Polymeric prodrugs.
Polymeric prodrugs can be defined as latent pharmaceutical agents which must undergo chemical or enzymatic transformation to the active or parent drug in the organism after administration. Polymeric prodrugs may also be considered special types of drug delivery systems where the drug release is realized by cleavage of a chemical bond. The concept of polymeric prodrugs finds application in the design of novel agents when pharmacokinetical modification of a parent drug is necessary, or when the aim is to achieve selective action at a target site, utilizing enzymatic activation specific for that site. The types of polymeric prodrugs synthetized in the last decade are reviewed regarding the chemical structure of the carrier backbone and the drug linkages applied. Relationship between the chemical structure, physicochemical characteristics of polymeric prodrugs, and their physiological behavior is discussed, with special regard to the bioavailability, body distribution, and rate of elimination of the carrier from the living organism. In vitro and in vivo experimental data concerning drug activation processes, as well as potential clinical applications of polymeric prodrugs, are surveyed.


An important role for the alpha 1,3 fucosyltransferase, FucT-VII, in leukocyte adhesion to E-selectin.
E-selectin is an adhesion molecule expressed on the surface of activated endothelial cells, which has been shown to be important in the initial steps of leukocyte extravasation into inflamed tissues. E-selectin binds neutrophils, monocytes, eosinophils, basophils, natural killer (NK) cells, and subsets of lymphocytes, although the precise ligand(s) on these cells have not been identified. Several studies have proposed certain carbohydrate structures, including sLex and related structures, as E-selectin ligands. In contrast to these studies, we report here the identification of several human B cell lines that exhibit binding to E-selectin without expression of any of the previously identified E-selectin binding carbohydrate epitopes. The unique carbohydrate phenotype of these B cell lines suggests that they may express a novel, sialylated carbohydrate structure(s) that binds to E-selectin. To investigate the enzymatic basis of this novel form of E-selectin binding, we examined the expression of the two principal leukocyte alpha 1,3 fucosyltransferases, FucT-IV and FucT-VII, in a panel of human hematopoietic cell lines. FucT-VII was expressed in all E-selectin binding cell lines except one, whereas FucT-IV was expressed by nearly all cell lines, regardless of their ability to bind E-selectin. In addition, transfection of cells with cDNA encoding FucT-VII conferred E-selectin binding ability. Taken together, these data suggest that, regardless of surface carbohydrate phenotype, E-selectin binding ability is determined largely by expression of FucT-VII.


Sonographic findings of total colonic aganglionosis in a neonate with Haddad syndrome: A case report.
Haddad syndrome is a rare congenital disorder characterized by congenital central hypoventilation syndrome and Hirschsprung disease. Total colonic aganglionosis is a rare and long-segment form of Hirschsprung disease, which is primarily diagnosed using contrast enemas. However, the diagnostic performance of contrast enemas is relatively low, making the diagnosis of total colonic aganglionosis challenging. In neonates, ultrasound may be used as an additional imaging modality for the diagnosis of Hirschsprung disease. We describe the unique sonographic findings of total colonic aganglionosis in a term neonate with failure to pass meconium and respiratory distress, who was subsequently diagnosed with Haddad syndrome.


Life-cycle assessment of municipal solid waste management alternatives with consideration of uncertainty: SIWMS development and application.
This paper describes the development and application of the Stochastic Integrated Waste Management Simulator (SIWMS) model. SIWMS provides a detailed view of the environmental impacts and associated costs of municipal solid waste (MSW) management alternatives under conditions of uncertainty. The model follows a life-cycle inventory approach extended with compensatory systems to provide more equitable bases for comparing different alternatives. Economic performance is measured by the net present value. The model is verified against four publicly available models under deterministic conditions and then used to study the impact of uncertainty on Sydney's MSW management 'best practices'. Uncertainty has a significant effect on all impact categories. The greatest effect is observed in the global warming category where a reversal of impact direction is predicted. The reliability of the system is most sensitive to uncertainties in the waste processing and disposal. The results highlight the importance of incorporating uncertainty at all stages to better understand the behaviour of the MSW system.


Salutogenic-based interventions among community-dwelling older adults: a systematic review and meta-analysis.
Salutogenesis is a health-promoting orientation and sense of coherence (SOC) is a vital coping factor associated with quality of life (QOL) and self-efficacy. Although salutogenic-based interventions showed potential in improving health outcomes, the application of salutogenic concepts and effectiveness on SOC, QOL and self-efficacy among community-dwelling older adults remained unclear. This review aimed to consolidate evidence on salutogenic approaches and evaluate the effectiveness of salutogenic-based interventions on SOC, QOL and self-efficacy in community-dwelling older adults. Databases systematically searched include PubMed, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Scopus, Medline, PsycINFO and ProQuest Dissertations & Theses Global electronic databases. Two reviewers screened study eligibility, assessed risk of bias and extracted data of included studies independently. Meta-analyses on SOC and QOL were performed using RevMan. Where meta-analysis was not possible, narrative synthesis was employed. Eight studies involving 1201 older adults were included in this review. Subgroup analysis on SOC showed significant effects favouring salutogenic-based interventions using the empowering self-management model or strengths/resource-based approaches. However, results were mixed for the reflection-based approach. No significant effect favouring salutogenic-based interventions on QOL outcomes were found. High heterogeneity was observed for the outcome on self-efficacy. Two SOC strengthening processes, empowerment and reflection, were found to potentially underlie salutogenic-based intervention mechanisms. Effectiveness of salutogenic-based interventions on SOC, QOL and self-efficacy among community-dwelling older adults remained inconclusive due to high heterogeneity. Future salutogenic-based interventions should employ longitudinal designs and standardization on intervention delivery, utilizing a dual pathway via empowerment and reflection.


Antimitotic activity of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones.
We report the synthesis of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones and their biological activity as antitumor agents. These molecules were initially evaluated for their ability to induce cell cycle arrest in the G2/M phase. Compounds that showed significant G2/M cell cycle arrest were tested for antiproliferative activity using both the MTT assay and the NCI in vitro 60 cell line human tumor screen. The 5-hydroxy-7-methoxy-2-phenyl-4-quinolone (3a) and 2-(3-fluorophenyl)-5-hydroxy-7-methoxy-4-quinolone (3f) were the most active in the cell cycle arrest test whereas 3f was found to be the most active in the MTT assay. In terms of structural requirements, we found that the presence of a 5-hydroxyl group, a 7-methoxy group, and an unsubstituted N1 were essential for the antimitotic activity. In accordance with the literature, a fluoro group at the 3'- or 2'-position and a methoxy or a chloro group at the 3'-position were found to be highly advantageous for both the cell cycle arrest and the antiproliferative activities.


Deriving quantitative constraints on T cell selection from data on the mature T cell repertoire.
The T cell repertoire is shaped in the thymus through positive and negative selection. Thus, data about the mature repertoire may be used to infer information on how TCR generation and selection operate. Assuming that T cell selection is affinity driven, we derive the quantitative constraints that the parameters driving these processes must fulfill to account for the experimentally observed levels of alloreactivity, self MHC restriction and the frequency of cells recognizing a given foreign Ag. We find that affinity-driven selection is compatible with experimental estimates of these latter quantities only if 1) TCRs see more peptide residues than MHC polymorphic residues, 2) the majority of positively selected clones are deleted by negative selection, 3) between 1 and 3.6 clonal divisions occur on average in the thymus after completion of TCR rearrangement, and 4) selection is driven by 103-105 self peptides.


ChIPmix: mixture model of regressions for two-color ChIP-chip analysis.
Chromatin immunoprecipitation (ChIP) combined with DNA microarray is a high-throughput technology to investigate DNA-protein binding or chromatin/histone modifications. ChIP-chip data require adapted statistical method in order to identify enriched regions. All methods already proposed are based on the analysis of the log ratio (Ip/Input). Nevertheless, the assumption that the log ratio is a pertinent quantity to assess the probe status is not always veri.ed and it leads to a poor data interpretation. Instead of working on the log ratio, we directly work with the Ip and Input signals of each probe by modeling the distribution of the Ip signal conditional to the Input signal. We propose a method named ChIPmix based on a linear regression mixture model to identify actual binding targets of the protein under study. Moreover, we are able to control the proportion of false positives. The efficiency of ChIPmix is illustrated on several datasets obtained from different organisms and hybridized either on tiling or promoter arrays. This validation shows that ChIPmix is convenient for any two-color array whatever its density and provides promising results. The ChIPmix method is implemented in R and is available at http://www.agroparistech.fr/mia/outil_A.html.


Morphology and infraciliature of two new marine urostylid ciliates: Metaurostylopsis struederkypkeae n. sp. and Thigmokeronopsis stoecki n. sp. (Ciliophora, Hypotrichida) from China.
The morphology and infraciliature of two new marine urostylid ciliates, Metaurostylopsis struederkypkeae n. sp. and Thigmokeronopsis stoecki n. sp., collected from the coastal waters off Qingdao (Tsingtao), China, have been investigated. Metaurostylopsis struederkypkeae n. sp. is characterized by the slender body shape, small size, rose-reddish cell colour, and having two kinds of pigment-like granules. The larger pigment-like granules are yellow-green or grass-green in colour, oval in shape, and flattened, whereas the smaller ones are wine-reddish. Infraciliature and nuclear apparatus are similar to the well-known Metaurostylopsis marina. Thigmokeronopsis stoecki n. sp. is characterized by its large size with dark brown cell colour and grass-green cortical granules, which are large, blood-cell shaped, and sparsely distributed. The thigmotactic ciliature is conspicuous: 11-14 rows of densely arranged cirri occupy the most postoral area. Keys are provided for all the known species in both genera.


