Proptosis and diplopia following traumatic asphyxia.
We describe a previously unreported complication of traumatic asphyxia. An 11-year-old boy developed proptosis and diplopia following a crush injury in an automatic garage door. Computed tomography scan confirmed displacement of the eye. There was no retrobulbar hemorrhage or skull fracture, and the proptosis appeared secondary to traumatic displacement of orbital fat. Proptosis and diplopia resolved completely over six weeks. Visual disorders may be overlooked as a complication of trauma.


Advanced Ventilation and Monitoring During Helicopter Hoist Extraction of an Intubated Patient.
The intubated and ventilated patient in austere and inaccessible environments requiring helicopter hoist extraction presents significant procedural and logistical challenges. This case report describes the use of a mechanical ventilator and visible advanced monitoring throughout the entirety of the patient journey from the prehospital scene to the hospital, including the period during hoist extraction as human external cargo.


Antigen presentation by liposomes as model system for T-B cell interaction.
Using the earlier established liposome system for antigen presentation, in which liposomes bearing major histocompatibility complex (MHC)-class II molecules inserted into and protein antigen covalently linked to the membrane were found to be sufficient for an antigen-specific and MHC-restricted activation of T cells, the minimal requirements for T-B cell interaction were investigated. Liposomes carrying MHC class II molecules and antigen-specific monoclonal antibodies were constructed and tested for their ability to present soluble antigen to T cells. With the antigens lactate dehydrogenase B and pigeon cytochrome c, a specific stimulation of T cell clones and hybridomas could be obtained. These results demonstrate the possibility of a direct involvement of the immunoglobulins on the B cell surface in their interaction with T cells.


Staphylococcus xylosus and Staphylococcus aureus as commensals and pathogens on murine skin.
Skin ulcers, skin dermatitis and skin infections are common phenomena in colonies of laboratory mice and are often found at increased prevalence in certain immunocompromised strains. While in many cases these skin conditions are mild, in other cases they can be severe and lead to animal morbidity. Furthermore, the presence of skin infections and ulcerations can complicate the interpretation of experimental protocols, including those examining immune cell activation. Bacterial species in the genus Staphylococcus are the most common pathogens recovered from skin lesions in mice. In particular, Staphylococcus aureus and Staphylococcus xylosus have both been implicated as pathogens on murine skin. Staphylococcus aureus is a well-known pathogen of human skin, but S. xylosus skin infections in humans have not been described, indicating that there is a species-specific difference in the ability of S. xylosus to serve as a skin pathogen. The aim of this review is to summarize studies that link S. aureus and S. xylosus to skin infections of mice and to describe factors involved in their adherence to tissue and their virulence. We discuss potential differences in mouse and human skin that might underlie the ability of S. xylosus to act as a pathogen on murine skin, but not human skin. Finally, we also describe mouse mutants that have shown increased susceptibility to skin infections with staphylococcal bacteria. These mutants point to pathways that are important in the control of commensal staphylococcal bacteria. The information here may be useful to researchers who are working with mouse strains that are prone to skin infections with staphylococcal bacteria.


Partially Resorbable Mesh Inclusion between Dissected Layers during Surgical Repair of Aortic Dissection.
Surgical management of aortic dissection is technically challenging for different reasons. Reapproximation of dissected layers because of fragility of the dissected aortic wall layers is of major concern. Many techniques have been described to restore the integrity of aortic wall. Inclusion of a partially resorbable mesh fixed with glue, between the dissected layers, may be a simple and effective method for providing a secure and viable end-to-end anastomosis between aortic stump and a Dacron graft.


Robotic-Assisted Spinal Surgery: Current Generation Instrumentation and New Applications.
In contrast to other surgical fields, robotics is relatively new to spinal surgery. The initial focus for spinal robotics has been on accurate pedicle screw placement, which early studies have shown to be successful. Beyond pedicle screw placement, however, newer generation spinal robots have the capability of navigation, which can impact other aspects of a spinal procedure. In this study, pedicle screw placement with the recently introduced Excelsius GPS robot (Globus) was similarly found to be accurate in a cohort of patients undergoing both open and minimally invasive fusion. Potential applications of the spinal robot's navigation capability are demonstrated.


Hypertonic (3%) saline vs 0.93% saline nebulization for acute viral bronchiolitis: a randomized controlled trial.
To compare the length of hospital stay (primary) and improvement in clinical severity scores (secondary) among children with bronchiolitis nebulized with 3 % hypertonic saline or 0.9% saline. Randomized double blind controlled trial. Tertiary care teaching hospital. Hospitalized children (1-24 months) with acute bronchiolitis of moderate severity. Nebulization of 4 ml of 3% hypertonic saline or 4 mL of 0.9% saline, along with 2.5 mg salbutamol, at 4-hourly intervals till the patient was ready for discharge. Baseline characteristics were similar in two groups. Median clinical severity score at admission was 6 (IQR-1) in both the groups. Clinical severity scores monitored afterwards 12-hourly till discharge (132 h) did not show statistically significant differences in 3% and 0.9% saline groups. Mean length of hospital stay (time to reach predefined clinical severity score<3) was 63.93 ± 22.43 h in 3% saline group and 63.51 ± 21.27 h in 0.9% saline group (P=0.878). No adverse events were reported by the parents, caregivers or treating medical attendants in both groups. Nebulized 3 % saline is not superior to 0.9% saline in infants with clinically diagnosed acute bronchiolitis.


Estimation of the accessory pathway location of the manifest Wolf-Parkinson-White syndrome using synthesized right-sided chest leads.
The classification using QRS morphology of V1 lead is a useful simple predictor of accessory pathway location (type A, R or Rs pattern; type B, rS pattern; type C, QS or Qr pattern), but often leads to misdiagnosis of accessory pathway location, especially in types B and C. The synthesized 18-lead electrocardiography (ECG) derived from standard 12-lead ECG can provide virtual waveforms of right-sided chest leads. This study aimed to evaluate the usefulness of the right-sided chest lead ECG for prediction of accessory pathway location. This retrospective study included 44 patients in whom successful ablation of manifest Wolff-Parkinson-White (WPW) syndrome was performed. Synthesized ECG waveforms were automatically generated, and ECG data obtained before the procedure. There were 26, 4, and 14 patients with left, right, and septal accessory pathways, respectively. All left accessory pathway cases have type A in V1 and syn-V4R leads. Of the 4 right accessory pathway cases, 2 have type B in V1 and syn-V4R leads. Other 2 of 4 cases have type C. In V1 lead, 5 of 14 septal accessory pathway cases have type C, 7 of 14 cases have type B, and 2 of 14cases have type A. In syn-V4R lead, all 14 septal accessory pathway cases have type C. The QRS morphology of V1 and syn-V4 leads could predict the site of accessory pathway with overall accuracy of 79% and 95%, respectively. QRS morphology of syn-V4R lead may be useful for predicting accessory pathway location of manifest WPW syndrome.


Targeting antioxidative signal transduction and stress response system: control of pathogenic Aspergillus with phenolics that inhibit mitochondrial function.
The aim of this study was to show whether antioxidative response systems are potentially useful molecular targets for control of Aspergillus fumigatus and Aspergillus flavus. Selected phenolic agents are used in target-gene-based bioassays to determine their impact on mitochondrial respiration. Vanillyl acetone, vanillic acid, vanillin, cinnamic acid, veratraldehyde, m-coumaric acid (phenolic agents to which Saccharomyces cerevisiae sod2delta mutant showed sensitivity), carboxin (inhibits complex II of the mitochondrial respiratory chain), strobilurins/antimycin A (inhibits complex III of the mitochondrial respiratory chain) and fludioxonil/fenpiclonil [antifungals potentiated by mitogen-activated protein kinase (MAPK)] were examined in A. fumigatus, A. flavus and S. cerevisiae. Individual or combined application of phenolics with inhibitors of mitochondrial respiration showed some of the phenolics effectively inhibited fungal growth. Target-gene bioassays were performed using a sakAdelta (MAPK deletion) strain of A. fumigatus and a complementation analysis using the mitochondrial superoxide dismutase (Mn-SOD) gene (sodA) of A. flavus in the ortholog mutant, sod2delta, of S. cerevisiae. The results demonstrated that mitochondrial antioxidative stress system plays important roles in fungal response to antifungal agents tested. Antioxidative response systems of fungi can be an efficient molecular target of phenolics for pathogen control. Combined application of phenolics with inhibitors of mitochondrial respiration can effectively suppress the growth of fungi. Natural compounds that do not pose any significant medical or environmental risks could serve as useful alternatives or additives to conventional antifungals. Identifying the antioxidative response systems in other pathogens could improve methods for fungal control.


Taste-dependent sociophobia: when food and company do not mix.
Using a combination of the paradigm of conditioned taste aversion (CTA) and of the paradigm of social interactions, we report here that in the rat, eating while anxious may result in long-term alterations in social behavior. In the conventional CTA, the subject learns to associate a tastant (the conditioned stimulus, CS) with delayed toxicosis (an unconditioned stimulus, UCS) to yield taste aversion (the conditioned response, CR). However, the association of taste with delayed negative internal states that could generate CRs that are different from taste aversion should not be neglected. Such associations may contribute to the ontogenesis, reinforcement and symptoms of some types of taste- and food-related disorders. We have recently reported that a delayed anxiety-like state, induced by the anxiogenic drug meta-chlorophenylpiperazine (mCPP), can specifically associate with taste to produce CTA. We now show that a similar protocol results in a marked lingering impairment in social interactions in response to the conditioned taste. This is hence a learned situation in which food and company do not mix well.


