and 0.5 g L(-1) Edamin(®) K are crucial for an increased erinacine C production. Besides, different carbon to nitrogen ratios of 25, 64, and 103 do not affect the erinacine C synthesis. The investigated approach enables the production of 2.73 g erinacine C per litre main cultivation broth, which is tenfold higher than published data. In addition, erinacine C biosynthesis is determined to occur mainly in the first six days of main cultivation.


In vivo posterior cruciate ligament elongation in running activity after anatomic and non-anatomic anterior cruciate ligament reconstruction.
The goals of this study were to (1) investigate the in vivo elongation behaviour of the posterior cruciate ligament (PCL) during running in the uninjured knee and (2) evaluate changes in PCL elongation during running after anatomic or non-anatomic anterior cruciate ligament (ACL) reconstruction. Seventeen unilateral ACL-injured subjects were recruited after undergoing anatomic (n = 9) or non-anatomic (n = 8) ACL reconstruction. Bilateral high-resolution CT scans were obtained to produce 3D models. Anterolateral (AL) and posteromedial (PM) bundles insertion sites of the PCL were identified on the 3D CT scan reconstructions. Dynamic knee function was assessed during running using a dynamic stereo X-ray (DSX) system. The lengths of the AL and PM bundles were estimated from late swing through mid-stance. The contralateral knees served as normal controls. Control knees demonstrated a slight decrease in AL bundle and a significant decrease in PM bundle length following foot strike. Length and elongation patterns of the both bundles of the PCL in the anatomic ACL reconstruction group were similar to the controls. However, the change in dynamic PCL length was significantly greater in the non-anatomic group than in the anatomic reconstruction group after foot strike (p < 0.05). The AL bundle length decreased slightly, and the PM bundle length significantly decreased after foot strike during running in uninjured knees. Anatomic ACL reconstruction maintained normal PCL elongation patterns more effectively than non-anatomic ACL reconstruction during high-demand, functional loading. These results support the use of anatomic ACL reconstruction to achieve normal knee function in high-demand activities. Case-control study, Level III.


Editorial Commentary: The Importance of Capsular Closure Following Hip Arthroscopy-Leave No Trace: An Outdoorsman's Ramblings.
After a decade-long paradigm shift and an evidence-based enormous increase in the prevalence of hip arthroscopic procedures, hip capsular closure following arthroscopy, once a rare procedure, is now performed in the majority of surgical cases. This results from improved surgeon experience, refined surgical technologies and techniques and an explosion of research regarding stability of the hip joint. Once viewed as inherently stable, it is become clear that meticulous capsular management and closure can not only maintain joint stability but is a treatment for and/or prevents micro-instability. Recent research shows that hip capsular closure can improve outcomes and return to sport rates in the highest demand athletes having hip arthroscopy. Close the capsule!


Vergence eye movement control and multivalent perception of autostereograms.
We introduce a dynamical model for automatic vergence eye movement control. In connection with our dynamical system of binocular model neurons that solves the correspondence problem of stereo-vision, we present a complete model for stereo-vision. Our automatic vergence eye movement control adjusts an image segment, which is of momentary interest to the observer. The adjustment is done in such a way that we only need to define a disparity search range of minimal extension. Recently, a new method of encoding (3D) three-dimensional information in 2D pictures was designed in the form of computer-generated patterns of colored dots. At first glimpse, these so-called autostereograms appear as structured but meaningless patterns. After a certain period of observation, a 3D pattern emerges suddenly in an impressive way. Applying our algorithm to autostereograms, we find a fully satisfactory agreement with the multivalent perception experienced by humans. As in nature, in our model the phase transition between the initial state and the 3D perception state takes place in a very short time. Our algorithm is very robust against noise, and there is no need to interpolate a sparse depth map.


Reorientation behavior in the helical motility of light-responsive spiral droplets.
The physico-chemical processes supporting life's purposeful movement remain essentially unknown. Self-propelling chiral droplets offer a minimalistic model of swimming cells and, in surfactant-rich water, droplets of chiral nematic liquid crystals follow the threads of a screw. We demonstrate that the geometry of their trajectory is determined by both the number of turns in, and the handedness of, their spiral organization. Using molecular motors as photo-invertible chiral dopants allows converting between right-handed and left-handed trajectories dynamically, and droplets subjected to such an inversion reorient in a direction that is also encoded by the number of spiral turns. This motile behavior stems from dynamic transmission of chirality, from the artificial molecular motors to the liquid crystal in confinement and eventually to the helical trajectory, in analogy with the chirality-operated motion and reorientation of swimming cells and unicellular organisms.


Rho, Rac, Pak and angiogenesis: old roles and newly identified responsibilities in endothelial cells.
Angiogenesis-the develoment of microvasculature-requires, in part, directed endothelial cell motility and responsiveness to external signals. Several of the proteins, which modulate and/or direct endothelial cell motility and morphology in angiogenesis are the Rho GTPases (Rho, Rac, and Cdc42) and Pak (a downstream effector of Rac and Cdc42). Previously, overexpression and activation of Rho GTPases and Pak had been implicated in the development of cancer, through their roles in cancer cell transformation, stimulation of proliferation, inhibition of apoptosis, and migration. Yet regardless of the transformed status of cells within a tumor, without a blood supply most tumors cannot grow larger than 1-2 mm. The blood supply in tumors is provided by capillaries formed of endothelial cells in a process called angiogenesis. Consequently, there is enormous interest in the role of the wild type endothelial cells-and the signaling mechanisms required to support angiogenesis and subsequent growth of metastatic and aggressive cancers. Recent work has begun to uncover the roles of the Rho GTPases and Pak in the regulation of normal endothelial cell function. This review will discuss the current literature regarding the roles of Rho and Rac, and the Rac effector-Pak, in endothelial cells, and we will propose new avenues of research for interaction of the AGC kinase-PKG, with the Rho GTPases and Pak in the cell motility and cell morphology of endothelial cells.


Cortical networks for vision and language in dyslexic and normal children of variable socio-economic status.
In dyslexia, anomalous activations have been described in both left temporo-parietal language cortices and in left ventral visual occipito-temporal cortex. However, the reproducibility, task-dependency, and presence of these brain anomalies in childhood rather than adulthood remain debated. We probed the large-scale organization of ventral visual and spoken language areas in dyslexic children using minimal target-detection tasks that were performed equally well by all groups. In 23 normal and 23 dyslexic 10-year-old children from two different socio-economic status (SES) backgrounds, we compared fMRI activity to visually presented houses, faces, and written strings, and to spoken sentences in the native or in a foreign language. Our results confirm a disorganization of both ventral visual and spoken language areas in dyslexic children. Visually, dyslexic children showed a normal lateral-to-medial mosaic of preferences, as well as normal responses to houses and checkerboards, but a reduced activation to words in the visual word form area (VWFA) and to faces in the right fusiform face area (FFA). Auditorily, dyslexic children exhibited reduced responses to speech in posterior temporal cortex, left insula and supplementary motor area, as well as reduced responses to maternal language in subparts of the planum temporale, left basal language area and VWFA. By correlating these two findings, we identify spoken-language predictors of VWFA activation to written words, which differ for dyslexic and normal readers. Similarities in fMRI deficits in both SES groups emphasize the existence of a core set of brain activation anomalies in dyslexia, regardless of culture, language and SES, without however resolving whether these anomalies are a cause or a consequence of impaired reading.


Meconium contaminated amniotic fluid and infant otitis media. Is it a risk factor in children surviving aspiration and initial distress of respiration?
Histological studies show that amniotic fluid cellular content (AFCC) causes in the middle ear a foreign body reaction, the extent and severity of which depends upon the massiveness of contamination. We studied how factors related to birth and environment affect proneness to acute otitis media (AOM) in infants born through meconium contaminated amniotic fluid. From the birth records of infants born from 1996 to 2000 a list was made of those born through meconium contaminated amniotic fluid with pulmonary aspiration and tracheal suctioning, followed by treatment in a neonatal intensive care unit. Thirty-seven such children formed the study group, 43 children matching the study cases but born through clear fluids formed the control group. Birth and environmental factors together with the frequency and number of episodes of AOM were analyzed in all, based on a verified questionnaire. In addition, 27 children in the study group and 21 in the control group received a specialist ENT examination, hearing tests and tympanometry. The events at delivery were highly significantly different between the two groups, manifested by the lower Apgar points in the study group (p<0.001) while other birth and environmental factors appeared equalized. The first episode of AOM in the study group came earlier than in the control group and their frequency was significantly higher during the 1st and 2nd year of life and during the entire observation period (p<0.001). Tympanostomy was performed more often in the study group. Tympanometry showed more cases of reduced static admittance and negative pressure than in the control group and hearing was poorer. Cases with compromised delivery through meconium contaminated fluids, resulting in pulmonary aspiration and in need of intensive care treatment, form a risk group, which should be closely followed. Early nasopharyngeal suctioning of AFCC may reduce its entry into the middle ear. A prolonged episode of AOM suggests mucosal involvement of several middle ear compartments, shown by histological studies to occur in all cases of massive contamination. Placement of a ventilation tube after the first prolonged AOM allows regression of the granulation tissue in the air spaces together with the secretory elements in the mucosa.


