Effects of peak time of myocardial injury biomarkers on mid-term outcomes of patients undergoing OPCABG.
With the development of cardiac surgery techniques, myocardial injury is gradually reduced, but cannot be completely avoided. Myocardial injury biomarkers (MIBs) can quickly and specifically reflect the degree of myocardial injury. Due to various reasons, there is no consensus on the specific values of MIBs in evaluating postoperative prognosis. This retrospective study was aimed to investigate the impact of MIBs on the mid-term prognosis of patients undergoing off-pump coronary artery bypass grafting (OPCABG). Totally 564 patients undergoing OPCABG with normal courses were included. Cardiac troponin T (cTnT) and creatine kinase myocardial band (CK-MB) were assessed within 48 h before operation and at 6, 12, 24, 48, 72, 96 and 120 h after operation. Patients were grouped by peak values and peak time courses of MIBs. The profile of MIBs and clinical variables as well as their correlations with mid-term prognosis were analyzed by univariable and multivariable Cox regression models. Continuous assessment showed that MIBs increased first (12 h after surgery) and then decreased. The peak cTnT and peak CK-MB occurred within 24 h after operation in 76.8% and 67.7% of the patients respectively. No significant correlation was found between CK-MB and mid-term mortality. Delayed cTnT peak (peak cTnT elevated after 24 h after operation) was correlated with lower creatinine clearance rate (69.36 ± 21.67 vs. 82.18 ± 25.17 ml/min/1.73 m2), body mass index (24.35 ± 2.58 vs. 25.27 ± 3.26 kg/m2), less arterial grafts (1.24 ± 0.77 vs. 1.45 ± 0.86), higher EuroSCORE II (2.22 ± 1.12 vs.1.72 ± 0.91) and mid-term mortality (26.5 vs.7.9%). Age (HR: 1.067, CI: 1.006-1.133), left ventricular ejection fraction (HR: 0.950, CI: 0.910-0.993), New York Heart Association score (HR: 1.839, CI: 1.159-2.917), total venous grafting (HR: 2.833, CI: 1.054-7.614) and cTnT peak occurrence within 24 h (HR: 0.362, CI: 0.196-0.668) were independent predictors of mid-term mortality. cTnT is a better indicator than CK-MB. The peak value and peak occurrence of cTnT are related to mid-term mortality in patients undergoing OPCABG, and the peak phases have stronger predictive ability. Chinese Clinical Trial Registry, ChiCTR2000033850. Registered 14 June 2020, http://www.chictr.org.cn/edit.aspx?pid=55162&htm=4 .


Orally administered tetracycline for phlyctenular keratoconjunctivitis.
We treated six patients who had recurrent episodes of nontuberculous phlyctenular keratoconjunctivitis and progressive corneal vascularization and scarring with oral tetracycline. This treatment resulted in rapid relief of symptoms and the apparent arrest of this disease. There have been no complications secondary to the use of tetracycline. To date, there has been only one recurrence in the patients treated with tetracycline which consisted of mild conjunctival hyperemia. We believe oral tetracycline is a safe and effective treatment for resistant and recurrent nontuberculous phlyctenular keratoconjunctivitis and an alternative to topical corticosteroid treatment in those patients suffering from corticosteroid-induced complications.


Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model.
To enhance the osteogenic activity of BMP, combination BMP2 and BMP7 gene transfer was performed. This approach led to a significant increase in osteoblastic differentiation of mesenchymal precursors compared with single BMP gene transfer in vitro. When tested in 78 rats, combination gene transfer enhanced mechanically stable spine fusion and bone formation rate versus single BMP gene transfer. Although clinical bone morphogenetic protein (BMP) therapy is effective, required doses are very high. Previous studies have suggested that the co-expression of two different BMP genes can result in the production of heterodimeric BMPs that may be more potent than homodimers. In this study, combined BMP2 and BMP7 gene transfer was performed to test whether this approach improves osteoblastic differentiation and bone formation compared with single BMP gene transfer. A producer cell (A549) was co-transfected with adenovirus vectors encoding BMP2 (AdBMP2) and BMP7 (AdBMP7) or, as controls, each vector alone, AdNull (with no transgene) or no virus. Supernatants were compared for their ability to stimulate osteoblastic differentiation of C2C12 myoblasts and MC3T3-E1 pre-osteoblasts. In a rat posterolateral spine fusion model, co-administration of AdBMP2 and AdBMP7 was compared with treatment with each vector alone, AdNull or no virus in 78 rats. The spines were assessed 8 weeks after surgery for radiographic and mechanical fusion, bone formation, and mineralization. BMP2 and BMP7 were co-precipitated from supernatants of cells co-transfected with AdBMP2 and AdBMP7, indicating the presence of BMP2/7 heterodimer. Supernatants of co-transfected cells containing relatively low doses (7-140 ng/ml) of BMPs induced osteocalcin expression and alkaline phosphatase activity in both C2C12 and MC3T3-E1 cells, that were up to 6- and 40-fold higher, respectively, than levels induced by maximal doses (200-1000 ng/ml) of either BMP2 or BMP7 alone. In the spine fusion model, co-administration of AdBMP2 and AdBMP7 resulted in a significantly greater number of mechanically stable fusions and also 2-fold higher mineralization rate and bone volume in the fusion mass versus single BMP gene transfer (p < 0.02, all comparisons). Combined BMP2 and BMP7 gene transfer is significantly more effective in inducing osteoblastic differentiation and spine fusion than individual BMP gene transfer.


Antimicrobial cellulose paper tuned with chitosan fibers for high-flux oil/water separation.
Separating films with both high efficiency and large flux are desperately needed to meet the rising demand for the treatment of oily wastewater, while traditional oil/water separation papers with high separation efficiency usually suffered from low flux due to the unsuitable size of filtration pores. Herein, we report a bio-based porous, superhydrophobic, and antimicrobial hybrid cellulose paper with tunable porous structures for high flux oil/water separation. The size of pores in the hybrid paper can be tuned by both physical supports provided by the chitosan fibers and the chemical shielding supplied by the hydrophobic modification. The hybrid paper with increased porosity (20.73 μm; 35.15 %) and excellent antibacterial properties can efficiently separate a wide range of oil/water mixtures, solely by gravity, with outstanding flux (maximum of 23,692.69 L m-2 h-1), tiny oil interception, and high efficiency of over 99 %. This work provides new sights in the development of durable and low-cost functional papers for rapid and efficient oil/water separation.


In Vitro Testing of Sunscreens for Dermal Absorption: A Platform for Product Selection for Maximal Usage Clinical Trials.
Sunscreen products contain UV filters as active ingredients for the protection of the skin against UVR. The US Food and Drug Administration (FDA) issued a new proposed rule in 2019 (84.FR.6204) for sunscreens and identified the need for additional safety data for certain UV filters including their dermal absorption data. Dermal absorption data reveal systemic exposure of UV filters in humans, which can be obtained from clinical maximal usage trials. FDA guidance recommends conducting in vitro skin permeation tests (IVPTs) to help select formulations for maximal usage clinical trials as IVPT results may be indicative of in vivo absorption. This case study reports in vitro methodologies used for the selection of sunscreen products for an FDA-sponsored proof-of-concept maximal usage clinical trial. An IVPT method was developed using human cadaver skin. Commercially available sunscreen products were tested to determine the skin absorption potential of common UV filters using the IVPT. All the studied sunscreen products demonstrated a certain degree of skin absorption of UV filters using IVPT, and a formulation rank order was obtained. These sunscreen products were also characterized for several formulation properties including the globule size in emulsions, which was found to be an indicator for the rank order.


Isolation of plasma membranes from Xenopus embryos.
Plasma membranes were isolated in high yield from Xenopus gastrulae by repeated sedimentation in discontinuous sucrose gradients. Most of the yolk was separated by lowspeed sedimentation before centrifugation on the discontinuous sucrose gradients. The isolation of plasma membranes was followed by covalent labelling of the surface of dissociated gastrula cells with diazoniobenzene sulphonate, by electron microscopy and the distribution of enzymatic markers. The isolated plasma membranes have a low neural inducing activity as compared to other cell constituents.


The antitumor effects of methyl-β-cyclodextrin against primary effusion lymphoma via the depletion of cholesterol from lipid rafts.
Primary effusion lymphoma (PEL) is a subtype of aggressive and chemotherapy-resistant non-Hodgkin lymphoma that occurs predominantly in patients with advanced AIDS. In this study, we examined the antitumor activity of methyl-β-cyclodextrin (M-β-CyD) in vitro and in vivo. M-β-CyD quickly induced caspase-dependent apoptosis in PEL cells via cholesterol depletion from the plasma membrane. In a PEL xenograft mouse model, M-β-CyD significantly inhibited the growth and invasion of PEL cells without apparent adverse effects. These results strongly suggest that M-β-CyD has the potential to be an effective antitumor agent against PEL.


The uptake of distearoylphosphatidylcholine/cholesterol liposomes by rat intestinal sacs in vitro.
The uptake of free and liposome-entrapped 125I-labelled polyvinylpyrrolidone was measured in an intestinal sac preparation from adult rats. At an equal concentration of 125I-labelled polyvinylpyrrolidone, the rate of uptake of the liposome-entrapped macromolecule by the tissue was over 4-times that of the free macromolecule. The quantity of 125I-labelled polyvinylpyrrolidone present in the serosal fluid of gut sacs, cultured for 2 h, was 1.8-times greater when the macromolecule was entrapped in liposomes than when it was free in the culture medium. When gut sacs were cultured with liposome-entrapped macromolecule, approx. 50% of the total 125I-labelled polyvinylpyrrolidone present in the serosal fluid was associated with a 100 000 X g liposomal pellet.


