ANEXdb: an integrated animal ANnotation and microarray EXpression database.
To determine annotations of the sequence elements on microarrays used for transcriptional profiling experiments in livestock species, currently researchers must either use the sparse direct annotations available for these species or create their own annotations. ANEXdb ( http://www.anexdb.org ) is an open-source web application that supports integrated access of two databases that house microarray expression (ExpressDB) and EST annotation (AnnotDB) data. The expression database currently supports storage and querying of Affymetrix-based expression data as well as retrieval of experiments in a form ready for NCBI-GEO submission; these services are available online. AnnotDB currently houses a novel assembly of approximately 1.6 million unique porcine-expressed sequence reads called the Iowa Porcine Assembly (IPA), which consists of 140,087 consensus sequences, the Iowa Tentative Consensus (ITC) sequences, and 103,888 singletons. The IPA has been annotated via transfer of information from homologs identified through sequence alignment to NCBI RefSeq. These annotated sequences have been mapped to the Affymetrix porcine array elements, providing annotation for 22,569 of the 23,937 (94%) porcine-specific probe sets, of which 19,253 (80%) are linked to an NCBI RefSeq entry. The ITC has also been mined for sequence variation, providing evidence for up to 202,383 SNPs, 62,048 deletions, and 958 insertions in porcine-expressed sequence. These results create a single location to obtain porcine annotation of and sequence variation in differently expressed genes in expression experiments, thus permitting possible identification of causal variants in such genes of interest. The ANEXdb application is open source and available from SourceForge.net.


Electrical source localization by LORETA in patients with epilepsy: Confirmation by postoperative MRI.
Few studies have been conducted that have compared electrical source localization (ESL) results obtained by analyzing ictal patterns in scalp electroencephalogram (EEG) with the brain areas that are found to be responsible for seizures using other brain imaging techniques. Additionally, adequate studies have not been performed to confirm the accuracy of ESL methods. In this study, ESL was conducted using LORETA (Low Resolution Brain Electromagnetic Tomography) in 9 patients with lesions apparent on magnetic resonance imaging (MRI) and in 6 patients who did not exhibit lesions on their MRIs. EEGs of patients who underwent surgery for epilepsy and had follow-ups for at least 1 year after operations were analyzed for ictal spike, rhythmic, paroxysmal fast, and obscured EEG activities. Epileptogenic zones identified in postoperative MRIs were then compared with localizations obtained by LORETA model we employed. We found that brain areas determined via ESL were in concordance with resected brain areas for 13 of the 15 patients evaluated, and those 13 patients were post-operatively determined as being seizure-free. ESL, which is a noninvasive technique, may contribute to the correct delineation of epileptogenic zones in patients who will eventually undergo surgery to treat epilepsy, (regardless of neuroimaging status). Moreover, ESL may aid in deciding on the number and localization of intracranial electrodes to be used in patients who are candidates for invasive recording.


Receptor for soluble C3 and C3b on human lymphoblastoid (RAJI) cells. Properties and biologocal significance.
This study describes the presence of a receptor for fluid phase human C3 and C3b on Raji cell membranes. The binding of C3 and C3b was demonstrated indirectly by a fluoresceinated anti-C3 serum and directly by using radioiodinated proteins. No other complement proteins or serum factors were needed to mediate binding of C3 and C3b to the receptor. The possibility of enzymatic cleavage of C3 before or after its attachment on the cell membrane was ruled out by the demonstration of antigenically intact C3 on Raji cells. Inhibition and dissociation of Raji cell-EAC1423 rosettes by C3 and C3b indicated that both of these proteins bind to the same receptor site or closely associated receptor sites on Raji cells. C3b-bearing Raji cells were immune adherence negative, indicating that C3b binding to the receptor is brought about through the immune adherence region of the molecule and not the C3d portion. The C3 receptor on Raji cell membranes is uniformly distributed and can move on the membrane plane. Approximately 4 x 10(5) molecules of C3 or C3b bind per Raji cell. The receptor had a higher affinity for C3 than C3b, as was shown by uptake experiments and inhibition of Raji cell-EAC1423 rosette formation. Apart from the described receptor for C3 and C3b another specific receptor for C3b inactivator-cleaved C3b (C3d) bound to red cells was shown to be present on Raji cells. Raji cells cultured in medium containing fresh normal human serum and cobra venom factor were lysed. Similar results were obtained when C3b-bearing Raji cells were cultured in medium with fresh normal human serum. The lytic effect could be abolished by inactivating serum C3 proactivator (C3PA) and required C6. It was concluded that C3b bound to the Raji cell membrane activates the complement system through the alternate pathway and results in membrane damage and cytolysis. It is postulated that cell destruction by this mechanism may play an important role in vivo in controlling cell growth.