Juvenile myoclonic epilepsy and human leukocyte antigens.
The idiopathic generalized epilepsies (IGE) occur with a high aggregation within families. Juvenile myoclonic epilepsy (JME) is recognized as a commonly occurring form of idiopathic generalized epilepsy. A possible association between JME and HLA antigens was investigated by serological typing of human leukocyte antigens (HLA) class I antigens and by DNA oligotyping of class II antigens. Twenty-four patients and 129 controls, all Caucasians of Scandinavian descent, were tested. Uncorrected there was a significant positive association (Relative risk (RR) = 8.07) to B17 and a significant negative association (RR = 0.13) to B8 as well as DRB1*3. The negative association to DQ alleles DQA1*0501 and DQB1*0201, which are in strong linkage disequilibrium with the alleles B8 and DRB1*3, was weaker and not significant, thus giving no clue as to a primary HLA-DQ association of JME.


A new species of Amalothrips Ananthakhrishnan from Malaysia, with first description of male.
Amalothrips noorazlani sp. n. is described from Malaysia based on both sexes, and a key is provided to the species of this genus. This is the first record of Amalothrips species outside India, and the first description of a male Amalothrips. The male has a pair of drepanae, the tergal posteromargin bears a toothed craspedum, but there are no sternal pore plates.


Distribution of immunoreactive adenohypophysial cell types in the pituitaries of the Atlantic and the Pacific hagfish, Myxine glutinosa and Eptatretus burgeri.
The hagfish is considered the most primitive vertebrate known, living or extinct. It remains an enigma whether adenohypophysial hormones similar to those of more advanced vertebrates are present in the hagfish pituitary gland or not. The present study aimed to detect immunoreactive adenohypophysial hormones in the hagfish pituitary gland, using antisera to tetrapod and fish adenohypophysial hormones as immunohistochemical probes. For this purpose, two species of hagfish, the Atlantic hagfish, Myxine glutinosa, and the Pacific hagfish, Eptatretus burgeri, were used. In both species, three different types of immunoreactive cells were detected in the adenohypophysis. (1) The first type of cells was gonadotropin (GTH)-like cells which were stained by antisera to LH-related GTHs, such as ovine LHbeta, human LHbeta, bullfrog LH, salmon LHbeta and sturgeon LHbeta in both species of hagfish. (2) The second type of cells that were detected was growth hormone (GH)/prolactin (PRL)-like cells. In M. glutinosa the cells were stained by antisera to salmon GH, salmon PRL, sturgeon GH, sturgeon PRL, blue shark GH, and lamprey GH. In E. burgeri the cells were only stained by anti-human GH and anti-sturgeon PRL. (3) The last type of cells was adrenocorticotropin (ACTH)-like cells. These cells were stained by antisera to lamprey ACTH and human beta-endorphin. In both species of hagfish, GTH-like cells were relatively abundant, and were distributed throughout the adenohypophysis, whereas GH/PRL-like and ACTH-like cells were few in number in the adenohypophysis. Based on these findings, we suggest that hagfish may have retained ancestral characteristics of key anterior pituitary hormones.


The E.A.E.S. Consensus Development Conferences on laparoscopic cholecystectomy, appendectomy, and hernia repair. Consensus statements--September 1994. The Educational Committee of the European Association for Endoscopic Surgery.
Under the mandate of the Educational Committee of the European Association of Endoscopic Surgery (E.A.E.S.), three consensus development conferences (CDCs) were performed in order to assess the current status of the endoscopic surgical approaches for the treatment of cholelithiasis, appendicitis, and inguinal hernia. Consensus panels for the different disease states (10-13 members each) selected by the education committee on the basis of members' clinical expertise, academic activity, community influence, and geographical location weighed the evidence on the basis of published results according to the criteria for technology assessment: feasibility, efficacy, effectiveness, economy. Draft statements were prepared, discussed by the panels, and presented at plenary sessions of the 2nd European Congress of the E.A.E.S. in Madrid September 15-17, 1994. Following discussions final consensus statements were formulated to provide specific answers for each topic to a minimum of the following questions: 1. What stage of technological development is the endoscopic surgical procedure at (in September 1994)? 2. Is endoscopic surgery safe and feasible? 3. Is it beneficial to the patients? 4. Who should undergo endoscopic surgery? 5. What are the training recommendations? Laparoscopic cholecystectomy is the procedure of choice for symptomatic cholelithiasis. Laparoscopic appendectomy is presently at the efficacy stage of development, because most of the data on feasibility and safety originate from centers with special interest in endoscopic surgery: it is not yet the gold standard for acute appendicitis. Endoscopic hernia repair is presently a feasible alternative for conventional hernia repair if performed by experienced endoscopic surgeons. It appears to be efficacious in the short-term. The full text of the consensus panel's statements is given in this publication.


[Treatment of toxic hepatitis in COVID-19 patients].
The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented. The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19. On the basis of the newly created infection centers of the Central Clinical Hospital "RZhD-Medicine" and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy. On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower - 122 (55.2%) and 134 (58.8%); p<0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients. The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.


Porphyrin-functionalized porous polysulfone membrane towards an optical sensor membrane for sorption and detection of cadmium(II).
In this study, an optical sensor membrane was prepared for sorption and detection of cadmium(II) (Cd(II)) in aqueous solution. A polyanion, poly(sodium 4-styrenesulfonate) (PNaSS), was grafted onto the chloromethylated polysulfone (CMPSF) microporous membrane via surface-initiated ATRP. 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin p-toluenesulfonate (TMPyP) was immobilized onto the PNaSS-grafted polysulfone (PSF-PNaSS) membrane through electrostatic interaction. The TMPyP-functionalized membrane exhibited an enhanced sorption for, and distinct color and spectral response to cadmium(II) (Cd(II)) in aqueous solution. Larger immobilization capacity of TMPyP on the membrane led to stronger sorption for Cd(II), and smaller one made the optical sensor have a faster (in minutes) and more sensitive response to the ion. The detection limit study indicated that the functional membrane with proper amount of TMPyP (<0.5 mg/g) could still have color and spectral response to Cd(II) solutions at an extreme low concentration (10(-4) mg/L). The optical sensor membrane exhibited good stability and reusability which made it efficient for various sorptive removal and detection applications.


Molecular-field-based three-dimensional similarity studies on quinoline-based CNS active agents.
A series of quinoline-based agents with CNS activity have been analyzed for their three-dimensional similarity with respect to a set of standard atypical antipsychotics. The method aligns the molecules based on their molecular fields represented as local extrema of electrostatic, van der Waals, and hydrophobic potentials of the molecule termed "field points." The compounds in the series were found to demonstrate relatively lesser 3D similarity to the dibenzodiazepine derivative clozapine. Similarity values were higher with respect to extended chain compounds ketanserin, ziprasidone, and risperidone. The results obtained were found to agree with the physicochemical similarity of the compounds reported earlier.


Identification and separation of normal hematopoietic stem cells and leukemia stem cells from patients with acute myeloid leukemia.
Mounting evidences indicate that leukemic cells in patients with acute myeloid leukemia (AML) are derived from leukemia stem cells (LSC). In analogy to normal hematopoietic stem cells (HSC), LSC remain mostly dormant and are hence resistant to conventional chemotherapy. Residual, physiological HSC exist alongside with LSC, with heterogeneous dominance of LSC over HSC in individual patients. We have devised a flow cytometric method for the identification and separation of these two stem cell populations based on surface antigen markers such as CD34, CD38, lineage aberrant markers, and aldehyde dehydrogenase (ALDH) enzyme activity.


Kindler syndrome.
Kindler syndrome is a rare, autosomal recessive skin fragility disorder characterized by blistering in infancy, followed by photosensitivity and progressive poikiloderma. Ultrastructural examination reveals marked basement membrane reduplication and variable levels of cleavage at the dermal-epidermal junction. The molecular pathology underlying Kindler syndrome has recently been shown to involve loss-of-function mutations in a novel gene, KIND1, encoding kindlin-1. Immunofluorescence, gene expression and cell biology studies have shown that kindlin-1 is expressed mainly in basal keratinocytes and plays a role in the attachment of the actin cytoskeleton via focal contacts to the extracellular matrix. Thus, Kindler syndrome is the first genodermatosis caused by a defect in actin-extracellular matrix linkage rather than the classic keratin-extracellular matrix linkage underlying the pathology of other inherited skin fragility disorders such as epidermolysis bullosa. This article reviews the clinical features as well as the molecular and cellular pathology of Kindler syndrome and highlights the importance of the new protein, kindlin-1, in cell-matrix adhesion and its intriguing link to photosensitivity.


Quantitative analysis of colon perfusion pattern using indocyanine green (ICG) angiography in laparoscopic colorectal surgery.
This study aimed to quantitatively evaluate colon perfusion patterns using indocyanine green (ICG) angiography to find the most reliable predictive factor of anastomotic complications after laparoscopic colorectal surgery. Laparoscopic fluorescence imaging was applied to colorectal cancer patients (n = 86) from July 2015 to December 2017. ICG (0.25 mg/kg) was slowly injected into peripheral blood vessels, and the fluorescence intensity of colonic flow was measured sequentially, producing perfusion graphs using a video analysis and modeling tool. Colon perfusion patterns were categorized as either fast, moderate, or slow based on their fluorescence slope, T1/2MAX and time ratio (TR = T1/2MAX/TMAX). Clinical factors and quantitative perfusion factors were analyzed to identify predictors for anastomotic complications. The mean age of patients was 65.4 years, and the male-to-female ratio was 63:23. Their operations were laparoscopic low anterior resection (55 cases) and anterior resection (31 cases). The incidence of anastomotic complication was 7%, including colonic necrosis (n = 1), anastomotic leak (n = 3), delayed pelvic abscess (n = 1), and delayed anastomotic dehiscence (n = 1). Based on quantitative analysis, the fluorescence slope, T1/2MAX, and TR were related with anastomotic complications. The cut-off value of TR to categorize the perfusion pattern was determined to be 0.6, as shown by ROC curve analysis (AUC 0.929, P < 0.001). Slow perfusion (TR > 0.6) was independent factor for anastomotic complications in a logistic regression model (OR 130.84; 95% CI 6.45-2654.75; P = 0.002). Anastomotic complications were significantly correlated with the novel factor TR (> 0.6) as the most reliable predictor of perfusion and anastomotic complications. Quantitative analysis of ICG perfusion patterns using T1/2MAX and TR can be applied to detect segments with poor perfusion, thereby reducing anastomotic complications during laparoscopic colorectal surgery.