Serology of abnormal fracture healing: the role of PIIINP, PICP, and BsALP.
To determine whether poorly healing tibial shaft fractures exhibit a serological response of bone-specific alkaline phosphatase (BsALP), collagen I carboxy-terminal propeptide (PICP), collagen III amino-terminal propeptide (PIIINP), and collagen I carboxy-terminal telopeptide (ICTP) different from that of normally healing fractures. Prospective. Twenty consecutive patients with isolated tibial shaft fractures with or without fracture of the fibula. Assays of BsALP, PICP, PIIINP, and ICTP were performed with serum samples taken at standard intervals from twenty-four hours to twenty weeks after fracture. Fracture healing was assessed at five, ten, fourteen, and twenty weeks for clinical and radiological evidence of union. Seventeen fractures united within the twenty-week study period. The three fractures exhibiting delayed union demonstrated significantly lower PICP levels and marginally lower BsALP levels at twenty weeks. PIIINP levels were significantly higher in these three fractures at ten weeks. There was no difference in ICTP between the seventeen united and the three ununited fractures. This study identified three serological features of a poor healing response in tibial shaft fractures. First, matrix collagen I and III production in the first ten weeks of healing was adequate, with evidence of significantly increased production of type III collagen. Second, there was no serological evidence of a deficient osteoblast response, as indicated by normal levels of BsALP and PICP, during this early period. Third, evidence of a deficient osteoblast response appeared only at twenty weeks after injury.


Multiple arterial thromboses associated with anabolic androgenic steroids.
The use of supraphysiological doses of anabolic androgenic steroids can have serious side effects. This article reports the case of a young man who suffered potentially life-threatening arterial thromboses following the use of these drugs.


Diagnosis of childhood BK virus cystitis by electron microscopy and PCR.
A case of BK virus cystitis in a 5 year old boy is reported. This patient, who was not immunocompromised, had had acute cystitis for two weeks. Many intracytoplasmic inclusions were observed in urinary sediment smears stained by the Papanicolaou method. Electron microscopic examination showed virus particles, presumed to be human polyomavirus, in the nuclei of the degenerated urothelial cells. A DNA sequence of the BK virus was detected in 200-300 urothelial cells in Papanicolaou stained smears by the polymerase chain reaction. BK virus is an unusual cause of symptomatic cystitis in a healthy child.


Irritancy of industrial hand cleansers tested by repeated open application on human skin.
The aim of this study was to compare the irritancy potential of 2 industrial hand cleansers with a brand leader of "mild" children's hand cleanser and with an emollient. The products were tested using repeated open application tests (ROATs) on the forearms of 40 subjects. Scoring of signs and symptoms (itching or burning), transepidermal water loss (TEWL) and stratum corneum hydration (Corneometer) evaluated responses. On all assessments, the children's hand cleanser was more irritant than the 2 industrial hand cleansers. The children's hand cleanser and industrial hand cleansers were more irritant than the emollient. The finding that a hand cleanser for children was more irritant than 2 industrial hand cleansers was surprising, and one which might hold serious implications for inducing or exacerbating atopic eczema in children. The combination of visual scoring, TEWL and Corneometer readings on ROATs is a potentially useful way of assessing irritancy strength of soap products on human skin.


Further characterization of phage T1 DNA clones.
A series of phage T1 DNA clones containing Sau3A fragments of 1 kb or more were tested for their ability to rescue the defects of amber mutations representing all known T1 genes. Rescue was detected by either complementation or recombination. These data have extended the correlation of the T1 genetic and physical maps and provided more conclusive proof that the large map distances at the left end of the genetic map reflect both increased physical separation of the known genetic markers and enhanced recombination and that the right and left chromosomal ends are recombinogenic to the same extent.


Tamoxifen-stimulated growth of human endometrial carcinoma.
An estrogen receptor and progesterone receptor positive endometrial carcinoma (EnCa101) will grow in response to either estradiol or tamoxifen when transplanted into athymic mice. We have tested several antiestrogens with different properties to determine their ability to support endometrial tumor growth. Trioxifene, enclomiphene and nafoxidine are all as active as tamoxifen whereas the antiestrogen keoxifene, that has reduced estrogen-like properties, will partially inhibit tamoxifen-stimulated growth. Furthermore, the pure antiestrogen ICI 164,384 will block tamoxifen-stimulated growth without having any effect itself on tumor growth rate. Overall, the ability of antiestrogens to stimulate the growth of human endometrial carcinoma EnCa101 appears to be related to their intrinsic estrogenic activity.


Interoceptive cues predicting exteroceptive events.
The growing body of research on interoceptive conditioning has predominantly focused on associative learning paradigms that investigated the formation of intero-interoceptive or extero-interoceptive associations. Yet, little research has explored whether interoceptive sensations can enter an intero-exteroceptive association. Therefore, in an interoceptive conditioning paradigm, healthy participants experienced a respiratory resistance for 8s, causing mild dyspnea (interoceptive conditioned stimulus, CS), that was either paired to an aversive electrocutaneous stimulus (unconditioned stimulus, US) (experimental condition, n=25), or presented in an unpaired fashion (control condition, n=25) during the acquisition phase. In a subsequent extinction phase, the US was not delivered anymore. US-expectancy, skin conductance responses (SCR), and eyeblink startle EMG were used as indices of associative learning. During acquisition, we observed stronger US expectancies during the CS as compared to the intertrial interval in the experimental group, but not in the control group, nor during extinction. In line, only in the experimental group did skin conductance responses to the CS increase across acquisition. The pattern of the eyeblink startle data did not reach statistical significance. In sum, interoceptive sensations can become associated with exteroceptive events.


[Gaps on China's Engagement in Global Governance of Neglected Tropical Diseases].
In this review, we used gap analysis to find out the inadeqency of China's engagement in global elimination and control of neglected tropical diseases (NTDs). Meanwhile, important facets on which our work should concentrate and some abilities that need to be improved were proposed, in the aim to stimulate the progress of global prevention and control of NTDs.


Complete nucleotide sequence of Ig V genes in three cases of Burkitt lymphoma associated with AIDS.
To investigate the role of polyclonal stimulation and antigen driven selection in the pathogenesis of acquired immunodeficiency syndrome (AIDS) related lymphomas, we studied the variable region nucleotide sequence of heavy (VH) and light (VL) chains expressed by 3 Burkitt lymphomas (BL) associated with HIV infection. Two cases expressed the VH3-30P1 gene with 88.6% and 86.7% homology when compared to their germinal counterpart, whereas the VH4-18 was rearranged in the third one (89% identity). All these genes displayed high numbers of mutations (27, 22, 28 respectively), predominating in CDR regions. The encoded light chain genes determined for cases 1 and 2 expressed the same V kappa I-018 gene. These results indicate that: 1) Although, it is difficult to address the issue of VH usage based on the limited number of cases studied, Burkitt's lymphoma associated with AIDS may use a restricted repertoire of Ig genes. 2) Mutations and/or replacements predominated in CDR regions, which might suggest the occurrence of an antigen driven selection process, at least in some AIDS associated lymphomas. However, the high ratio of mutations observed in framework (FW) regions also favors the possibility that the antigen selection process is associated with polyclonal B cell stimulation.


Bipart: Learning Block Structure for Activity Detection.
Physical activity consists complex behavior, typically structured in bouts which can consist of one continuous movement (e.g. exercise) or many sporadic movements (e.g. household chores). Each bout can be represented as a block of feature vectors corresponding to the same activity type. This paper introduces a general distance metric technique to use this block representation to first predict activity type, and then uses the predicted activity to estimate energy expenditure within a novel framework. This distance metric, dubbed Bipart, learns block-level information from both training and test sets, combining both to form a projection space which materializes block-level constraints. Thus, Bipart provides a space which can improve the bout classification performance of all classifiers. We also propose an energy expenditure estimation framework which leverages activity classification in order to improve estimates. Comprehensive experiments on waist-mounted accelerometer data, comparing Bipart against many similar methods as well as other classifiers, demonstrate the superior activity recognition of Bipart, especially in low-information experimental settings.


Orientation-selected 15N-HYSCORE detection of weakly coupled nitrogens around the archaeal rieske [2Fe-2S] center.
The weakly coupled 15N atoms around a reduced Rieske [2Fe-2S] cluster of the uniformly 15N-labeled, hyperthermostable archaeal Rieske protein appear to produce readily observable cross-peaks in the HYSCORE spectra, with the well-resolved couplings of 0.3-0.4 MHz for the Nepsilon and 1.1 MHz for the peptide backbone nitrogens, in addition to the contributions from the coordinated Ndelta atoms. These features can be used for structure-mechanism studies of the biological redox protein system involving the weakly coupled nitrogens in coupled electron-proton transfer reactions.


Molecular forms of prostate-specific antigen in malignant and benign prostatic tissue: biochemical and diagnostic implications.
Patients with prostate cancer (PCa) show a lower ratio of free prostate-specific antigen (fPSA) to total PSA (tPSA) in serum than patients with benign prostatic hyperplasia (BPH). The patterns of the intracellular PSA isoforms in malignant and benign prostatic tissue have been studied as potential molecular reasons for this phenomenon. Prostatic tissue samples were obtained after cystoprostatectomy from patients with bladder cancer (n = 10), from BPH patients (transurethral resection of the prostate, n = 10; adenomectomy, n = 10), and from the cancerous and noncancerous parts of the same prostates removed surgically by prostatectomy because of PCa (n = 20). PSA pattern was characterized by gel filtration, immunoblotting, and immunoassays for tPSA, fPSA, alpha(1)-antichymotrypsin-PSA (ACT-PSA), and complexed PSA (Bayer Immuno 1 assay). Comparisons were made with the PSA concentrations in serum. The major portion of tPSA in all tissue samples was fPSA; complexed PSA forms were <2%. Samples from cystoprostatectomy patients had the lowest and those from adenomectomy patients the highest values of tPSA and fPSA. PSA concentrations were lower in cancerous than in the noncancerous parts of the prostate. No significant correlations were found between tumor stage or grade and the amounts of tPSA, fPSA, and ACT-PSA in tissue. Tissue PSA values were not correlated with the serum PSA concentrations nor with the ratios fPSA/tPSA and ACT-PSA/tPSA in sera. The amounts of tPSA and the PSA isoforms in prostatic tissue explain neither the concentrations of tPSA and PSA isoforms in serum nor the behavior of the ratio fPSA/tPSA in patients with BPH and PCa.