Ophthalmology residency programs on social media.
With the transition from away rotations and in-person interviews during the COVID-19 pandemic came a search for alternative methods to represent and promote residency programs. We investigated utilization of social media by ophthalmology residency programs in response to the pandemic. Social media accounts of accredited ophthalmology residency programs were found through a manual search on Facebook, Instagram, and Twitter. Each program's geographical region (Northeast, Midwest, South, or West) was identified, and year of account creation (2009-2021) was noted. An exponential regression model was used to model total number of social media accounts over time. Comparisons of total number of social media accounts before/after the pandemic and by region, stratified by social media platform, were evaluated through chi-square analysis. Of 125 ophthalmology residency programs, 63% (n = 79) had at least one account on a social platform. 142 acc. Instagram held the most accounts (45%, n = 64), followed by Facebook (29%, n = 41) and Twitter (26%, n = 37). From 2009 to 2021, there has been an exponential increase in social media accounts (R2 = 0.962). 45% (n = 65) of all accounts were created after March 2020. Instagram increased the most, with 45 ophthalmology residency accounts created after the pandemic as compared to 19 created prior (p < 0.001). The number of social media accounts did not vary by region. Based on current trends, the presence of ophthalmology residency programs on social media will likely continue expanding, with major social platforms becoming a vaster source of information for ophthalmology residency applicants.


A few molecules can control the enantiomeric outcome. Evidence supporting absolute asymmetric synthesis using the Soai asymmetric autocatalysis.
[reaction: see text] Experiments were carried out to investigate whether the Soai asymmetric autocatalysis can accomplish true absolute asymmetric synthesis. In 54 reactions, R and S enantiomeric products were obtained 27 times each. Of 25 pairs of side-by-side identical reactions, 12 afforded opposite enantiomers. In a test of the mechanistic viability of a random-chance process, it was found that a very few molecules (approximately 60 000) were sufficient to control the enantiomeric outcome of these reactions. These observations appear most consistent with asymmetric synthesis originating from the chance enantiomeric excess in a racemate.


Personalization of regorafenib treatment in metastatic gastrointestinal stromal tumours in real-life clinical practice.
Regorafenib (REG) has now been approved as the standard third-line therapy in metastatic gastrointestinal stromal tumour (GIST) patients at the recommended dose and schedule of 160 mg once daily for the first 3 weeks of each 4-week cycle. However, it has a relevant toxicity profile that mainly occurs within the first cycles of therapy, and dose and schedule adjustments are often required to reduce the frequency or severity of adverse events and to avoid early treatment discontinuation. To date, large amounts of data on the use of REG in metastatic GIST patients in daily clinical practice are not available, and we lack information about how this treatment personalization really affects the quality of life (QoL) of patients. The aim of the present retrospective study is to build a comprehensive picture of all alternative REG strategies adopted in daily clinical practice for use in metastatic GIST patients. Metastatic GIST patients treated with dose adjustment or alternative schedules of REG at seven reference Italian centres were retrospectively included. For a total of 62 metastatic GIST patients, we confirmed that REG treatment adjustment is common in clinical practice and that it is very heterogeneous, with approximately 20 different strategies being adopted. Independent of which strategy is chosen, treatment personalization has led to a clinical benefit defined as complete or partial resolution of side effects in almost all patients, affecting the duration of REG treatment. The personalization of REG, even if it is heterogeneous, seems to be crucial to maximize the overall treatment duration.


Scaffold-free, label-free and nozzle-free biofabrication technology using magnetic levitational assembly.
Tissue spheroids have been proposed as building blocks in 3D biofabrication. Conventional magnetic force-driven 2D patterning of tissue spheroids requires prior cell labeling by magnetic nanoparticles, meanwhile a label-free approach for 3D magnetic levitational assembly has been introduced. Here we present first time report on rapid assembly of 3D tissue construct using scaffold-free, nozzle-free and label-free magnetic levitation of tissue spheroids. Chondrospheres of standard size, shape and capable to fusion have been biofabricated from primary sheep chondrocytes using non-adhesive technology. Label-free magnetic levitation was performed using a prototype device equipped with permanent magnets in presence of gadolinium (Gd3+) in culture media, which enables magnetic levitation. Mathematical modeling and computer simulations were used for prediction of magnetic field and kinetics of tissue spheroids assembly into 3D tissue constructs. First, we used polystyrene beads to simulate the assembly of tissue spheroids and to determine the optimal settings for magnetic levitation in presence of Gd3+. Second, we proved the ability of chondrospheres to assemble rapidly into 3D tissue construct in the permanent magnetic field in the presence of Gd3+. Thus, scaffold- and label-free magnetic levitation of tissue spheroids is a promising approach for rapid 3D biofabrication and attractive alternative to label-based magnetic force-driven tissue engineering.


Azobenzene photoswitches for biomolecules.
The photoisomerization of azobenzene has been known for almost 75 years but only recently has this process been widely applied to biological systems. The central challenge of how to productively couple the isomerization process to a large functional change in a biomolecule has been met in a number of instances and it appears that effective photocontrol of a large variety of biomolecules may be possible. This critical review summarizes key properties of azobenzene that enable its use as a photoswitch in biological systems and describes strategies for using azobenzene photoswitches to drive functional changes in peptides, proteins, nucleic acids, lipids, and carbohydrates (192 references).