Chondrocyte acting as phagocyte to internalize polyethylene wear particles and leads to the elevations of osteoarthritis associated NO and PGE2.
It remains a mystery about the role of chondrocyte or cartilage on the co-existence of ultra-high molecular weight polyethylene (UHMWPE) wear particles from partial joint arthroplasty. An inverted co-culture system was performed to investigate the interactions between chondrocytes and UHMWPE wear particles. It was first time observed that chondrocytes can engulf UHMWPE particles and release osteoarthritis associated pro-inflammatory factors. TEM observation and flow cytometric analysis demonstrated the phagocytosis of particles by chondrocytes. It was found that polyethylene particles may reduce the viability of chondrocytes, and enhance the secretion of nitric oxide (NO) and PGE(2). In conclusion, all these phenomena may contribute to further cartilage degeneration after partial joint arthroplasty surgery. It is first identified in this study that the chondrocyte acts as phagocyte to internalize wear particles and leads to the elevations of precursor mediators of osteoarthritis.


Sign iconicity: single-sign receptive vocabulary skills of nonsigning hearing preschoolers.
This study examined hearing preschoolers' ability to use iconic cues to comprehend signs. Twelve nonsigning 3-year-old hearing children served as subjects. Scores obtained from oral presentations of the Peabody Picture Vocabulary Test--Revised (PPVT-R) were compared with the scores obtained from the manual (signed) presentations of the PPVT-R. Results suggest that even in a limited choice context, the resemblance of signs to their referents does not enable hearing children to decipher the meaning of most of the presented signs. Discussion focuses on the relevance of these findings to the selection and use of adapted assessment instruments with young hearing-impaired children.


Coronavirus Disease: Subacute to Chronic Neuroimaging Findings.
Several neurologic disorders are associated with coronavirus disease 2019 (COVID-19). In this article, clinical syndromes typically occurring in the subacute to chronic phase of illness and their neuroimaging findings are described with discussion of their COVID-19 specific features and prognosis. Proposed pathogenic mechanisms of these neuroimaging findings and challenges in determining etiology are reviewed.


The stability of thiamine in total parenteral nutrition mixtures stored in EVA and multi-layered bags.
The compounding of complete total parenteral nutrition (TPN) mixtures into big bags with extended shelf-lives has been made more possible by the introduction of reduced gas permeable bags, using multi-layered plastic laminates. Since this produces a highly reduced chemical environment, the stability of thiamine; which degrades by reduction, may be compromised. It was the purpose of this study to investigate the degradation of thiamine at two different concentrations in TPN mixtures containing different commercial amino acid sources stored for extended periods in EVA or multi-layered bags. Results indicated that thiamine was unstable in mixtures containing Freamine III 8.5%, a metabisulphite-containing amino acid infusion, but was relatively stable in mixtures containing Vamin 14, Aminoplex 12 or Eloamin 15% as the amino acid source. Degradation of thiamine in Freamine III 8.5%-containing mixtures stored in multi-layered bags was more rapid than in EVA bags. Degradation rate was not greatly influenced by thiamine concentration. Results indicate that thiamine is stable in complete TPN mixtures for periods of at least 28 days in multi-layered bags, provided metabisulphite containing amino acid infusions are avoided. The shelf-life of complete mixtures containing Freamine III should be restricted to ensure patient receive minimum acceptable daily thiamine requirements.


Nonlinear optical molecular switches as selective cation sensors.
This work demonstrates that the recognition of cations by molecular switches can give rise to large contrasts of the second-order nonlinear optical (NLO) properties, which can therefore be used as a powerful and multi-usage detection tool. The proof of concept is given by evidencing, by means of ab initio calculations, the ability of spiropyran/merocyanine systems to selectively detect alkali, alkaline earth, and transition-metal cations.


Transcriptional expression analysis of ABC efflux transporters and xenobiotic-metabolizing enzymes in the Chinese rare minnow.
In the present study, the cDNA fragments of five ABC transporter genes (ABCB1, ABCB11, ABCC1, ABCC2, and ABCG2) in the rare minnow were cloned, and their tissue-specific expression patterns were evaluated across eight rare minnow tissues (liver, gill, intestine, kidney, spleen, brain, skin, and muscle). Furthermore, the transcriptional effects on these ABC transporter genes and five xenobiotic-metabolizing enzyme genes (CYP1A, GSTm, GSTp1, GCLC, and UGT1a) were determined in the rare minnow liver after 12 days of pyrene exposure. Basal expression analysis showed that the tissues with high expression of the ABC transporters included the liver, kidney, and intestine. Moreover, the most highly expressed of the ABC genes were ABCB1 and ABCC2 in all eight of the tissues tested. The ABCB11 gene was almost exclusively expressed in the liver of the rare minnow, whereas ABCC1 and ABCG2 showed weak expression in all eight tissues compared to ABCB1 and ABCC2. Our results provide the first thorough examination of the expression patterns of toxicologically relevant ABC transporters in the rare minnow and serve as a necessary basis for further studies of these ABC transporters in fish. Furthermore, synergistic up-regulation of CYP1A, GSTp1, GCLC, UGT1a, and ABCC2 was observed in the rare minnow liver following pyrene exposure, while GSTm, ABCB1, ABCB11, ABCC1, and ABCG2 were not significantly affected (p < 0.05). The synergistic up-regulation of the xenobiotic-metabolizing enzymes and ABC transporters by pyrene suggests a possible involvement and cooperation of these genes in the detoxification process in rare minnows.


Association of age at diagnosis and ulcerative colitis phenotype.
Ulcerative colitis (UC) primarily affects young adults; however, 12% of patients are diagnosed at an advanced age. Previous studies report that older patients are less likely to have pancolitis and more likely to have distal disease location. Our objective was to compare UC phenotype by age of diagnosis in a tertiary referral cohort. Retrospective database analysis. Demographics, disease extent, and EIM were compared by the following age of diagnosis groups: <17 years, 17-40 years, and >40 years. A total of 260 patients evaluated between July 1, 2004 and April 19, 2010 were included. Race, smoking history, extraintestinal manifestations of disease, and disease duration were significantly associated with age of diagnosis. As age of diagnosis increased, the proportion of non-white patients increased (p = 0.04), former smoking history increased (p < 0.001), extraintestinal manifestations of disease decreased (p < 0.017), and disease duration decreased (p < 0.0001). As age of diagnosis increased, there was a trend for a higher proportion of patients with proctitis and a decreased proportion of patients with pancolitis. Multivariable analysis adjusting for sex, race, smoking history, family history, and disease duration demonstrated that diagnosis at >40 years was associated with a decreased likelihood for pancolitis compared to younger cohorts (OR 0.43, 95% CI 0.24, 0.76). Diagnosis of ulcerative colitis after age 40 years was associated with decreased disease extent compared to younger age groups, even after adjustment for sex, race, smoking history, family history, and disease duration. Our results suggest that older patients have distinct clinical phenotypes.


Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.
An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD). A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328). Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes). The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group. Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset. Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%. This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.


Phase II study of prolonged infusion of Taxol in patients with metastatic colorectal carcinoma.
Taxol represents a new class of anticancer agents with activity against a wide variety of solid tumors. In preclinical systems, its cytotoxicity is schedule dependent with prolonged exposure being more effective. We studied a 120-hour infusion schedule of Taxol in patients with metastatic measurable colorectal carcinoma who had had one prior 5-FU-based chemotherapy. Patients with measurable metastatic colorectal carcinoma were eligible. Patients had to have normal liver, renal, and bone marrow functions. Written informed consent was obtained from all patients. The starting dose of Taxol was 150 mg/m2 infused over 120-hours in the outpatient setting. Taxol was repeated every 21 days. Fifteen patients were registered. Among 14 evaluable patients, we did not observe any complete or partial response. Major toxicity included myelosuppression and mucositis. There was no treatment-related death. Taxol administered by this schedule was found ineffective in patients with metastatic colorectal carcinoma who had previously received one 5-FU-based chemotherapy.


Impact of the COVID-19 pandemic and control measures on air quality and aerosol light absorption in Southwestern China.
China has been performing nationwide social lockdown by releasing the Level 1 response to major public health emergencies (RMPHE) to struggle against the COVID-19 (SARS-CoV-2) outbreak since late January 2020. During the Level 1 RMPHE, social production and public transport were maintained at minimal levels, and residents stayed in and worked from home. The universal impact of anthropogenic activities on air pollution can be evaluated by comparing it with air quality under such extreme conditions. We investigated the concentration of both gaseous and particulate pollutants and aerosol light absorption at different levels of (RMPHE) in an urban area of southwestern China. During the lockdown, PM2.5, PM10, SO2, NOx, and BC decreased by 30-50%, compared to the pre-Level 1 RMPHE period. Meanwhile, the decrease of NOx caused the rise of O3 by up to 2.3 times due to the volatile organic compounds (VOCs) limitation. The aerosol light absorption coefficient at multiple wavelengths decreased by 50%, and AAE decreased by 20% during the Level 1 RMPHE. BrC played essential roles in light absorption after the RMPHE was announced, accounting for 54.0% of the aerosol absorption coefficient at 370 nm. Moreover, the lockdown down-weighted the fraction of fossil fuel in BC concentrations to 0.43 (minima). This study characterizes air pollution at the most basic level and can provide policymakers with references for the "baseline."


Interaction of ladder-shaped polyethers with transmembrane alpha-helix of glycophorin A as evidenced by saturation transfer difference NMR and surface plasmon resonance.
Ladder-shaped polyether (LSP) compounds are thought to interact with transmembrane alpha-helices, but direct evidence has scarcely obtained for these interactions. We adopted a transmembrane alpha-helix of glycophorin A, and quantitatively evaluated its interaction with LSPs such as yessotoxin (YTX), desulfated YTX and artificial LSPs, using surface plasmon resonance and saturation transfer difference NMR. As a result, dissociation constants (K(D)) of YTX and desulfated YTX to a transmembrane domain peptide of glycophorin A were determined to be in the submillimolar range. Furthermore, in saturation transfer difference NMR, the signals at the polyene side chain and the angular methyl groups of YTX were significantly attenuated, which probably comprised an interacting interface of LSPs with a transmembrane alpha-helix. These results suggest that hydrophobic interaction plays an important role in molecular recognition of the alpha-helix peptide by LSPs.