An early warning surveillance programme for detecting upper limb deterioration after treatment for breast cancer: A novel technology supported system.
Upper limb morbidity is a well-recognised consequence of treatment for breast cancer that can develop for up to 6 years after treatment. However, the capacity to fully integrate evidence-based rehabilitation pathways into routine care for all patients is questionable due to limited resources. A long term surveillance programme must therefore be accessible to all patients, should identify those at risk of developing morbidity and target the interventions at the high risk population of patients. The proposed model uses a surrogate marker for assessing risk of morbidity, incorporated into an Early Warning System (EWS), to produce a technology-lead, prospective surveillance programme.


The synergistic effect of oxygen-containing functional groups on CO2 adsorption by the glucose-potassium citrate-derived activated carbon.
A high surface area activated carbon prepared by an innovative approach using glucose as a carbon source and neutral potassium citrate (PC) as an activator was compared with the porous carbon from glucose using corrosive potassium hydroxide (KOH) as an activator. The PC method showed two notable advantages over KOH activation. The PC method not only significantly increased the yield of the activated carbon, particularly at high carbonization temperatures without sacrificing porosity, but also enhanced the oxygen content in the activated carbon. After investigating CO2 adsorption on these activated carbons, a remarkable uptake of 3.57 mmol g-1 at 25 °C at 1 bar was observed by the glucose-PC-derived carbon sample, which possessed the highest oxygen content. In addition, the glucose-PC-derived carbon samples exhibited higher CO2/N2 selectivity than the glucose-KOH derived samples. Coupled with the density functional theory (DFT) analysis that focused on the binding energy calculation, the doped oxygen-containing functional groups, such as carboxyl and hydroxyl groups, could effectively enhance the adsorption of CO2.


Correction: Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway.
[This corrects the article DOI: 10.18632/oncotarget.22930.].


The multifaceted mechanisms of pristimerin in the treatment of tumors state-of-the-art.
As a globally complicated disease, malignant tumor has long been posing a threat to human health with increasingly high morbidity and mortality. Notably, existing treatments for tumors like chemotherapy generally carry intolerable toxicity, necessitating novel agents balancing safety and potency. Among them, the anti-tumor potency of herbs, featuring few adverse effects and promising efficacy, has attracted much attention recently. Pristimerin, a Quinone formamide triterpenoid compound extracted from Celastraceae and Portulacaceae, carries pronounced anti-tumor activity. It applies to various malignant tumors, including breast cancer, bile duct cancer, gastric cancer, pancreatic cancer, prostate cancer, glioblastoma, colorectal cancer, oral squamous cell carcinoma, cervical cancer, and lung cancer. In state-of-the-art understanding, pristimerin, alone or combined, can inhibit tumor cell proliferation, induce tumor cell apoptosis, inhibit tumor migration and invasion, inhibit angiogenesis, induce tumor cell autophagy, regulate the occurrence of inflammation related tumors, enhance chemosensitivity and regulate tumor microenvironment and immune cells. Despite the abundance of pristimerin-based research, systematic reviews on its anti-tumor mechanism remain needed. This study presented the anti-tumor mechanism of pristimerin by literature review, which might serve as a reference for further research and clinical practice.


Solute-solvent interactions in micellar electrokinetic chromatography. III. Characterization of the selectivity of micellar electrokinetic chromatography systems.
Several micellar electrokinetic chromatography (MEKC) systems (sodium dodecyl sulfate, lithium dodecyl sulfate, lithium perfluorooctanesulfonate, sodium cholate, sodium deoxycholate, tetradecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide) have been characterized by means of the solvation parameter model. It has been observed that the coefficients of the correlation equations depend strongly on the particular set of compounds analyzed. Principal component analysis has been used to characterize the 2975 compounds with available solute descriptors and to select an appropriate subset of compounds to be analyzed by MEKC. With this set of compounds, the MEKC systems have been characterized. Principal component analysis has also been used to show the similarities and differences between the properties of the surfactants characterized by MEKC.


A randomized control trial of Expand Your Horizon: An intervention for women with weight bias internalization.
Weight bias internalization (WBI) is associated with a myriad of negative health outcomes, but there are few effective treatments that address this concern. This randomized controlled trial examined the preliminary effectiveness of a previously developed body gratitude journaling intervention (i.e., Expand Your Horizon) compared with an active control writing condition (i.e., expressive writing) in emerging adult women with WBI. Participants (N = 135) completed baseline measures and were then randomized to either Expand Your Horizon (n = 72) or the active control condition (n = 63). Participants in both conditions completed three writing tasks over one week. Assessments occurred at baseline, post-test, and follow-up (one-week). Participants in both conditions experienced improvements in WBI, functionality appreciation, and self-compassion at follow-up, though improvements were greater in the Expand Your Horizon condition. Further, participants in the Expand Your Horizon had greater improvement in healthcare stress at follow-up. In sum, Expand Your Horizon appeared accessible and demonstrated preliminary effectiveness in a sample of emerging adult women with WBI. Avenues for future research include evaluating this intervention in more diverse populations with a longer follow-up.


β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells.
Despite the widespread clinical application of chemotherapeutic anticancer drugs, their adverse side effects and inefficient performances remain ongoing issues. A drug delivery system (DDS) designed for a specific cancer may therefore overcome the drawbacks of single chemotherapeutic drugs and provide precise and synergistical cancer treatment by introducing exclusive stimulus responsiveness and combined chemotherapy properties. Herein, we report the design and synthesis of a supramolecular drug delivery assembly 1 constructed by orthogonal self-assembly technique in aqueous media specifically for application in liver cancer therapy. Complex 1 incorporates the β-cyclodextrin host molecule-functionalized organoplatinum(II) metallacycle 2 with two specific stimulus-responsive motifs to the signaling molecule nitric oxide (NO), in addition to the three-armed polyethylene glycol (PEG) functionalized ferrocene 3 with redox responsiveness. With this molecular design, the particularly low critical aggregation concentration (CAC) of assembly 1 allowed encapsulation of the commercial anticancer drug doxorubicin (DOX). Controlled drug release was also achieved by morphological transfer via a sensitive response to the endogenous redox and NO stimuli, which are specifically related to the microenvironment of liver tumor cells. Upon combination of these properties with the anticancer ability from the platinum acceptor, in vitro studies demonstrated that DOX-loaded 1 is able to codeliver anticancer drugs and exhibit therapeutic effectiveness to liver tumor sites via a synergistic effect, thereby revealing a potential DDS platform for precise liver cancer therapeutics.


Comparing the Surgical Response of Bisphosphonate-Related Versus Denosumab-Related Osteonecrosis of the Jaws.
The pathophysiology and treatment of medication-related osteonecrosis of the jaws (MRONJ) remain unclear after nearly two decades of recorded observation and discussion. The purpose of this study was to assess outcomes of surgical resection of MRONJ in patients exposed to denosumab. A literature review was performed in conjunction with experts at the University of Illinois at Chicago Library. The primary outcome of interest was surgical success defined by maintenance of complete mucosal closure without bone exposure and infection after surgical resection. Secondary interests included demographics, MRONJ stage, location of the focus of osteonecrosis, and the primary underlying disease necessitating antiresorptive treatment. Statistical analysis was performed by χ2, analysis of variance, or t test (P < .05 and b = 0.2 or a power of 0.8). A total of 70 articles were identified and 14 met inclusion criteria. Twenty patients were included (13 women; 7 men); age 61.8 years ± 12.9 (range 19 to 77); and MRONJ stage I (40.0%), II (35.0%), and III (25.0%). Most cases occurred in the mandible (65.0%), followed by the maxilla (30.0%). The success rate of surgical intervention for MRONJ secondary to denosumab was in 16 of 20 (80.0%) patients. Stage I MRONJ lesions achieved mucosal closure in 100% of patients, stage II in 71.4%, and stage III in 60.0%. The surgical success rate was 83.3% in the maxilla and 76.9% in the mandible. The surgical success rate for MRONJ secondary to denosumab was 80.0%, similar to that reported in bisphosphonates of 85 to 95%; however, more evidence must be reported and analyzed.


Food preference, food quality and diets of three herbivorous gastropods (Trochidae: Tegula) in a temperate kelp forest habitat.
The relationship between food preference and food quality (i.e. a food's contribution to growth and reproductive development) was examined in the laboratory for 3 species of herbivorous kelp forest gastropods (Tegula). The preference hierarchies of the 3 Tegula for 6 common algal species are the same: giant kelp (Macrocystis) is the most preferred food and brown algae are consumed at higher rates than red algae. Despite their strong preference for Macrocystis, the 3 species had significantly greater growth and/or reproductive development on a mixed-algae diet than on either brown or red algae alone. Laboratory preferences of the snails did not correspond closely with caloric content, estimated availability or quality of the algal species used in this study. However, the 3 Tegula are subject to strong benthic predation and Macrocystis provides an important spatial refuge in nature. The potential role of non-nutritional factors such as predator avoidance on the formation of food preferences is discussed.