Overexpression of ligase defective E6-associated protein, E6-AP, results in mammary tumorigenesis.
E6-associated protein (E6-AP) is a dual function protein. It acts as an E3 ubiquitin-protein ligase enzyme and coactivator of steroid hormone receptors such as estrogen (ERα) and progesterone (PR) receptors. It promotes the degradation of ERα and PR through the ubiquitin-proteasome pathway. Furthermore, it has been shown that the levels of E6-AP are inversely associated with that of ERα in human breast tumors. But the role of wild-type human E6-AP and its ubiquitin-protein ligase activity in mammary tumorigenesis is still unknown. To investigate this role, the authors utilized transgenic mice lines that specifically overexpress either the wild-type human E6-AP (E6-AP(WT)) or the ubiquitin-protein ligase defective E6-AP that contains C833S mutation (E6-AP(C833S)) in the mammary gland. To further substantiate the role of E6-AP in the development of breast tumorigenesis, it was also examined the expression of E6-AP in a large cohort of human breast cancer samples. The transgenic mice that overexpress wild-type E6-AP (E6-AP(WT)) fail to develop mammary tumors. Unlike the E6-AP(WT) mice, the E6-AP(C833S) mice that overexpress ubiquitin-protein ligase defective E6-AP protein develop mammary hyperplasia with a median latency of 18 months. These observations suggest that the inactivation of the ubiquitin-protein ligase function of E6-AP is sufficient to initiate the process of mammary tumor development. Furthermore, the data also suggests that E6-AP exerts its effects on target cells by modulating the protein levels and functions of ERα and PR. In addition, it was found in human breast cancer patients that the level of E6-AP is decreased in invasive breast tumors compared to normal breast tissue. Moreover, the authors also show that the survival patterns for E6-AP negative patients were worse compared to E6-AP positive patients. Taken together, these data suggests that E6-AP may act as a tumor suppressor in breast.


Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
Epidemiological studies demonstrate an association between classes of obesity and psychiatric disorders, although little is known about shared genetics and causality of association. Thus, we aimed to investigate shared genetics and causal link between different classes of obesity and psychiatric disorders. We used genome-wide association study (GWAS) summary data range from 9725 to 500,199 sample sizes of European descent, conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between the classes of obesity and anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. We conducted transcriptome-wide association study analysis (TWAS) to identified variants regulated gene expression in those related disorders. Finally, pathway enrichment analysis to identified major pathways. In the combined analysis, we replicated 211 previously reported loci and discovered 58 novel independent loci that were associated with all three classes of obesity and related psychiatric disorders. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to exocrine/endocrine, digestive, circulatory, adipose, digestive, respiratory, and nervous systems, such as DCC, NEGR1, INO80E. Mendelian randomization analyses suggested that there may be a two-way or one-way causal relationship between obesity and psychiatric disorders. This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between classes of obesity and psychiatric disorders (attention deficit hyperactivity disorder, autism spectrum disorder, anorexia nervosa, major depressive disorder, schizophrenia, and obsessive-compulsive disorder). Such shared genetics suggests potential new biological functions in common among them.


Neuroprotective effects of ethanolic extract from dry Rhodiola rosea L. rhizomes.
Rhodiola rosea L. rhizome has been used as a traditional medicine to treat fatigue, depression, and cognitive dysfunction. We aimed to authenticate R. rosea L. rhizome using the DNA barcoding technique and to quantify its main compounds, total phenolics, total flavonoids, and antioxidant capacity, and then to investigate their neuroprotective effects. The sequences of internal transcribed spacer and trnH-psbA of R. rosea L. rhizomes showed a 99% identity with those of NCBI GenBank database according to BLAST searches. Analysis using reversed-phase HPLC revealed five main compounds in R. rosea L. rhizome. Rhodiola rosea L. rhizome and two bioactive compounds, salidroside and tyrosol, showed free radical scavenging activity. Rhodiola rosea L. rhizome and its identified compounds protected neuronal PC-12 cells against oxidative stress and showed moderate acetylcholinesterase inhibition. Taken together, these results suggest that R. rosea L. rhizomes with bioactives can be used as a functional ingredient with potential for neuroprotection. The online version of this article (doi:10.1007/s10068-020-00868-7) contains supplementary material, which is available to authorized users.


anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells.
Aberrant vascular network is a hallmark of cancer. However, the role of vascular endothelial cells (VECs)-expressing PD-L1 in tumor immune microenvironment and antiangiogenic therapy remains unclear. In this study, we used the specimens of cancer patients for immunohistochemical staining to observe the number of PD-L1+ CD34+ VECs and infiltrated immune cells inside tumor specimens. Immunofluorescence staining and flow cytometry were performed to observe the infiltration of CD8+ T cells and FoxP3+ T cells in tumor tissues. Here, we found that PD-L1 expression on VECs determined CD8+ T cells', FoxP3+ T cells' infiltration, and the prognosis of patients with lung adenocarcinoma. Anlotinib downregulated PD-L1 expression on VECs through the inactivation of AKT pathway, thereby improving the ratio of CD8/FoxP3 inside tumor and remolding the immune microenvironment. In conclusion, our results demonstrate that PD-L1 high expression on VECs inhibits the infiltration of CD8+ T cells, whereas promotes the aggregation of FoxP3+ T cells into tumor tissues, thus becoming an "immunosuppressive barrier". Anlotinib can ameliorate the immuno-microenvironment by downregulating PD-L1 expression on VECs to inhibit tumor growth.


Incorporating patients' views in guideline development: a systematic review of guidance documents.
To assess how guidance documents for developing clinical guidelines (CGs) address the incorporation of patients' views in CGs. Systematic review to identify the methodology provided in guidance documents for incorporating (1) patients or representatives and (2) patients' views in the CG development process. The search was performed in 2017 in five databases. Two authors selected the studies, and data extraction was double-checked. We included guidance documents from 56 institutions. Of those, 40 (71.4%) recommended the inclusion of patients or their representatives, mainly for developing recommendations (14/40, 35.0%); reviewing the final version (13/40, 32.5%); formulating clinical questions (13/40, 32.5%); defining the scope and objectives (10/40, 25.0%); and dissemination and implementation (10/40, 25.0%). Concrete methods on how to incorporate patients were provided by 47.5% (19/40) of institutions. Forty (71.4%) institutions provided additional strategies to incorporate patients' views. The majority (30/40, 75.0%) suggested sources for obtaining these views (consultation with patients [24/40, 60.0%], using panels' judgment [10/40, 25.0%], conducting de novo research [10/40, 25.0%], or a systematic review [9/40, 22.5%]). Although most institutions suggest incorporating patients and their views when developing CGs, little detail is provided on how to do this. Institutions should provide more guidance as this could have a positive impact in guideline applicability.


Acute carpal tunnel syndrome resulting from haemorrhage into the carpal tunnel in a patient on warfarin.
A case of acute compression neuropathy of the median nerve associated with haemorrhage into the carpal tunnel is presented. The condition occurred spontaneously in a patient on Warfarin for previous deep venous thrombosis. The signs and symptoms were those of acute tenosynovitis originating in the common flexor synovial sheath at the wrist with associated paraesthesia in the distribution area of the median nerve in the hand. The patient was afebrile and blood tests were normal.


Intelligence quotient and cognitive functions in severe restricting-type anorexia nervosa before and after weight gain.
Restricting-type anorexia nervosa (AN-R), characterized by severe emaciation with long-term food restriction, is often difficult to treat. The present study investigated the overall intelligence quotient (IQ) scores and cognitive functions of patients with AN-R. Fourteen female inpatients with AN-R (body mass index 12.84 ± 0.41 kg/m²) and 10 healthy female participants participated in this study from 2007 through 2010. The Wechsler Adult Intelligence Scale, Third Edition and the Eating Disorder Inventory-II were administered. This research was performed at Kagoshima University Hospital. In the AN-R group, overall IQ scores showed borderline intelligence (e.g., full-scale IQ 75.86 ± 1.79, P < 0.01); the scores were significantly lower than those in the comparison group. There were negative correlations between lower IQs and higher Eating Disorder Inventory-II scores. After the weight restoration, the IQ scores of subjects with AN-R with regard to the visuospatial scales were significantly higher than before (P < 0.01); however, the auditory cognitive scores were unchanged. These lower IQ scores could be connected to the psychological and behavioral traits in patients with AN-R. These problems should be considered by medical staff members who seek to treat patients with AN-R successfully.


Relationship between intact parathyroid hormone and all-cause death, cardiovascular events, and ectopic calcification in patients with diabetic kidney disease: A retrospective study.
We aimed to investigate the relationship between intact parathyroid hormone (iPTH) levels and all-cause death, cardiovascular events, and ectopic calcification in patients with diabetic kidney disease (DKD). In this retrospective cohort study, we collected the clinical data of 508 patients with clinically diagnosed DKD. The primary and secondary outcomes were all-cause death or cardiovascular events and ectopic calcification, respectively. We used different regression methods to analyze the relationship between various clinical parameters and the two clinical outcomes. We found that iPTH was a risk factor for all-cause death and cardiovascular events (hazards ration [HR]: 2.817, 95% confidence interval [CI]: 1.045-6.562, P = 0.016). Meanwhile, diabetes duration (HR: 1.090, 95% CI: 1.045-1.138, P < 0.0001), triglycerides (TG) (HR: 1.254, 95% CI: 1.049-1.499, P = 0.013), and iPTH (HR: 1.954, 95% CI: 1.001-3.813, P = 0.049) were independent risk factors for ectopic calcification. In contrast to patients with lower iPTH levels (iPTH < 31.7 pg/mL), patients with higher iPTH levels (iPTH ≥ 31.7 pg/mL) had increased ectopic calcification rate (P = 0.002) and decreased survival time (P < 0.001). In patients with DKD, higher iPTH levels were significantly related to worsen clinical outcomes.


Induction profile of HSP70-cognate genes by environmental pollutants in Chironomidae.
Several species of invertebrates have been studied to examine the toxicological effects of chemicals that include insecticides and heavy metals. We characterized heat-shock protein (hsp) genes from the ubiquitous midge, Chironomidae. More than 70 fold induction of hsp70 expression was detected by quantitative PCR after 37°C treatment in the midge. Expression of hsp70 was induced not only by heat but also by exposure to insecticides and heavy metals such as cadmium and copper. Expression time courses for hsp70 were highly specific to each chemical. When midges were exposed to sub-lethal level of a pyrethroid insecticide, ethofenprox, hsp70 expression was increased over 20 fold with a transient peak at 1.5h. Heavy metal exposure led to delayed hsp70 up regulation of 7 fold at 6-7h. Expression of another hsp70-cognate gene (hsc70) was also characterized. Using these genes we propose a novel system for biomonitoring of heavy metals and other pollutants.