Motor neurone disease: A point-prevalence study of patient reported symptom prevalence, severity and palliative care needs.
Motor neurone disease is a rare but debilitating illness with incomplete evidence regarding patients' symptom burden. Palliative care and generalist clinicians are often in-experienced in caring for these patients and assessing their needs. To identify the symptom prevalence and severity experienced by patients with motor neurone disease. Secondary objectives were to examine differences in symptom burden and clusters according to phenotype, functional status, palliative care provision and those in their last months of life. A point prevalence study assessing patient-reported symptoms using a modified IPOS-Neuro assessment tool, incorporating 41 symptom items. Patients with motor neurone disease attending the State-wide Progressive Neurological Disease Service or inpatient unit at Calvary Health Care Bethlehem, Melbourne Australia, from March to December 2021. A total of 102 patients participated, the majority diagnosed with lumber-onset (30.4%), bulbar-onset (28.4%) and cervical-onset (25.5%) phenotypes. Patients experienced a median of 17 symptoms (range 2-32) with a median of 3 symptoms rated as severe/overwhelming (range 0-13). Motor and functional symptoms predominated, with differences in symptom clusters present according to phenotype. Patients had a higher number of severe/overwhelming symptoms if they were accessing palliative care services (p = 0.005), in their last 6 months of life (p = 0.003) and experiencing moderate or severe functional impairment (p < 0.001). Patients with motor neurone disease report high symptom burden. A validated motor neurone disease-specific symptom assessment tool is needed to accurately assess patients, including important variations in symptom clusters according to phenotype. Further research must focus on evidence-based treatment guidelines for symptoms experienced commonly and severely.


Enhancing Resistance to Chloride Corrosion by Controlling the Morphologies of PtNi Electrocatalysts for Alkaline Seawater Hydrogen Evolution.
A solvothermal method to prepare PtNi alloys that have differing morphologies is described. By adjusting the feed ratio of Pt and Ni precursors in this process, PtNi alloys with different compositions (Pt : Ni atomic ratio from 1 : 3 to 3 : 1) and morphologies (evolution from nanobranches to nanoparticles) are generated. The prepared Pt48 Ni52 alloy, which has a composite morphology comprised of nanobranches and nanoparticles, exhibits superior activity and durability towards the hydrogen evolution reaction (HER) in seawater compared to those of commercial Pt/C catalyst and other PtNi alloys that have different compositions and morphologies. The excellent seawater HER performance of Pt48 Ni52 is ascribed to its nanobranch/nanoparticle morphology that optimally facilitates electron accumulation on Pt, which enhances resistance to chloride corrosion in seawater.


How Do Spinal Parameters Change in Patients Who Have Improvement of Low Back Pain After Total Hip Arthroplasty? A Propensity Score-Matched Cohort Study.
Many studies have demonstrated that low back pain (LBP) improves after total hip arthroplasty (THA). However, the mechanism underlying this improvement remains unclear. We aimed to investigate changes in the spinal parameters of patients who had LBP improvement after THA to elucidate the mechanism of LBP improvement. We included 261 patients who underwent primary THA between December 2015 and June 2021 and had a preoperative visual analog scale score of ≥ 2 for LBP. The patients were classified into the LBP-improved or LBP-continued groups based on the visual analog scale for LBP at 1 year after THA. Preoperative and postoperative changes in the coronal and sagittal spinal parameters were compared between the 2 groups after propensity score matching for age, sex, body mass index, and preoperative spinal parameters. A total of 161 patients (61.7%) were classified into the LBP-improved group. After 85 patients in both groups were matched, the LBP-improved group showed significant differences in spinal parameter changes, which were a higher lumbar lordosis (LL) (P = .04) and lower sagittal vertical axis (SVA) (P = .02) and pelvic incidence (PI) minus LL (PI-LL) (P = .01) postoperatively, whereas the LBP-continued group showed worsened changes in LL and SVA and PI-LL mismatch. Patients who had LBP improvement after THA had significant differences in spinal parameter changes in LL, SVA, and PI-LL. These spinal parameters may be the key factors in the mechanism of LBP improvement after THA.


Curbside Consultation for the Nurse Practitioner: Qualitative Inquiry for Education, Policy, and Practice.
Curbside consultation (CC), defined as pursuing information or recommendation regarding patient care, without request for formal consultation is a favored information source for nurse practitioners (NPs) when making clinical decisions in practice settings. Research and education concerning CC among NPs is lacking. The purpose of this study was to obtain an understanding of NP perceptions of interpersonal aspects of the CC process to inform NP clinical practice and education. Qualitative descriptive design and inductive content analysis was used. Twenty primary care and specialty care NP were recruited using purposive sampling for conduct of individual interviews. Content analysis identified themes describing interpersonal components of the CC process. NP practiced in collaboration with physicians in variable roles within primary care and specialty care settings. These collaborations varied dependent upon supervisory relationships with physicians. Additional themes concerned NP professional experience and characteristics of experts desired for CC. These characteristics included NP perceptions of colleague experience and expertise, trust, and interpersonal relationship dynamics. CC processes for NPs are multidimensional, including interpersonal themes as components of this communication exchange. Given CC is a highly utilized resource for NPs, further inquiry is critical for understanding of its implications for NP practice, policy, and education internationally.


Lactate monooxygenase. III. Additive contributions of active site residues to catalytic efficiency and stabilization of an anionic transition state.
Lactate monooxygenase catalyzes the conversion of L-lactate to acetate, CO2, and water with incorporation of molecular oxygen. Several amino acid residues of lactate monooxygenase had been postulated to interact in specific ways with the bound substrate (Giegel, D. A., Williams, C. H., Jr., and Massey, V. (1990) J. Biol. Chem. 265, 6626-6632). Tyrosine 44 and arginine 293 were proposed to form a hydrogen bond and a salt bridge to the carboxyl-moiety of lactate. Tyrosine 152 was suggested to form a hydrogen bond to the alpha-hydroxyl group and could be involved in stabilizing a transient carbanionic intermediate of the substrate. The tyrosine residues were replaced with phenylalanines (Y44F, Y152F), and arginine 293 was mutated to a lysine (R293K). In all cases catalysis was significantly decreased; however, the binding affinity for L-lactate did not decrease. Instead, the Kd measured for Y152F was 10-fold lower than that for the wild type enzyme. The products of turnover with Y152F were similar to those with wild type enzyme, with 70-80% of the reaction proceeding to form acetate, CO2, and H2O. The catalytic reactions with both Y44F and R293K were substantially uncoupled, with between 60 and 80% of the catalytic turnover forming pyruvate and H2O2. For all mutant forms the reoxidation of enzyme with oxygen in the absence of pyruvate occurred at a rate similar to that measured for the wild type enzyme. The most important effect of the mutations was in the ability to stabilize the transition state analog oxalate. A linear relationship was found between the rate of reduction of the enzyme flavin and the dissociation constant for the binding of oxalate, demonstrating that many individual residues contribute to the lowering of the energy of the transition state, in addition to specific functions being assignable to some specific residues.


Science and public policy.
Politicians generally do not look to scientists to help them get votes. But issues of science policy become extremely important when politicians and scientists, together, grasp the degree to which science and technology are transforming the business of the president and Congress. The author discusses the uneasy relationship of two institutions--political governance and the progress of science--that, while possibly irreconcilable, have an ongoing alliance of convenience. The author indicates issues confronting the Bush presidency in which scientific and technical factors are crucial, raises questions about the future relationship of science and government, defines the political framework for this relationship, and documents the encouraging and significant science-policy commitments made by president-elect Bush.


Magnet facility credits communication for success.
Task forces include ancillary departments, so key messages can be spread to the entire facility. Dashboards display performance information on system, facility, and unit levels. Multiple publications reinforce education on key quality improvement goals.


Clinical approach to patients with acid-base disorders.
Simple relationships that hold during compensation for metabolic or respiratory acid-base disturbances have been emphasized. When considered by the physician, they should allow for the interpretation and diagnosis of both simple and mixed disturbances. Since the correct diagnosis of an acid-base disturbance is central to initiation of correct therapy, these considerations are not merely academic exercises but are essential steps to follow in careful management. Table 6 summarizes the stepwise approach to diagnosis of an acid-base disorder. Application of these principles in a routine fashion combined with a careful history and physical examination often results in the successful diagnosis of complicated disturbances. Understanding of the pathophysiologic derangements in each specific disorder is necessary for full appreciation of acid-base balance in disease.


[The arthroscopic distal pole resection of the scaphoid: clinical results in STT osteoarthritis].
We present the results of surgical treatment of eight patients operated in the service of osteoarthritis scapho-trapézo-trapézoidienne (STT) by resection of the distal pole of the scaphoid under arthroscopic. Studies have already shown the good results of this technique in open surgery. This is a retrospective study of eight patients of mean age 70 years. They had an isolated STT osteoarthritis, which is not relieved by medical treatment. They were operated between 2004 and 2007 by the same surgeon and were reviewed at a mean of 13 months by an independent examiner. The evaluation was focused on pain, range of motion and grip strength. A radiological assessment was conducted to examine a possible carpal mal-alignment. Two patients were excluded because they had received a trapeziectomy for rhizarthrosis associated. The pain had decreased in seven cases with complete disappearance in six cases. The force had been increased or stabilized in seven cases and the mobility is the same in six cases. We got six very good results, one good result and one bad result without aggravation. Furthermore, no patient had been taken, nor any complications noted. The good results obtained with this minimally invasive outpatient surgery, encourages us to offer first-line therapy in patients with isolated STT osteoarthritis is not relieved by medical treatment. The resection of the distal pole of the scaphoide under arthoscopy gives less burdensome and less complication that the arthrodesis, while providing very good results.