Structural, functional and molecular docking study to characterize GMI1 from Arabidopsis thaliana.
γ-irradiation and Mitomycin C Induced 1 (GMI1), is a member of the SMC-hinge domain-containing protein family that takes part in double stranded break repair mechanism in eukaryotic cells. In this study we hypothesize a small molecule-Adenosine Tri Phosphate (ATP) binding region of novel SMC like GM1 protein in model organism Arabidopsis thaliana using in silico modeling. Initially, analyzing sequence information for the protein indicated presence of motifs - 'Walker A nucleotide-binding domain' that are required to interact with nucleotides along with 'Walker B' motif and ABC signature sequences. This was further proven through GMI1-ATP docking experiment and results were verified by comparing the values with controls. In negative control, no binding was seen in the same binding region of GMI1 structure for small molecules randomly selected form PubChem database, whereas in positive control binding affinity of other known proteins with ATP binding potential resembled GMI1-ATP binding affinity of -5.4 kcal/mol. Furthermore we also docked small molecules that shares structural similarity with ATP to GMI1 and found that Purine Mononucleotide bound the region with the best affinity, which implies that the compound may bind the protein with strong binding and can work as a potential agonist/antagonist to GMI1. We believe that the study would shed more light into the GM1 mechanism of action. Although the computational predictions made here are based on concrete confidence, it should be mentioned that in vitro experimentation does not fall into the scopes of this study and thus the results found here have to be further validated in vitro.


Biodegradation of polyester polyurethane by Aspergillus tubingensis.
The xenobiotic nature and lack of degradability of polymeric materials has resulted in vast levels of environmental pollution and numerous health hazards. Different strategies have been developed and still more research is being in progress to reduce the impact of these polymeric materials. This work aimed to isolate and characterize polyester polyurethane (PU) degrading fungi from the soil of a general city waste disposal site in Islamabad, Pakistan. A novel PU degrading fungus was isolated from soil and identified as Aspergillus tubingensis on the basis of colony morphology, macro- and micro-morphology, molecular and phylogenetic analyses. The PU degrading ability of the fungus was tested in three different ways in the presence of 2% glucose: (a) on SDA agar plate, (b) in liquid MSM, and (c) after burial in soil. Our results indicated that this strain of A. tubingensis was capable of degrading PU. Using scanning electron microscopy (SEM), we were able to visually confirm that the mycelium of A. tubingensis colonized the PU material, causing surface degradation and scarring. The formation or breakage of chemical bonds during the biodegradation process of PU was confirmed using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy. The biodegradation of PU was higher when plate culture method was employed, followed by the liquid culture method and soil burial technique. Notably, after two months in liquid medium, the PU film was totally degraded into smaller pieces. Based on a comprehensive literature search, it can be stated that this is the first report showing A. tubingensis capable of degrading PU. This work provides insight into the role of A. tubingensis towards solving the dilemma of PU wastes through biodegradation.


Reduction of retinal sensitivity in eyes with reticular pseudodrusen.
To evaluate the effect of macular reticular pseudodrusen on retinal function using multiple imaging methods. Prospective cross-sectional study. Thirteen eyes with reticular pseudodrusen, but without any other macular abnormality or glaucoma, and 20 normal eyes were evaluated. All subjects underwent color fundus photography, infrared reflectance (IR), fundus autofluorescence (FAF), and microperimetry. The similarity in the number of reticular pseudodrusen was evaluated through inter-observer intraclass correlation coefficients, which ranged from 0.852-0.944. IR could detect reticular pseudodrusen within the center circle area in 12 eyes, whereas blue-channel fundus photography and FAF could only detect these lesions in 1 and 3 eyes, respectively. The number of reticular pseudodrusen correlated among the different imaging modalities (P < .001 for all) for all areas of the macula, except the center. The mean retinal sensitivity in eyes with reticular pseudodrusen was lower in all areas of the macula, compared with normal eyes (P < .001 for all). The number of reticular pseudodrusen correlated with retinal sensitivity in all areas by IR imaging (P = .003, P < .001, P = .003 for center, inner ring, outer ring, respectively), in the inner and outer rings by blue-channel fundus photography (P < .001 for both), and in the inner and outer rings by FAF (P < .001 and P = .001, respectively). Although multiple imaging modalities are capable of quantifying reticular pseudodrusen, IR appears to have the best ability to do so as compared to blue-channel photography and FAF. The distribution and number of reticular pseudodrusen lesions are closely associated with retinal sensitivity.


Cerebral venous thrombosis in Argentina: clinical presentation, predisposing factors, outcomes and literature review.
Cerebral venous thrombosis (CVT) is a rare medical condition that primarily affects young adults. The clinical spectrum is broad and its recognition remains a challenge for clinicians. Limited information is available on CVT in Argentina. Our goal was to report the results of the first National registry on CVT in Argentina and to compare clinical presentation, predisposing factors and outcomes with other international registries. The Argentinian National Registry on CVT (ANR-CVT) is a multicenter retrospective cohort study comprising patients aged 18 and older with a diagnosis of CVT from January 2015 to January 2019. We evaluated demographics, predisposing factors, clinical presentation, and radiological characteristics (e.g. number of involved sinuses, venous infarction or hemorrhage on CT and MRI scans at admission), therapeutic interventions and functional outcomes at discharge and at 90 days. Our results were compared to a literature review of CVT registries. Overall, one hundred and sixty-two patients met the inclusion criteria. The mean age was 42 (±17) years; 72% were women. Seventy percent of patients were younger than 50 years. The most common presenting symptom was headache (82%). The transverse sinus was the most common site of thrombosis (70%) followed by the sigmoid sinus (46%). The main predisposing factor in women was contraceptive use (44%), 3% of the events occurred during pregnancy and 9% during the puerperium. Participants 50 years and older had a higher frequency on malignancy related (7.5% vs. 30%, p = 0.0001) and infections (2% vs. 11%, p = 0.001). The modified Rankin Scale (mRS) ≤2 at discharge was 81% and the rate of mortality at discharge was 4%. At 90 days, the mRS≤2 was 93%. When the ANR-CVT was compared with larger registries from Europe and Asia, the prevalence of cancer among patients with CVT was two to five-fold higher (15% vs. 7% and 3%, respectively; p = 0.002 and p < 0.001). Anticoagulation rates at discharge were also higher (94%) compared to registries from Asia (ASCVT - 68%) or Turkey (VENOST - 67%). Participants in the first ANR-CVT had a low mortality and disability at 90 days. Clinical and radiological characteristics were similar to CVT from other international registries with a higher prevalence of cancer. There was a high variability in treatment adherence to guidelines as reflected by anticoagulation rates (range 54.5%-100%) at discharge.


Status epilepticus during vigabatrin treatment: a report of three cases.
Vigabatrin (gamma-vinyl-GABA or GVG) is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), which is an enzyme responsible for gamma-aminobutyric acid (GABA) catabolism. Inhibition of GABA catabolism increases brain concentration of GABA, a neural inhibitor. GVG has been found to be a potent new anti-epileptic drug, especially in the treatment of refractory epilepsy, in particular of complex partial seizures. Three patients who developed a severe status epilepitus while on GVG treatment are reported. A possible proconvulsive effect of GVG is hypothesized, which might result from disinhibition in the nigro-collicular pathway due to increased GABA-levels.


Changes in chromatin basic proteins during male gametogenesis of grass carp.
1. The composition of basic of chromatin protein fractions has been studied in the course of male spermatogenesis of grass carp (Ctenopharyngodon idella). 2. Electrophoretic mobility of H1, H2B and H2A histones of grass carp is shown to differ from that of corresponding fraction of calf thymus histones. 3. Comparison of chromatin protein fractions from liver, mature and immature testis and sperm of grass carp has revealed subtle tissue specificity of H2B and H2A histones. 4. Maturation of spermatozoa in grass carp is accompanied by a marked accumulation of the TH1 subfraction (TH1-1), disappearance of some acid-soluble non-histone proteins and of a protein similar to the mammalian A24 protein.


Treatment of posterior cruciate ligament tibial avulsion fractures through a modified open posterior approach: operative technique and 12- to 48-month outcomes.
To report clinical and functional outcomes following fixation of tibial posterior cruciate ligament (PCL) avulsion fractures through a modified open posterior approach when combined with a rehabilitation program emphasizing early range of motion. Retrospective case series. Level I trauma center. From March 4, 2000 to May 8, 2003, there were 16 cases of PCL tibial avulsion injuries presented to our institution, with 10 patients available for follow up at 12 to 48 months (mean 28 months). Fixation of tibial PCL avulsion fractures was with a lag screw and washer placed through a modified open posterior approach. Range of motion was begun on postoperative day 1. Clinical stability, range of motion, gastrocnemius muscle strength, radiographic appearance, and each patient's overall health-related quality of life (using the musculoskeletal functional assessment tool) were evaluated at final follow up. The average musculoskeletal functional assessment score was 14. (Musculoskeletal functional assessment scores range from 0-100, with higher scores indicating poorer function.) All patients achieved union of their fracture and had clinically stable knees at the latest follow-up. Flexion difference greater than 10 degrees (P = 0.16), extension difference greater than 2 degrees (P = 0.38), and heel raise difference more than 8 repetitions (P = 0.23) were not demonstrated in comparison to the normal side. Treatment of tibial PCL avulsion fractures, which includes fixation through a modified open posterior approach and early postoperative range of motion, results in healing of the fracture, good functional outcomes, stability to posterior draw testing, and does not lead to gastrocnemius weakness or significant range of motion deficits at 12 to 48 months postoperatively.