Macrophage Migration Inhibitory Factor Promotes Expression of Matrix Metalloproteinases 1 and 3 in Spinal Cord Astrocytes following Gecko Tail Amputation.
The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play a variety of physiological and pathological roles in development, remodeling of tissues and diseases, mainly through degradation of various components of the extracellular matrix (ECM). Particularly, the MMPs have increasingly been found to mediate neuropathology following spinal cord injury (SCI). Proinflammatory mediators are potent activators of the MMPs. However, how the spinal cord regenerative vertebrates circumvent MMPs-mediated neuropathogenesis following SCI remains unclear. Following the establishment of gecko tail amputation model, the correlation of MMP-1 (gMMP-1) and MMP-3 (gMMP-3) expression with that of macrophage migration inhibitory factor in gecko (gMIF) was assayed by RT-PCR, Western blot and immunohistochemistry. Transcriptome sequencing of primary astrocytes was performed to analyze the intracellular signal transduction of macrophage migration inhibitory factor (MIF). The effects of MMP-1 and MMP-3 induced by MIF on astrocyte migration were assessed by transwell migration assay. The expression of gMIF significantly increased at lesion site of the injured cord, in parallel with those of gMMP-1 and gMMP-3 in the gecko astrocytes (gAS). Transcriptome sequencing and in vitro cell model revealed that gMIF efficiently promoted the expression of gMMP-1 and gMMP-3 in gAS, which in turn contributed to the migration of gAS. Inhibition of gMIF activity following gecko SCI remarkably attenuated astrocytic expression of the two MMPs, and further influenced gecko tail regeneration. Gecko SCI following tail amputation promoted production of gMIF, which induced the expression of gMMP-1 and gMMP-3 in gAS. The gMIF-mediated gMMP-1 and gMMP-3 expression was involved in gAS migration and successful tail regeneration.


Expression of codon optimized major capsid protein (L1) of human papillomavirus type 16 and 18 in Pichia pastoris; purification and characterization of the virus-like particles.
The major capsid protein (L1) of human papillomaviruses (HPV) expressed in heterologous systems assembles into virus-like particles (VLPs). We report cloning and expression of codon optimized HPV L1 genes of the two high-risk HPV types 16 and 18 in methylotropic yeast, Pichia pastoris. The VLPs produced in P. pastoris were subjected to three step purification method involving density gradient centrifugations and size exclusion chromatography. The enriched VLPs were characterized using conformation-specific monoclonal antibodies in ELISA and by transmission electron microscopy. Mice immunized with a bivalent HPV16 and HPV18 VLPs developed high serum antibody titers to both HPV types that persisted for 190 days post vaccination. Serum of mice immunized with the HPV-VLP preparations could neutralize homologous pseudoviruses in an in vitro assays. Our results demonstrate that the L1 proteins expressed in P. pastoris fold properly as evidenced by assembly into VLPs and induction of type-specific neutralizing antibody response in mice. This work constitutes a step towards developing an alternate production platform for generating an affordable HPV vaccine to meet the needs of developing countries.


Mechanical effects of needle texture on acupoint tissue.
This study aims to clarify how the stimulation of acupuncture points is achieved by needles with different surface texture during acupuncture; it also seeks to lessen injury at the insertion site and increase the therapeutic efficacy of acupuncture, by simulating the mechanical effects of various needle surface patterns on Zusanli (ST36) without changing the radius of acupuncture needles. Five acupuncture needle models with different surface patterns, including the smooth needle, the lined needle, the ringed needle, the left-hand threaded needle and the right-hand threaded needle, and a layered model of the Zusanli acupoint were used to investigate how to reduce tissue damage and increase stimulation during acupuncture treatment. Puncturing of the skin as well as lifting-inserting and twisting needle manipulations were simulated using these models, and the degree of damage and force of stimulation caused by the acupuncture needles with different surface patterns during acupuncture were compared. The smooth needle and the lined needle caused the least tissue damage during insertion, while the left-hand threaded and the right-hand threaded needles caused the most damage. The ringed needle, the left-hand threaded needle and the right-hand threaded needle stimulated the acupoint tissue more during lifting-inserting manipulations, while the lined needle and the smooth needle produced less stimulation. The stimulation of the lined needle on the acupoint tissue was the largest during twisting manipulation, whereas the left-hand threaded needle and the right-hand threaded needle had smaller effects. In lifting-inserting and twisting manipulations, both the left-hand threaded needle and right-hand threaded needle provided more stimulation, but the torsion direction in which they produced better stimulation was the opposite. According to the simulation results, the ringed pattern enhances stimulation best in the lifting-inserting manipulation, whereas the lined pattern enhances stimulation best in the twisting manipulation. Both the right-hand and left-hand thread patterns have certain enhancing effects in these two operations. Taking the geometric properties of the pattern into account, the left-hand thread pattern and the right-hand thread pattern have the geometric characteristics of both the lined pattern and the ringed pattern. To conclude, a pattern perpendicular to the movement direction during the acupuncture manipulation creates more stimulation. These results have significance for future needle design. Please cite this article as: Sun MZ, Wang X, Li YC, Yao W, Gu W. Mechanical effects of needle texture on acupoint tissue. J Integr Med. 2023; 21(3): 254-267.


Therapeutic use of exchange transfusion in malaria.
In the case reported here, a patient with severe Plasmodium falciparum infection with 20% of erythrocytes parasitized was cured by exchange transfusion in conjunction with classical drug therapy.


User Experience of Training Pediatric Students on Interactive Simulator During COVID-19 Pandemic.
COVID-19 pandemic is a reason to revise traditional approaches to medical education. The disadvantage of online education is inability to train practical skills. To evaluate the effectiveness of training students on an interactive pediatric simulator during distance learning. An online survey was conducted during quarantine COVID-19 to clear out the attitude to distance learning of third-year students of the Sechenov First Moscow State Medical University (n = 150). During training the level of students' motivation to learn decreased, and what is most important their practical skills deteriorated. Eighty-four out of 150 students had the effectiveness of their training on the multimedia simulator "Filatov. Pediatrics" analyzed. The simulator reproduces clinical tasks using three-dimensional models of children of different ages and genders and has access to personal computers of students. The cases include imitation of a dialogue with a virtual patient, methods of physical examination, the appointment of laboratory and instrumental methods of research, treatment. The use of a pediatric simulator showed greater efficiency in mastering practical skills compared to a group of students who did not use the simulator in class. Summing up the results of the intermediate objective structured clinical exam (OSCE) on physical examination on dummies of the Simulation and Accreditation Center showed better results in the main group (n = 48) compared to the control (n = 36). The students who additionally studied on the simulator completed the tasks on the checklist on a cardiology dummy by 98.3 ± 1.5%. In the control group, the percentage of completed tasks was 94.3 ± 1.3 (p = 0.05). The OSCE for examining the respiratory system on an auscultative dummy revealed 97.3 ± 1.5 and 93.1 ± 1.4%, respectively (p = 0.05). The interactive pediatric simulator is a tool for mastering practical skills of medical students during the COVID-19 pandemic, with the use of which the OSCE results are significantly higher.


Comparison of measures of visual acuity in infants: Teller acuity cards and sweep visual evoked potentials.
This study compares the development of acuity in the same infants during one testing session using Teller acuity cards (TAC) and sweep visual evoked potentials (sVEP). We asked whether different testing methods in two centers would produce different developmental time courses. Forty-eight infants were tested in two centers. The standard procedure for TAC was used. For sVEP acuity, the amplitude response curve derived from time-locked cortical activity was used to extrapolate to zero response, giving an acuity estimate for each infant. sVEP acuity was generally higher than TAC acuity. The rate of development was steeper for TAC than sVEP acuity with TAC starting at a much lower level. The ratio of sVEP to TAC acuity decreased exponentially with age reaching an asymptote of about 1.44 at 6 months. Results were indistinguishable between centers suggesting that comparison of acuity measures obtained using variations of these methods across centers is possible.


The journey to Magnet: establishing a research infrastructure.
Developing and sustaining a research infrastructure that meets Magnet program requirements are daunting responsibilities. Our Lady of the Lake Regional Medical Center in Louisiana created the program director of nursing research position to coordinate the research council and ongoing projects. This article discusses the process of developing and improving a nursing research program.


Prevalence of type 1 diabetes mellitus in 6-18-yr-old school children living in Istanbul, Turkey.
Type 1 diabetes mellitus (T1DM) is among the most common chronic diseases in childhood and the incidence of T1DM is increasing worldwide. There is no actual data regarding the frequency of T1DM in Turkish children. We aimed to assess current prevalence of T1DM in 6-18-yr-old school children living in Istanbul. Total number of students and children on insulin treatment were reported by the schools, as the first part of the study. At the second step, the study team visited 203 schools for confirmation of the reported data. One thousand and ninety children in a population of 1 630 751 school children were reported to have T1DM, which made the total prevalence of T1DM 0.67/1000 (95% confidence interval 0.6/1000-0.7/1000). A population of 217 030 children (α=0.05 and β=0.20) from 203 schools were screened. The difference between the reported and detected prevalence was 0.032/1000 (215 detected vs. 222 reported, p>0.05). Comparison of the current data with the prevalence reported in a smaller population in Ankara, Turkey, 16 yr ago, demonstrated that the prevalence of T1DM is higher in the current study (0.46/1000 vs. 0.16/1000, 0.57/1000 vs. 0.34/1000, and 0.92/1000 vs. 0.69/1000 at primary, secondary, and high schools, respectively). This first pediatric T1DM prevalence data in a large pediatric population in Istanbul, Turkey, estimated the prevalence of T1DM as 0.67/1000. This prevalence is 2.5-fold higher than that reported in Ankara, Turkey, in 1993, suggesting that T1DM prevalence is increasing in Turkey as in the other parts of the world.