Evaluation of Norplant use among Bangladeshi women.
Among 600 women in Bangladesh who initiated use of Norplant, 38% still had their implant at the end of its 5-year life span. To evaluate the contraceptive effectiveness, safety and acceptability of the implant, researchers recruited 200 women from each of 3 clinics in Dhaka who began using the method in 1985. Most of the participants were young (mean age 27), had had little or no formal education and had had an average of 3.4 live births. Participants were followed up at 1, 3, and 6 months after insertion, then every 6 months after insertion, then every 6 months until removal. The 5-year study was completed by 228 (38%) participants; 31 were lost to follow-up. 2 pregnancies were reported during the study; these were believed to have occurred prior to insertion of Norplant. Of the 340 removals during the course of the study, 45% were requested because of menstrual problems, 15% because of other side effects or medical reasons, 20% because the women desired the pregnancy and 20% for other personal reasons. Most of the women (86%) who completed the study planned to continue using a contraceptive method; of these, one-third planned to use Norplant again.


First report of turnip yellows virus infecting cabbage (Brassica oleracea var. capitata) in the USA.
During the spring of 2021, cabbage (Brassica oleracea var. capitata) planted in the research farm at the University of Georgia, Tifton, exhibited leaf distortion, yellow and purple discoloration at the leaf margin of older leaves, and severe stunting. Symptoms were present on nearly 30% of the plants in the field. To identify the potential agents associated, leaf tissues from two symptomatic plants were sent for high throughput sequencing (HTS) of small RNA (sRNA; DNB sequencing, SE read 1x75bp) to Beijing Genomics Institute, China. From each sample, ~ 18 million raw reads were generated. The reads with poor quality and adapter sequences were removed using CLC Genomics Workbench 21.2 (Qiagen, Germantown, MD). Of the total reads, 2,093 and 3,889 reads aligned to the genome of turnip yellows virus (TuYV) in samples one and two, respectively. Reads of turnip mosaic virus (TuMV) were also detected (data not shown). Partial sequences of TuYV assembled from samples one and two showed 89.5% and 89.9% match and 86% and 93% coverage, respectively, with the genome of the type isolate of TuYV (NC_003743) from the United Kingdom. To confirm the presence of TuYV in the samples collected from the same location, specific primers were designed targeting the P0 region (FP- 5'ACAAAAGAAACCAG- GAGGGAATCC3'; RP-5'GCCTTTTCATACAAACATTTCGGTG3') and coat protein (CP) region (FP-5'GTTAATGAATACGGTCGTGGGTAG3'; RP-5'ATTCTGAAAGAACCAGCT- ATCGATG3') of the virus. Eight of 20 (40%) symptomatic samples were determined to be infected with TuYV based on the amplification of expected size products of the P0 (786 nt) and the CP gene (581 nt) in reverse transcription-PCR (RT-PCR). All samples were also tested for the presence of TuMV by RT-PCR as in Sanchez et al. (2003), but none tested positive despite being identified in HTS. Symptoms on samples from which eithervirus could not be detected indicates the involvement of other factors and would require further studies. The partial P0 and CP gene amplicons of TuYV from two samples each were Sanger sequenced bi-directionally at Genewiz (South Plainfield, NJ) and confirmed as TuYV using BLASTn. The partial CP gene sequences from two samples shared 98.7% nucleotide sequence identity with each other and 88.0% (OK349421) and 87.1% (OK349422) identity with the type isolate. The partial P0 gene sequences (OK349423 and OK349424) shared 99.6% nucleotide sequence identity with each other and 92.2% identity with the type isolate. TuYV, formerly known as beet western yellows virus (BWYV) (Mayo, 2002), genus Palerovirus, family Solemoviridae (Walker et al., 2021), is transmitted persistently by aphids (Stevens et al., 2008), and is distributed throughout temperate regions of the world (Kawakubo et al., 2021). TuYV has a wide host range, including brassica, vegetables and weeds (Stevens et al., 2008). However, losses have been reported primarily on canola (B. napus) in Australia (Jones, 2007) and Europe (Stevens et al., 2008). On cabbage, TuYV infections have been reported from China (Zhang et al., 2016), Serbia (Milošević et al., 2020) and the Philippines (Buxton-Kirk et al, 2020). TuYV (BWYV) has been found infecting shepherd's purse (Capsella bursa-pastoris) in California (Falk and Duffus, 1984), but there are no reports of the virus from any cultivated crops in the USA. To our knowledge, this is the first report of TuYV in cabbage in the USA. More studies are needed to understand its occurrence and impact on cabbage crops in Georgia as well as other regions in the USA.


Study protocol of the Restore4Stroke self-management study: a multicenter randomized controlled trial in stroke patients and their partners.
Many stroke patients and their partners report long-term negative consequences of stroke on their health-related quality of life. Adequate self-management abilities may help manage the consequences of the stroke, but it is unknown what specific intervention might be effective to enhance self-management abilities of stroke patients and their partners. The study aims to investigate the effectiveness of a 10-week group self-management intervention addressing proactive coping strategies compared with a group education intervention in stroke patients and their partners. The study is a multicenter randomized controlled trial. A total of 106 stroke patients with, if applicable, their partners are randomly assigned to the self-management intervention or the education intervention within each of the 10 participating hospitals and rehabilitation centers. The main inclusion criteria are a symptomatic stroke at least six-weeks ago, living at home, and reporting at least two participation restrictions on the Utrecht Scale for Evaluation of Rehabilitation-Participation's restriction scale. Measurements are performed at baseline, immediately after intervention, three-months, and nine-months postintervention. Primary outcome measures are stroke patients' and partners' proactive coping competencies (Proactive Competence Inventory) and societal participation (Utrecht Scale for Evaluation of Rehabilitation-Participation's restriction scale). If effective, the results of this study will enable stroke patients and their partners to deal better with the lasting consequences of stroke. In the context of the growing number of people returning home after stroke, a large number of people may profit from this intervention.


Observing and Identifying Hospitalist Best Communication Practices in Patient Interactions.
This study identifies actual hospitalist best communication practices that optimize patient interactions in a busy hospital context. We observed and rated 36 hospitalists and 206 patient encounters using the Kalamazoo Essential Elements of Communication Checklist-Adapted (KEECC-A). We collected descriptive statistics of checklist scores and thematically analyzed fieldnotes to identify communication patterns. Results show hospitalists score highest and most frequently use three of seven KEECC-A dimensions: builds a relationship, shares information, and gathers information. We first identify exemplar behaviors and then provide statistical comparisons by professional and hospital tenure, gender, and day of rounding observed for these three dimensions. Male hospitalists scored higher than females for shares information and significant differences were found for gender between cross-sex patient-hospitalist interactions. Hospitalists early in their professional and hospital tenure received significantly lower ratings than mid-to-late career hospitalists in the three KEECC dimensions. Hospitalists observed on the first day of rounding received significantly higher ratings than those observed on a middle or last day. We offer interpretations to explain study findings and suggest interventions to help hospitalists with less-than-desirable communication skills.


[Sphenoid fissure syndrome in orbital fractures. Case presentation and literature review].
The superior orbital syndrome has been reported as a very rare complication of orbital fracture. In emergency clinical examination and computed tomography of the cranio-orbital region have provided diagnosis of the compression of the superior orbital fissure content by oedema and/or hematoma. These examinations have determined the type of cranio-orbital fractures and the absence of extra-dural haemorrhage, optical nerve damage or compression, which required emergency treatment. After surgical treatment of the cranio-orbital fracture by temporal and transconjunctival approach, the orbital fissure syndrome has required supervision. The recovery of ophthalmoplegia has taken several months. Minor after effects have been observed for the patient reported.


Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma.
A high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present study a novel metastasis-related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) of metastatic tumors. Functional studies found that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion in vitro and tumor metastasis in vivo in an experimental mouse model. Moreover, inhibition of EIF5A by small interfering RNA (siRNA) or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 was able to induce epithelial-mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized by down-regulation of epithelial markers (E-cadherin and beta-catenin) and up-regulation of mesenchymal markers (fibronectin, N-cadherin, alpha-SMA, and vimentin). In addition, EIF5A2 could also activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia. EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1.


Community-based study on the relationship between serum cholesterol/triglyceride and dietary habits/life styles in Pu-Li, Taiwan.
This is a community-based study on the relationship between serum cholesterol (CHO)/triglyceride (TG) and dietary habits/life styles of persons living in a central Taiwan Town. Door-to-door interviews were carried out by the Yang-Ming Crusade, and fasting blood for CHO and TG tests was drawn by public health nurses from Pu-Li Health Station. Univariate analysis found that significant variables correlated with CHO were age (+), locality, non-fish seafood (+) and pungent food (+). Significant variables correlated with TG were age (+), sex, locality, smoking (+), alcohol (+) and physical activity (-). Stratified by age (> or = 50 and < 50) and by sex respectively, only one significant interaction item--age x organ meat consumption--was found; those who consumed organ meat more frequently had higher TG, if they were less than 50 years of age. This was not true for those aged 50 and over. Multivariate analysis using logistic regression revealed that after controlling for all of the other covariates, significant variables correlated with CHO were age (OR = 1.92, 95% C.I. = 1.37-2.69), pungent food (OR = 1.91, 95% C.I. = 1.26-2.89); locality (OR = 0.53, 95% C.I. = 0.35-0.80 for sub urban area; and OR = 0.74, 95% C.I. = 0.50-1.08 for rural area); sea food consumption (OR = 1.50, 95% C.I. = 0.94-2.40); and smoking (OR = 0.69, 95% C.I. = 0.48-0.99).(ABSTRACT TRUNCATED AT 250 WORDS)


Estimation of economic values for traits of dairy sheep: I. Model development.
A bioeconomic model was developed to estimate effects of change in production and functional traits on profit of dairy or dual-purpose milked sheep under alternative management systems. The flock structure was described in terms of animal categories and probabilities of transitions among them, and a Markov chain approach was used to calculate the stationary state of the resultant ewe flock. The model included both deterministic and stochastic components. Performance for most traits was simulated as the population average, but variation in several traits was taken into account. Management options included lambing intervals, mating system, and culling strategy for ewes, weaning and marketing strategy for progeny, and feeding system. The present value of profit computed as the difference between total revenues and total costs per ewe per year, both discounted to the birth date of the animals, was used as the criterion for economic efficiency of the production system in the stationary state. Economic values (change in system profit per unit change in the trait) of up to 35 milk production, growth, carcass, wool, and functional traits may be estimated.