Experimental approaches to cognitive abnormality in posttraumatic stress disorder.
During the past decade, experimental psychopathologists have increasingly applied the concepts and methods of cognitive psychology to elucidate information-processing abnormalities in people with posttraumatic stress disorder (PTSD). These studies have shown that individuals with PTSD: (a) selectively process trauma-relevant material in the emotional Stroop paradigm; (b) exhibit enhanced memory for material related to trauma in explicit and perhaps implicit tests; (c) exhibit difficulty forgetting trauma words during directed forgetting; and (d) exhibit problems retrieving specific autobiographical memories in response to cue words, instead recalling "overgeneral" memories. These studies suggest that experimental methods can complement traditional, self-report methods for studying cognitive disturbances in PTSD.


Anterior Segment Imaging Predicts Incident Gonioscopic Angle Closure.
To investigate the incidence of gonioscopic angle closure after 4 years in subjects with gonioscopically open angles but varying degrees of angle closure detected on anterior segment optical coherence tomography (AS OCT; Visante; Carl Zeiss Meditec, Dublin, CA) at baseline. Prospective, observational study. Three hundred forty-two subjects, mostly Chinese, 50 years of age or older, were recruited, of whom 65 were controls with open angles on gonioscopy and AS OCT at baseline, and 277 were cases with baseline open angles on gonioscopy but closed angles (1-4 quadrants) on AS OCT scans. All subjects underwent gonioscopy and AS OCT at baseline (horizontal and vertical single scans) and after 4 years. The examiner performing gonioscopy was masked to the baseline and AS OCT data. Angle closure in a quadrant was defined as nonvisibility of the posterior trabecular meshwork by gonioscopy and visible iridotrabecular contact beyond the scleral spur in AS OCT scans. Gonioscopic angle closure in 2 or 3 quadrants after 4 years. There were no statistically significant differences in age, ethnicity, or gender between cases and controls. None of the control subjects demonstrated gonioscopic angle closure after 4 years. Forty-eight of the 277 subjects (17.3%; 95% confidence interval [CI], 12.8-23; P < 0.0001) with at least 1 quadrant of angle closure on AS OCT at baseline demonstrated gonioscopic angle closure in 2 or more quadrants, whereas 28 subjects (10.1%; 95% CI, 6.7-14.6; P < 0.004) demonstrated gonioscopic angle closure in 3 or more quadrants after 4 years. Individuals with more quadrants of angle closure on baseline AS OCT scans had a greater likelihood of gonioscopic angle closure developing after 4 years (P < 0.0001, chi-square test for trend for both definitions of angle closure). Anterior segment OCT imaging at baseline predicts incident gonioscopic angle closure after 4 years among subjects who have gonioscopically open angles and iridotrabecular contact on AS OCT at baseline.


Multispectral imaging: Review of current applications.
Multispectral imaging (MSI) is a unique layer-by-layer imaging technique that allows the visualization of a wide array of retinal and choroidal pathologies including retinovascular disorders, retinal pigment epithelial changes, and choroidal lesions. Herein, we summarize the basic imaging principles and current applications of MSI together with recent technology advances in the field. MSI detects reflectance signal from both normal chorioretinal tissue and pathological lesions. Either hyperreflectance or hyporeflectance reveals the absorption activity of pigments such as hemoglobin and melanin and the reflection from interfaces such as the posterior hyaloid. Advances in MSI technique include creation of a retinal and choroidal oxy-deoxy map that could provide a better understanding of blood oxygen saturation within lesions as well as better interpretation of reflectance phenomenon of MSI images such as the different reflectance from the Sattler and Haller layers described in this review.


Quantitative determination of canagliflozin in human plasma samples using a validated HPTLC method and its application to a pharmacokinetic study in rats.
Canagliflozin (CNZ) is the first sodium-glucose co-transporter-2 inhibitor approved for treatment of type 2 diabetes mellitus. In the proposed work, a sensitive, rapid and validated high-performance thin-layer chromatography (HPTLC) method was established for the estimation of CNZ in human plasma for the first time. HPTLC analysis of CNZ and internal standard (sildenafil) was performed on glass coated silica gel 60 F254 HPTLC plates using a binary mixture of chloroform-methanol 9:1 (%, v/v) as the mobile phase. Densitometric detection was done at 295 nm. Retardation factor values were obtained as 0.22 and 0.52 for the CNZ and the IS, respectively. The linearity range of CNZ was obtained as 200-3,200 ng/ml. A simple protein precipitation method was used for the extraction of analyte from plasma using methanol. The proposed HPTLC technique was validated for linearity, accuracy, precision and robustness. The proposed HPTLC technique was successfully utilized for the assessment of pharmacokinetic profile of CNZ in rats after oral administration. After oral administration, the peak plasma concentration of CNZ was obtained as 1458.01 ng/ml in 2 h. The proposed HPTLC method could be applied to the study of the pharmacokinetic profile of pharmaceutical formulations containing CNZ.


Mammalian lipid droplets: structural, pathological, immunological and anti-toxicological roles.
Mammalian lipid droplets (LDs) are specialized cytosolic organelles consisting of a neutral lipid core surrounded by a membrane made up of a phospholipid monolayer and a specific population of proteins that varies according to the location and function of each LD. Over the past decade, there have been significant advances in the understanding of LD biogenesis and functions. LDs are now recognized as dynamic organelles that participate in many aspects of cellular homeostasis plus other vital functions. LD biogenesis is a complex, highly-regulated process with assembly occurring on the endoplasmic reticulum although aspects of the underpinning molecular mechanisms remain elusive. For example, it is unclear how many enzymes participate in the biosynthesis of the neutral lipid components of LDs and how this process is coordinated in response to different metabolic cues to promote or suppress LD formation and turnover. In addition to enzymes involved in the biosynthesis of neutral lipids, various scaffolding proteins play roles in coordinating LD formation. Despite their lack of ultrastructural diversity, LDs in different mammalian cell types are involved in a wide range of biological functions. These include roles in membrane homeostasis, regulation of hypoxia, neoplastic inflammatory responses, cellular oxidative status, lipid peroxidation, and protection against potentially toxic intracellular fatty acids and lipophilic xenobiotics. Herein, the roles of mammalian LDs and their associated proteins are reviewed with a particular focus on their roles in pathological, immunological and anti-toxicological processes.


Differential expression of the rat gamma-glutamyl transpeptidase gene promoters along with differentiation of hepatoblasts into biliary or hepatocytic lineage.
gamma-Glutamyl transpeptidase (GGT), a major enzyme of glutathione (GSH) homeostasis, is often used as a biliary marker to follow the differentiation of hepatic precursor cells. The expression of the GGT gene is driven by different promoters and yields multiple mRNAs, depending on the cell type or the stage of differentiation. In the present study, we analyzed the GGT mRNA expression pattern by quantitative reverse transcriptase-polymerase chain reaction or by in situ hybridization i) in the liver, in vivo, at early stages of development; ii) in oval cells, which proliferate and differentiate into hepatocytes in response to galactosamine injury in vivo; and finally, iii) during hepatoblast differentiation, in vitro. We show that GGT gene transcription originates from promoters P3, P4, and P5 in rat hepatic precursor cells. Differentiation of these cells induces profound alterations in GGT gene expression, leading to extinction of promoters P4 and P5, when they differentiate into the hepatocytic pathway, and to extinction of promoters P3 and P5 when they differentiate into the biliary pathway. This diversity in GGT mRNA expression provides unique molecular probes to follow hepatic precursor cell differentiation. Furthermore, the identification of factors governing GGT P5 and P4 promoter expression should provide further insight into the molecular events that occur as the liver precursor cell differentiates into the hepatic lineages.


Repeated low-dose organophosphate DFP exposure leads to the development of depression and cognitive impairment in a rat model of Gulf War Illness.
Approximately 175,000-250,000 of the returning veterans from the 1991 Persian Gulf War exhibit chronic multi-symptom illnesses that includes neurologic co-morbidities such as depression, anxiety and cognitive impairments. Amongst a host of causative factors, exposure to low levels of the nerve agent Sarin has been strongly implicated for expression of Gulf War Illness (GWI). Nerve agents similar to pesticides are organophosphate (OP) compounds. There is evidence from civilian population that exposure to OPs such as in agricultural workers and nerve agents such as the survivors and first-responders of the Tokyo subway Sarin gas attack suffer from chronic neurological problems similar to GWI symptoms. Given this unique chemical profile, OPs are ideal to study the effects of nerve agents and develop models of GWI in civilian laboratories. In this study, we used repeated low-dose exposure to OP agent diisopropyl fluorophosphate (DFP) over a 5-day period to approximate the duration and level of Sarin exposure during the Persian Gulf War. We tested the rats at 3-months post DFP exposure. Using a battery of behavioral assays, we observed the presence of symptoms of chronic depression, anxiety and memory problems as characterized by increased immobility time in the Forced Swim Test, anhedonia in the Sucrose Preference Test, anxiety in the Elevated Plus Maze, and spatial memory impairments in the Object Location Test, respectively. Chronic low dose DFP exposure was also associated with hippocampal neuronal damage as characterized by the presence of Fluoro-Jade staining. Given that OP exposure is considered a leading cause of GWI related morbidities, this animal model will be ideally suited to study underlying molecular mechanisms for the expression of GWI neurological symptoms and identify drugs for the effective treatment of GWIs.


Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis.
The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA). We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8). For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.


A novel mathematics model of covid-19 with fractional derivative. Stability and numerical analysis.
a mathematical model depicting the spread of covid-19 epidemic and implementation of population covid-19 intervention in Italy. The model has 8 components leading to system of 8 ordinary differential equations. In this paper, we investigate the model using the concept of fractional differential operator. A numerical method based on the Lagrange polynomial was used to solve the system equations depicting the spread of COVID-19. A detailed investigation of stability including reproductive number using the next generation matrix, and the Lyapunov were presented in detail. Numerical simulations are depicted for various fractional orders.


Conditional recurrence analysis of intrahepatic cholangiocarcinoma: Changes in recurrence rate and survival after recurrence resection by disease-free interval.
The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC. This study included patients who underwent hepatectomy for ICC during 1995-2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed. A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2 years after initial resection and 2.6% in patients free from recurrence at 4 years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11-0.40, p < 0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05-5.40, p = 0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95-1.00, p = 0.067) were significantly associated with longer OS after recurrence. Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.


[The surgical treatment of tetralogy of fallot in 136 adults].
To summarize the experience of surgical treatment of tetralogy of Fallot (TOF) in adults. From April 1975 to December 1997, 136 adult patients underwent total corrective repair of tetralogy of Fallot. The patient age ranged from 14 to 52 years old. The ventricular septal defects were closed with Dacron patch in 112 patients, with pericardial patch in 24 patients. A right ventricular outflow patch was required to eliminate right ventricular outflow tract obstruction in 126 patients. Five patients died during hospitalization, with a hospital mortality of 3.68%. Four early postoperative deaths were due to severe low cardiac output syndrome. In view of current improved and standardized techniques, we conclude that the total corrective repair of TOF may have an excellent result in adult patients.


Phenolic constituents of Carex vulpinoidea seeds and their tyrosinase inhibitory activities.
Two new phenolics, a stilbenoid, vulpinoideol A (1), and a chalcone, vulpinoideol B (2), along with ten known compounds (3-12) were isolated from Carex vulpinoidea Michx. seeds. The structures of compounds 1-12 were elucidated based on spectrometric and spectroscopic analyses including HRESIMS, 1D and 2D NMR data. All compounds were evaluated for their tyrosinase enzyme inhibitory activities.


Hybrid chromophobe renal cell neoplasm.
Hybrid renal cell neoplasms (HRCNs) containing areas of tumor cells displaying cytological features of chromophobe renal cell carcinoma (CHRCC) and renal oncocytoma (RO) have been recently described in patients with renal oncocytosis and Birt-Hogg-Dube (BHD) syndrome (autosomal dominant genodermatosis). In this study, we identified cases of sporadic HRCN. We reviewed 425 consecutive renal cell carcinomas (RCC), 18 CHRCC, six HRCN, and 25 RO. Five HRCN were identified, including four from the group of RCC and two from RO. Patient age ranged from 40 to 68 years (mean age: 54 years), and the male:female ratio was 4:1. Tumors measured from 1.8 to 5 cm (mean diameter: 3.0 cm). Tumoral necrosis was not seen. Vascular invasion into medium-sized veins was identified in one HRCN. Chromophobe cells accounted for 20-80% of the tumors. Hale's colloidal stain showed weak to moderate diffuse cytoplasmic staining in scattered cells corresponding to those displaying routine staining features of chromophobe cells. Areas of oncocytic cells in studied tumors and control oncocytomas showed negative or focal cytoplasmic staining usually bordering extra- or intra-cytoplasmic lumina. Immunostaining for cytokeratin 7 and vimentin showed focal immunoreactivity in three cases and negative reactivity in all six cases, respectively. None of the study cases had microscopic RO, as commonly seen in renal oncocytosis, or were associated with BHD syndrome Sporadic HRCN accounted for 1% of RCC. They were of smaller size than RCC and were associated with a favorable prognosis.


Characterization of solubilized bradykinin B2 receptors from smooth muscle and mucosa of guinea pig ileum.
Bradykinin (BK) B2 receptors in guinea pig ileum were characterized in both membrane and soluble form. [3H]BK bound to a single class of sites with almost identical affinities in membranes prepared from the longitudinal muscle, circular muscle and mucosal layers of the ileum. The pharmacology of the binding in the distinct layers was indistinguishable. The detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS) maximally solubilized nearly 80% of membrane binding activity in a very stable conformation. In soluble preparations, [3H]BK labeled a single class of sites but with about 10-fold lower affinity. The affinities of BK analogs in competition studies were similarly reduced. There was no difference in the pharmacology of the binding in soluble receptors prepared from the different layers of the ileum. The results show that the ileum is a good source of solubilized B2 receptors and that the receptors in the smooth muscle and the mucosa are very similar.


L-theanine, a Component of Green Tea Prevents 3-Nitropropionic Acid (3-NP)-Induced Striatal Toxicity by Modulating Nitric Oxide Pathway.
L-theanine is unique amino acid which readily crosses blood brain barrier and possesses neuroprotective potential against neurodegenerative disorders including Huntington disease (HD). HD is characterized by selective loss of GABAergic medium spiny neurons. 3-nitropropionic acid (3-NP) induces a spectrum of HD-like neuropathology in rat striatum and widely used as experimental tool to study HD. Therefore, the present study was intended to investigate the effect of L-theanine against 3-NP-induced striatal toxicity and to explore its possible mechanism. Rats were administered with 3-NP for 21 days. L-theanine was given once a day, 1 h prior to 3-NP treatment for 21 days and L-NAME (10 mg/kg, i.p.), NO inhibitor and L-arginine (50 mg/kg; i.p.), NO precursor were administered 1 h prior to L-theanine treatment. Body weight and behavioral observation were made on weekly basis. On the 22nd day, animals were sacrificed, and the striatum was isolated for biochemical (LPO, GSH, and nitrite), pro-inflammatory cytokines and neurochemical analysis. 3-NP treatment significantly altered body weight, locomotor activity, motor coordination, mitochondrial complex-II activity, oxidative defense, pro-inflammatory mediators, and striatal neurotransmitters level. L-theanine pre-treatment (25 and 50 mg/kg/day, p.o.) significantly prevented these alterations. In addition, concurrent treatment of L-NAME with L-theanine (25 mg/kg/day, p.o.) significantly enhanced protective effect of L-theanine (25 mg/kg/day, p.o.) whereas concurrent treatment of L-arginine with L-theanine (50 mg/kg/day, p.o.) significantly ameliorated the protective effect of L-theanine (50 mg/kg/day, p.o.). The neuroprotective potential of L-theanine involves inhibition of detrimental nitric oxide production and prevention of neurotransmitters alteration in the striatum.


Body composition, bone mineral density and fractures in late postmenopausal women with polycystic ovary syndrome - a long-term follow-up study.
Hyperandrogenism is one of the characteristic features of the polycystic ovary syndrome (PCOS). Androgens are important for bone mass. Studies on bone mineral density (BMD) and fractures in postmenopausal women with PCOS are lacking. The aim of this study was to investigate whether postmenopausal women with PCOS differ from controls regarding body composition, BMD and prevalence of fractures, and to compare women with PCOS with controls regarding correlations between total BMD and sex hormones. A prospective 21-year follow-up study. Anthropometry, hormonal measurements and questionnaires were performed in 1987 and in 2008. Fractures were X-ray-verified. BMD measurements were taken in 1992, using single-photon absorptiometry (SPA), and in 2008, using dual-energy X-ray absorptiometry (DXA), to also enable measurements of body composition. Twenty-five women with PCOS (Rotterdam criteria), aged 61-78 years, and 68 randomly allocated age-matched controls. Body composition, BMD, fractures and sex steroids. At follow-up, the postmenopausal women with PCOS maintained a higher free androgen index (FAI), but had similar body fat, lean mass and BMD compared with controls. The hip circumference increased only in women with PCOS (P < 0·01), during follow-up. The fracture incidence was similar to that of controls (56% vs 41%, ns). In the controls, total BMD was positively correlated with oestradiol (R = 0·322, P < 0·01) and FAI (R = 0·307, P < 0·05) and negatively correlated with SHBG (R = -0·429, P < 0·001), but not in the women with PCOS. Postmenopausal women with PCOS with persistently higher FAI had similar muscle mass, BMD and fracture incidence as controls during this long-term follow-up.