Tensions of network security and collaborative work practice: understanding a single sign-on deployment in a regional hospital.
Healthcare providers and their IT staff, working in an effort to balance appropriate accessibility with stricter security mandates, are considering the use of a single network sign-on approach for authentication and password management. Single sign-on (SSO) promises to improve usability of authentication for multiple-system users, increase compliance, and help curb system maintenance costs. However, complexities are introduced when SSO is placed within a collaborative environment. These complexities include unanticipated workflow implications that introduce greater security vulnerability for the individual user. OBJECTIVES AND METHODOLOGY: In this work, we examine the challenges of implementing a single sign-on authentication technology in a hospital environment. The aim of the study was to document the factors that affected SSO adoption within the context of use. The ultimate goal is to better inform the design of usable authentication systems within collaborative healthcare work sites. The primary data collection techniques used are ethnographically informed - observation, contextual interviews, and document review. The study included a cross-section of individuals from various departments and varying rolls. These participants were a mix of both clinical and administrative staff, as well as the Information Technology group. The field work revealed fundamental mis-matches between the technology and routine work practices that will significantly impact its effective adoption. While single sign-on was effective in the administrative offices, SSO was not a good fit for collaborative areas. The collaborative needs of the clinical staff unearthed tensions in its implementation. An analysis of the findings revealed that the workflow, activities, and physical environment of the clinical areas create increased security vulnerabilities for the individual user. The clinical users were cognizant of these vulnerabilities and this created resistance to the implementation due to a concern for privacy. From a preliminary analysis of our on-going field study at a community hospital, there appears to be a number of mismatches between the SSO vision and the realities of routine work. While we cannot conclusively say if a SSO adoption will be effective in meeting its goals in a hospital environment, we do know that it will affect the work practice and that will make the management of the SSO system problematic.


Effects of Mercapto-functionalized Nanosilica on Cd Stabilization and Uptake by Wheat Seedling (Triticum aestivum L.) in an Agricultural Soil.
In the present study, a pot-culture experiment was conducted to investigate the influences of mercapto-functionalized nanosilica (MPTS/nano-silica) on Cd stabilization and uptake by wheat seedling. Four different dosages of MPTS/nano-silica were applied: 0%, 0.3%, 0.6% and 1% (w/w), and the changes of DTPA-extractable Cd in soil, soil properties, wheat biomass, and uptake of Cd to wheat tissues (shoots and roots) were measured throughout the experiment. The results showed that the application of MPTS/nano-silica (at dose of 1%) reduced the DTPA-extractable Cd from 4.21 to 1.45 mg/kg in the soil. Whereas the addition of MPTS/nano-silica hardly changed soil properties and slightly decreased the biomass of wheat seedling. In addition, Cd concentration in wheat tissues decreased from 6.388 to 2.625 mg/kg for shoot, and from 18.622 to 6.368 mg/kg for root. These results indicated that MPTS/nano-silica is an ideal candidate for remediation of Cd contaminated agricultural soil.


Urinary extracellular vesicles. A promising shortcut to novel biomarker discoveries.
Proteomic and genomic techniques have reached full maturity and are providing unforeseen details for the comprehensive understanding of disease pathologies at a fraction of previous costs. However, for kidney diseases, many gaps in such information remain to inhibit major advances in the prevention, treatment and diagnostics of these devastating diseases, which have enormous global impact. The discovery of ubiquitous extracellular vesicles (EV) in all bodily fluids is rapidly increasing the fundamental knowledge of disease mechanisms and the ways in which cells communicate with distant locations in processes of cancer spread, immunological regulation, barrier functions and general modulation of cellular activity. In this review, we describe some of the most prominent research streams and findings utilizing urinary extracellular vesicles as highly versatile and dynamic tools with their extraordinary protein and small regulatory RNA species. While being a highly promising approach, the relatively young field of EV research suffers from a lack of adherence to strict standardization and carefully scrutinized methods for obtaining fully reproducible results. With the appropriate guidelines and standardization achieved, urine is foreseen as forming a unique, robust and easy route for determining accurate and personalized disease signatures and as providing highly useful early biomarkers of the disease pathology of the kidney and beyond.


BanI/D13S141/D13S175 represents a novel informative haplotype at the GJB2 gene region in the Iranian population.
Non-syndromic sensorineural hearing loss (NSHL) represents the most common cause of hearing loss in the Iranian patients. In view of the large numbers of mutations identified in GJB2, mutations analysis of the gene has been time-consuming and cost-ineffective. Alternatively, molecular markers that are highly linked to the GJB2 gene have proven to be useful in carrier detection and prenatal diagnosis of NSHL families. These markers usually show a population-dependent-based haplotype frequency. However, to date, no information on the genotyping and frequency of the markers is present for the Iranian population. In this study, genotyping and analysis of the haplotype frequency of three markers, including BanI, D13S141, and D13S175, at the GJB2 region were investigated. The haplotype frequency was estimated using PHASE program. The input data contained two alleles (+ and -) for BanI, four alleles for D13S141, and seven alleles for D13S175. Among the 42 possible haplotypes examined, four haplotypes showed relatively high frequencies (≥5%). Therefore, a combination of BanI/D13S141/D13S175 could be suggested as an informative haplotype for possible carrier detection and prenatal diagnosis of NSHL in the Iranian population.


Altered patterns and synthesis of extracellular matrix macromolecules in early osteoarthritis.
The synthesis and contents of extracellular non-collagenous matrix macromolecules was studied in early and late human osteoarthritic (OA) cartilage obtained at surgery for sarcomas in the lower extremities (normal and early OA) or for total knee replacement (late stage OA). The early OA samples were those that had some fibrillation in the joint by visual examination. One group had fibrillation in the area sampled and the other group had no fibrillation. Cartilage was taken from the same topographical area on the medial femoral condyle in all the samples, labeled with [3H]leucine and [35S]sulfate for 4 h at 37 degrees C and extracted with 4 M guanidine-HCl. Analysis of the extracts showed that the total amount of proteoglycans relative to hydroxyproline content was higher in the early and late OA than in the normal cartilage. These proteoglycans showed a relatively lower [35S]sulfate incorporation into GAG chains and a higher [3H]leucine incorporation. The pattern of newly synthesized proteins was altered similarly in early and late OA. Notably, synthesis of cartilage oligomeric matrix protein (COMP), fibronectin, and cartilage intermediate layer protein (CILP) was increased, also reflected in their abundance as determined by enzyme-linked immunosorbent assay (ELISA). Collagen synthesis appeared significantly increased only in the late stage OA. The observed altered composition and pattern of biosynthesis indicate that the joint undergoes metabolic alterations early in the disease process, even before there is overt fibrillation of the tissue. The early OA samples studied appear to represent two distinct groups of early lesions in different stages of the process of cartilage deterioration as shown by their differences in relative rates of synthesis and abundance of proteins.


Processing of self-initiated sound motion in the human brain.
Interacting with objects in our environment usually leads to audible noise. Brain responses to such self-initiated sounds have been shown to be attenuated, in particular the so-called N1 component measured with electroencephalography (EEG). This attenuation has been proposed to be the effect of an internal forward model that allows for cancellation of the sensory consequences of a motor command. In the current study we asked whether the attenuation due to self-initiation of a sound also affects a later event-related potential - the so-called motion-onset response - that arises in response to moving sounds. To this end, volunteers were instructed to move their index fingers either left or rightward which resulted in virtual movement of a sound either to the left or to the right. In Experiment 1, sound motion was induced with in-ear head-phones by shifting interaural time and intensity differences and thus shifting the intracranial sound image. We compared the motion-onset responses under two conditions: a) congruent, and b) incongruent. In the congruent condition, the sound image moved in the direction of the finger movement, while in the incongruent condition sound motion was in the opposite direction of the finger movement. Clear motion-onset responses with a negative cN1 component peaking at about 160 ms and a positive cP2 component peaking at about 230 ms after motion-onset were obtained for both the congruent and incongruent conditions. However, the motion-onset responses did not significantly differ between congruent and incongruent conditions in amplitude or latency. In Experiment 2, in which sounds were presented with loudspeakers, we observed attenuation for self-induced versus externally triggered sound motion-onset, but again, there was no difference between congruent and incongruent conditions. In sum, these two experiments suggest that the motion-onset response measured by EEG can be attenuated for self-generated sounds. However, our result did not indicate that this attenuation depended on congruency of action and sound motion direction.


The inducibility of human cytochrome P450 1A by environmental-relevant xenobiotics in the human hepatoma derived cell line HepG2.
Overexpression of the CYP1 family, independent of gender, is focal to the evaluation of the risk of human cancer. We have analysed the ability of 17 anthropogenic environmental xenobiotics widely used in Europe within households and agriculture to induce the human cytochrome P450 1A (CYP1A) in the human hepatoma derived cell line HepG2. The xenobiotics were potent to concomitantly induce both CYP1A mRNA and CYP1A activity in a dose-response relationship. Exceptions were shown by the organophosphate insecticide chlorpyrifos and the imidazole fungicide prochloraz in high concentrations which were capable of both inhibiting the basal or abolishing the initially induced CYP1A activity, respectively. A CYP1A induction has been shown for the first time by the aromatic xenobiotics irgasan, permethrin and azoxystrobin, the nonaromatic tributyltinoxide and for humans by the piperonylbutoxide. The xenobiotics additionally differed by their induced CYP1A isoenzyme pattern. A pronounced CYP1A1 and CYP1A2 mRNA induction was given by the phenyl urea herbicide diuron and benzodiazole insecticide piperonylbutoxide, respectively. In conclusion, out of the environmental xenobiotics, we described new members of human CYP1A inducers which extend chemical structures of biotransformation activators.


Impaction of a shrapnel splinter in the common bile duct after migrating from the right thoracic cavity: report of a case.
Biliary obstruction is rarely caused by a foreign body. This report describes the case of a 60-year-old Japanese man with jaundice caused by an impacted shrapnel splinter in the common bile duct (CBD) that had migrated from the right thoracic cavity 36 years after initial injury. Biochemical data showed a total bilirubin level of 4.2 mg/dl with a direct bilirubin level of 3.1mg/dl, an alanine aminotransferase level of 24IU/l, and an alkaline phosphatase level of 18.5KA units. It was serially documented that the shrapnel had migrated toward the diaphragm, then burrowed into the liver, settling in the CBD, and causing obstructive jaundice. Choledochotomy and T-tube drainage was performed and the postoperative course was uneventful. To our knowledge, this is the first case report of this type of occurrence in the Japanese literature. Although there are few reports of combat injury in Japan, this diagnosis should be considered in the evaluation of any patient with jaundice who has suffered a previous chest wound involving a foreign body.