Proline-rich domain of human ALIX contains multiple TSG101-UEV interaction sites and forms phosphorylation-mediated reversible amyloids.
Proline-rich domains (PRDs) are among the most prevalent signaling modules of eukaryotes but often unexplored by biophysical techniques as their heterologous recombinant expression poses significant difficulties. Using a "divide-and-conquer" approach, we present a detailed investigation of a PRD (166 residues; ∼30% prolines) belonging to a human protein ALIX, a versatile adaptor protein involved in essential cellular processes including ESCRT-mediated membrane remodeling, cell adhesion, and apoptosis. In solution, the N-terminal fragment of ALIX-PRD is dynamically disordered. It contains three tandem sequentially similar proline-rich motifs that compete for a single binding site on its signaling partner, TSG101-UEV, as evidenced by heteronuclear NMR spectroscopy. Global fitting of relaxation dispersion data, measured as a function of TSG101-UEV concentration, allowed precise quantitation of these interactions. In contrast to the soluble N-terminal portion, the C-terminal tyrosine-rich fragment of ALIX-PRD forms amyloid fibrils and viscous gels validated using dye-binding assays with amyloid-specific probes, congo red and thioflavin T (ThT), and visualized by transmission electron microscopy. Remarkably, fibrils dissolve at low temperatures (2 to 6 °C) or upon hyperphosphorylation with Src kinase. Aggregation kinetics monitored by ThT fluorescence shows that charge repulsion dictates phosphorylation-mediated fibril dissolution and that the hydrophobic effect drives fibril formation. These data illuminate the mechanistic interplay between interactions of ALIX-PRD with TSG101-UEV and polymerization of ALIX-PRD and its central role in regulating ALIX function. This study also demonstrates the broad functional repertoires of PRDs and uncovers the impact of posttranslational modifications in the modulation of reversible amyloids.


Autonomic nervous system may be affected after carpal tunnel syndrome surgery: A possible mechanism for persistence of symptoms after surgery.
After carpal tunnel surgery, some patients report complaints such as edema, pain, and numbness. Purpose - The aim of this study was to evaluate autonomic nervous system function in patients with a history of carpal tunnel surgery using sympathetic skin response (SSR). Thirty three patients (55 ±10 years old) with a history of unilateral operation for carpal tunnel syndrome were included in the study. The SSR test was performed for both hands. Both upper extremities median and ulnar nerve conduction results were recorded. A reduced amplitude (p=0.006) and delayed latency (p<0.0001) were detected in the SSR test on the operated side compared to contralateral side. There was no correlation between SSR and carpal tunnel syndrome severity. Although complex regional pain syndrome does not develop in patients after carpal tunnel surgery, some of the complaints may be caused by effects on the autonomic nervous system.


Exon shuffling in vivo can generate novel HLA class I molecules.
The human class I histocompatibility molecule HLA-Aw69 has serological and structural properties which suggested it was a hybrid of the allelic products HLA-A2 and HLA-Aw68. We have now isolated three genes for HLA-Aw69 and one gene for HLA-Aw68. The sequences of exons encoding the entire extracellular portion of the molecule and of intron 2 have been determined. Their comparison with the published sequence of HLA-A2 proves that HLA-Aw69 is a hybrid molecule with complete identity to HLA-Aw68 in the alpha 1 domain and with HLA-A2 in the alpha 2 and alpha 3 domains. This comparison also localised regions involved in the epitopes recognised by monoclonal antibodies. The three HLA-Aw69 genes obtained from unrelated individuals of diverse ethnic backgrounds are identical. All results are consistent with HLA-Aw69 having arisen by a single reciprocal recombination event between the HLA-Aw68 and HLA-A2 genes somewhere in a region of 86 bp about the 3' donor splice site of exon 2. Estimates of the silent mutation rate in HLA genes suggest this event occurred not more than 330 000 years ago. Intra-allelic reciprocal recombination thus represents a further mechanism in addition to gene conversion for the generation of novel class I histocompatibility alleles.


Ultraviolet radiation and malignant melanoma.
Essential features of the epidemiology and photobiology of cutaneous malignant melanoma (CMM) in Norway were studied in comparison with data from countries at lower latitudes. Arguments for and against a relationship between ultraviolet radiation (UV) from sun and sun beds are discussed. Our data indicate that UV is a carcinogen for CMM and that intermittent exposures are notably melanomagenic. This hypothesis was supported both by latitude gradients, by time trends and by changing patterns of tumor density on different body localizations. However, even though UV radiation generates CMM, it may also have a protective action and/or an action that improves prognosis. The same may be true for a number of internal cancers. There appears to be no, or even an inverse latitude gradient for CMM arising on non-UV exposed body localizations (uveal melanoma). Furthermore, CMM prognosis was gradually improved over all years of increasing incidence (up to 1990), but during the last 10 to 15 years, incidence rates decreased and prognosis was not further improved. While CMM incidence rates are twice as high in South Norway as in North Norway, the ratios of death rates to incidence rates are higher in the North, where the annual UV fluences are lower. Death- and incidence rates in Australia and New Zealand fully support this. Comparisons of skin cancer data from Norway and Australia/New Zealand indicate that squamous cell carcinoma and basal cell carcinoma are mainly related to annual solar UVB fluences, while UVA fluences play a larger role for CMM.


High-Reynolds Microfluidic Sorting of Large Yeast Populations.
Microfluidic sorting offers a unique ability to isolate large numbers of cells for bulk proteomic or metabolomics studies but is currently limited by low throughput and persistent clogging at low flow rates. Recently we uncovered the physical principles governing the inertial focusing of particles in high-Reynolds numbers. Here, we superimpose high Reynolds inertial focusing on Dean vortices, to rapidly isolate large quantities of young and adult yeast from mixed populations at a rate of 107 cells/min/channel. Using a new algorithm to rapidly quantify budding scars in isolated yeast populations and system-wide proteomic analysis, we demonstrate that protein quality control and expression of established yeast aging markers such as CalM, RPL5, and SAM1 may change after the very first replication events, rather than later in the aging process as previously thought. Our technique enables the large-scale isolation of microorganisms based on minute differences in size (±1.5 μm), a feat unmatched by other technologies.


Differential roles of the dorsal hippocampal regions in the acquisition of spatial and temporal aspects of episodic-like memory.
Episodic memory refers to the recollection of what, where and when an event occurred. Computational models suggest that the dentate gyrus (DG) and the CA3 hippocampal subregions are involved in pattern separation and the rapid acquisition of episodes, while CA1 is involved in the formation of a temporal context. Most of the studies performed to test this hypothesis failed to simultaneously address the aspects of episodic memory. Recently, a new task of object recognition was validated in rats. In the first sample trial, the rat is exposed to four copies of an object. In second sample, the rat is exposed to four copies of a different object. In the test trial, two copies of each of the previous objects are presented. One copy of the object used in sample trial one is located in a different place, and it is expected to be the most explored. Our goal was to evaluate whether the pharmacological inactivation of the dorsal DG/CA3 and CA1 subregions could differentially impair the acquisition of the task. Inactivation of the DG/CA3 subregions impaired the spatial discrimination, while the temporal discrimination was preserved. Rats treated with muscimol in CA1 explored all the objects equally well, irrespective of place or presentation time. Our results are consistent with computational models that postulate a role for DG/CA3 in rapid encoding and in spatial pattern separation, and a role for CA1 in the in the formation of the temporal context of events and as well as in detecting spatial novelty.


A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating.
TRP cation channels function as cellular sensors in uni- and multicellular eukaryotes. Despite intensive study, the mechanisms of TRP channel activation by chemical or physical stimuli remain poorly understood. To identify amino acid residues crucial for TRP channel gating, we developed an unbiased, high-throughput genetic screen in yeast that uncovered rare, constitutively active mutants of the capsaicin receptor, TRPV1. We show that mutations within the pore helix domain dramatically increase basal channel activity and responsiveness to chemical and thermal stimuli. Mutation of corresponding residues within two related TRPV channels leads to comparable effects on their activation properties. Our data suggest that conformational changes in the outer pore region are critical for determining the balance between open and closed states, providing evidence for a general role for this domain in TRP channel activation.


Endogenous ornithine in search for CNS functions and therapeutic applications.
The vertebrate brain has the machinery to transport arginine and ornithine, and to form within nerve endings from these amino acids glutamate and GABA, the major excitatory and inhibitory neurotransmitters. Ornithine aminotransferase is a key enzyme of the Arg-->Orn-->Glu-->GABA pathway; the physiological significance of this pathway is still unclear. With 5-fluoromethylornithine, a selective inactivator of ornithine aminotransferase, a tool is in our hands that allows us to study biochemical and behavioral consequences of elevated tissue ornithine concentrations. Increase of the rate of hepatic urea formation, and of ornithine decarboxylation are the most important changes in vertebrates following inactivation of ornithine aminotransferase. Administration of 5-fluoromethylornithine prevented the accumulation of lethal concentrations of ammonia in brain, and ameliorated pathological consequences of thioacetamide intoxication. Inhibition of ornithine catabolism has, therefore, potentials in the therapy of those hyperammonemic states which are characterized by a conditional deficiency of ornithine. The enhancement of polyamine formation due to elevated ornithine concentrations may allow us to favorably affect tissue regeneration following injury.


Autoradiographic localisation of muscarinic receptors on guinea pig intracardiac neurones and atrial myocytes in culture.
Muscarinic receptors were localised on cells cultured from the atria and interatrial septum of newborn guinea pig heart by autoradiography using [3H]propylbenzilylcholine mustard. All of the intracardiac neurones observed in these cultures were specifically labelled: both the neuronal cell body and processes were evenly labelled over their entire surface. Autoradiographic grains were also uniformly distributed over atrial myocytes in culture. This even pattern of labelling of both neurones and atrial myocytes was not changed by the substitution of serum-supplemented growth medium with serum-free, hormone-supplemented, defined medium. The demonstration of muscarinic receptors on intracardiac neurones has important implications for studies on the roles of these neurones in the mammalian heart.