[Intralobar sequestration in elderly patient; report of a case].
A 71-year-old woman who had been treated as bronchitis was diagnosed as intralobar sequestration by a computed tomography scan. She had 2 episodes of hemosputum in recent 30 years but the amounts were small and they spontaneously stopped in a day. She had an abnormal vessel from thoracic descending aorta of which diameter was 1 cm draining to the basal segment of the left lung. She was operated on a left lower lobectomy with ligation of the vessel via a thoracotomy. Postoperative course was uneventful, and she discharged home on the 9th postoperative day.


Isolation and characterization of human pituitary chorionic gonadotropin.
Human CG (hCG) is the hormone associated with the maintenance of pregnancy. Although three related glycoprotein hormones, LH, hFSH, and hTSH, are secreted by the pituitary, HCG is the only one of this family of glycoprotein hormones that is produced by the placenta in primates to maintain the steroid hormone secretions of the corpus luteum. Although hCG is not considered to be a pituitary hormone, hCG-like immunoreactive materials have been reported in pituitary tissue, blood, and urine from healthy nonpregnant individuals for 2 decades, but it was never isolated. We now report the purification and characterization of pituitary hCG from acetone-preserved human pituitary glands. After gell permeation chromatography, the fractions containing hCG molecules were pooled and purified by immunoaffinity chromatography using antibodies to the COOH-terminal region of hCGbeta. Amino acid analyses, amino-terminal sequence analyses, as well as mass spectrometric studies gave similar results for both pituitary hCG and hCG purified from the urine of pregnant women. Analyses for sulfate and sialic acid contents demonstrated that pituitary hCG contained both sulfate and sialic acid. In vitro biological activity of pituitary hCG indicated that it was 50% as active as hCG purified from the urine of pregnant women in cAMP assays.


Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer.
Characterization of the genomic changes that drive an individual patient's disease is critical in management of many cancers. In patients with non-small-cell lung cancer (NSCLC), obtaining tumor samples of sufficient size for genomic profiling on recurrence is often challenging. We undertook this study to compare genomic alterations identified in archived primary tumors from patients with NSCLC with those identified in metachronous or synchronous metastases. Primary and matched metastatic tumor pairs from 15 patients were analyzed by using a targeted next-generation sequencing assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. Among 30 tumors, 311 genomic alterations were identified of which 63 were known recurrent (32 in primary tumor, 31 in metastasis) and 248 were nonrecurrent (likely passenger). TP53 mutations were the most frequently observed recurrent alterations (12 patients). Tumors harbored two or more (maximum four) recurrent alterations in 10 patients. Comparative analysis of recurrent alterations between primary tumor and matched metastasis revealed a concordance rate of 94% compared with 63% for likely passenger alterations. This high concordance suggests that for the purposes of genomic profiling, use of archived primary tumor can identify the key recurrent somatic alterations present in matched NSCLC metastases and may provide much of the relevant genomic information required to guide treatment on recurrence.


A tRNA gene transcription initiation site is similar to mRNA and rRNA promoters in plant mitochondria.
The gene for tRNA(Phe) is located 292 nucleotides upstream of the tRNA(Pro) gene in the Oenothera mitochondrial genome. Hybridization with in vitro capped primary transcripts indicates a transcription initiation site in the 5' region of the gene for tRNA(Phe). Primer extension experiments show the presence of precursor transcripts covering tRNA(Phe) and adjacent sequences up to a transcription initiation site 181 or 180 nucleotides upstream of the tRNA gene. The genomic sequence at this transcription initiation site contains the consensus motif derived for putative promoters of mitochondrial protein and rRNA coding genes in dicotyledonous plants. This sequence similarity suggests that tRNAs, rRNAs and mRNAs can be transcribed from homologous promoters in plant mitochondria.


Enhancement of Ethylene Release from Leaf Tissue during Glycolate Decarboxylation : A Possible Role for Photorespiration.
When leaf discs of Xanthium strumarium L. and Salvia splendens L. are incubated in sealed flasks in the light, more C(2)H(4) gas is released in the presence of added CO(2) (30-200 millimolar NaHCO(3)) than without CO(2). In Salvia, the maximum rate of C(2)H(4) release occurs when sufficient CO(2) (above 125 millimolar NaHCO(3)) is added to saturate photosynthesis confirming previous studies. The maximum rate of C(2)H(4) release from illuminated discs is similar to the rate in the dark with or without CO(2) in both species. Glycolate enhances a CO(2)-dependent C(2)H(4) evolution from illuminated leaf discs. However, the maximum rate of C(2)H(4) release with glycolate is the same as that observed with saturating CO(2). When photosynthesis is inhibited by darkness or by 3-(3,4-dichlorophenyl)-1,1-dimethylurea, glycolate has no effect.Studies with [2,3-(14)C]-1-aminocyclopropane-1-carboxylic acid (ACC) show that the pattern of C(2)H(4) release and the specific activity of the (14)C(2)H(4) in the presence and absence of glycolate is similar to that described above, indicating that glycolate does not alter uptake of the exogenously supplied precursor (ACC) or stimulate C(2)H(4) release from an endogenous source at appreciable rates. Glycolate oxidase in vitro generates H(2)O(2) which stimulates a slow breakdown of ACC to C(2)H(4), but since exogenous glycolate is oxidized to CO(2) in both the light and the dark it is argued that the glycolate-dependent increase in C(2)H(4) release from illuminated leaf discs is not mediated directly by the action of enzymes of glycolate catabolism. The effects of glycolate and CO(2) are not easily explained by changes in stomatal resistance. The data support the view that glycolate decarboxylation at subsaturating levels of CO(2) in the light stimulates C(2)H(4) release by raising the CO(2) level in the tissue.


RNA Sequencing Reveals LINC00167 as a Potential Diagnosis Biomarker for Primary Osteoarthritis: A Multi-Stage Study.
Given the roles played by lncRNA in human diseases and the high incidence of OA, this study investigated the pivotal pathways involved in the disease and identified potential biomarkers for OA diagnosis. We first performed an exploration of RNA-sequencing in peripheral blood leukocytes from six subjects (3 OA and 3 healthy controls). Promising candidate lncRNAs were evaluated in first stage validation using a GEO dataset (GSE114007) of 38 subjects (20 OA and 18 healthy controls), followed by a second stage validation using quantitative PCR analysis with 101 subjects (67 OA and 34 controls). The third stage investigated the potential value of validated lncRNA in the early diagnosis of OA in peripheral blood leukocytes from a total of 120 participants (60 cases and 60 controls). The dataset identified a total of 1,380 up-regulated and 719 down-regulated mRNAs and 5,743 up-regulated and 7,384 down-regulated lncRNAs. The up-regulated DEGs were mainly enriched in the extracellular matrix, while the down-regulated DEGs were mainly enriched in the IL-17 and wnt signaling pathways. 18 overlapping candidate lncRNAs survived after first-stage validation. 3 hub lncRNAs were selected for the second validation stage and qualified in an external sample, and lncRNA LINC00167 was further confirmed with a similar result (down-expressed in both stages). Receiver operating characteristic analysis showed that LINC00167 can distinguish OA cases from healthy controls with a high area under the curve of 0.879 (95%CI: 0.819, 0.938; P < 0.001), with a sensitivity of 80.7% and specificity of 83.5%. The expression profile of OA was identified and critical pathways were elucidated by an integrated approach to RNA-seq from easily accessible blood. LINC00167 may serve as a potential early diagnosis marker for OA in clinical practice. The detailed mechanism of action of this lncRNA requires further elucidation in future studies.


Genome-wide association analysis identifies three new breast cancer susceptibility loci.
Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.


Palladium-catalyzed C-H activation/C-C cross-coupling reactions via electrochemistry.
Palladium-catalyzed C-H activation/C-C cross-coupling reactions typically require stoichiometric chemical oxidants and exogenous ligands. However, there are significant disadvantages associated with the use of traditional stoichiometric oxidants. To overcome these issues, we have developed an electrochemical strategy to achieve methylation and acylation.


Third party reimbursement.
The decisions made by materiel managers will continue to be driven to a great extent by cost and budgetary considerations. In fact, the movement to more fixed-rate payment systems tends to create even a greater emphasis on materiel management programs. However, there are strategies that are available to materiel managers to react to the various third party payment systems. In most cases, implementation of these strategies will require coordination between accounting/finance personnel and materiel managers.


A procedural, pragmatist account of ethical objectivity.
This article offers a procedural, pragmatist account of objectivity in the domain of the good that is inspired by pragmatic and feminist critiques of objectivity in philosophy of science and epistemology. I begin by asking first what we want to capture--or ought to want to capture--with a notion of ethical objectivity and in answer to this question I identify four "points" to ethical objectivity: undergirding the possibility of mistakenness, making genuine disagreement possible, making sense of our appreciation of the ethical perspectives of others, and making possible a sense of ethical improvement or learning. I then lay out a process-based account of objectivity in ethics that makes good on the four points I have identified. Finally, I consider worries related to convergence, bias, and ontology and defend the procedural, pragmatist account in light of those potential objections.