Assessment of PINK1 (PARK6) polymorphisms in Finnish PD.
Recent data has demonstrated that mutations in PINK1, encoding PTEN-induced kinase 1, are a cause of early onset recessive parkinsonism (PARK6 locus). Common variability in genes implicated in hereditary forms of parkinsonism may be a predisposing factor in sporadic Parkinson's disease (PD). We analyzed whether six different genetic variants within and surrounding PINK1 contribute to the risk of sporadic PD in a Finnish case-control series. Our results indicate that this gene does not play a major role in the genetic predisposition to PD in this population.


Memory and the efficient use of information.
We consider the problem of how an animal's memory should be designed in order to cope with a stochastic and changing environment. In particular we consider the problem of forming the best estimate of an unknown and possibly changing environmental parameter. Under the simple model we consider, the effect of an observation is to update this estimate using a linear operator. Two models of a changing environment are analysed. For each model we show how estimates change as a function of time elapsed and observations taken. The effect of a regular sequence of observations is also considered, and it is shown that an exponential weighting of past observations is a sufficient statistic on which to base decisions. The weighting factors are different in the two model environments considered, but each is shown to be a function of the rate at which the environment is changing.


Native and/or asialo-Tamm-Horsfall glycoproteins Sd(a+) are important receptors for Triticum vulgaris (wheat germ) agglutinin and for three toxic lectins (abrin-a, ricin and mistletoe toxic lectin-I).
The binding properties of human Tamm-Horsfall Sd(a+) urinary glycoprotein (THGP) and asialo-THGP with Triticum vulgaris agglutinin(WGA) and three toxic lectins (abrin-a, ricin, and Mistletoe toxic lectin-I) were investigated by quantitative precipitin and precipitin inhibition assays. Both glycoproteins reacted strongly with abrin-a, precipitating over 80% of the lectin nitrogen tested. THGP also bound well to mistletoe toxic lectin-I and precipitated 86% of this lectin added, while the precipitability of its asialo product decreased by 28%. The native glycoprotein completely precipitated the WGA added, but its reactivity was reduced dramatically after desialylation. On the contrary, the poor reactivity of THGP with ricin increased substantially after removal of sialic acid and completely precipitated the lectin added. The glycoprotein-lectin interactions were inhibited by one or several of the following haptens, p-NO2-phenyl alpha GalNAc, p-NO2-phenyl beta GalNAc, Gal beta 1-->4GlcNAc, Gal beta 1-->4Glc, GlcNac beta 1-->4GlcNAc and/or GlcNAc. From the above results, it is concluded that native and/or Tamm-Horsfall glycoproteins serve as important receptors for these three toxic lectins and for WGA.


[Effect of hydrocortisone and insulin on the energy metabolism and nucleic acid content of albino rat liver and spleen].
Hydrocortisone, single administered into rats 5 hrs before the experiment, did not alter oxidative phosphorylation in liver mitochondria but inhibited the process in spleen. In spleen a decrease in content of SH-groups and of nucleic acids was also observed. An inhibition of oxidative phosphorylation and a decrease in content of SH-groups occurred in mitochondria of spleen and liver tissues after administration of hydrocortisone within 5 days. Together with the phenomenon content of RNA and DNA was decreased in nuclei and homogenates of the tissues studied. The trend to normalization of the phosphorylation process and the increase in content of sulfhydryl groups were found in mitochondria after simultaneous administration of insulin. In this case content of nucleic acids was also increased in nuclei and homogenates of spleen and liver tissues. Possible mechanisms of the normalizing effect of insulin on the energy production and the nucleic acids accumulation in these tissues, impaired by administration of hydrocortisone, are discussed.


Anticancer activities of PPARγ in breast cancer are context-dependent.
This Commentary highlights the article by Nakles et al, who described that PPARγ activation suppresses non-invasive tumor development and induces ER-positivity without affecting invasive tumor development.


Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair.
Cross-talk between distinct protein post-translational modifications is critical for an effective DNA damage response. Arginine methylation plays an important role in maintaining genome stability, but how this modification integrates with other enzymatic activities is largely unknown. Here, we identify the deubiquitylating enzyme USP11 as a previously uncharacterised PRMT1 substrate, and demonstrate that the methylation of USP11 promotes DNA end-resection and the repair of DNA double strand breaks (DSB) by homologous recombination (HR), an event that is independent from another USP11-HR activity, the deubiquitylation of PALB2. We also show that PRMT1 is a ubiquitylated protein that it is targeted for deubiquitylation by USP11, which regulates the ability of PRMT1 to bind to and methylate MRE11. Taken together, our findings reveal a specific role for USP11 during the early stages of DSB repair, which is mediated through its ability to regulate the activity of the PRMT1-MRE11 pathway.


Cardiopulmonary outcomes following high flow nasal cannula in pediatric population: A systematic review.
The high-flow nasal cannula (HFNC) has received much attention in various clinical settings and has been approved recently for application in pediatric care. To determine whether HFNC use improves cardiopulmonary outcomes in pediatric patients with the cardiac disease more effectively than alternative oxygen therapies. Systematic review was performed using PubMed, Scopus, and Web of Science databases. Randomized controlled trials comparing HFNC with alternative oxygen therapies and observational studies that solely reported on the use of HFNC in the pediatric population were included between 2012 and 2022. Nine studies with approximately 656 patients were reported in this review. HFNC significantly increased systemic oxygen saturation across all literature investigating this parameter. Other notable outcomes in HFNC patients included normalizing heart rate, partial blood pressure, and PaO2/FiO2 ratio. However, some studies reported a complication rate concurrent with traditional oxygen therapies, and a suggested HFNC failure rate of 50% was observed. Compared with traditional oxygen therapies, HFNC can reduce anatomical dead space and normalize systemic oxygen saturation, PaO2/FiO2 ratio, heart rate, and partial blood pressure. We advocate using HFNC therapy in children with cardiac diseases as the currently available evidence supports HFNC use over other oxygenation treatments in the pediatric population.


Discontinuation of biologic therapy in patients with rheumatoid arthritis and ankylosing spondylitis: analysis from multicenter cohort study.
Despite of the availability of several effective bDMARDs, a significant proportion of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients discontinued bDMARDs. The aims of this study were to analyze causes of bDMARDs discontinuation in RA and AS included in the Moroccan registry RBSMR. A historical prospective multicenter cohort study based on the RBSMR database at 12 months of follow-up, which included 225 RA and 170 AS. Using T student, Mann-Whitney U, chi-squared or Fischer exact tests, baseline demographic and clinical features were compared between patients discontinuing bDMARDs and patients remaining on initiated bDMARDs or switching bDMARDs. Logistic regression models were used to identify factors associated with drugs discontinuation. 61 RA discontinued bDMARDs and 47 AS interrupted anti-TNF. The most common reasons for drugs discontinuation were adverse events (7.5%) in RA patients and social security reimbursement problems (16.8%) in AS. RA patients discontinuing bDMARDs were more frequently first-line biological drugs users, more frequently female and had more comorbidities and lower DAS28 CRP than RA patients remaining on initiated bDMARDs or switching bDMARDs (p < 0.001, p = 0.01, p < 0.001 and p < 0.001 respectively). Female sex and comorbidities were the significant predictors of bDMARDs discontinuation in RA patients. Higher baseline BASDAI had a protective role on anti-TNF interruption in AS patients. Adverse events and social security reimbursement problems were the main reasons for drugs discontinuation in RA and AS patients respectively. Female sex and comorbidities in RA patients, baseline BASDAI in AS patients impacted bDMARDs discontinuation in real-life settings.


Mind-body therapies for older adults with dementia: a systematic review and meta-analysis.
This systematic review of randomised controlled trials (RCTs) aimed to determine the effects of mind-body therapies (MBTs) among older adults with dementia. We searched five electronic databases (PubMed, PsycINFO, Web of Science, EMBASE, and the Cochrane Library) for publications investigating the effect of MBTs until July 14th, 2020. We included published peer-reviewed RCTs among participants with a mean age of 60 and above and a diagnosis of any dementia. Eligible studies included measurements for all types of health outcomes, including cognitive function, neuropsychiatric inventory, depressive syndromes, agitation, psychosocial status, and other health outcomes. Two investigators extracted data, the risk of bias for each study was evaluated through Review Manager, and statistical meta-analysis was performed using Stata. A total of nine studies met the eligibility criteria, with full-text available for systematic review. Five of them, with 338 participants, were included in the meta-analysis. For most included RCTs of the review, the methodological quality was moderate. The meta-analysis showed that Tai Chi had a mild effect on global cognitive function (Mini-Mental State Examination, SMD = 0.40, 95% CI 0.10-0.70). Yoga and aromatherapy may also be beneficial for depression, and these three MBTs improved quality of life. The current review suggested that MBTs may act as potential non-pharmaceutical approaches to improve certain health outcomes among older populations with dementia. Systematic review and meta-analysis registration: PROSPERO CRD42021198514.