Supraspinal inhibition of the excitation of dorsal horn neurones by impulses in unmyelinated primary afferents: lack of effect by strychnine and bicuculline.
In barbiturate anaesthetized cats, tonic descending inhibition of the excitation of lumbar dorsal horn neurones by impulses in unmyelinated primary afferents was measured by reversibly cooling a more cephalic segment. Administered electrophoretically in the substantia gelatinosa and at sites progressively closer to cell bodies, amounts of bicuculline and strychnine adequate to reduce segmental inhibition failed to reduce supraspinal inhibition. Intravenous bicuculline and strychnine also failed to reduce supraspinal inhibition.


Differential regulation of duplicate alcohol dehydrogenase genes in Drosophila mojavensis.
These studies report the existence of multiple forms of alcohol dehydrogenase in extracts of Drosophila mojavensis. The existence of these forms can be best explained by the hypothesis of a duplication for the Adh locus in D. mojavensis. Electrophoretic variants at each locus have been identified and crosses between individuals carrying alternative alleles at each locus result in F1 progeny with six bands of ADH. This pattern is consistent with these individuals being heterozygous at two loci. The loci have been named Adh-1 and Adh-2. Examination of the isozyme content during development shows that the two Adh genes are not coordinately controlled but have separate developmental programs. In embryos and first and second instar larvae only Adh-1 is expressed. At about the time of the second molt Adh-2 expression commences in some of the same cells that previously expressed and continue to express Adh-1. This is evidenced by the existence of an interlocus heterodimer in third instar larvae. Both genes are expressed throughout pupation. Shortly after emergence Adh-1 expression declines. In mature males only ADH-2 is present. In mature females both Adh-1 and Adh-2 are expressed but not in the same cells since the interlocus heterodimer is absent. Examination of specific tissues reveals that most of the larval ADH is found in fat body cells and as in most tissues of third instar larvae both Adh-1 and Adh-2 are expressed. The single exception appears to be larval gut which contains ADH-1 but little if any ADH-2. In mature males and female flies all ADH containing tissues have only ADH-2. However, mature ovaries contain substantial quantities of ADH-1 which is apparently deposited into eggs. Given the extensive amount of available information on the Adh gene-enzyme system of D. melanogaster and the tools that can be applied to the analysis of homologous systems, the ADH duplication of D. mojavensis, and its regulation may be a useful one for studying differential gene regulation in specific cell types.


Impact of motivational interviewing training on emergency department nurses' skills: A one-group pretest-posttest pilot study.
Overdose from opioid abuse is an increasing cause of mortality worldwide. Emergency department nurses experience barriers when caring for patients with illicit opioid use. Motivational interviewing (MI) may help address these barriers. A one-group pretest-posttest design was used to investigate the impact of an eight-hour MI training workshop for 39 emergency department nurses at a community hospital. Audio-recorded interviews of nurses with standardized patients were assessed before, immediately after, and three to five months after training. Proficiency was assessed using the Motivational Interviewing Treatment Integrity 4.2.1. Paired t-test analysis found statistically significant technical score increases from 2.20 (SD = 0.64) to 2.51 (SD = 0.52, p = 0.02) but not in relational scores, 2.04 (SD = 0.59) to 2.46 (SD = 0.53, p = 0.06), during the immediate pretest-posttest period. At follow-up, proficiency in MI was unattained and both technical (2.35, SD = 0.61, p = 0.49) and relational scores regressed (2.08, SD 0.74, p = 0.19). Although short-term improvements in technical scores were observed, proficiency in MI was not attained and skills regressed over time. This suggests that a one-day training session may be inadequate. On-going coaching and supervision may be beneficial to maintain MI skills.


Group- and individual-level coincidence of the 'Fatmax' and lactate accumulation in adolescents.
Fatmax and lactate increase above baseline (LIAB) were measured in 11 adolescent girls and 8 adolescent boys during incremental cycling. Fatmax was the exercise intensity at the point of maximal fat oxidation rate (MFO). The LIAB was the exercise intensity coincident with a sustained increase in blood (lactate) above an initial baseline. We defined the minimum important difference (MID) between the exercise intensity at Fatmax and LIAB as +/-8% of both peak VO2 and peak heart rate (HR). Systematic bias was examined via the mean difference between parameters and its uncertainty, with inference based on the disposition of the confidence interval to the MID. Individual-level agreement was the proportion of differences between Fatmax and LIAB falling within the MID. MFO was at 35 (6)% peak VO2 with LIAB at 39 (7)% peak VO2 Systematic bias was -3.8% of peak VO2 and -4.4% of peak HR. The estimated population proportion with between-variable agreement within +/-8% was 0.76 for both % peak VO2 and % peak HR. Within the tolerance limits of the MID, the mean bias is 'almost certainly not' important; similarly, there is good agreement between the two parameters at the individual level. We conclude that Fatmax and lactate increase above baseline coincide in adolescents.


Immunohistochemical detection of sphingosine-1-phosphate and sphingosine kinase-1 in human tissue samples.
Sphingosine-1-phosphate (S1P) and the enzyme primarily responsible for its production, sphingosine kinase-1 (SphK-1), are thought to be dysregulated in multiple human diseases including cancer, multiple sclerosis (MS), diabetes, neurological diseases, fibrosis, and certain pathologies associated with impaired angiogenesis such as, age-related macular degeneration (AMD). Antibody-based techniques to identify and localize S1P and SphK-1 within cells and tissue specimens represent powerful tools not only to understand the biological role of these molecules but also to validate these unique in-class targets in multiple state diseases. Consequently, the potential applications of these molecules for therapy and diagnostic purposes are currently under investigation. Here, we describe two staining procedures for identification of S1P and SphK-1 in human frozen tissue samples and the challenges encountered in the process of localization in tissue samples of lipid molecules, such as S1P.


Alcohol dependence promotes systemic IFN-γ and IL-17 responses in mice.
Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. AUD is associated with a variety of physiological changes and is a substantial risk factor for numerous diseases. We aimed to characterize systemic alterations in immune responses using a well-established mouse model of chronic intermittent alcohol exposure to induce alcohol dependence. We exposed mice to chronic intermittent ethanol vapor for 4 weeks and analyzed the expression of cytokines IFN-γ, IL-4, IL-10, IL-12 and IL-17 by different immune cells in the blood, spleen and liver of alcohol dependent and non-dependent control mice through multiparametric flow cytometry. We found increases in IFN-γ and IL-17 expression in a cell type- and organ-specific manner. Often, B cells and neutrophils were primary contributors to increased IFN-γ and IL-17 levels while other cell types played a secondary role. We conclude that chronic alcohol exposure promotes systemic pro-inflammatory IFN-γ and IL-17 responses in mice. These responses are likely important in the development of alcohol-related diseases, but further characterization is necessary to understand the initiation and effects of systemic inflammatory responses to chronic alcohol exposure.


Genetic damage induced by ethyl alcohol in Aspergillus nidulans.
Heterozygous diploid conidia of Aspergillus nidulans were treated during germination with ethyl alcohol in concentrations ranging from 0.25% to 20% (v/v). The diploid strain carried three recessive conidial color mutations, in addition to genetic markers on all eight pairs of linkage groups. It was thereby possible to detect events of crossing over, non-disjunction, and mutation. An increase in the dose of ethanol was associated with a decrease in conidial viability and an increase in the relative and absolute frequencies of formation of (a) normal colonies which produced colored sectors and (b) phenotypically abnormal colonies, the majority of which (83.1%) produced normal sectors. At a concentration of 5% (v/v) ethanol, the survivors included 17.59% of the former and 44.7% of the latter colonies. Genetic analysis of the various segregants suggested that the frequencies of both mitotic crossing over and non-disjunction or the misdistribution of chromosomes were increased by ethanol. Among 133 abnormal colonies which segregated normal clones, 79 (59.4%) were associated with one of these genetic events. A total of 297 haploids and 130 diploids arose as normal segregants from the abnormal colonies. There were 31 recognizable events of non-disjunction and 14 crossing over in linkage groups I and II, where these events could be distinguished. These data suggested that the predominant effect of ethanol was a disruption of chromosome distribution. A cytological examination of ethanol-treated, germinating conidia revealed an interference with the mitotic spindle apparatus. The frequency of detectable spindles decreased more than 3-fold after 8 h exposure to 5% (v/v) ethanol. This finding supported the conclusion that ethanol disrupted chromosome distribution, and suggested the mechanism by which it does so. Human clinical data on alcohol consumption were examined in light of these findings.


Poststroke depression and its multifactorial nature: results from a prospective longitudinal study.
Poststroke depression (PSD) is commonly observed in stroke patients and has a negative impact on functional outcome and quality of life. Therefore, a prospective, longitudinal epidemiological study was conducted aiming to determine prevalence and risk factors for PSD at 1, 3, 6, 12 and 18 months poststroke. A total of 222 patients were included in the study and 201 patients entered data analysis. Demographic data, vascular risk factors, stroke characteristics, functional and neurocognitive outcome measures and psychosocial factors were considered as potential risk factors for PSD. Clinically significant signs and symptoms of PSD were quantified by means of the Cornell Scale for Depression (CSD) and the Montgomery and Åsberg Depression Rating Scale (MADRS). PSD was present at 1, 3, 6, 12 and 18 months poststroke in 24.5%, 27.1%, 28.3%, 19.8% and 26.3% of the patients respectively. Univariate regression analyses revealed that PSD was significantly associated with stroke severity, physical disability, cognitive impairment and stroke outcome during the 18 months time frame of the study. Reduced social activities and the presence of apraxia were consistently associated with PSD whereas aphasia was only significantly associated in the first 6 months after stroke. Patients with relational problems had a 3 times greater risk of becoming depressed at 18 months poststroke than patients without relational problems (OR=3.09; 95% CI=1.31-7.26). Risk factors for PSD seem variable indicating the need for clinicians to consider the dynamic and multifactorial nature of PSD emphasizing the importance of a rigorous and long-term monitoring and support of stroke patients and their caregivers.