Runx-dependent regulation of G-protein gamma3 expression in T-cells.
Heterotrimeric G-proteins control diverse biological processes by conveying signals from seven-transmembrane receptors to intracellular effectors. Although their signaling roles were originally ascribed to their GTP-bound alpha-subunits, more recent evidence points to the equally active roles played by their betagamma-dimers. To elucidate the individual contributions of their gamma-subtypes, we used a gene targeting approach to show that mice lacking the gamma3-subtype display a defective T-cell dependent immune response. To identify the cellular basis for this defect, we demonstrated that gamma3-mRNA is strongly induced in activated CD4+ T-cells. To determine the mechanism for this regulated expression, we used several strategies to identify the importance of a Runx consensus sequence element in the first intron of the gamma3 gene and the Runx1 protein. Overall, these data provide the first genetic evidence for the tight regulation and involvement of the G protein gamma3-subtype in mounting an effective immune response in mice.


Exogenous nerve growth factor reverses age-related structural changes in neocortical neurons in the aging rat. A quantitative Golgi study.
The role of chronic exogenous intracerebroventricular administration of nerve growth factor (NGF) on the morphology of layer V pyramidal cell dendrites in aging rats was quantified using Golgi impregnations. Both dendritic branching and dendritic spines from the basilar tree of randomly selected pyramidal neurons of the frontal cortex were evaluated in young control (4-month-old) Fischer 344 rats, in old controls (24-month-old), and in 24-month-old rats administered NGF for 4 weeks. Sholl analysis of basilar dendritic trees showed that neuronal branching in older rats was significantly greater than that in young rats (probably due to compensatory dendritic hypertrophy). The extent of dendritic material in aged rats receiving NGF, however, was identical to that in young rats, that is, the dendritic tree had regressed in size. Dendritic spine response to NGF treatment depended on the region of the dendritic tree sampled. Normal aging resulted in spine loss. However, NGF treatment restored dendritic spine densities to those seen in young controls on terminal tip segments ("plastic" regions). Internal branch segments ("nonplastic" regions) showed no response to NGF. As dendritic spines are thought to represent the neuroanatomic basis of learning and memory, results suggest that NGF can influence the morphology of cortical neurons (probably indirectly via the basal forebrain projections) and therefore may play an efficacious role in the treatment of geriatric cognitive dysfunction and even perhaps in Alzheimer's disease.


[General practitioners in palliative care in Germany: a systematic review].
To investigate the role of general practitioners among the increasing specialization in outpatient palliative care, meaningful research topics, developments of new collaborations and structures in the outpatient sector of palliative care, 52 articles were reviewed. Results have shown that general practitioners are still involved in outpatient palliative care research and show a distinct participation in quality development. Typical research topics in outpatient palliative care research are quality of care and structures. However, cooperative structures between general practitioners and palliative specialists are rare in the field of outpatient palliative care research.


A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.
Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-β superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).


Age-related changes in petal membranes from attached and detached rose flowers.
Changes in petal membrane properties during aging were studied in cut and in attached rose flowers (Rosa hybrida L., cv Mercedes). Both cut and attached flowers exhibited a growth phase characterized by an increase in fresh weight and an accumulation of membrane components. The growth phase, which was more pronounced in the attached than in the cut flowers, was followed by a senescence phase, characterized by a decrease in fresh weight and a decline in membrane components. In cut flowers, both the growth and the senescence phases were accompanied by a decrease in membrane fluidity and in the ratio of unsaturated to saturated fatty acids, but the ratio of sterol to phospholipid increased. In attached flowers, while both the membrane fluidity and the sterol-to-phospholipid ratio remained unchanged during the growth phase, the senescence phase was accompanied (as in cut flowers) by a decrease in membrane fluidity and an increase in the sterol-to-phospholipid ratio. Unlike in cut flowers, however, the age-related changes in the ratio of unsaturation of fatty acids were not correlated with those of fluidity. Changes in the saturation of phospholipid acyl chains are commonly thought to influence membrane fluidity. Our observations question this view and suggest instead that the ratio of sterol to phospholipid may play the major role in maintaining membrane lipid fluidity.


Vaccine-induced immune thrombotic thrombocytopenia with atypical vein thrombosis: Implications for clinical practice.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a new and rare syndrome resulting from the largest vaccination campaign against SARS-CoV-2 in the history of mankind. The aim of this review is to clarify underlying mechanisms, pathology, diagnosis, and therapy, with the related clinical implications. We performed a comprehensive literature review in order to collect the clinical and treatment data about patients suffering from VITT. PubMed, Ovid Medline, Ovid EMBASE, Scopus, and Web of Science were screened regarding patients who developed VITT. Last search was launched on June 30th 2021. Abdominal and/or neurological symptoms develop between 5 and 20 days after vaccine administration and do not involve the lower extremities. VITT is suspected if the platelet count is lower than 100.000/mm3 and D-dimer is higher than the age-adjusted range. Medical treatment is mainly based on intravenous immunoglobulins, corticosteroids, and anticoagulant drugs with a short plasma half-life, but the complete avoidance of low molecular weight heparin is recommended. Endovascular treatment and/or decompressive craniectomy might be an option in a minority of cases. Due to widespread vaccination concerns, the vascular specialist and phlebologist are increasingly consulted to prevent or diagnose VITT. The latter has peculiar and completely different localizations, symptoms, and treatment compared to the common pictures of venous thrombosis.


Effects of Erwinia-asparaginase on the coagulation system.
L-Asparaginase treatment during induction therapy in acute lymphoblastic leukaemia (ALL) is known to be frequently complicated by thromboembolic events. It was recently suggested that L-asparaginase derived from Erwinia chrysanthemi alters the coagulation system less severely than does Escherichia coli asparaginase. In a series of 11 adult patients with ALL, we investigated some parameters of the coagulation system during treatment with Erwinia asparaginase. The doses employed were rather high; all patients below the age of 60 years received 15,000 U/m2 daily over 14 days. In accordance with what is known from treatment with E. coli asparaginase, we observed significant lowering of antithrombin as well as of fibrinogen. However, as to fibrinogen indeed a significant decrease had occurred prior to the institution of Erwinia asparaginase treatment. The most striking observation in the present study was that the levels of prothrombin complex, reflecting the function of K-vitamin dependent coagulation factors II, VII and X, remained within normal ranges during treatment. This indicates that these coagulation factors were not affected by Erwinia asparaginase, an observation at variance with several reports where E. coli asparaginase was investigated. This latter observation was the only finding which could lend support to the view that Erwinia asparaginase affects the coagulation system less than E. coli asparaginase. Finally, one of our patients developed a sinus thrombosis, a severe thrombotic complication.


Epithelial injury induced by exposure to residual oil fly-ash particles: role of reactive oxygen species?
Exposure of animals to airborne particulates is associated with pulmonary injury and inflammation. In the studies described here, primary cultures of rat tracheal epithelial (RTE) cells were exposed to suspensions of residual oil fly ash (ROFA). ROFA exposure resulted in progressive cytotoxicity whereby the amount of lactate dehydrogenase (LDH) released was significantly greater at 24 h than at 6 h after exposure. In a dose-dependent manner, exposure to 5, 10, or 20 microg/cm2 of ROFA for 24 h resulted in cytotoxicity and detachment of cells from the collagen matrix, along with altered permeability of the RTE cell layer. ROFA exposure caused cellular glutathione levels to decrease, producing a condition of oxidative stress in the RTE cells. Treatment of RTE cells with buthionine sulfoxamine, an inhibitor of gamma-glutamyl cysteine synthetase, was found to augment ROFA-induced cytotoxicity. Treatment with dimethylthiourea (DMTU) inhibited ROFA-induced LDH release and permeability changes in a dose-dependent manner. Treatment with the nitric oxide synthase inhibitor NG-monomethyl-D-arginine (D-NMA) for 24 h was without effect. In rats intratracheally instilled with ROFA (500 microg/rat), intraperitoneal administration of DMTU (500 mg/kg) significantly ameliorated the degree of pulmonary neutrophilic inflammation present at 24 h. Overall, these in vitro findings suggest that ROFA-induced RTE cell injury may be mediated by hydroxyl-radical-like reactive oxygen species (i.e., species scavenged by DMTU) that are generated via non-nitric oxide pathways. The delay in induction of maximal RTE cell injury may reflect the time necessary to produce an oxidative burden by depleting antioxidant defenses such as cellular glutathione.


Intestinal Carriage of Third-Generation Cephalosporin-Resistant and Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Healthy US Children.
The epidemiology of antibiotic-resistant Enterobacteriaceae intestinal carriage in healthy US children has not been well characterized. Children between 14 days and 14 years of age were enrolled during well-child visits in Oakland, California, Kansas City, Kansas, and Nashville, Tennessee, between December 2013 and March 2015. Data on recent antibiotic use by the child and travel and hospitalization history of all members of each child's household were obtained with a risk-factor survey. Stool specimens collected from the subjects were screened for extended-spectrum β-lactamase-producing (ESBL-P) bacteria using CHROMagar ESBL medium. Putative ESBL-P Escherichia coli and Klebsiella colonies underwent phenotypic confirmation by double-disk synergy testing; confirmed third-generation cephalosporin-resistant (3GCR) isolates underwent additional antibiotic-susceptibility testing. In 519 subjects, the overall 3GCR Enterobacteriaceae carriage rate was 4.4% (n = 23) and ranged from 3.4% to 5.1% among the study sites. The ESBL-P Enterobacteriaceae carriage rate was 3.5% (n = 18). The rates of 3GCR Enterobacteriaceae carriage was highest in 1 to <2 year olds at 6.5%, and was 5.2% in <5 year-olds vs 1.7% in ≥5-year-olds (P = .11). 3GCR and ESBL-P Enterobacteriaceae carriage was associated with international travel within the previous year; 11.1% of ESBL-P Enterobacteriaceae carriers reported this history compared with 1.6% of noncarriers (P = .004). No other queried factor was found to increase risk. Of the 24 analyzed 3GCR isolates, 58% were multidrug resistant. The 3GCR Enterobacteriaceae carriage rate exceeds 5% in healthy US children <5 years of age. International travel within the previous year increased the risk of 3GCR and ESBL-P Enterobacteriaceae carriage. In contrast, we found no differences in the rates of hospitalization or recent antibiotic exposure between carriers and noncarriers. Young children, who have the highest prevalence of colonization, might be a sentinel population to study to gain a better understanding of community sources of antibiotic-resistant Enterobacteriaceae.