Relationship between body condition score at calving and reproductive performance in young postpartum cows grazing native range.
Body condition score is used as a management tool to predict competency of reproduction in beef cows. Therefore, a retrospective study was performed to evaluate association of BCS at calving with subsequent pregnancy rate, days to first postpartum ovulation, nutrient status (assessed by blood metabolites), and calf BW change in 2- and 3-yr-old cows (n = 351) managed and selected to fit their environment of grazing native range over 6 yr at the Corona Range and Livestock Research Center, Corona, NM. Cows were managed similarly before calving, without manipulation of management, to achieve predetermined BCS at parturition. Palpable BCS (scale of 1 to 9) were determined by 2 experienced technicians before calving. Cows were classified to 1 of 3 BCS groups prior calving: BCS 4 (mean BCS = 4.3 ± 0.02), 5 (mean BCS = 5.0 ± 0.03), or 6 (mean BCS = 5.8 ± 0.06). Cows were weighed weekly after calving and serum was collected once weekly (1 yr) or twice weekly (5 yr) for progesterone analysis to estimate first postpartum ovulation beginning 35 d postpartum. Year effects also were evaluated, with years identified as either above or below average precipitation. Days to first postpartum ovulation did not differ among calving BCS groups (P = 0.93). Pregnancy rates were not influenced by calving BCS (P = 0.83; 92%, 91%, 90% for BCS 4, 5, and 6, respectively). Days to BW nadir was not influenced by BCS at calving (P = 0.95). Cow BW was different at all measuring points (P < 0.01) with BCS 6 cows having the heaviest BW and cows with BCS 4 the lightest. Cows with calving BCS 4 and 5 lost more (P = 0.06) BW from the initiation of the study to the end of breeding than cows with BCS 6. However, cow BW change at all other measurement periods was not different (P ≥ 0.49) among calving BCS groups. Serum glucose and NEFA concentrations were not influenced by calving BCS (P ≥ 0.51). Calf BW at birth (P = 0.60), branding (55-d BW; P = 0.76), and weaning (205-d BW; P = 0.60) were not impacted by cow calving BCS. Body condition score did not influence overall pregnancy rates, indicating that young cows can have a reduced BCS and still be reproductively punctual. Therefore, these results indicate that reproductive performance of young cows with reduced BCS may not be affected when managed in extensive range conditions.


Trends in Longevity in the Americas: Disparities in Life Expectancy in Women and Men, 1965-2010.
We describe trends in life expectancy at birth (LE) and between-country LE disparities since 1965, in Latin America and the Caribbean. LE trends since 1965 are described for three geographical sub-regions: the Caribbean, Central America, and South America. LE disparities are explored using a suite of absolute and relative disparity metrics, with measurement consensus providing confidence to observed differences. LE has increased throughout Latin America and the Caribbean. Compared to the Caribbean, LE has increased by an additional 6.6 years in Central America and 4.1 years in South America. Since 1965, average reductions in between-country LE disparities were 14% (absolute disparity) and 23% (relative disparity) in the Caribbean, 55% and 51% in Central America, 55% and 52% in South America. LE in Latin America and the Caribbean is exceeding 'minimum standard' international targets, and is improving relative to the world region with the highest human longevity. The Caribbean, which had the highest LE and the lowest between-country LE disparities in Latin America and the Caribbean in 1965-70, had the lowest LE and the highest LE disparities by 2005-10. Caribbean Governments have championed a collaborative solution to the growing burden of non-communicable disease, with 15 territories signing on to the Declaration of Port of Spain, signalling regional commitment to a coordinated public-health response. The persistent LE inequity between Caribbean countries suggests that public health interventions should be tailored to individual countries to be most effective. Between- and within-country disparity monitoring for a range of health metrics should be a priority, first to guide country-level policy initiatives, then to contribute to the assessment of policy success.


Coordinate and noncoordinate regulation of synaptic vesicle protein genes during embryonic development.
Because the formation of a mature nerve terminal requires the accumulation of large quantities of synaptic vesicles, the expression of synaptic vesicle proteins would be expected to correlate with synaptogenesis. However, previous studies have provided conflicting evidence on this point. We have examined the developmental pattern of expression of mRNA and protein for three RNAs derived from two genes coding for synaptic vesicle membrane proteins. For these experiments, we cloned a chick p65 (synaptotagmin) cDNA using a reduced stringency screen with a rat p65 cDNA probe. We examined p65 expression in chick forebrain in conjunction with that of synaptophysin II. RNase protection assays for p65 and the two isoforms of synaptophysin II (Bixby, 1992) show essentially coordinate increases of these three mRNAs in embryonic forebrain during the peak period of synaptogenesis (E17 to E20). However, each of the three mRNAs has a distinct temporal pattern of expression during the early stages of embryogenesis. In the ciliary ganglion, upregulation of synaptophysin II mRNA correlates very well with synaptogenesis. Our results suggest that the regulation of expression of vesicle membrane protein mRNA can serve as a marker for synaptogenesis, despite temporal differences in early expression patterns. In contrast to mRNA expression, assays for vesicle protein expression show a relatively steady rise in both p65 and synaptophysin II throughout the embryonic period, without a sharp increase corresponding to that seen in message levels. These results suggest that the expression both of the p65 and of the synaptophysin II proteins is post-transcriptionally regulated.


Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis.
Porcine alveolar macrophages (AMphi) are the dominant cell type that supports the replication of porcine reproductive and respiratory syndrome virus (PRRSV) in vivo and in vitro. In order to determine the characteristics of the virus-receptor interaction, the attachment of PRRSV to cells was examined by using biotinylated virus in a series of flow cytometric assays. PRRSV bound specifically to AMphi in a dose-dependent manner. Binding of PRRSV to AMphi increased gradually and reached a maximum within 60 min at 4 degrees C. By confocal microscopy, it was shown that different degrees of PRRSV binding exist and that entry is by endocytosis. Virus uptake in vesicles is a clathrin-dependent process, as it was blocked by the addition of cytochalasin D and co-localization of PRRSV and clathrin was found. Furthermore, by the use of two weak bases, NH4Cl and chloroquine, it was demonstrated that PRRSV uses a low pH-dependent entry pathway. In the presence of these reagents, input virions accumulated in large vacuoles, indicating that uncoating was prevented. These results indicate that PRRSV entry into AMphi involves attachment to a specific virus receptor(s) followed by a process of endocytosis, by which virions are taken into the cell within vesicles by a clathrin-dependent pathway. A subsequent drop in pH is required for proper virus replication.


Studies on the mechanism of nitrofurantoin-mediated red cell toxicity.
The mechanism of nitrofurantoin-mediated depletion of red cell reduced glutathione (GSH) was investigated. Nitrofurantoin caused cellular depletion of GSH in vitro under aerobic and oxygen-depleted conditions, an effect which could be partially inhibited by coincubation with the hemeprotein ligand ethyl isocyanide, or completely prevented by coincubation with 2'-AMP, an inhibitor of NADPH-dependent reductase enzymes. Covalent binding of nitrofurantoin to red cell macromolecules appeared to be a minor process and was not substantially inhibited by either ethyl isocyanide or 2'-AMP. Covalent binding was only slightly greater under oxygen-depleted conditions. Nitrofurantoin increased the rate of superoxide formation in red cell lysate, an effect inhibited by ethyl isocyanide but not by 2'-AMP. These data suggest different mechanisms for nitrofurantoin-mediated depletion of GSH under aerobic and oxygen-depleted conditions. In the presence of oxygen, nitrofurantoin causes the release of superoxide from oxyhemoglobin. The superoxide thus formed may deplete GSH via several mechanisms. In the absence of oxygen, nitrofurantoin is reduced to reactive metabolites via reactions which appear to require the participation of both an NADPH-dependent flavoprotein and hemoglobin.


HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors: a systematic review.
Human epididymis protein 4 (HE4) has received major attention as a potential tumor marker in epithelial ovarian cancer; however, evidence of significant overexpression of HE4 in several other human cancers is expanding. To assess the possible limitations or benefits of HE4 in a clinical setting, this review aims to systematically outline published results of HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors. Our findings suggest scientific basis for a potential diagnostic ability of HE4 in gynecologic cancer and lung cancer, and further research is needed regarding other cancers. Yet, it is important to recognize that other malignancies can cause increased HE4 levels. Furthermore, attention should be paid to the influence of age and renal function on HE4 serum levels in future studies as well as in the clinic for proper interpretation of serum HE4 test results. Cancer Epidemiol Biomarkers Prev; 23(11); 2285-95. ©2014 AACR.


Gene amplification in Tetrahymena thermophila: formation of extrachromosomal palindromic genes coding for rRNA.
Tetrahymena thermophila contains in the macronucleus multiple copies of extrachromosomal palindromic genes coding for rRNA (rDNA) which are generated from a single chromosomal copy during development. In this study we isolated the chromosomal copy of rDNA and determined the structure and developmental fate of the sequence surrounding its 5' junction. The result indicates that specific chromosomal breakage occurs at or near the 5' junction of rDNA during development. The breakage event is associated with DNA elimination and telomeric sequence addition. Similar results were also found previously for the 3' junction of this gene. These results could explain how the extrachromosomal rDNA is first generated. Near both junctions of the chromosomal rDNA, a pair of 20-nucleotide repeats was found. These sequences might serve as signals for site-specific breakage. In addition, we found a pair of perfect inverted repeats at the 5' junction of this gene. The repeats are 42 nucleotides long and are separated by 28 nucleotides. The existence of this structure provides a simple explanation for the formation of the palindromic rDNA.