Isolation and characterization of insulin receptors from rat kidney glomeruli and tubules.
In order to directly compare the structural characteristics of renal glomerular and tubular insulin receptors, the purified isolated nephron subunits were extracted with 1% Triton X-102, fractionated by DEAE-Sephacel ion exchange column chromatography and the fractions containing insulin binding proteins were identified by the precipitation of 125I-insulin-protein complexes with polyethylene glycol (PEG). The fractions containing insulin binding proteins were pooled, incubated with 125I-insulin and covalently cross-linked with disuccinimidyl suberate, followed by chromatography of the cross-linked samples on Sepharose CL-6B. From both glomeruli and tubules, three 125I-insulin-binding complexes with molecular weights of 560 KDa, 220 KDa and 95 KDa were found. SDS-PAGE of these complexes from glomeruli and tubules under both reducing and nonreducing conditions gave similar patterns of 125I-insulin-crosslinked components, with the exception of the polypeptide pattern from the 560 KDa peak fraction which was markedly different between glomeruli and tubules with the former giving major labeled components at 170 and 68 KDa while the latter showed labeled components of 125 KDa and greater than 250 KDa. Glomerular and tubular insulin receptors, therefore, display similar subunit composition under reducing conditions, but differ in the non-reduced state, suggesting that these complexes may differ in the extent and/or nature of disulfide bonding.


Adolescents' right to confidential health care: knowledge, attitudes and practice of pediatricians and gynecologists in the primary healthcare sector in Belgrade, Serbia.
Confidential counseling is a critical condition of the healthcare quality in adolescent medicine. This study aimed at assessing knowledge, attitudes and practice of primary healthcare pediatricians and gynecologists regarding adolescents' rights to confidentiality. A cross-sectional study was conducted in a sample of 152 pediatricians and gynecologists who are employed at 13 primary healthcare centers in Belgrade, Serbia, in 2017-2018. Data were collected by a self-administered questionnaire purposefully constructed for this study. The questionnaire examined knowledge and attitudes toward adolescents' right to confidentiality as well as whether participating physicians practice confidential health care with adolescents. Physicians scored 4 out of 7 on a knowledge scale, but they overall supported adolescents' right to confidential health care (average attitude score was 71 out of 95). On average, physicians scored 21 out of 30 on practice of confidentiality scale. Multivariate analysis showed that better knowledge and stronger positive attitudes toward duty of confidentiality were associated with consistent practice of confidential health care. Knowledge about adolescents' rights to confidentiality and attitudes toward keeping adolescents' information confidential influence the practice of providing confidential services.


Health outcome convergence in Africa: the roles of immunization and public health spending.
Reducing health outcomes disparities in Africa is a major concern for policymakers. Inter-country disparities in Africa is well documented. However, little is known about the accurate trajectory of these disparities over time. Thus, this paper investigates the convergence hypothesis in health outcomes in 40 African countries using data from the World Development Indicators. The study used panel data from 2000 to 2019. The study employs a nonlinear time-varying factor model to test the convergence hypothesis on infant mortality rate, under-five mortality, and life expectancy at birth. Then, we use the marginal effects of the ordered logit regression model to investigate the factors that explain club memberships. The findings showed the absence of overall convergence for the three variables of interest. However, we identified the presence of convergence clubs. Moreover, we observed substantial gaps between the estimated clubs. The marginal effect results reveal that real GDP per capita, population structure, urbanization, trade, access to basic sanitation, and external health expenditure are essential to club formation. In addition, DTP immunization and the general government health expenditure as a percentage of the general government expenditure (our Abuja Declaration instrument) also play a significant role in explaining the club membership. The findings suggest that policymakers should develop and implement targeted club-specific health policies. Furthermore, interventions to promote increased immunization, particularly among children, should be encouraged. Governments should also make substantial efforts to increase the share of their national budget allocated to the health sector by at least 15 percent.


Factors controlling induction of reproduction in algae--review: the text.
This review surveys on the influence of different environmental factors like light (intensity, quality, photoperiod), temperature, season, nutrients (inorganic, organic), biotic factors (algal extracellular products, bacterial association, animals grazing), osmotic stress, pH of the medium, wave motion and mechanical shock, pollution, and radiations (UV, X-rays, gamma radiation) on the induction (or inhibition) of algal reproduction like cell division in unicellular algae, and formation of zoospores, aplanospores, akinetes, cysts, antheridia, oogonia, zygospores, etc.


The role of ICOS and other costimulatory molecules in allergy and asthma.
Activation and differentiation of T cells play a critical role in the pathogenesis of allergies and asthma. Upon encounter with specific antigen, naïve T helper precursor (ThP) cells become activated, an event that is regulated not only by engagement of the T cell receptor (TCR) with peptide presented in the context of MHC class II molecules, but also by a number of costimulatory signals. CD28 engagement by B7-1 and B7-2 on resting ThP cells provides a critical signal for initial cell cycle progression, interleukin-2 production and clonal expansion. However, in recent years, other related members of the immunoglobulin (Ig) family, such as inducible costimulatory molecules (ICOS) and the TNF receptor family members which include OX40, have also been demonstrated to play an important role in providing unique and complementary signals that regulate the outcome of immune responses. These positive costimulatory signals are counterbalanced by signals that dampen down immune responses and include CTLA-4, PD-1 and the recently described Ig superfamily members BTLA and TIM-3. This review discusses the role of these costimulatory signals and their potential involvement in the pathogenesis of asthma and allergic responses.


7-Phenyl-imidazoquinolin-4(5H)-one derivatives as selective and orally available mPGES-1 inhibitors.
To identify compounds with strong mPGES-1 inhibitory activity and clear in vitro ADME profile, we optimized the lead compound 1 by carrying our substitutions at the C(7)- and C(8)-positions. Replacement of the bromine atom of 1 with various substituents led to identification of the phenyl group as the best C(7)-substituent giving strong inhibitory activity with good in vitro ADME profile. Further SAR examination on both the C(2)- and the C(7)-phenyl groups provided compound 39 as the best candidate for further development. Compound 39 exhibited strong mPGES-1 inhibitory activity (IC50=4.1 nM), potent cell-based functional activity (IC50=33 nM) with good mPGES-1 selectivity (over 700-fold), excellent in vitro ADME profile, and good oral absorption in rat PK study.


Synthesis and in vitro cytotoxicity of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives.
A series of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives were synthesized and their anticancer cytotoxicity were evaluated in in vitro assay. It was found that the bulky aryl functionality in the 5-position of the 2-cyanoimino-4-imidazolidinone compounds was essential for the cytotoxicity of these heterocyclic compounds. Some of the derivatives exhibited modest cytotoxicity against a variety of cancer cell lines. One of the derivatives, [1-[6-(4-chlorophenoxy)hexyl]-5-oxo-4-phenyl-3-(4-pyridyl)tetrahydro-1H-2-imidazolyliden]aminomethanenitrile (Compound 11), exhibited the most potent cytotoxic activity with IC(50) in the nanomolar range. The cytotoxicity of these derivatives was selection with no apparent toxic effect toward normal fibroblasts.


Blood-Sparing Techniques in Head and Neck Surgery.
Given the risks and potential complications of allogenic blood transfusion (ABT), as well as the expanding population of patients for whom ABT may not be an option, it is important for the treating physician, anesthesiologist, and surgeon to be well-versed in various alternatives. A good grasp of the concepts discussed in this article will help to customize a treatment plan that is specific to each patient's underlying disease and personal preferences without compromising appropriate medical care.


Structural characterization of a recombinant monoclonal antibody by electrospray time-of-flight mass spectrometry.
The aim of this study was to perform structural characterization of a recombinant monoclonal antibody (MAb), huN901, by electrospray time-of-flight mass spectrometry (ESI-TOFMS) using both "top-down" and "bottom-up" approaches. In the top-down approach, the molecular masses of the deglycosylated huN901 and the light and heavy chains of the antibody were measured by direct infusion MS and liquid chromatography-mass spectrometry (LC-MS). In the bottom-up approach, trypsin and Asp-N protease were used to digest the separated, reduced and alkylated light and heavy chains followed by LC-MS analysis of the digests. The primary structure and post-translational modifications of huN901 were characterized by both top-down and bottom-up MS approaches. Modifications of N-terminal pyroglutamate formation, cleavage of C-terminal lysine, glycosylation, and deamidation were identified in the antibody heavy chain by both protein mass measurement and peptide mapping. No modifications were found in the complementarity determining regions (CDRs) of both chains. Both trypsin and Asp-N protease digestion had an average sequence recovery of 97%, and generated complimentary mapping results with complete sequence recovery. ESI-TOFMS is a superior tool to characterize MAb and other complex protein pharmaceuticals.


A new approach for the detection of obesity-related airway obstruction in lung-healthy individuals.
Subjects with obesity show an increased prevalence of airway obstruction but it is not clear in each case whether this reflects genuine lung disease. Via intentional increase in end-expiratory lung volume we studied the detection of obesity-induced airway obstruction in lung-healthy obese subjects. The primary study population comprised 66 lung-healthy obese subjects and 23 normal weight subjects. Measurements were performed in a body plethysmograph allowing for recording and quantification of breathing loops in terms of specific airway resistance at both normal and intentionally elevated end-expiratory lung volume. The change in volume was documented by a shutter maneuver. The voluntary increase of lung volume led to a significant reduction of expiratory airway resistance in 11 of the 66 obese subjects. This reduction could be quantified by a change of total expiratory resistance (sRtEX) of >1 kPa*s but was also clearly visible in the breathing loops. sRtEX showed the largest change among all resistance parameters. The loops of normal weight subjects remained virtually unaffected by the change in lung volume. Moreover, those of 5 obese patients with COPD who were measured for comparison partially showed a reduction of resistance but airway obstruction remained. The proposed breathing maneuver was simple to perform and allowed for a quantitative and qualitative detection of obesity-induced airway obstruction. This might help in reducing the likelihood of misdiagnosis and overtreatment of obese patients.