Light-sheet fluorescence imaging charts the gastrula origin of vascular endothelial cells in early zebrafish embryos.
It remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application of in toto light-sheet fluorescence imaging of embryos to trace the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously reported method to embryo mounting and light-sheet imaging, created an alignment, fusion, and extraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal-ventral and anterior-posterior axes, of which the dorsal-anterior cells contributed to cerebral ECs, the dorsal-lateral cells to anterior trunk ECs, and the ventral-lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.


Rubinstein-Taybi syndrome with agenesis of corpus callosum.
Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder with characteristic morphological anomaly. Our patient was a 4.5-year-old girl came with features like broad thumbs, downward slanting palpebral fissures and mental retardation. Systemic abnormalities such as repeated infection, seizure with developmental delay were also associated with it. She was having head banging behavior abnormal slurring speech, incoordination while transferring things from one hand to other. Galaxy of clinical pictures and magnetic resonance imaging report helped to clinch the diagnosis as a case of "RSTS with corpus callosal agenesis" which to the best of our knowledge has never been reported in past from India.


N-homocysteinylation of apolipoprotein A-I impairs the protein's antioxidant ability but not its cholesterol efflux capacity.
A high homocysteine (Hcy) level is a risk factor for atherosclerosis. Hcy can be added to proteins through a process known as N-homocysteinylation. This is thought to be a potential cause of atherosclerosis induction. We previously reported that N-homocysteinylated apolipoprotein A-I (N-Hcy-apoA-I) was identified in normal human plasma. In this study, the effect of N-homocysteinylation on the functions of apoA-I was examined. A kinetic study using dimyristoyl phosphatidylcholine (DMPC) liposomes indicated that N-Hcy-apoA-I showed increased lipid-binding activity compared to wild-type apoA-I. Two reconstituted high-density lipoprotein (rHDL) particles of different sizes (approximately 8.2 nm and 7.6 nm in diameter) were produced by mixing apoA-I and 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). However, an increased ratio of large to small particles was found in rHDL prepared with N-Hcy-apoA-I. The normal apoA-I antioxidant ability, estimated by the suppression of conjugated diene formation in low-density lipoprotein (LDL) induced by copper sulfate oxidation, was considerably impaired when using N-Hcy-apoA-I. Although N-Hcy-apoA-I functioned as an oxidant, no significant difference was observed in the cholesterol efflux capacity from THP-1 macrophages between wild-type apoA-I and N-Hcy-apoA-I. These results suggest that N-Hcy-apoA-I might be proatherogenic due to its oxidative behavior but not an attenuation of cholesterol efflux capacity.


Trends in incidence of AIDS illnesses in Australia from 1983 to 1994: the Australian AIDS cohort.
To assess time trends in incidence of AIDS illnesses in Australia, a retrospective cohort of people diagnosed with AIDS from January 1, 1983 to December 31, 1994 in three HIV medicine units in Sydney, Melbourne, and Perth was established. Data on initial and subsequent AIDS illnesses were available for 2580 AIDS cases, or 45% of Australian AIDS notifications over the study period. Males represented 97.2% of the cohort, and HIV exposure category was homosexual contact for 89.9%. Subcohorts were formed by interval of AIDS diagnosis: 1983 through 1987, 1988 through 1990, and 1991 through 1994, with estimation of cumulative risk for each AIDS illness by the Kaplan-Meier method. The cumulative risk declined for Pneumocystis carinii pneumonia (PCP) (p < 0.0001) and for Kaposi's sarcoma (KS) (p < 0.0001); PCP cumulative risk estimates 2 years following AIDS diagnosis were 70% for people diagnosed with AIDS in 1983 through 1987 and 48% in 1991 through 1994, and KS cumulative risk estimates 2 years following AIDS diagnosis were 44% in 1983 through 1987 and 32% in 1991 through 1994. In contrast, cumulative risk increased from 34% to 40% for cytomegalovirus (CMV) disease (p = 0.005), from 47% to 50% for Mycobacterium avium complex (MAC) (p < 0.0001), and from 26% to 33% for esophageal candidiasis (p < 0.0001). Corresponding to this changing spectrum of AIDS illness has been an increase in severity of immunodeficiency at AIDS, with median CD4 cell count declining from 54 cells/mm3 in 1983 through 1987 to 34/mm3 in 1991 through 1994 (p = 0.002).


Endothelial transdifferentiation of human HGC-27 gastric cancer cells in vitro.
Malignant tumor cells are able to transdifferentiate into other cell types in various tissues or organs. Recent studies have demonstrated the ability of cancer cells to transdifferentiate into functional endothelial cells (ECs). However, whether human gastric cancer (GC) cells are able to transdifferentiate into other cell types has remained largely elusive. Furthermore, whether HGC-27 cells are able to participate in GC angiogenesis remains to be clarified. In the present study, the HGC-27 cell line grown under hypoxic conditions for 4 days exhibited the typical 'flagstone' appearance, which is typical for cultured ECs. HGC-27 cells cultured on Matrigel under hypoxic conditions gradually formed net-like structures. Furthermore, the cultured HGC-27 cells expressed CD31, CD34 and von Willebrand factor, the molecular markers for ECs, under hypoxic conditions. These results indicated that HGC-27 cells, cultured under hypoxic conditions, are able to transdifferentiate into EC-like cells in vitro.


Effect of latex and vinyl examination gloves on canine spermatozoal motility.
Two experiments were conducted to determine whether contact with latex or vinyl examination gloves affects canine spermatozoal motility. In experiment 1, semen was collected by digital manipulation from each of 5 dogs, and initial spermatozoal motility was assessed. The ejaculate was divided into 5 equal subsamples of 2 ml each, then randomly assigned to a control group, or treated with a 0.5-cm2 piece of latex or vinyl glove with or without talcum powder. After such exposure, spermatozoal motility was assessed at 1 and 5 minutes. Talcum powder within latex or vinyl glove treatments had no significant effect on spermatozoal motility at either period. Spermatozoal motility in samples did not differ between the control and vinyl glove groups; however, latex glove-treated samples were found to have a significant (P less than 0.05) decrease in spermatozoal motility at 1 and 5 minutes. In experiment 2, the effects of latex and vinyl gloves on canine spermatozoal motility during a sham laboratory manipulation was performed. Three ejaculates of approximately 10 ml were collected from each of 5 dogs and randomly assigned, within each dog, to be either a control (no glove exposure) or allowed to briefly contact either a latex or vinyl glove during sample manipulation. Spermatozoal motility was assessed for each sample immediately prior to and at 1 minute after manipulation. Exposure of semen to latex gloves significantly (P less than 0.05) decreased sample spermatozoal motility, whereas vinyl glove exposure had a minimal (P greater than 0.05) effect.(ABSTRACT TRUNCATED AT 250 WORDS)


A radiologic diagnostic scoring model based on CT features for differentiating gastric schwannoma from gastric gastrointestinal stromal tumors.
We aimed to further explore the CT features of gastric schwannoma (GS), propose and validate a convenient diagnostic scoring system to distinguish GS from gastric gastrointestinal stromal tumors (GISTs) preoperatively. 170 patients with submucosal tumors pathologically confirmed (GS n=35; gastric GISTs n=135) from Hospital 1 were analyzed retrospectively as the training cohort, and 72 patients (GS=11; gastric GISTs=61) from Hospital 2 were enrolled as the validation cohort. We searched for significant CT imaging characteristics and constructed the scoring system via binary logistic regression and converted regression coefficients to weighted scores. The ROC curves, AUCs and calibration tests were carried out to evaluate the scoring models in both the training cohort and the validation cohort. For convenient assessment, the system was further divided into four score ranges and their diagnostic probability of GS was calculated respectively. Four CT imaging characteristics were ultimately enrolled in this scoring system, including transverse position (2 points), location (5 points), perilesional lymph nodes (6 points) and pattern of enhancement (2 points). The AUC of the scoring model in the training cohort were 0.873 (95% CI, 0.816-0.929) and the cutoff point was 6 points. In the validation cohort, the AUC was 0.898 (95% CI, 0.804-0.957) and the cutoff value was 5 points. Four score ranges were as follows: 0-3 points for very low probability of GS, 4-7 points for low probability; 8-9 points for middle probability; 10-15 points for very high probability. A convenient scoring model to preoperatively discriminate GS from gastric GISTs was finally proposed.


Effect of Varying Recovery Duration on Postactivation Potentiation of Explosive Jump and Short Sprint in Elite Young Soccer Players.
Köklü, Y, Köklü, Ö, Işıkdemir, E, and Alemdaroğlu, U. Effect of varying recovery duration on postactivation potentiation of explosive jump and short sprint in elite young soccer players. J Strength Cond Res 36(2): 534-539, 2022-The purpose of this study was to investigate the effects of postactivation potentiation (PAP) on vertical jump and sprint performances with different recovery durations. Twelve elite young soccer players (average age: 17.0 ± 0.6 years; body mass: 67.0 ± 5.4 kg; height: 175.0 ± 3.5 cm) voluntarily performed countermovement jump (CMJ) and 30-m sprints (with 10-m split times) under unloaded and 4 different recovery duration conditions (R1: 1 minute, R2: 2 minutes, R3: 3 minutes, and R4: 4 minutes) after a set of 3 repetitions of half-squat exercises at 90% of 1-repetition maximum. Electromyographic assessments of both limbs' vastus lateralis (VL) and semitendinosus (ST) muscle activity were also made during the tests. Vertical jump height, sprint time, and VL and ST muscle activity root mean square (RMS) values were analyzed. The results show that players demonstrated significantly better CMJ, 10-, and 30-m sprint performances in the R4 condition compared with the unloaded condition (p < 0.05). The players also showed significantly higher RMS values for VL and ST muscle activity in the CMJ and 30-m test performances for both legs in the R4 condition compared with the unloaded, R1, R2, and R3 conditions (p < 0.05). According to these results, if sports scientists and coaches desire to increase the PAP effect after heavy resistance training, 4 minutes of recovery time instead of 1, 2, or 3 minutes for CMJ, 10-, and 30-m sprint performances is recommended.