Closing-in behaviour and motor distractibility.
This study relates two behaviours, each well documented within its own literature but not previously considered together: closing-in behaviour (CIB) and the effect of visual distractors on reaching. CIB is common in typically developing children, and in adults with dementia, and classically manifests as the tendency to perform graphic copying tasks very close to, or on the top of the model. The effect of visual distractors on reaching has been studied extensively in normal adults. Distractors induce characteristic deviations of the reach, usually away from the distractor, which imply that a competing response towards the distractor is automatically primed, and actively suppressed. It is possible that CIB reflects a failure to inhibit motor distraction, such that the acting hand is attracted automatically to a salient stimulus (the model, during copying tasks). This hypothesis predicts that CIB should be associated with distractor effects during reaching, characterised by veering towards, rather than away from the distractor. We tested this prediction in groups of pre-school children with and without CIB, and in young adults, using task-relevant and task-irrelevant distractors. Both groups of children showed greater veering towards distractors than did adults, implying a lower capacity to inhibit automatic responses. Crucially, this effect was stronger in children with CIB than without CIB when a task-irrelevant distractor was presented. These findings support the idea that CIB reflects a failure to inhibit automatically primed actions towards salient stimuli.


RAPID--a new method for fast imaging using a single slice of Z-magnetization.
A single slice of z-magnetization is used to generate high-speed images. The slice selection step is achieved using two sin-sinc pulses. This procedure eliminates the need for continual slice gradient reversal, a requirement for the FLASH technique. The RAPID imaging method has less inherent T1 and/or T2 dependence than current fast imaging methods and is more sensitive.


Prognostic Impact of Palliative Primary Tumor Resection for Unresectable Stage 4 Colorectal Cancer: Using a Propensity Score Analysis.
The benefits that palliative resection of the primary tumor offers patients with unresectable stage 4 colorectal cancer, specifically with regard to overall survival, are controversial, and the issue is complicated by marked differences in patient backgrounds and characteristics. The study enrolled 770 consecutive patients with unresectable stage 4 colorectal cancer referred to the divisions of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1997 to 2013. Of these patients, 429 (56 %) underwent palliative resection of the primary tumor, whereas 341 (44 %) did not. To lessen the effects of confounding factors between the groups, including age, year, severe symptoms, number of organs involved by metastases, primary tumor site, and carcinoembryonic antigen (CEA) value, propensity score analyses were used for regression adjustment, stratification, and matching, with overall survival as the primary end point. The regression adjustment including the propensity score as a linear predictor in the model showed that palliative resection was associated with a significantly improved overall survival (hazard ratio [HR] 0.60; 95 % confidence interval [CI] 0.50-0.71; p < 0.01)]. Stratification analysis showed that in all five strata, palliative resection was associated with better overall survival (HR 0.43-0.73). Similarly, the propensity score-matched cohort (267 matched pairs) yielded an HR of 0.58 (95 % CI 0.48-0.70; p < 0.01). The findings suggest that palliative resection of the primary tumor may be associated with improved overall survival. Further investigations such as prospective randomized trials are needed to confirm this result.


On the free radical scavenging and metallic ion chelating activities of pyridoxal - Could the pro-oxidant risk be competitive?
Primary and secondary antioxidant activities of pyridoxal have been investigated by using density functional theory (DFT) at the M05-2X level combined with 6-311++G(d,p) basis set for non-metallic atoms and LanL2DZ for metallic ions. The former has been examined by its free radical scavenging activity towards HOO●, HO●, and NO2●via different mechanisms including formal hydrogen transfer (FHT), proton transfer (PT), single electron transfer (SET), and radical adduct formation (RAF). The latter has been accomplished through its transition metal-chelating ability with Fe(III)/Fe(II) and Cu(II)/Cu(I) ions. The results show that pyridoxal illustrates as an efficient radical scavenger, especially, for HO● and NO2● in water. The overall rate constants (koverall) for the reactions with HOO●, HO●, and NO2● radicals are 1.30 × 104, 5.76 × 109, and 1.43 × 109 M-1s-1, respectively. The SET from the anionic state is the most dominant for the HOO● and NO2● scavenging reactions, while both RAF and SET contribute largely to the reaction with highly reactive HO● radicals. Moreover, the anionic form of pyridoxal demonstrates a better role as a metal chelator than the neutral. However, the pro-oxidant risks of the formed complexes could be observed if there are superoxide radical anion (O2●-) and ascorbate (Asc-) in aqueous media.


Distinct profiles of functional discrimination among G proteins determine the actions of G protein-coupled receptors.
Members of the heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) family play key roles in many physiological functions and are extensively exploited pharmacologically to treat diseases. Many of the diverse effects of individual GPCRs on cellular physiology are transduced by heterotrimeric G proteins, which are composed of α, β, and γ subunits. GPCRs interact with and stimulate the binding of guanosine triphosphate (GTP) to the α subunit to initiate signaling. Mammalian genomes encode 16 different G protein α subunits, each one of which has distinct properties. We developed a single-platform, optical strategy to monitor G protein activation in live cells. With this system, we profiled the coupling ability of individual GPCRs for different α subunits, simultaneously quantifying the magnitude of the signal and the rates at which the receptors activated the G proteins. We found that individual receptors engaged multiple G proteins with varying efficacy and kinetics, generating fingerprint-like profiles. Different classes of GPCR ligands, including full and partial agonists, allosteric modulators, and antagonists, distinctly affected these fingerprints to functionally bias GPCR signaling. Finally, we showed that intracellular signaling modulators further altered the G protein-coupling profiles of GPCRs, which suggests that their differential abundance may alter signaling outcomes in a cell-specific manner. These observations suggest that the diversity of the effects of GPCRs on cellular physiology may be determined by their differential engagement of multiple G proteins, coupling to which produces signals with varying signal magnitudes and activation kinetics, properties that may be exploited pharmacologically.


Comparison of survival outcomes after CyberKnife® radiotherapy in Taiwan using preapproved insurance-based reimbursement versus out-of-pocket expenditure.
With technological advances, radiotherapy has progressed from simple irradiation to robotic arm-based stereotactic radiosurgery systems (SRS, in this case, CyberKnife®). This equipment is high-priced and might be cost-effective or not. The National Health Insurance (NHI) in Taiwan has a premedical claims review process for approving CyberKnife® treatment; however, patients might have to pay for the procedure themselves if the NHI rejects the practice. Under the high treatment cost and such an insurance system, a sketch of patients treated by these high-cost machines and whether the prereview of insurance for reimbursement is reasonable without hindering the patient's right to undergo treatment should be investigated. In this study, the patients of CyberKnife® radiotherapy in our institute were investigated as an example for this purpose. Patients who underwent CyberKnife® radiotherapy in our department were investigated retrospectively. Their demographic characteristics, disease patterns, and treatment sites were analyzed. Survivals were compared according to clinical features, and treatment expenses were reimbursed after prereview or out-of-pocket. From October 19, 2014, to January 30, 2018, there were 331 patients included in this study, 205 (55.3%) of whom underwent CyberKnife® radiotherapy at their own expense, while 166 (44.7%) had their expenses approved for reimbursement after prereview by NHI. Most patients were treated for metastatic tumors (37.5%), and the brain was the most frequent treatment site (46.1%). The 1-year overall survival was 67.1%, and the 2-year overall survival was 56.3% after CyberKinfe® radiotherapy. The best survival rate (96.8% at 1 year) was for patients with brain tumors. In patient's characteristics, A better Eastern Cooperative Oncology Group (ECOG) performance status, treatment for primary tumors, and outpatient treatment were independent factors for superior survival after CyberKnife® radiotherapy. The survivals for patients whose treatment expenses were approved for reimbursement after prereview by NHI were also better than out-of-pocket. Besides the patients' characteristics, the treatment expense could be approved or rejected for reimbursement by the NHI prereview was an independent factor for survival in CyberKnife® radiotherapy. Prereview to reimburse expensive treatment is not an unreasonable requirement.


Splicing Factor Mutations in Cancer.
Many cancers demonstrate aberrant splicing patterns that contribute to their development and progression. Recently, recurrent somatic mutations of genes encoding core subunits of the spliceosome have been identified in several different cancer types. These mutations are most common in hematologic malignancies like the myelodysplastic syndromes (MDS), acute myeloid leukemia, and chronic lymphocytic leukemia, but also in occur in several solid tumors at lower frequency. The most frequent mutations occur in SF3B1, U2AF1, SRSF2, and ZRSR2 and are largely exclusive of each other. Mutations in SF3B1, U2AF1, and SRSF2 acquire heterozygous missense mutations in specific codons, resembling oncogenes. ZRSR2 mutations include clear loss-of-function variants, a pattern more common to tumor suppressor genes. These splicing factors are associated with distinct clinical phenotypes and patterns of mutation in different malignancies. Mutations have both diagnostic and prognostic relevance. Splicing factor mutations appear to affect only a minority of transcripts which show little overlap by mutation type. How differences in splicing caused by somatic mutations of spliceosome subunits lead to oncogenesis is not clear and may involve different targets in each disease type. However, cells with mutated splicing machinery may be particularly vulnerable to further disruption of the spliceosome suggesting a novel strategy for the targeted therapy of cancers.


Homing in on homeostatic plasticity.
In this issue of Neuron, Orr et al.1 demonstrate a detailed molecular cascade that drives presynaptic homeostatic plasticity and enhances presynaptic vesicle fusion in response to reduced postsynaptic activity. Two large presynaptic signaling complexes are central hubs.