Sensitivity to angiotensin II dose in patients with vasodilatory shock: a prespecified analysis of the ATHOS-3 trial.
Early clinical data showed that some patients with vasodilatory shock are responsive to low doses of angiotensin II. The objective of this analysis was to compare clinical outcomes in patients requiring ≤ 5 ng kg-1 min-1 angiotensin II at 30 min (≤ 5 ng kg-1 min-1 subgroup) to maintain mean arterial pressure (MAP) ≥ 75 mmHg versus patients receiving > 5 ng kg-1 min-1 angiotensin II at 30 min (> 5 ng kg-1 min-1 subgroup). Data from angiotensin II-treated patients enrolled in the ATHOS-3 trial were used. The subgroup of patients whose angiotensin II dose was down-titrated from 20 ng kg-1 min-1 at treatment initiation to ≤ 5 ng kg-1 min-1 at 30 min (79/163) had significantly lower endogenous serum angiotensin II levels and norepinephrine-equivalent doses and significantly higher MAP versus the > 5 ng kg-1 min-1 subgroup (84/163). Patients in the ≤ 5 ng kg-1 min-1 subgroup were more likely to have a MAP response at 3 h versus those in the > 5 ng kg-1 min-1 subgroup (90% vs. 51%, respectively; odds ratio, 8.46 [95% CI 3.63-19.7], P < 0.001). Day 28 survival was also higher in the ≤ 5 ng kg-1 min-1 subgroup versus the > 5 ng kg-1 min-1 subgroup (59% vs. 33%, respectively; hazard ratio, 0.48 [95% CI 0.28-0.72], P = 0.0007); multivariate analyses supported the survival benefit in patients with lower angiotensin II levels. The ≤ 5 ng kg-1 min-1 subgroup had a more favorable safety profile and lower treatment discontinuation rate than the > 5 ng kg-1 min-1 subgroup. This prespecified analysis showed that down-titration to ≤ 5 ng kg-1 min-1 angiotensin II at 30 min is an early predictor of favorable clinical outcomes which may be related to relative angiotensin II insufficiency.


APR-246 induces early cell death by ferroptosis in acute myeloid leukemia.
APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). APR-246 reactivates the transcriptional activity of p53 mutants by facilitating their binding to DNA target sites. Recent studies in solid cancers have found that APR-246 can also induce p53-independent cell death. In this study, we demonstrate that AML cell death occurring early after APR-246 exposure is suppressed by iron chelators, lipophilic antioxidants and inhibitors of lipid peroxidation, and correlates with the accumulation of markers of lipid peroxidation, thus fulfilling the definition of ferroptosis, a recently described cell death process. The capacity of AML cells to detoxify lipid peroxides by increasing their cystine uptake to maintain major antioxidant molecule glutathione biosynthesis after exposure to APR-246 may be a key determinant of sensitivity to this compound. The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo.


Secondary-structure characterization of two proficient kinase deoxyribozymes.
Dk1 and Dk2 are two catalytically proficient, manganese-dependent, guanine-rich deoxyribozymes previously isolated for DNA phosphorylation. In this study, we carried out a series of experiments that aimed to understand the structural properties of Dk1 and Dk2 and compare the structural similarities or differences of these two distinct deoxyribozymes that carry out similar catalytic functions. First, we performed reselections from two partially randomized DNA libraries on the basis of the original Dk1 and Dk2 sequences to isolate catalytically active sequence variants and identify nucleotides that are invariable, well-conserved, or highly mutagenized. Sequence analysis of these variants assisted by secondary-structure predictions led to the identification of possible Watson-Crick base-pairing regions within each deoxyribozyme. Sequence truncation and base-pair partner exchange experiments were conducted to confirm, or rule out, the existence of the predicted secondary-structure elements. Finally, methylation interference experiments were applied to identify nucleotides that are potentially important for the tertiary structure folding of the deoxyribozymes. Our data suggest that Dk1 and Dk2, despite the differences in their primary sequences and NTP requirements, use an analogous stem-loop element to anchor a structural domain of substantial tertiary interactions to execute their catalytic functions.


Maximizing Information Transfer in SSVEP-Based Brain-Computer Interfaces.
Compared to the different brain signals used in brain-computer interface (BCI) paradigms, the s teady-state visually evoked potential (SSVEP) features a high signal to noise ratio, enabling reliable and fast classification of neural activity patterns without extensive training requirements. In this paper, we present methods to further increase the information transfer rates (ITRs) of SSVEP-based BCIs. Starting with stimulus parameter optimizations methods, we develop an improved approach for the use of Canonical correlation analysis and analyze properties of the SSVEP when the user fixates a target and during transitions between targets. These transitions show a negative effect on the system's ITR which we trace back to delays and dead times of the SSVEP. Using two classifier types adapted to continuous and transient SSVEPs and two control modes (fast feedback and fast input), we present a simulated online BCI implementation which addresses the challenges introduced by transient SSVEPs. The resulting system reaches an average ITR of 181 Bits/min and peak ITR values of up to 295 Bits/min for individual users.