Influence of sevoflurane on the metabolism and renal effects of compound A in rats.
The sevoflurane degradation product compound A is nephrotoxic in rats. In contrast, patient exposure to compound A during sevoflurane anesthesia has no clinically significant renal effects. The mechanism for this difference is incompletely understood. One possibility is that the metabolism and toxicity of compound A in humans is prevented by sevoflurane. However, the effect of sevoflurane on compound A metabolism and nephrotoxicity is unknown. Thus, the purpose of this investigation was to determine the effect of sevoflurane on the metabolism and renal toxicity of compound A in rats. Male rats received 0.25 mmol/kg intraperitoneal compound A, alone and during sevoflurane anesthesia (3%, 1.3 minimum alveolar concentration, for 3 h). Compound A metabolites in urine were quantified, and renal function was evaluated by serum creatinine and urea nitrogen, urine volume, osmolality, protein excretion, and renal tubular histology. Sevoflurane coadministration with compound A inhibited compound A defluorination while increasing relative metabolism through pathways of sulfoxidation and beta-lyase-catalyzed metabolism, which mediate toxicity. Sevoflurane coadministration with compound A increased some (serum creatinine and urea nitrogen, and necrosis) but not other (urine volume, osmolality, and protein excretion) indices of renal toxicity. Sevoflurane does not suppress compound A nephrotoxicity in rats in vivo. These results do not suggest that lack of nephrotoxicity in surgical patients exposed to compound A during sevoflurane anesthesia results from an inhibitory effect of sevoflurane on compound A metabolism and toxicity. Rather, these results are consistent with differences between rats and humans in compound A exposure and inherent susceptibility to compound A nephrotoxicity.


Assessment of the patient's subjective experience in acute neuroleptic treatment: implications for compliance and outcome.
The concept of subjective response to neuroleptics in schizophrenia was reviewed with particular focus on scales for its measurement. The significance of recognizing such a phenomenon early on in the course of treatment has been illustrated by research data linking it to compliance, clinical improvement, quality of life, suicidal behaviour and comorbid drug abuse. Negative subjective response to neuroleptics has been identified as a strong predictor of compliance and outcome. Awareness of this subjective response in the management of the acute phase of the illness would require the physician to develop specific or additional approaches to the management of such dysphoric patients on neuroleptics at the time of discharge.


Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells.
Multidrug resistance (MDR) limits the beneficial outcomes of conventional breast cancer chemotherapy. Ras-related nuclear protein (Ran-GTP) plays a key role in these resistance mechanisms, assisting cancer cells to repair damage to DNA. Herein, we investigate the co-delivery of Ran-RCC1 inhibitory peptide (RAN-IP) and doxorubicin (DOX) to breast cancer cells using liposomal nanocarriers. A liposomal delivery system, co-encapsulating DOX, and RAN-IP, was prepared using a thin-film rehydration technique. Dual-loaded liposomes were optimized by systematic modification of formulation variables. Real-Time-Polymerase Chain Reaction was used to determine Ran-GTP mRNA expression. In vitro cell lines were used to evaluate the effect of loaded liposomes on the viability of breast and lung cancer cell lines. In vivo testing was performed on a murine Solid Ehrlich Carcinoma model. RAN-IP reversed the Ran-expression-mediated MDR by inhibiting the Ran DNA damage repair function. Co-administration of RAN-IP enhanced sensitivity of DOX in breast cancer cell lines. Finally, liposome-mediated co-delivery with RAN-IP improved the anti-tumor effect of DOX in tumor-bearing mice when compared to single therapy. This study is the first to show the simultaneous delivery of RAN-IP and DOX using liposomes can be synergistic with DOX and lead to tumor regression in vitro and in vivo.


Resolving Malpractice Claims after Tort Reform: Experience in a Self-Insured Texas Public Academic Health System.
To describe the litigation experience in a state with strict tort reform of a large public university health system that has committed to transparency with patients and families in resolving medical errors. Secondary data collected from The University of Texas System, which self-insures approximately 6,000 physicians at six health campuses across the state. We obtained internal case management data for all medical malpractice claims closed during 1 year before and 6 recent years following the enactment of state tort reform legislation. We retrospectively reviewed information about malpractice claimants, malpractice claims, and the process and outcome of dispute resolution. We accessed an internal case management database, supplemented by both electronic and paper records compiled by the university's Office of General Counsel. Closed claims dropped from 244 in 2001-2002 to an annual mean of 96 in 2009-2015, closures following lawsuits from 136 in 2001-2002 to an annual mean of 28 in 2009-2015, and paid claims from 60 in 2001 to an annual mean of 20 in 2009-2015. Patterns of resolution suggest efforts by the university to provide some compensation to injured patients in cases that were no longer economically viable for plaintiffs' lawyers to litigate. The percentage of payments relating to cases in which lawsuits had been filed decreased from 82 percent in 2001-2002 to 47 percent in 2009-2012 and again to 29 percent in 2012-2015, although most paid claimants were represented by attorneys. Unrepresented patients received payment in 13 cases closed in 2009-2012 (22 percent of payments; mean amount $60,566) and in 24 cases closed in 2012-2015 (41 percent of payments; mean amount $109,410). Even after tort reform, however, claims that resulted in payment remained slow to resolve, which was worsened for claimants subject to Medicare secondary payer rules. Strict confidentiality became a more common condition of settlement, although restrictions were subsequently relaxed in order to further transparency and improve patient safety. Malpractice litigation risk diminished substantially for a public university health system in Texas following legal changes that reduced rights to sue and available damages. Health systems operating in a low-tort environment should work with policy makers, plaintiffs' attorneys, and patient groups to assist unrepresented patients, facilitate early mediation, limit nondisclosure obligations following settlement, and expedite the resolution of Medicare liens.


COVID-19 Therapeutic Options Under Investigation.
Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexamethasone have been so far shown to reduce COVID-19-associated death. Here, we provide a review of the potential therapeutic agents being considered for the treatment and management of COVID-19 patients.


Visual SLAM-Based Robotic Mapping Method for Planetary Construction.
With the recent discovery of water-ice and lava tubes on the Moon and Mars along with the development of in-situ resource utilization (ISRU) technology, the recent planetary exploration has focused on rover (or lander)-based surface missions toward the base construction for long-term human exploration and habitation. However, a 3D terrain map, mostly based on orbiters' terrain images, has insufficient resolutions for construction purposes. In this regard, this paper introduces the visual simultaneous localization and mapping (SLAM)-based robotic mapping method employing a stereo camera system on a rover. In the method, S-PTAM is utilized as a base framework, with which the disparity map from the self-supervised deep learning is combined to enhance the mapping capabilities under homogeneous and unstructured environments of planetary terrains. The overall performance of the proposed method was evaluated in the emulated planetary terrain and validated with potential results.


Tannic Acid Inhibits Salmonella enterica Serovar Typhimurium Infection by Targeting the Type III Secretion System.
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen that can cause food poisoning and diarrhea in both humans and animals worldwide. The Salmonella pathogenicity island (SPI) genes encoded type III secretion system (T3SS) is important for S. Typhimurium invasion and replication in host cells. Due to the increasing problem of antibiotic resistance, antibiotic treatment for clinical Salmonella infection has gradually been limited. Anti-virulence inhibitors are a promising alternative to antibiotics because they do not easily induce bacterial antibiotic resistance. Here, we systematically evaluated the therapeutic effect of tannic acid (TA) on Salmonella-infected mice and elucidated its anti-infection mechanism. TA treatment improved the survival rate of S. Typhimurium-infected mice and alleviated cecum pathological lesions. In addition, TA inhibited S. Typhimurium invasion to HeLa cells without affecting their growth. Further studies showed that TA could inhibit the expression of sipA and sipB. This inhibition may be implemented by inhibiting the transcription of key regulatory and structural genes of the T3SS. This study provides an alternative anti-virulence strategy for Salmonella infection treatment.


Effects of Cycloheximide on Indoleacetic Acid-induced Ethylene Production in Pea Root Tips.
Cycloheximide inhibited ethylene production in excised pea root tips treated with high levels of indoleacetic acid (100 mum and 10 mum). In contrast, cycloheximide did not inhibit ethylene production induced by a lower concentration (1 mum) of indoleacetic acid unless it was added 2 hours before the indoleacetic acid treatment. These observations suggest that indoleacetic acid has two effects on the enzyme system involved in ethylene synthesis. At low concentrations (1 mum) indoleacetic acid increases ethylene production without protein synthesis, whereas at the higher concentrations, the synthesis of new protein is associated with increased ethylene production.


Solvent-dependent stereoselectivity in a Still-Wittig rearrangement: an experimental and ab initio study.
[see reaction]. The Still-Wittig rearrangement gave opposite selectivities for (Z:E)-alkenes in THF (3:1) vs toluene (1:3) in the synthesis of serine-proline dipeptide amide isosteres. Four transition states leading to (Z)-and (E)-alkenes with THF and without (representing toluene) were identified by ab initio calculations at the 3-21G* level. The calculated (Z:E)-ratios with THF (4.7:1) and without THF (1:3.2) suggested that the transition state geometries and energies were well-represented by the calculations.


Successful Return to Performance After COVID-19 Infection in an Elite Athlete.
To present training load (TL) and heart-rate variability (HRV) in an elite sprinter monitored before, during, and after a COVID-19 infection until successful return to performance. TL, subjective morning fatigue (MF), and supine HRV were monitored during a 12-week period. During a high-TL period (training camp), MF and heart rate increased and vagally mediated HRV variables decreased. MF increased and stayed high 3 days after the camp despite decrease in TL. In contrast, 4 days after the camp, heart rate decreased and vagally mediated HRV variables increased, reflecting parasympathetic hyperactivity. Elevated MF and suboptimal training performance led to a PCR test decision, which returned positive. After a 10-day training suspension, TL was progressively increased with low MF and high vagal tone. The athlete was able to return to competition 17 days after medical clearance for return to participation and 1 week later beat his indoor 60-m personal best. In this athlete, COVID-19 infection induced parasympathetic hyperactivity with subjective fatigue. This case report presents how performance capacity was only negatively influenced by a COVID-19 infection in the short term, with a quick and successful return to performance, thanks to state-of-the-art medical management. This highlights the importance of TL and HRV monitoring in return-to-participation and return-to-competition decisions.