Açaí seed extract (ASE) rich in proanthocyanidins improves cardiovascular remodeling by increasing antioxidant response in obese high-fat diet-fed mice.
Obesity is recognized as an independent risk factor for cardiovascular diseases and is an important contributor to cardiac mortality. Açaí seed extract (ASE), rich in proanthocyanidins, has been shown to have potential anti-obesity effects. This study aimed to investigate the therapeutic effect of ASE in cardiovascular remodeling associated with obesity and compare it with that of rosuvastatin. Male C57BL/6 mice were fed a high-fat diet or a standard diet for 12 weeks. The ASE (300 mg/kg/day) and rosuvastatin (20 mg/kg/day) treatments started in the 8th week until the 12th week, totaling 4 weeks of treatment. Our data showed that treatment with ASE and rosuvastatin reduced body weight, ameliorated lipid profile, and improved cardiovascular remodeling. Treatment with ASE but not rosuvastatin reduced hyperglycemia and oxidative stress by reducing immunostaining of 8-isoprostane and increasing SOD-1 and GPx expression in HFD mice. ASE and rosuvastatin reduced NOX4 expression, increased SIRT-1 and Nrf2 expression and catalase and GPx activities, and improved vascular and cardiac remodeling in HFD mice. The therapeutic effect of ASE was similar to that of rosuvastatin in reducing dyslipidemia and cardiovascular remodeling but was superior in reducing oxidative damage and hyperglycemia, suggesting that ASE was a promising natural product for the treatment of cardiovascular alterations associated with obesity.


LINC01140 Alleviates the Oxidized Low-Density Lipoprotein-Induced Inflammatory Response in Macrophages via Suppressing miR-23b.
Our previous study has demonstrated that miR-23b enhances oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of macrophages through the A20/NF-κB signaling pathway, thus contributing to atherosclerosis. This study aims to further investigate the upstream regulators of miR-23b in mediating oxLDL-induced inflammatory response. Human monocyte cell line THP1 was induced to differentiate into macrophages followed by the oxLDL stimulation of inflammatory response. The expression of miR-23b, LINC01140, and p53 mRNA was detected by quantitative PCR. The combination of miR-23b and LINC01140 was confirmed by luciferase reporter assay and RNA immunoprecipitation. The binding of p53 and LINC01140 promoter was determined by luciferase reporter assay. The level of inflammatory cytokines, including MCP-1, TNF-α, and IL-1β, was assessed by enzyme-linked immunosorbent assay. LINC01140 was downregulated, while p53 and miR-23b were upregulated in oxLDL-induced inflammatory response of macrophages. Overexpression of LINC01140 reduced NF-κB activity by reducing miR-23b and increasing A20. The transcription of LINC01140 was inhibited by binding of p53 and the LINC01140 promoter region. Knockdown of p53 significantly reduced NF-κB activity and level of inflammatory cytokines by promoting LINC01140 expression. Our findings demonstrated that LINC01140 acts as an anti-inflammatory factor through negatively regulating miR-23/A20 axis. In addition, p53 is identified as a transcriptional repressor of LINC01140.


Cystoid macular edema in aphakic and pseudophakic eyes.
A prospective fluorescein angiographic study, comparing the incidence of cystoid macular edema in patients 67 years or older after intracapsular cataract extraction with a Binkhorst 4-loop implant, extracapsular cataract extraction with a Binkhorst 2-loop or 4-loop implant, and intracapsular cataract extraction with no implant (controls) was begun at the Bascom Palmer Eye Institute of the University of Miami School of Medicine on May 14, 1974. Excluded from these groups were all patients whom we did not consider to be suitable candidates for lens implant surgery. Fundus fluorescein angiograms were taken four, eight, and 16 to 24 months postoperatively. The surgery was performed by one group of surgeons and the angiograms were read by a group of retinal specialists. The intracapsular cataract extraction-implant and intracapsular-no implant groups had a comparable incidence of cystoid macular edema four, eight, and 16 to 24 months postoperatively. The extra capsular cataract extraction-implant and an intact posterior capsule group had a significantly lower incidence of cystoid macular edema than the intracapsular cataract extraction-implant group 16 to 24 months postoperatively. The differences were less significant at four and eight months. Visual function as measured by visual acuity was 6/12 (20/40) or better in approximately 80% of eyes with angiographic-proven cystoid macular edema.


Potential risk of excising the femoral insertion of the popliteus tendon during primary total knee arthroplasty: a biometric study.
During total knee arthroplasty (TKA), excision of the popliteus tendon leads to extensive static gaps and reduced mobility. The purpose of this study was to determine the positional relationship between the femoral insertion of the popliteus tendon and the bone cutting lines of various TKA systems. This study included 21 cadaveric right femurs presenting no macroscopic deformity. The lateral image of the femur and the template of the femoral component were overlaid to determine the preservation/excision of the popliteus tendon insertion. TKA systems used were Genesis II, NexGen, low contact stress (LCS), PFC Σ, Scorpio, and Vanguard. The knees in which the insertion was preserved in all implants or excised in at least one implant were classified into intact or the high-risk groups, respectively. The popliteus tendon was preserved in all specimens with the LCS system. In contrast, the popliteus tendon insertion was excised in ≥1/3 of the specimens with the other systems. The anteroposterior diameter was significantly larger in the intact group than that in the high-risk group (58.1 ± 4.5 mm vs. 53.7 ± 2.7 mm; p = 0.018). The high-risk group included more knees from female cadavers than the intact group (70 vs. 9 %; p = 0.008). During primary TKA, the femoral insertion of the popliteus tendon could be inevitably excised, regardless of technical problems. We demonstrate that the unique design of the LCS system preserves the popliteus tendon insertion. In addition, small knees and females may be risk factors for excision of the insertion.


The RhoA-ROCK-PTEN pathway as a molecular switch for anchorage dependent cell behavior.
The proliferation of anchorage-dependent cells of mesenchymal origin requires the attachment of the cells to substrates. Thus, cells that are poorly attached to substrates exhibit retarded cell cycle progression or apoptotic death. A major disadvantage of most polymers used in tissue engineering is their hydrophobicity; hydrophobic surfaces do not allow cells to attach firmly and, therefore, do not allow normal proliferation rates. In this study, we investigated the molecular mechanism underlying the reduced proliferation rate of cells that are poorly attached to substrates. There was an inverse relationship between the activity of the small GTPase RhoA (RhoA) and the cell proliferation rate. RhoA activity correlated inversely with the strength of cell adhesion to the substrates. The high RhoA activity in the cells poorly attached to substrates caused an increase in the activity of Rho-associated kinase (ROCK), a well-known effector of RhoA that upregulated the activity of phosphatase and tensin homolog (PTEN). The resulting activated PTEN downregulated Akt activity, which is essential for cell proliferation. Thus, the cells that were poorly attached to substrates showed low levels of cell proliferation because the RhoA-ROCK-PTEN pathway was hyperactive. In addition, RhoA activity seemed to be related to focal adhesion kinase (FAK) activity. Weak FAK activity in these poorly attached cells failed to downregulate the high RhoA activity that restrained cell proliferation. Interestingly, reducing the expression of any component of the RhoA-ROCK-PTEN pathway rescued the proliferation rate without physico-chemical surface modifications. Based on these results, we suggest that the RhoA-ROCK-PTEN pathway acts as a molecular switch to control cell proliferation and determine anchorage dependence. In cells that are poorly attached to substrates, its inhibition is sufficient to restore cell proliferation without the need for physico-chemical modification of the material surface.


Tube dysfunction following percutaneous endoscopic gastrostomy and jejunostomy.
Percutaneous endoscopic gastrostomy (PEG) and jejunostomy (PEJ) have supplanted their surgical counterparts in many institutions. Previous reports have claimed advantages in placing PEJ tubes because of reduced gastroesophageal reflux, prevention of aspiration, and improved tube anchoring distally. We reviewed the records of 191 patients who underwent placement of PEG/J tubes. Data collected included incidence of tube dysfunction, need for tube replacement or removal, and aspiration after PEG or PEJ tube placement. Tube dysfunction, defined as peritube leakage, plugging, fracture, or migration, occurred in 36% of patients over a mean follow-up period of 275 days and was significantly more common and likely to necessitate tube replacement in PEJ patients. Tube trade-out or removal and aspiration within a 30-day period after tube placement occurred in 28% and 10% of patients, respectively. These complications were significantly more common in PEJ patients than in PEG patients. Because of the increased incidence of tube dysfunction and the failure to prevent aspiration in predisposed patients, PEJ tube placement is not routinely indicated in patients requiring tube feedings.


Postprandial VLDL-TG metabolism in type 2 diabetes.
Type 2 diabetes is associated with excess postprandial lipemia due to accumulation of chylomicrons and VLDL particles. This is a risk factor for development of cardiovascular disease. However, whether the excess lipemia is associated with an impaired suppression of VLDL-TG secretion and/or reduced clearance into adipose tissue is unknown. We measured the postprandial VLDL-TG secretion, clearance and adipose tissue storage to test the hypothesis that impaired postprandial suppression of VLDL-TG secretion, combined with impaired VLDL-TG storage in adipose tissue, is associated with excess postprandial lipemia. We studied 11 men with type 2 diabetes and 10 weight-matched non-diabetic men using ex-vivo labeled VLDL-TG tracers during an oral high-fat mixed-meal tolerance test to measure postprandial VLDL-TG secretion, clearance and storage. In addition, adipose tissue biopsies were analyzed for LPL activity and cellular storage factors. Men with type 2 diabetes had greater postprandial VLDL-TG concentration compared to non-diabetic men. However, postprandial VLDL-TG secretion rate was similar in the two groups with equal suppression of VLDL-TG secretion rate (≈50%) and clearance rate. In addition, postprandial VLDL-TG storage was similar in the two groups in both upper body and lower body subcutaneous adipose tissue. Despite greater postprandial VLDL-TG concentration, men with type 2 diabetes have similar postprandial suppression of VLDL-TG secretion and a similar ability to store VLDL-TG in adipose tissue compared to non-diabetic men. This may indicate that abnormalities in postprandial VLDL-TG metabolism are a consequence of obesity/insulin resistance more than a result of type 2 diabetes per se.