Distribution of hepatitis c virus (hcv) genotypes in patients with chronic infection from Rondônia, Brazil.
Hepatitis C virus (HCV) is an important human pathogen affecting around 3% of the human population. In Brazil, it is estimated that there are approximately 2 to 3 million HCV chronic carriers. There are few reports of HCV prevalence in Rondônia State (RO), but it was estimated in 9.7% from 1999 to 2005. The aim of this study was to characterize HCV genotypes in 58 chronic HCV infected patients from Porto Velho, Rondônia (RO), Brazil. A fragment of 380 bp of NS5B region was amplified by nested PCR for genotyping analysis. Viral sequences were characterized by phylogenetic analysis using reference sequences obtained from the GenBank (n = 173). Sequences were aligned using Muscle software and edited in the SE-AL software. Phylogenetic analyses were conducted using Bayesian Markov chain Monte Carlo simulation (MCMC) to obtain the MCC tree using BEAST v.1.5.3. From 58 anti-HCV positive samples, 22 were positive to the NS5B fragment and successfully sequenced. Genotype 1b was the most prevalent in this population (50%), followed by 1a (27.2%), 2b (13.6%) and 3a (9.0%). This study is the first report of HCV genotypes from Rondônia State and subtype 1b was found to be the most prevalent. This subtype is mostly found among people who have a previous history of blood transfusion but more detailed studies with a larger number of patients are necessary to understand the HCV dynamics in the population of Rondônia State, Brazil.


Ocular Manifestations in Rheumatoid Arthritis, Connective Tissue Disease, and Vasculitis: A Systematic Review and Metaanalysis.
Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review. A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis. There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome ("dry eye"; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3-28) and 6% (95% CI 3-9) of patients, respectively. Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.


Measuring healthcare outcomes to improve quality of care across post--acute care provider settings.
Post-acute care (PAC) occurs in a variety of settings-skilled nursing facilities (nursing homes), rehabilitation facilities, and home health agencies. To evaluate the impact of care processes on clinical outcomes and implement changes designed to improve outcomes, one must begin by measuring outcomes in a valid, reliable manner that allows for comparisons to reference or benchmarking data. Currently, several data sets exist in PAC settings for the purpose of outcome measurement. However, there is a need for comparable information across settings to ensure the quality and continuity of care. This article reviews various existing data sets used in PAC settings, examines ongoing projects to create a single set of measures, and suggests some directions for future research.


Rheological, adhesive and release characterisation of semisolid Carbopol/tetraglycol systems.
Gels dosage forms are successfully used as drug delivery systems considering their ability to control drug release and to protect medicaments from an hostile environment. This study deals with the gelation properties of Carbopol 971 e 974 polymeric systems in tetraglycol, a water-miscible cosolvent. In this paper, the attention was noted of the thickening properties of the different Carbopol in tetraglycol solvent at increasing temperatures, in order to obtain gels avoiding neutralisation and, at the same time, to make possible the dissolution in these gels of insoluble or poorly soluble water drugs. Samples were prepared by simply dispersing different Carbopols amount (0.5-4%) were added to tetraglycol and different systems were prepared at room temperature and by heating at 70 degrees C. All these systems were then characterised rheologically. Frequency sweep, creep-recovery, temperature sweep and time sweep analyses outlined that Carbopol 971 and 974 in tetraglycol gave rise after heating to gels with satisfactory rheological behaviour: the elastic modulus was greater than the viscous one and a remarkable elastic character was found to be present. Systems obtained by heating procedure were examined also from a mechanical point of view using a texture profile analysis. Besides, being Carbopols well known mucoadhesive polymers, gels adhesive properties were also studied using the ex vivo method. Texture and adhesion characterisation confirmed rheological results pointing out a certain greater elasticity and adhesiveness of Carbopol 974 systems. Then, the possible cutaneous irritation was also tested using the in vivo method (Draize test). No signs of cutaneous irritation were obtained for all the samples that were analysed. After rheological and mucoadhesive properties were set, paracetamol as a model drug was inserted in the composition of the gels and the release characteristics were defined. Dissolution tests pointed out the greater release control properties of tetraglycol/Carbopol 971 samples. These studies showed tetraglycol/Carbopol systems as a first-rate alternative to traditional water gels when low water-soluble drugs have to be added.


Leukonychias.
White discolorations of the nails are frequent changes. Mostly they are conditioned by traumatic injuries, but many other causes including hereditary diseases, different skin diseases, systemic diseases, and intoxications and exogenous influences can induce complete or partial whitening of the nail. For the diagnostic purpose of these signs, it is necessary to differentiate between leukonychias caused by alteration of the nail plate and conditions caused by modification of the subungeal tissue. Beyond this, the appearance of whitening--total, subtotal, punctuated, striated--has to be considered. For practical identification, the different forms of leukonychias are discussed according to their clinical picture.


Dog training as a complementary intervention to support Veteran mental health and well-being: A scoping review.
Military veterans in the United States face a number of complex issues and barriers to successful civilian reintegration. Dog training programs offered to these individuals are being used as a complementary intervention to support multiple aspects of veteran reintegration. This scoping review explored the existing literature on dog training programs as a support for veteran mental health and well-being. A scoping review was conducted in accordance with PRISMA guidelines to analyze the existing research on this topic. Five overarching themes were identified, including improvements to mental health, social benefits, a developed sense of purpose, differing impacts of training methods, and potential negative outcomes associated with stressful demands of training. The results of this review suggested dog training programs have potentially positive effects on veteran mental health but also revealed a few potential negative impacts and the need for further research on this animal-assisted intervention.


The 2016 SFB congress focused on 'non-thermal burns', and this session lasted the whole day of Thursday 2nd June. While the reports on radiation-induced burns are currently being prepared by the presenters themselves, this paper on chemical and electrical burns was put together by the above-mentioned authors using notes taken during the session and video of the presentations. Any reader desiring further information on a topic can contact the author of the relevant presentation directly.


The Pai-associated leuX specific tRNA5(Leu) affects type 1 fimbriation in pathogenic Escherichia coli by control of FimB recombinase expression.
The uropathogenic Escherichia coli strain 536 (06:K15:H31) carries two large chromosomal pathogenicity islands (Pais). Both Pais are flanked by tRNA genes. Spontaneous deletion of Pai II results in truncation of the leuX tRNA5Leu gene. This tRNA is required for the expression of type 1 fimbriae (Fim) and other virulence factors. Transcription of fimA, encoding the major type 1 fimbrial subunit is controlled by an invertable DNA switch. The inversion is catalysed by two recombinases, FimB and FimE. FimB is able to turn the switch on, FimE only off. The fimB gene of strain 536 contains five TTG codons recognized by tRNA5Leu, fimE contains only two. It was proposed that turning on the fim switch requires efficient translation of FimB, in turn requiring tRNA5Leu. Strains in which the TTG codons in fimB were replaced with CTG codons at the wild-type locus were able to produce type 1 fimbriae in the absence of leuX. fimB transcription was influenced by the presence of leuX, but only slightly affected by the presence or absence of leuX codons in fimB. FimB translation was significantly higher from codon-replaced fimB genes than that of wild-type fimB genes in various strain backgrounds. The fim switch was shown to be switched off in leuX-derivatives of E. coli 536, but could be found in the on position when the codon-altered fimB gene was exchanged into the chromosome of these strains. From these data, it is apparent that tRNA5Leu is required for efficient translation of FimB, in turn, leading to type 1 fimbrial expression.


Plasma "cold-insoluble globulin" protects cytotoxic lymphocytes from ATP inhibition: 2. Immunization against viral cell surface antigen stimulates cytotoxic cells to lyse tumor cells.
The present studies examined the immunoregulatory factors that modulate T-lymphocyte cytotoxic activity against tumor cells. At 30 days postvaccination with hepatitis B virus surface antigen(s) (HBsAg), peripheral blood lymphocytes (PBL) from HBsAb-seropositive healthy donors showed 8-10-fold increase in their cytotoxic activity against human hepatocellular carcinoma PLC/PRF/5 cells. However, there was no effect against human embryonic liver or lung fibroblasts (WI-35) cells. After cloning, these cytotoxic lymphocytes responded to HBsAg, phytohemagglutinin (PHA), and neuraminidase (VCN) with significant increases in cytotoxicity. These cloned, activated PBL also had no effect on human embryonic liver or lung fibroblasts. Exogenous 5'-triphosphate (ATP) inhibited the lymphocyte cytotoxic activities. The inhibition was ATP concentration-dependent. Also, colchicine, a tubuline depolymerizing agent, inhibited effector cell cytotoxic lymphocyte activity. Colchicine binds to the target cells without causing cell lysis. Preincubation of the cytotoxic lymphocytes with "cold-insoluble globulin" (CIg) protected the cells from ATP and colchicine inhibition.


Quantification of Gd-DTPA concentration in neuroimaging using T₁3D MP-RAGE sequence at 3.0 T.
To propose a simple and accurate quantitative method based on the linear relationship between magnetic resonance (MR) signal enhancement (ΔSI=SI(postcontrast)-SI(precontrast)) and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) concentration (C) by using T₁-weighted three-dimensional magnetization-prepared rapid acquisition gradient-echo (T₁3D MP-RAGE) sequence for the in vivo measurement of Gd-DTPA concentration in real-time neuroimaging at 3.0 T. Phantom experiment was carried out to study the linear fitting of signal intensity change vs. Gd-DTPA concentration (ΔSI-C) curve. A goodness-of-fit test was performed to compare the accuracy between the proposed method and the conventional method based on longitudinal relaxation rate (R₁=1/T₁) measurement. The influences on the goodness of fit (R²) and the signal-to-noise ratio (SNR) by sequence parameters were explored. Six human subjects with different brain tumors, who underwent a Gd-DTPA-enhanced MRI, were enrolled for in vivo application of the novel method. A good linear relationship between ΔSI and Gd-DTPA concentration existed over the concentration range of 0-1 mM (R²=0.985). The linearity of the ΔSI-C curve was as good as that of the 1/T₁-C curve (R²=0.988). Concentrations calculated by both methods had a strong correlation (R²=0.920). An improved linearity of the ΔSI-C curve and an increased SNR can be achieved using sequences with a shorter inversion time (TI) and a higher flip angle. The concentration range of Gd-DTPA in human brain tumors was within the quantitative scope of 0-1 mM. The proposed quantitative method based on ΔSI measurement is accurate and applicable for real-time neuroimaging at 3.0 T.