Treatment of a case of phonological alexia with agraphia using the Auditory Discrimination in Depth (ADD) program.
Phonological alexia and agraphia are acquired disorders characterized by an impaired ability to convert graphemes to phonemes (alexia) or phonemes to graphemes (agraphia). These disorders result in phonological errors typified by adding, omitting, shifting, or repeating phonemes in words during reading or graphemes when spelling. In developmental dyslexia, similar phonological errors are believed to result from deficient phonological awareness, an oral language skill that manifests itself in the ability to notice, think about, or manipulate the individual sounds in words. The Auditory Discrimination in Depth (ADD) program has been reported to train phonological awareness in developmental dyslexia and dysgraphia. We used a multiple-probe design to evaluate the ADD program's effectiveness with a patient with a mild phonological alexia and mixed agraphia following a left hemisphere infarction. Large gains in phonological awareness, reading and spelling nonwords, and reading and spelling real words were demonstrated. A follow-up reassessment, 2 months posttreatment, found the patient had maintained treatment gains in phonological awareness and reading, and attained additional improvement in real word reading.


Microfluidic characterization of sustained solute release from porous supraparticles.
We present a novel microfluidic technique for precise characterization of controlled release of solute from porous latex supraparticles in a laminar flow environment. Dye-infused supraparticles are fabricated via dry self-assembly method using droplet templates dispensed on superhydrophobic substrates. A water-soluble dye is used as a model compound, the release rate of which is measured colorimetrically. The sustained release rates of dye from supraparticles and dye pellets are quantified and compared to common diffusion/dissolution mass transfer models. The results illustrate the potential of microfluidics as a tool in monitoring controlled release process and the role of the uniformly porous supraparticle matrix for the prolonged continuous solute delivery.


Quicksilver: a novel publish and subscribe clinical messaging platform.
The authors introduce and describe the features of Quicksilver, a novel clinical messaging platform deployed in a multidisciplinary academic primary care clinic. The system follows a publication-subscription messaging paradigm employing dynamic role-based addressing. Quicksilver leverages the open-source XMPP, a powerful and extensible protocol for efficient asynchronous and synchronous communication commonly used in instant messaging applications.


Well-Arranged and Confined Incorporation of PdCo Nanoparticles within a Hollow and Porous Metal-Organic Framework for Superior Catalytic Activity.
A convenient method for the confined incorporation of highly active bimetallic PdCo nanocatalysts within a hollow and porous metal-organic framework (MOF) support is presented. Several chemical conversions occur simultaneously during the one-step low temperature pyrolysis of well-designed polystyrene@ZIF-67/Pd2+ core-shell microspheres, where ZIF (zeolitic imidazolate framework) is a subclass of MOF: the polystyrene core is removed, resulting in a beneficial hollow and porous ZIF support; the ZIF-67 shell acts as a well-defined porous support and as a felicitous Co2+ supplier for metal nanoparticle formation; and Pd2+ and Co2+ are reduced to form catalytically active bimetallic PdCo nanoparticles in the well-defined micropores, inducing the confined growth of PdCo nanoparticles with excellent dispersity.


Genetic engineering of snake toxins. Role of invariant residues in the structural and functional properties of a curaremimetic toxin, as probed by site-directed mutagenesis.
To study the site by which erabutoxin a (Ea) from Laticauda semifasciata binds to the nicotinic acetylcholine receptor, we mutated most residues that are shared with other curaremimetic toxins and studied the structural and biological consequences of introduced mutations. By site-directed mutagenesis, we changed Ser-8 into Gly (EaS8G), Lys-27 into Glu (EaK27E), Trp-29 into Phe (EaW29F) and His (EaW29H), Asp-31 into His (EaD31H), Phe-32 into Leu (EaF32L), Arg-33 into Lys (EaR33K) and Glu (EaR33E), Gly-34 into Ser (EaG34S), Glu-38 into Gln (EaE38Q) and Lys (EaE38K), Gly-49 into Val (EaG49V), and Leu-52 into Ala (EaL52A). All mutants were homogeneous as judged by various analytical procedures. EaE38Q, EaG49V, and EaL52A bound the nicotinic acetylcholine receptor with apparent Kd values close to 10(-10) M, virtually identical to wild Ea. Therefore, Glu-38, Gly-49, and Leu-52 are not important elements in the expression of curaremimetic function in Ea. Mutations of Phe-32 and Gly-34 provoked a 7-fold affinity decrease, suggesting that these residues moderately contribute to function. The 176-fold affinity decrease due to mutation of Ser-8 may reflect some structural change that operates in the polypeptide chain of the mutant, as detected by circular dichroism. Decreases in affinity by a factor of 175, 67, 46, and 318 were seen upon mutations of Lys-27 into Glu, Trp-29 into Phe, Asp-31 into His, and Arg-33 into Glu, with no concomitant change in secondary structure. These residues appear to be important elements of the curaremimetic function of Ea. Thus, a picture of the contribution of conserved residues to the function of a curaremimetic toxin is proposed on the basis of experimental evidence.


Diagnosis of toxoplasmosis using a synthetic glycosylphosphatidylinositol glycan.
Around 2 billion people worldwide are infected with the apicomplexan parasite Toxoplasma gondii which induces a variety of medical conditions. For example, primary infection during pregnancy can result in fetal death or mental retardation of the child. Diagnosis of acute infections in pregnant women is challenging but crucially important as the drugs used to treat T. gondii infections are potentially harmful to the unborn child. Better, faster, more reliable, and cheaper means of diagnosis by using defined antigens for accurate serological tests are highly desirable. Synthetic pathogen-specific glycosylphosphatidylinositol (GPI) glycan antigens are diagnostic markers and have been used to distinguish between toxoplasmosis disease states using human sera.


Physiological characterization of Campylobacter jejuni under cold stresses conditions: its potential for public threat.
Campylobacter jejuni is the major cause of human gastroenteritis worldwide. Under stress conditions, C. jejuni can enter a viable but non-culturable (VBNC) state. We found that the C. jejuni was able to enter a VBNC state by prolonged incubation at 4°C. The standard isolation methods using pre-enrichment steps in Bolton broth or Preston broth could not detect the VBNC cells in spiked chicken meat. The transcription levels of virulence-associated genes (flaA, flaB, cadF, ciaB, cdtA, cdtB and cdtC) were expressed in VBNC cells but in low levels. The VBNC cells retained the ability to invade Caco-2 human intestinal epithelial cells in vitro. In most cases, VBNC cells failed to resuscitate in Caco-2 cells, but in some experiments, they formed colonies after co-incubation with host cells. Collectively, C. jejuni enters into a VBNC state at 4°C and the VBNC C. jejuni remains virulent which may possibly lead to disease in humans. C. jejuni in VBNC state is a potential concern for food safety.


KL-6 is a long-term disease-activity biomarker for interstitial lung disease associated with polymyositis/dermatomyositis, but is not a short-term disease-activity biomarker.
Objectives: We aimed to evaluate the usefulness of serum KL-6 for interstitial lung disease (ILD) with polymyositis/dermatomyositis (PM/DM). Methods: All consecutive and previously untreated adult patients with PM/DM who were admitted to our hospital from 2010 to 2015 were included. The associations between serum KL-6 levels and clinical information were retrospectively analyzed. Results: Baseline serum KL-6 levels were significantly higher in patients with ILD than in those without (n = 41 and 15, respectively; p < .001). In the 14 patients whose ILD improved within 4 weeks post-treatment, their serum KL-6 levels did not significantly decrease at 2 weeks, 4 weeks, or 3 months post-treatment (p = 1.00, 1.00, and .83, respectively). Conversely, their serum KL-6 levels significantly decreased at 6, 9, and 12 months post-treatment (p = .01 in all comparisons). In the 12 patients whose ILD remained unchanged or deteriorated in 4 weeks post-treatment, only the difference between their serum KL-6 levels at 3 and 12 months was significant (p = .003). Conclusions: The present study validated the serum KL-6 as a diagnostic marker for ILD in PM/DM. However, serum KL-6 is not a short-term disease-activity biomarker for ILD with PM/DM, but it is a long-term disease-activity biomarker.


Depolymerized holothurian glycosaminoglycan and heparin inhibit the intrinsic tenase complex by a common antithrombin-independent mechanism.
Depolymerized holothurian glycosaminoglycan (DHG) is a fucosylated chrondroitin sulfate that possesses antithrombin-independent antithrombotic properties and inhibits factor X activation by the intrinsic tenase complex (factor IXa-factor VIIIa). The mechanism and molecular target for intrinsic tenase inhibition were determined and compared with inhibition by low-molecular-weight heparin (LMWH). DHG inhibited factor X activation in a noncompetitive manner (reduced V(max(app))), with 50-fold higher apparent affinity than LMWH. DHG did not affect factor VIIIa half-life or chromogenic substrate cleavage by factor IXa-phospholipid but reduced the affinity of factor IXa for factor VIIIa. DHG competed factor IXa binding to immobilized LMWH with an EC(50) 35-fold lower than soluble LWMH. Analysis of intrinsic tenase inhibition, employing factor IXa with mutations in the heparin-binding exosite, demonstrated that relative affinity (K(i)) for DHG was as follows: wild type > K241A > H92A > R170A > > R233A, with partial rather than complete inhibition of the mutants. This rank order for DHG potency correlated with the effect of these mutations on factor IXa-LMWH affinity and the potency of LMWH for intrinsic tenase. DHG also accelerated decay of the intact intrinsic tenase complex. Thus, DHG binds to an exosite on factor IXa that overlaps with the binding sites for LMWH and factor VIIIa, disrupting critical factor IXa-factor VIIIa interactions.