Histogenesis of intracranial haemangiopericytoma and haemangioblastoma. An immunohistochemical study.
An immunohistochemical study was performed on three meningeal haemangiopericytomas and four cerebellar haemangioblastomas (paraffin embedded) in an attempt to elucidate the uncertain histogenesis of these tumours. The tumour cells of all meningeal haemangiopericytomas show no expression of alpha-smooth muscle actin and, thus, no immunohistochemical proof of their true pericytic nature can be obtained. The stromal cells of cerebellar haemangioblastomas show foci of positive staining for S-100 protein, neuron-specific enolase and synaptophysin, thereby clearly indicating their neuroectodermal origin. These results allow the conclusion that the present nomenclature of these tumours is at least arguable and probably incorrect.


Lipid-driven interleaflet coupling of plasma membrane order regulates FcεRI signaling in mast cells.
Interleaflet coupling-the influence of one leaflet on the properties of the opposing leaflet-is a fundamental plasma membrane organizational principle. This coupling is proposed to participate in maintaining steady-state biophysical properties of the plasma membrane, which in turn regulates some transmembrane signaling processes. A prominent example is antigen (Ag) stimulation of signaling by clustering transmembrane receptors for immunoglobulin E (IgE), FcεRI. This transmembrane signaling depends on the stabilization of ordered regions in the inner leaflet for sorting of intracellular signaling components. The resting inner leaflet has a lipid composition that is generally less ordered than the outer leaflet and that does not spontaneously phase separate in model membranes. We propose that interleaflet coupling can mediate ordering and disordering of the inner leaflet, which is poised in resting cells to reorganize upon stimulation. To test this in live cells, we first established a straightforward approach to evaluate induced changes in membrane order by measuring inner leaflet diffusion of lipid probes by imaging fluorescence correlation spectroscopy, by imaging fluorescence correlation spectroscopy (ImFCS), before and after methyl-α-cyclodexrin (mαCD)-catalyzed exchange of outer leaflet lipids (LEX) with exogenous order- or disorder-promoting phospholipids. We examined the functional impact of LEX by monitoring two Ag-stimulated responses: recruitment of cytoplasmic Syk kinase to the inner leaflet and exocytosis of secretory granules (degranulation). Based on the ImFCS data in resting cells, we observed global increase or decrease of inner leaflet order when outer leaflet is exchanged with order- or disorder-promoting lipids, respectively. We find that the degree of both stimulated Syk recruitment and degranulation correlates positively with LEX-mediated changes of inner leaflet order in resting cells. Overall, our results show that resting-state lipid ordering of the outer leaflet influences the ordering of the inner leaflet, likely via interleaflet coupling. This imposed lipid reorganization modulates transmembrane signaling stimulated by Ag clustering of IgE-FcεRI.


The influence of smoking and diet on the hypoxanthine phosphoribosyltransferase (hprt) mutant frequency in circulating T lymphocytes from a normal human population.
The influence of the dietary antioxidants vitamin C, alpha- and beta-carotene, lycopene, lutein/zeaxanthin, phytofluene, beta-cryptoxanthin, retinol and alpha- and gamma-tocopherol on the hypoxanthine phosphoribosyltransferase (hprt) mutant frequency in human peripheral T lymphocytes was investigated. Twenty-five male non-smokers and 27 male smokers in the age range 50-59 years were recruited. Smokers showed a significantly higher mutant frequency compared with non-smokers (X1.5, P < 0.01). In addition, there was a significant positive relationship between hprt mutant frequency and the number of cigarettes that individuals reported smoking daily (P < 0.01). Smokers showed significantly lower levels of plasma vitamin C and the carotenoid alpha-carotene than non-smokers (P < 0.01 and P < 0.05 respectively). Both hprt mutant frequency and lymphocyte plating efficiency were weakly inversely associated with plasma vitamin C levels (P < 0.07 and P < 0.06 respectively) suggesting that vitamin C may be protective against mutation at the hprt locus. This relationship was markedly stronger in smokers (P < 0.01).


Does money matter for child nutrition? Exploration of a preschool nutrition program in rural South-Central China.
The aim of this study was to examine the relationship between poverty and children's nutritional outcomes. Drawing on a 2018 survey of the preschool nutrition program conducted in the Xiangxi Autonomous Prefecture, Hunan Province, China, we applied propensity score matching to estimate the average treatment effects on the treated children. The most striking result was that although poverty is often used as predictive of poor childhood nutrition, this effect was only significant for weight-for-age z-score and height-for-age z-score, but not for other nutritional indicators, cognition, or social emotional indexes. The results varied using different measures of poverty. The weak linkage between poverty and children's nutritional outcomes was confirmed by a series of robustness checks by changing the covariates for matching, adopting other matching methods, using bootstrapping standard errors, and building on machine learning tools. A single tool of small money transfer would have limited effects, but considerable income increases that lift the poor out of poverty are important for the poor. Additionally, a mixed tool of financial support and nutritional knowledge may lead to better outcomes, especially for those living above the poverty line.


Interleukin-4 regulates connective tissue growth factor expression in human lung fibroblasts.
Transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) have fibrogenic properties and induce extracellular matrix production in a variety of lung diseases. Connective tissue growth factor (CTGF) is a matrix signaling molecule stimulated by TGF-beta that in part mediates alpha1(I) collagen mRNA expression. In these studies, the regulation of CTGF expression by IL-4 in human lung fibroblasts was examined. Following 6 h of stimulation with IL-4, basal CTGF mRNA levels were unchanged as assessed by Northern blot analysis. However, IL-4 attenuated the TGF-beta-stimulated induction of CTGF mRNA expression by 50%. This effect was selective because IL-4 did not affect fibronectin or alpha1(I) collagen mRNA expression induced by TGF-beta. Experiments employing the transcriptional inhibitor actinomycin D suggest that IL-4 did not affect the stability of the CTGF mRNA. Transient transfection assays with 3TP-Lux, a luciferase gene controlled by a TGF-beta inducible promoter, and with a CTGF promoter construct indicate that IL-4 interfered with the TGF-beta-induced transcriptional activation of the CTGF gene.


Megakaryoblast precursors in rodent bone marrow: specificity of acetylcholinesterase staining.
Small cells staining diffusely for acetylcholinesterase, corresponding closely to the description of Jackson (1973, 1974), have been quantitated in the bone marrow of mouse and rat. These cells fulfil the requirements of megakaryoblast precursors, showing elevation in numbers prior to megakaryocytes in response to thrombocytopenia, and carrying platelet-specific antigens demonstrated by immunofluorescence. Some show a clearly defined nucleus whilst in others the nucleus is obscured; the femoral content of both types follows the same time course after acute thrombocytopenia and the latter can be distinguished from megakaryocyte cytoplasmic fragments. Other small cells present in rodent bone marrow contain granular positivity after acetylcholinesterase staining but also granules staining with Luxol-Fast-Blue, suggesting that these cells are eosinophils. These cells are greatly increased in number with stimulation of eosinophilia by parasite infestation but show no response to acute thrombocytopenia. Peripheral blood eosinophils exhibit both acetylcholinesterase and Luxol-Fast-Blue staining. A number of properties ascribed to granular-staining small acetylcholinesterase-positive cells previously presumed to be megakaryoblast precursors will need to be reassessed.


A preliminary study on the evaluation of left atrial function of rheumatoid arthritis by two dimensional speckle tracking imaging.
To evaluate the changes of left atrial (LA) geometry and function in patients with rheumatoid arthritis (RA) by conventional echocardiography and two-dimensional speckle tracking imaging (2D-STI). We enrolled 46 RA patients with a duration of < 5 years as Group I, 40 RA patients with a duration of ≥ 5 years as Group II, and 40 normal subjects as the control group. Conventional echocardiography was conducted to measure traditional parameters. The LA strain during reservoir phase (LASr), LA strain during conduit phase (LAScd), LA strain during contraction phase (LASct), and LA global longitudinal strain (LAGLS) were obtained from 2D-STI. Related ultrasound results were compared. The LASct was significantly higher in Group I than in control group (P < 0.05). The LASr, LAScd, and LAGLS were significantly lower in Group I than in control group (all P < 0.05). The LASr, LAScd, LASct, and LAGLS were significantly lower in Group II than in control group and Group I (all P < 0.05). The function of LA impaired in RA patients, and the impairment aggravated with the clinical course of RA patients. 2D-STI technology can early and accurately evaluate the LA function of RA patients by evaluating LASr, LAScd, LASct, and LAGLS.


Biochemical characterization of the venom from the Mexican scorpion Centruroides ornatus, a dangerous species to humans.
Every year in Mexico, around 300,000 people suffer from accidents related to scorpion stings. Among the scorpion species dangerous to human is Centruroides ornatus, whose venom characterization is described here. From this venom, a total of 114 components were found using chromatographic separation and mass spectrometry analysis. The most abundant ones have molecular masses between 3000-4000 Da and 6000-8000 Da respectively, similar to other known K+ and Na+-channel specific scorpion peptides. Using intraperitoneal injections into CD1 mice, we were able to identify and fully sequenced three new lethal toxins. We propose to name them Co1, Co2 and Co3 toxins, which correspond to toxins 1 to 3 of the abbreviated species name (Co). Electrophysiology analysis of these peptides using heterologously expressed human Na+-channels revealed a typical β-toxin effect. Peptide Co52 (the most abundant peptide in the venom) showed no activity in our in vivo and in vitro model assays. A phylogenetic analysis groups the Co1, Co2 and Co3 among other β-toxins from Centruroides scorpions. Peptide Co52 segregates among peptides of unknown defined functions.