Structure of a modular polyketide synthase.
Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and keto-group processing reactions on intermediates covalently tethered to carrier domains. Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. A single reaction chamber provides access to all catalytic sites for the intramodule carrier domain. In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems.


Identification of a conserved linear B-cell epitope in the M protein of porcine epidemic diarrhea virus.
The major structural protein of coronaviruses, the membrane (M) protein, can elicit the formation of protective antibodies, but little information is available about the M protein of porcine epidemic diarrhea virus (PEDV). Identification of epitopes on the PEDV M protein will be helpful in the elucidation of the antigenic properties of this protein. One hybridoma cell line secreting anti-M protein monoclonal antibody (McAb) was generated and designated 4D4. To map the epitopes on the PEDV M protein, a total of 17 partially overlapping fragments covering the C-terminus of M protein were expressed as fusion proteins with a 6×His tag or a GST tag. A linear motif, 193TGWAFYVR200, was identified by enzyme-linked immunosorbent assay (ELISA) and western blot (WB) analysis using McAb 4D4. The motif 195WAFYVR200 was the minimal requirement for reactivity, as demonstrated by removing amino acids individually from both ends of the motif 193TGWAFYVR200. The result of WB analysis showed that the 4D4-defined epitope could be recognized by PEDV-positive serum, but not transmissible gastroenteritis virus (TGEV)-positive serum. Furthermore, this epitope was highly conserved among different PEDV strains, as shown by alignment and comparison of sequences. A McAb, 4D4, directed against the M protein of PEDV, was obtained, and the 4D4-defined minimal epitope sequence was 195WAFYVR200. The McAb could serve as a candidate for development of a McAb-based antigen capture ELISA for detection of PEDV. The epitope identified provides a basis for the development of epitope-based differential diagnostic techniques and may be useful in the design of epitope-based vaccines.


Problem gambling knowledge and perceived community impact among Asian-Pacific Islanders and non Asian-Pacific Islanders.
Emerging data suggest that problem/pathological gambling may be highly prevalent among Asian-Pacific Islanders (APIs) and that can be a major concern to their communities. This study surveyed problem/pathological gambling knowledge, attitudes, and perceived community impact of problem gambling among self-identified male and female APIs and non-APIs attending one of two API community events in Los Angeles County. Unexpectedly, our results indicated no effect for ethnicity with regards to ratings of problem/pathological gambling knowledge, community impact, or consequences. However, a gender effect with women reporting less problem/pathological-gambling-related knowledge than men, regardless of ethnicity was found. Over 40% of all respondents reported that problem/pathological gambling impacted their communities 'a lot', and the ratings for the impact of problem/pathological gambling was equal to ratings for other significant public health issues like diabetes, depression, drug abuse, and alcohol abuse. Based on these results, it is recommended that evidence-based legislation support the development of culturally-relevant prevention and intervention programs for problem/pathological gambling in Los Angeles County.


Effect of lipid A on the deformability, membrane rigidity and geometry of human adult red blood cells.
Lipid A is responsible for the activities of endotoxin and may cause circulatory failure and haemolysis. This study evaluated the effects of different lipid A concentrations on red blood cell (RBC) deformation (rheoscope), the aspiration pressure required to aspirate RBC into 3.3 microns pipettes, the membrane shear elastic modulus (i.e. membrane rigidity) and cellular geometry (micropipette system) after 15 min of incubation. Lipid A concentrations of 10 and 100 micrograms ml-1 of RBCs decreased RBC deformability by 26% and 39%, respectively. The aspiration pressure for RBCs into a 3.3 microns micropipette increased by 235% at a lipid A concentration of 10 micrograms ml-1 and by 586% at a concentration of 100 micrograms ml-1. The elastic shear modulus almost doubled at a lipid A concentration of 10 micrograms ml-1 and tripled at 100 micrograms ml-1. At a lipid A concentration of 100 micrograms ml-1, 37% of RBCs showed spicules. These echinocytes were less deformable than discocytes. Mean corpuscular volume, RBC volume and surface area were not affected by lipid A. We conclude that lipid A causes marked reduction of RBC deformability due to increasing membrane rigidity.


Effects of fasting on lipoprotein lipase activity in different depots of white and brown adipose tissues in diet-induced overweight rats.
The aim of the present study was to evaluate the effects of 24 hours of starvation on lipoprotein lipase (LPL) activity in various depots of white and brown adipose tissues in control rats and in rats with two different degrees of overweight, both induced by dietary treatment. In control rats, no changes in LPL immunoreactive mass were observed in either white or brown adipose tissues after fasting, whereas the effects of food deprivation on enzyme activity were opposite in white versus brown adipose tissues. The LPL activity response to fasting was impaired by obesity: White adipose depots of cafeteria obese rats showed a lower ability to downregulate LPL during fasting and the increased LPL activity induced by fasting in brown adipose depots was less intense in the obese rats compared with control animals. When the degree of overweight was reduced, the differences between obese and control rats were also attenuated.


Attenuation of Ischemic Stroke-Caused Brain Injury by a Monoamine Oxidase Inhibitor Involves Improved Proteostasis and Reduced Neuroinflammation.
Mitochondrial dysfunction and oxidative stress play a key role in ischemia/reperfusion (I/R) induced brain injury. We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R induced brain injury. We demonstrate here that nialamide (NM), a non-selective monoamine oxidase (MAO) inhibitor, upregulated Ublqn1 and protected neurons from oxygen-glucose deprivation- and I/R-caused cell death in in vitro and in vivo, respectively. Post-ischemic administration of the NM in a stroke mouse model even at 3 h following I/R still reduced neuronal injury and improved functional recovery and survival. Treating stroke animals with NM also increased the association of Ubqln1 with mitochondria and decreased the total oxidized and polyubiquitinated protein levels. Intriguingly, NM-enhanced proteostasis was also associated with reduced I/R-caused neuroinflammation, as reflected by attenuated activation of microglia and astrocytes as well as reduced TNF-α level. Thus, our results suggest that MAO inhibition-induced neuroprotection following I/R involves improved proteostasis and reduced neuroinflammation.


Tooth size discrepancy in orthodontic patients with skeletal anterior open bite.
To find out if there is any relationship between tooth size discrepancy (TSD) and skeletal anterior open bite (AOB) and to assess the correlation between the amount of AOB and TSD. A total of 100 Class I subjects were included in this study (average age 15.21 ± 2.84 years). Fifty patients had skeletal AOB (>3 mm) and 50 subjects acted as controls and had a normal overbite. Teeth mesio-distal widths were measured using a digital caliper. Anterior, overall, and posterior TSD ratios were calculated. An independent t-test was employed to assess differences between groups and between genders. Pearson correlation coefficient was used to assess the correlation between the amount of AOB and TSD. Significant differences in anterior (p = .038) and posterior (p = .015) TSD ratios were detected. In the skeletal AOB group, no significant gender differences were detected (p > .05), whereas in the normal bite and total sample group, males had smaller posterior teeth compared to females (p < .05). All the differences were smaller than 1 SD of Bolton's ratios. No significant correlation was found between the amount of AOB and TSD ratios (p > .05). Skeletal AOB had larger anterior and smaller posterior mandibular teeth, but the differences were less than 1 SD of Bolton's ratios. Males have smaller mandibular posterior teeth than females. The amount of AOB is not correlated with the TSD ratios.


Chemotherapy significantly improves long-term survival of small lesion node negative metaplastic breast carcinoma in T1c population rather than T1a and T1b.
Metaplastic breast carcinoma (MpBC) is considered a highly aggressive disease, the outcome of chemotherapy on small lesions (T1abcN0M0) MpBC patients remain unclear. We identified 890 female MpBC patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. After propensity score matching (PSM), 584 patients were matched. Survival probability was compared among T1a, T1b, and T1c patients and between patients with and without chemotherapy using Kaplan-Meier analysis and Cox proportional hazard analysis. Significance was set at two-sided P < 0.05. We classified 49, 166, and 675 patients as T1a, T1b, and T1c MpBC, respectively. The chemotherapy group included 404 patients (45.4%). Following PSM, survival analysis indicated that the patients who underwent chemotherapy had higher OS (P = 0.0002) and BCSS (P = 0.0276) in the T1c substage, but no significant difference was detected in T1a or T1b patients. In this population-based study, small lesion MpBC showed a favorable prognosis. Chemotherapy improved the prognosis of T1c MpBC patients but not T1a and T1b patients to a beneficial extent. Our findings may offer novel insight into a therapeutic strategy for MpBC.


The effect of testosterone replacement on plasma lipids and apolipoproteins.
Ten men with Klinefelter's syndrome were studied to assess the effect of testosterone replacement on plasma lipids and apolipoproteins. Measurements taken before the insertion of a testosterone ester implant were compared with those obtained 1 week and 4 weeks later. Mean plasma testosterone, androstenedione, total cholesterol and calculated LDL-cholesterol increased significantly after 1 and 4 weeks. No significant changes were seen in total plasma concentrations of HDL-cholesterol, HDL-cholesterol subfractions 2 and 3 or in apoplipoproteins A-I, A-II or B. A significant correlation was seen between total cholesterol and plasma oestradiol concentrations (Rs = 0.61; P less than 0.001). A significant negative correlation was seen between the concentrations of total testosterone and total triglyceride (Rs = -0.56; P less than 0.005) but not with the other lipid parameters. Testosterone replacement is associated with slight but potentially adverse changes in plasma cholesterol levels.


Effect of a U:G mispair on the water around DNA.
DNA repair proteins are able to discriminate DNA lesions among an abundance of intact DNA with high selectivity. To investigate detectable characteristics of one specific lesion, we compare statistical results from molecular dynamics simulations of two different DNA in water, one with an intact C:G pair and one that contains a U:G mispair, and perform a comparative analysis of the water dynamics around the two. Our data show that in addition to the local DNA conformation, also the surrounding water shell exhibits significant differences that may help mispair discrimination. The chemical groups which account for a U:G mispair to exhibit a wobble conformation instead of the 'proper' Watson-Crick pairing of a C:G pair, that is an oxygen atom (in uracil) instead of an amino group (in cytosine), also order the water molecules around the bases such that they act predominantly as hydrogen-bond donor or acceptor to the uracil or cytosine base, respectively. These changes in water conformation stretch into the second solvation shell, which may be exploited by repair enzymes to achieve lesion detection with high efficiency.