Effects of giardiasis on production in a domestic ruminant (lamb) model.
To examine the effects of giardiasis on production and carcass quality, using growing lambs as a domestic ruminant model. Randomized block. Giardia-free lambs: 23 in infected group, 24 in control group. Six-week-old, specific-pathogen-free lambs were infected with Giardia trophozoites; control lambs received saline solution. Clinical signs of infection, body weight, and feed intake were determined for 10 weeks. Carcass weight and quality were determined at slaughter weight of 45 kg. Giardia infection persisted from weeks 7 to 16. For 5 weeks after challenge exposure, abnormal feces were more frequently observed in infected lambs. Giardia infection was associated with a decrease in rate of weight gain and impairment in feed efficiency. Time to reach slaughter weight was extended in infected lambs, and the carcass weight of Giardia-infected lambs was lower than that of control lambs. Giardiasis has a negative effect on domestic ruminant production. Giardiasis in domestic ruminants is an economically important disease, thus necessitating control or elimination of the infection.


[Coronary bypass surgery without heart-lung-machine. First experiences and results after two years].
Results and experiences two years after the introduction of off-pump coronary artery bypass (OPCAB) are presented. The material includes 95 patients, where 24 patients had a high preoperative risk due to unstable angina, concomitant diseases or relative contraindications to conventional bypass surgery. Per- and postoperative course was characterized by low morbidity with ultra fast track recovery, no detectable levels of coronary enzyme release in the majority of patients, no reoperations for bleeding and early discharge from the hospital. There were two in-hospital deaths, both patients from the high risk group, where one patient died due to a preoperative myocardial infarction, while the other death was not related to cardiac disease. Follow-up results were fully satisfactory, where 86% of the patients were free from anginal symptoms three months after surgery. As a consequence of these positive experiences, OPCAB surgery is offered to an increasing number of patients, currently 25% of our CABG procedures.


Hypothermia inhibits the proliferation of bone marrow-derived mesenchymal stem cells and increases tolerance to hypoxia by enhancing SUMOylation.
Hypothermia therapy has a positive effect on patients with severe brain injury. Recent studies have shown that mild hypothermia increases the survival of bone marrow-derived mesenchymal stem cells (BMSCs) in a hypoxic environment; however, the underlying mechanisms are not yet fully understood. Small ubiquitin-like modifiers (SUMOs) are sensitive to temperature stress reactions and are considered to exert a protective effect. In this study, we examined the protective effects of hypothermia on BMSCs in terms of SUMO protein modification. First, we found that mild hypothermia inhibited the proliferation and differentiation of BMSCs and increased cell tolerance to a hypoxic environment. Second, hypothermia significantly increased the levels of SUMO modification of multiple proteins in BMSCs. The knockdown of SUMO1/2/3 induced the rapid aging of the BMSCs, while the inhibition of the SUMO-conjugating enzyme, Ubc9, reduced cell proliferation and increased the proportion of BMSCs differentiating into nerve cells. Moreover, the tolerance of BMSCs to the hypoxic environment was significantly decreased. Lastly, we investigated 4 reported SUMO target proteins, anti-proliferating cell nuclear antigen, octamer-binding transcription factor 4, p53 and hypoxia-inducible factor-1α, to confirm that SUMO modification was indeed involved in maintaining the proliferation, inhibiting differentiation and enhancing the resistance of BMSCs against adverse conditions. Taken together, our results indicate that the SUMO pathway is involved in the response to hypothermic stress, and that SUMOylation may be an important protective mechanism against hypothermia for the survival of BMSCs under unfavorable conditions.


Changes in open-field behavior of rats following spinal nerve root sectioning.
The open-field behavior of of 30 laboratory albino rats was measured after selective unilateral sectioning of either the L2, L3, L4 or L5 spinal nerve root using a novel abdominal entry. Although treated subjects displayed observable motor dysfunction of the operated limb, no differences were found in open-field ambulation, rearing, defecation or urination based either on the level of the sectioned nerve root or on the day the behavior was measured, suggesting that there was an effect of the treatment not measurable by standard statistical procedures, quite possibly due to the small sample size.


The effects of a single game of rugby on active cervical range of motion.
The cumulative effect of playing rugby over many years decreases active cervical range of motion, especially in the forwards. This in itself should influence long-term neck care; however, it leaves the important question of how noticeable the acute effects of active cervical range of motion are following a single game. The active cervical range of motion was measured in 21 elite rugby players (mean age 24.4 +/- 4.3 years; average professional career of 7 +/- 3.4 years) before and after a single game of rugby at the start of the season. The active cervical range of motion was recorded in flexion, extension, left and right side flexion, plus left and right rotation using a cervical range of motion device. The results show generally decreased active cervical range of motion from before to after a game independent of position played. Rugby backs had significantly (P < 0.05) reduced active cervical range of motion in flexion, while forwards were affected in extension and left lateral flexion (P < 0.05). These results highlight that a single game of rugby can reduce functional capacity of the neck (active cervical range of motion), and the affected neck movement appears to be related to the role of positional play. The authors suggest that neck training and muscle damage repair should be an important part of a rugby player's post-game recovery to limit the reduction in functional capacity.