[Comparative evaluation of the informativeness of computed serial renoscintigraphy and excretory urography in uterine cancer].
Computerized serial renoscintigraphy and excretory urography were carried out in 112 patients with uterine carcinoma. It was found that, in diagnosis of pathology of the urinary system, the effectiveness of radionephrologic procedure is higher than that of intravenous urography (31.7 and 27.6%, respectively). Also, computerized serial renoscintigraphy proved to be an objective means of assessing the recovery of urinary system function at various stages after therapy. Moreover, nephroscintigraphy plays an important role in timely detection of recurrences.


[The multidimensional geriatric assessment].
This review presents comprehensive geriatric assessment as a diagnostic process in steps: step 1-geriatric screening for purposes of case finding, step 2-basic geriatric assessment, step 3-extended problem-centred assessment. The article specifies situations in which comprehensive geriatric assessment is recommended and when not, as well as the vital risk situations for geriatric patients and the respective appropriate assessment tools. The goal of the process is a clear overview of the specific resources and deficits of the elderly patient. The results provide a basis for rational individual decision-making in various medical issues.


PulseCath, a new short-term ventricular assist device: our experience in off-pump coronary artery bypass graft surgery.
We utilized a new ventricular assist device, the PulseCath catheter, to perform an off-pump bypass procedure in a patient with low ejection fraction. The 21 Fr PulseCath catheter, driven by a standard intra-aortic balloon pump console, can generate a pulsatile flow of 2-3 l/min. The PulseCath coupled with an intra-aortic balloon pump device is an important tool for left ventricular assistance.


Dunning-Kruger effect and flat-earthers: An exploratory analysis.
This article aims to analyze the factors influencing belief in a flat Earth. We focus on Spain, a country that sadly has some of the most relevant figures on this topic in the Spanish-speaking world. After a qualitative analysis of YouTube videos on the main channels on the subject, a survey was carried out on 1252 individuals. The results point to two conclusions. First is the presence of a considerable Dunning-Kruger effect among flat-earthers. There is a significant negative correlation between science literacy-overall and practically all its dimensions-and overconfidence in science in this group. The second, evaluated through a regression tree, confirms that the interaction of low scientific literacy and overconfidence is highly relevant in explaining the belief in a flat earth. Neither factor alone is determinant, but the combination of the two (low scientific literacy and high overconfidence) leads to high levels of flat earth belief.


Acyl-coenzyme A carboxylase of the free-living nematode Turbatrix aceti. 1. Its isolation and molecular characteristics.
A biotin containing enzyme which carboxylates acetyl-CoA has been isolated from the nematode Turbatrix aceti and purified to homogeneity as judged by the criteria of polyacrylamide gel electrophoresis and ultracentrifugation. The enzyme has a sedimentation coefficient of 18.0 S and a molecular weight of 667 000. It is composed of four protomers having a molecular weight of 140 000 each. Each protomer, in turn, consists of two distinct polypeptide chains (molecular weights 82 000 and 58 000) and one biotinyl prosthetic group which is linked to the 82 000 peptide. The amino acid composition of the nematode carboxylase has also been determined.


Factors affecting hepatitis vaccination refusal at a sexually transmitted disease clinic among men who have sex with men.
Men who have sex with men (MSM) attending sexually transmitted disease (STD) clinics should be considered candidates for hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination. However, vaccination rates in STD clinics remain less than optimal. The goal was to identify factors that affect HAV and HBV vaccination refusals. A survey was administered to MSM eligible for the vaccinations attending an STD clinic. Vaccines were offered at the end of the clinic visit. Rates of refusal of HAV (RefuseA) and HBV (RefuseB) vaccinations were 36% and 38%. Health motivation was associated with acceptance, while clinical barriers such as "want to test first for immunity," and "want to talk to own doctor first" were associated with refusal. "Not enough time this evening" was most strongly predictive of refusal, relative to strongly disagree (risk ratios [RRstrongly agree] and 95% confidence limits for RefuseA and RefuseB were 2.69 [1.43, 5.05] and 2.02 [1.05, 3.87], respectively). To increase acceptance, patients less health-motivated should be identified for prevaccination counseling. Some perceived barriers such as time may be a partial excuse; staff should identify and address other perceptions that may be influencing patients' decisions.


Mechanisms of propeller jet-induced migration, release, and distribution of perfluoroalkyl acids in sediment-water systems.
Perfluoroalkyl acids (PFAAs) are continuously accumulated in surface sediments due to extensive and long-term application. However, the mechanisms through which disturbances induced by ship propeller jets at the riverbed cause secondary release of PFAAs from sediments remain unclear. In this study, the effects of different propeller rotational speeds on PFAA migration, release, and distribution in multiphase media were investigated by performing indoor flume experiments combined with particle tracking velocimetry. Moreover, key factors influencing PFAA migration and distribution were identified, and partial least squares regression (PLS) method was applied to develop quantitative prediction models of relationships among hydrodynamics, physicochemical parameters, and PFAA distribution coefficients. The total PFAA concentrations (ΣPFAAs) in overlying water under propeller jet action exhibited transient characteristics and hysteresis with time after the disturbance. In contrast, the ΣPFAAs in suspended particulate matter (SPM) exhibited an upward trend throughout the process with consistent characteristics. The spatial distribution trends of PFAAs in overlying water and SPM at different propeller rotational speeds featured vertical variability and axial consistency. Furthermore, PFAA release from sediments was driven by axial flow velocity (Vx) and Reynolds normal stress Ryy, while PFAA release from porewater was inextricably linked to Reynolds stresses Rxx, Rxy, and Rzz (p < 0.05). PLS regression models showed that variations in Vorticity, dissolved organic carbon, and pH influenced the decreases in PFAA distribution coefficients between SPM and overlying water (KD-SW) as propeller rotational speed increased, except for very long-chain PFAAs (C > 10). The increases in PFAA distribution coefficients between sediment and porewater (KD-SP) were mainly determined by physicochemical parameters of sediments, and the direct effect of hydrodynamics was relatively weak. Our study provides valuable information regarding the migration and distribution of PFAAs in multiphase media under propeller jet disturbance (both during and after disturbance).


Comparative toxicity of green and chemically synthesized CuO NPs during pregnancy and lactation in rats and offspring: Part I -hepatotoxicity.
Widespread applications of nanomaterials in food and health sciences have inevitable toxicological outcomes. Among nanomaterials, copper oxide nanoparticles (CuO NPs) are commonly used in all fields due to its distinctive characteristics. The study was designed to investigate the comparative hepatotoxic effect of green (GNPs) and chemically synthesized (CNPs) CuO NPs on spargue-dawely rats and their offspring. NPs (50 and 100 mg/kg) were orally administered to rats twice a week starting before mating. After birth the parents were continued dosing while pups were only on mother feed. Antioxidant, lipid peroxidation, genotoxicity, and histology were performed on liver tissue. In addition serum biochemistry of parents and offspring was also performed. The levels of catalase, peroxidase, and glutathione were significantly lowered only in CNPs treated parents while lipid peroxidation level was increased in these groups. Maximum genotoxicity (2.3%) in terms of percent tail DNA was observed in parent rats administered with high CNPs dose while other groups did not exhibit significant variation in genetoxic parameters. Gender and dose dependent effects were observed on liver function tests especially ALP and ALT in parents however no obvious differences were observed in offspring. Furthermore, dose dependent dilation and congestion of sinusoids was observed on CNPs administration. In GNPs treated rats and offspring histological alterations were observed. The study concludes that chemically synthesized CuO NPs exhibit dose dependent toxic effects on liver as compared to green synthesized CuO NPs. Furthermore lactation does not play significant role in the hepatotoxicity of offspring though minor oxidative stress was observed only on CNPs administration. The study also shows that pharmacological application of green synthesized NPs can be accomplished due to their biocompatible nature.


Influence of elevated carbon dioxide and temperature on belowground carbon allocation and enzyme activities in tropical flooded soil planted with rice.
Changes in the soil labile carbon fractions and soil biochemical properties to elevated carbon dioxide (CO2) and temperature reflect the changes in the functional capacity of soil ecosystems. The belowground root system and root-derived carbon products are the key factors for the rhizospheric carbon dynamics under elevated CO2 condition. However, the relationship between interactive effects of elevated CO2 and temperature on belowground soil carbon accrual is not very clear. To address this issue, a field experiment was laid out to study the changes of carbon allocation in tropical rice soil (Aeric Endoaquept) under elevated CO2 and elevated CO2 + elevated temperature conditions in open top chambers (OTCs). There were significant increase of root biomass by 39 and 44 % under elevated CO2 and elevated CO2 + temperature compared to ambient condition, respectively. A significant increase (55 %) of total organic carbon in the root exudates under elevated CO2 + temperature was noticed. Carbon dioxide enrichment associated with elevated temperature significantly increased soil labile carbon, microbial biomass carbon, and activities of carbon-transforming enzyme like β-glucosidase. Highly significant correlations were noticed among the different soil enzymes and soil labile carbon fractions.