DWA3, an Arabidopsis DWD protein, acts as a negative regulator in ABA signal transduction.
DWD (DDB1 binding WD40) proteins have been reported as substrate receptors for cullin-RING ubiquitin ligase 4 complexes (CRL4), a family of E3 ligases. Abscisic acid (ABA) plays an important role in plant responses to abiotic stresses, such as drought and salinity. Upon screening T-DNA mutants of DWD genes for ABA responses we obtained several candidates that exhibited ABA-hypersensitivity, and one was named DWA3 (DWD hypersensitive to ABA 3). DWA3 interacted with DDB1, which has been proposed to be an adaptor protein of the CUL4 E3 ligase complex, in yeast two-hybrid assays. Also, association between DWA3 and the DDB1-CUL4 machinery was detected in vivo by co-immunoprecipitation assays, indicating that DWA3 may function as a substrate receptor for CRL4. ABA-inducible transcription factors (ABI5 and AtMYC2) and their downstream genes were hyper-induced by ABA in dwa3. Taken together, we suggest that DWA3 is a negative regulator of ABA responses and may be involved in protein degradation mediated by CRL4.


A case of the Rett syndrome.
This is a case report of the Rett syndrome in a girl with normal general and psychomotor development during the first 12 mos. Afterwards developmental stagnation and retrogression appeared which led within one yr to dementia, autism, loss of purposeful hand use, truncal ataxia and apraxia of gait. Characteristic stereotypic movements of the hands occurred, and, furthermore, rhythmic truncal balancing and episodic hyperpnea. At 2 yrs, neurological examination showed slight hypertonia and hyperreflexia of the legs without extensor plantar signs, there was relative microcephaly, and visceral examination was normal. The diagnosis was made on the basis of clinical signs: all laboratory investigations were negative except EEG which showed unspecific modifications. We didn't find hyperammonemia. No progression of the symptoms appeared in the 15 mos following the diagnosis.


Algorithm for rational use of Film Array Pneumonia Panel in bacterial coinfections of critically ill ventilated COVID-19 patients.
The FilmArray Pneumonia Panel has proven to be an effective tool for rapid detection of main respiratory pathogens. However, its rational use needs appropriate knowledge and formation regarding its indication and interpretation. Herein, we provide some advices to help with success of its daily routine use, particularly in critically ill ventilated COVID-19 patients. Clinical Trial registration number: NCT04453540.


SerpinB2 deficiency modulates Th1⁄Th2 responses after schistosome infection.
SerpinB2, also known as plasminogen activator inhibitor type-2, is a major product of macrophages and is upregulated during many infections. Although SerpinB2 inhibits urokinase plasminogen activator in vitro, evidence that this represents its physiological role in vivo is not compelling. We have recently shown that SerpinB2-/-mice generate enhanced Th1 responses after immunization with a Th1 immunogen. Herein,we show that Schistosoma japonicum granulomas induced liver SerpinB2 mRNA expression by >600-fold in wild-type mice. In SerpinB2-/- mice, worm and egg burden, and granuloma number and volume were unaffected. However, granulomas in these mice were associated with reduced fibrosis (as determined by Sirius red staining and image analysis) and increased iNOS, IL-6, IL-10 and TNFa and decreased Arg 1 and IL-13 mRNA expression. SerpinB2-/- mice immunized with soluble egg antigen (SEA) also showed reduced levels of SEA-specific IgG1. SerpinB2 deficiency thus promoted certain Th1 and reduced certain Th2 responses in response to this Th2 immunogen.


[Psychological research on pain in Western Europe].
Utilizing MEDLINE and PSYCLIT, a search for articles covering psychological research on pain in the Western European countries was undertaken for the period from 1 January 1990 to 31 December 1994. A total of 398 publications were identified, of which 44 were classified as experimental research in the laboratory, 33 as psychodiagnostic and 225 as clinical studies. The most frequent diagnosis was back pain, followed by musculoskeletal pain and headache. With regard to the total number of publications, Germany was first, followed by The Netherlands and Great Britain. In an analysis of the subcategories, the leading position of Germany could only be confirmed with respect to laboratory studies; in psychodiagnostic publications, Germany fell back behind Great Britain and The Netherlands. In clinical studies, Germany was second to Sweden. Relating the number of publications to the number of personnel estimated to be engaged in research, The Netherlands and the Scandinavian countries demonstrate very high efficiency. Compared with Germany, these countries facilitate the integration of psychological procedures into an interdisciplinary management of pain.


Associations detected between measures of neighborhood environmental conditions and human microbiome diversity.
While emerging research suggests urban green space revegetation increases soil microbiota diversity and native plant species affect skin microbiome diversity, there is still a paucity of knowledge on relationships between neighborhood environmental conditions and the human microbiome. This study leveraged data on human microbiome samples (nose, mouth, rectum) taken at autopsy at the Wayne County Medical Examiner's Office (2014-2015). We evaluated relationships between the microbiome and five measures of environmental conditions (NDVI standard deviation, NDVI mean, percent trees, percent grassland and soil type) near the home of 126 decedents. For the rectum microbiome, NDVI sd had negative, significant associations with diversity (ASVs β = -0.20, p = 0.045; Faith PD β = -0.22, p = 0.026). In contrast, while insignificant, there were consistent, positive associations between diversity and NDVI sd for the mouth microbiome (ASVs β = 0.09, p = 0.337, Faith PD β = 0.14, p = 0.149, Shannon diversity β = 0.14, p = 0.159, Heip's evenness β = 0.11, p = 0.259) and a significant association for the nose microbiome (eigenvalues 3 β = 0.18, p = 0.057). We found consistent, significant, negative associations between percent grassland and diversity of the nose microbiome (ASVs β = -0.25, p = 0.008, Faith PD β = -0.25, p = 0.009, Shannon diversity β = -0.17, p = 0.062). For the mouth microbiome, we found a small effect of percent trees on diversity (eigenvalues 1 β = -0.08, p = 0.053). Clay loam soil was negatively (eigenvalues 2 β = -0.47, p = 0.053) and positively associated (eigenvalues 3 β = 0.65, p = 0.008) with rectum microbiome diversity, compared to loam soil. There was no potential indicator taxon among NDVI quartiles. These findings may be relevant for urban planning and management of urban outdoor spaces in ways that may support healthy human microbiomes. Still, future research is needed to link variation in NDVI, vegetation, plant and/or soil microbe diversity and to confirm or negate our findings that environmental conditions may have contrasting influence on the microbiome of the rectum versus the nose and mouth and that grasslands affect the nose microbiome.


Transparent conductive electrodes from graphene/PEDOT:PSS hybrid inks for ultrathin organic photodetectors.
A novel solution fabrication of large-area, highly conductive graphene films by spray-coating of a hybrid ink of exfoliated graphene (EG)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) (PH1000) is demonstrated. The fabricated graphene films exhibit excellent mechanical properties, thus enabling their application as bottom electrodes in ultrathin organic photodetector devices with performance comparable to that of the state-of-the-art Si-based inorganic photodetectors.


Trace element uptake by Eleocharis equisetina (spike rush) in an abandoned acid mine tailings pond, northeastern Australia: implications for land and water reclamation in tropical regions.
This study was conducted to determine the uptake of trace elements by the emergent wetland plant species Eleocharis equisetina at the historic Jumna tin processing plant, tropical Australia. The perennial emergent sedge was found growing in acid waters (pH 2.45) and metal-rich tailings (SnAsCuPbZn). E. equisetina displayed a pronounced acid tolerance and tendency to exclude environmentally significant elements (Al, As, Cd, Ce, Co, Cu, Fe, La, Ni, Pb, Se, Th, U, Y, Zn) from its above-substrate biomass. This study demonstrates that geobotanical and biogeochemical examinations of wetland plants at abandoned mined lands of tropical areas can reveal pioneering, metal-excluding macrophytes. Such aquatic macrophytes are of potential use in the remediation of acid mine waters and sulfidic tailings and the reclamation of disturbed acid sulfate soils in subtropical and tropical regions.


Growth hormone parameters at four ages in intact and castrated male and female cattle.
Plasma Growth hormone (GH) profiles, secretion rates (SR), metabolic clearance rates (MCR) of intravenously infused GH, and response to 0.0165, 0.067, and 0.267 microgram of growth hormone-releasing factor (GHRF)/kg body weight (bwt) were studied in intact and castrated male and female cattle (4 of each) at 5, 8, 12, and 15 mo of age. As cattle aged, overall GH levels in the plasma decreased (P less than .01), GH baseline concentrations declined (P less than .05), SR decreased (P less than .01), half-life of GH decreased (P less than .01), and the GH response to intravenous injections of GHRF declined (P less than .05). Bulls had elevated overall and baseline GH concentrations (P less than .05), greater amplitude and number of GH secretory periods (P less than .01), and greater SR (P less than .05) than steers, heifers, or ovariectomized heifers. Males had more frequent GH spikes and secretory periods of higher amplitudes, greater SR, and greater GH responses to 0.0165 microgram GHRF kg bwt (P less than .05) than females. Castration had no impact on the GH status of heifers. It is suggested that testosterone or its metabolites enhanced GH secretion in bulls.


Cytosolic delivery of inhibitory antibodies with cationic lipids.
Antibodies can be developed to directly inhibit almost any protein, but their inability to enter the cytosol limits inhibitory antibodies to membrane-associated or extracellular targets. Developing a cytosolic antibody delivery system would offer unique opportunities to directly inhibit and study intracellular protein function. Here we demonstrate that IgG antibodies that are conjugated with anionic polypeptides (ApPs) can be complexed with cationic lipids originally designed for nucleic acid delivery through electrostatic interactions, enabling close to 90% cytosolic delivery efficiency with only 500 nM IgG. The ApP is fused to a small photoreactive antibody-binding domain (pAbBD) that can be site-specifically photocrosslinked to nearly all off-the-shelf IgGs, enabling easy exchange of cargo IgGs. We show that cytosolically delivered IgGs can inhibit the drug efflux pump multidrug resistance-associated protein 1 (MRP1) and the transcription factor NFκB. This work establishes an approach for using existing antibody collections to modulate intracellular protein function.