Comparing Precision Machine Learning With Consumer, Quality, and Volume Metrics for Ranking Orthopedic Surgery Hospitals: Retrospective Study.
Patients' choices of providers when undergoing elective surgeries significantly impact both perioperative outcomes and costs. There exist a variety of approaches that are available to patients for evaluating between different hospital choices. This paper aims to compare differences in outcomes and costs between hospitals ranked using popular internet-based consumer ratings, quality stars, reputation rankings, average volumes, average outcomes, and precision machine learning-based rankings for hospital settings performing hip replacements in a large metropolitan area. Retrospective data from 4192 hip replacement surgeries among Medicare beneficiaries in 2018 in a the Chicago metropolitan area were analyzed for variations in outcomes (90-day postprocedure hospitalizations and emergency department visits) and costs (90-day total cost of care) between hospitals ranked through multiple approaches: internet-based consumer ratings, quality stars, reputation rankings, average yearly surgical volume, average outcome rates, and machine learning-based rankings. The average rates of outcomes and costs were compared between the patients who underwent surgery at a hospital using each ranking approach in unadjusted and propensity-based adjusted comparisons. Only a minority of patients (1159/4192, 27.6% to 2078/4192, 49.6%) were found to be matched to higher-ranked hospitals for each of the different approaches. Of the approaches considered, hip replacements at hospitals that were more highly ranked by consumer ratings, quality stars, and machine learning were all consistently associated with improvements in outcomes and costs in both adjusted and unadjusted analyses. The improvement was greatest across all metrics and analyses for machine learning-based rankings. There may be a substantive opportunity to increase the number of patients matched to appropriate hospitals across a broad variety of ranking approaches. Elective hip replacement surgeries performed at hospitals where patients were matched based on patient-specific machine learning were associated with better outcomes and lower total costs of care.


Reproductive isolation between Anopheles sinensis and Anopheles pullus in Korea.
Anopheles sinensis and An. pullus, the 2 predominant anopheline mosquito species in Korea, are major malaria vectors. Their morphological similarity makes them difficult to distinguish, and their taxonomic relationship remains unclear. Kanda and Oguma produced fertile F1 An. sinensis X An. pullus hybrids, suggesting a conspecific relationship. However, our recent internal transcribed spacer 2 DNA sequence comparison of these taxa revealed 32.9% divergence, suggesting that An. sinensis and An. pullus may be distinct species. In the present study, we reassessed the relationship of An. sinensis and An. pullus in hybridization experiments. Laboratory-raised isofemale lines of An. sinensis form B and An. pullus form A and B were reciprocally crossed. The 3 isofemale lines were established from fully engorged females caught from the wild and morphologically identified as An. sinensis or An. pullus. The isofemale lines represented 3 distinct metaphase karyotypes: An. sinensis form B (X, Y2) and An. pullus form A (X1, Y1) and form B (X2, Y2). The F1 hybrid larvae showed low viability and completely asynaptic salivary gland polytene chromosomes. The subset of F1 hybrids that developed to adults showed sex-ratio distortion; ovarian follicles developed abnormally in females, and males suffered atrophy of accessory glands and testes. These results strongly suggest that the Korean morphological species An. sinensis and An. pullus are biological species, separated by complete postzygotic reproductive isolation.


Nuclear PARP1-Targeted Photosensitizer as a Dual-Mode DNA-Damaging Agent and Immune Activator for Tumor Ablation.
Photodynamic therapy is a promising cancer therapeutic method that can damage DNA via photoinduced reactive oxygen species production. However, tumor cells can initiate DNA repair pathways to resist oxidative damage. In this study, a nuclear-targeted photosensitizer PARP-PS with a poly (ADP-ribose) polymerase 1 (PARP1) inhibitory effect is developed based on the reported PARP1 inhibitor, rucaparib. As a dual-mode DNA-damaging agent, PARP-PS damages DNA upon photoirradiation and enhances oxidative DNA damage by blocking the DNA repair pathway via PARP1 inhibition and degradation. Both in vitro and in vivo investigations demonstrate that PARP-PS exhibits high antitumor activity with few side effects in breast cancer. In addition, PARP-PS can act as an immunogenic cell death inducer to activate immune responses characterized by the promotion of cytotoxic T lymphocyte activation and tumor infiltration. Therefore, PARP-PS is a potential multimodal antitumor agent with synergistic phototherapeutic, chemotherapeutic, and immunotherapeutic effects.


Comparison of efficacy and safety of dabigatran, rivaroxaban and apixaban in patients with atrial fibrillation using network meta-analysis.
A network meta-analysis of the three new oral anticoagulants was performed from the three trials comparing dabigatran, rivaroxaban and apixaban with warfarin in patients with atrial fibrillation. Data were extracted of the RE-LY study of dabigatran 110 mg bid and dabigatran 150 mg bid, the ROCKET AF trial of rivaroxaban and the ARISTOTLE trial of apixaban for the composite outcome of ischemic stroke and systemic embolism, for major bleeding, intracerebral bleeding, mortality and myocardial infarction. Dabigatran (150 mg bid) showed superior efficacy in preventing ischemic stroke plus systemic embolism to dabigatran (110 mg bid, P=0.0364) and rivaroxaban (P=0.0388). Apixaban had equivalent efficacy with rivaroxaban and dabigatran (either dose). Apixaban was safer (less major bleeding) than dabigatran (150 mg bid, P=0.036) or rivaroxaban (P=0.0002). Intracerebral hemorrhage occurred with equal frequency for all agents except for rivaroxaban (higher risk than dabigatran 110 mg bid, P=0.0070). Myocardial infarction occurred less frequently with rivaroxaban and apixaban compared to either dose of dabigatran (all P<0.05). All-cause mortality was not different for any agent or regimen. In the absence of head-to-head comparisons, this network meta-analysis suggests that apixaban and dabigatran 110 mg bid may offer the best benefit-risk balance for stroke prevention in non-valvular atrial fibrillation. Dabigatran 150 mg bid may be preferred for patients with a high risk for embolism.


Intentional versus unintentional contact as a mechanism of injury in youth ice hockey.
Youth ice hockey injury rates and mechanisms have been described by various classification systems. Intentional versus unintentional contact was used to classify mechanisms of injuries. All injuries (n=247) in one youth hockey programme over a 5-year period were recorded and included in the analysis. To evaluate youth ice hockey injuries and compare programmes that allow body checking versus programmes that do not allow body checking. A primary goal was to determine whether programmes that allow body checking have increased injury rates from intentional body contact. Another goal was to describe the rates of injury across ages, levels of competitive play and during games versus practices. Rates of injury were compared for three levels of competition (house, select and representative) for approximately 3000 boys aged 4-18 years over a 5-year period. This represents 13 292 player years. Data were collected prospectively in this cohort study. All injuries were reported prospectively by a designated team official and verified by a physician. The log injury rate (per 1000 player hours) was modelled via Poisson regression with log player hours used as an offset. Rate ratio was used to explain the covariate-adjusted injury rate for each of three groups (all injuries, intentional injuries, unintentional injuries). Unintentional contacts accounted for 66.0% of overall injuries (95% CI 60.0 to 72.0), compared with 34.0% from intentional contacts (p<0.001; Z=5.25). Serious injuries (fractures, dislocations, concussions) resulted more often from unintentional collisions (p=0.04). Players in more competitive leagues that allow body checking had a greater incidence of total injuries than less competitive leagues. Most injuries in the youth hockey programme studied were the result of unintentional contact, and were generally more severe. These findings were not expected given previously published research.


Salient environmental and perceptual correlates of current and established smoking for 2 representative cohorts of Indiana adolescents.
A secondary analysis of 2000 and 2004 Indiana Youth Tobacco Survey (IYTS) data was conducted to investigate salient environmental and perceptual correlates of adolescents' current and established smoking while controlling for demographic variables such as gender, grade, and race/ethnicity and to compare the pattern of significant correlates between the years. The IYTS was an anonymous school-based survey regarding tobacco use; familiarity with pro- and anti-tobacco media messages; exposure to environmental tobacco smoke (ETS); minors' access to tobacco products; and general knowledge, attitudes, and beliefs about tobacco. In 2000, a representative sample of 1416 public high school students in grades 9-12 and 1516 public middle school students in grades 6-8 (71.44% and 72.53% response rates, respectively) were surveyed. In 2004, 3433 public high school students and 1990 public middle school students (63.04% and 65.44 % response rates, respectively) were surveyed. Significant predictors of adolescents' current and established smoking habits included exposure to ETS either in homes or in cars, exposure to pro-tobacco messages, perceived benefit of smoking, and perceived peer acceptance of smoking. The influence of exposure to pro-tobacco messages greatly outweighed exposure to any anti-tobacco messages. The findings of this study warrant that more efforts and resources be placed on preventing youth from being exposed to ETS, and to control pro-tobacco marketing and improve the tobacco counter-marketing messages. The perceived benefits of smoking found here indicate that smoking for relaxation and weight control may be major influencing factors on adolescent smoking.


Prognostic value of CD44s expression in urothelial bladder tumors.
Urothelial bladder carcinoma (UBC) includes a large group of malignancies with a variable clinical behavior. Despite remarkable developments in recognition of bladder carcinogenesis and prognostic factors, the recurrence rate is still high. Thus, identification of novel biomarkers involved in tumor cell invasion and metastatic dissemination is a constant challenge. To assess the prognostic impact of CD44 standard (CD44s) expression in UBT. We assessed the immunohistochemical expression of CD44 in 38 samples of endoscopically resected UBT. Only membranous staining was considered positive. We analyzed topographic distribution of CD44s staining. Correlation of CD44s expression, clinicopathological features and disease progression was analyzed by Chi2 and Fisher tests. Kaplan-Meier analysis was used to investigate CD44s prognostic value. The mean age of patients was 61,24 years with male to female ratio of 18/1. CD44s expression was positive in 33 cases (87%). There was no significant correlation between CD44 expression and the parameters: age, gender, tumor size, focality, tumor site, stage, recurrence and tumor progression. CD44s loss of expression is, nevertheless, correlated with a high tumor grade. Topographic distribution of CD44s staining was associated with focality, grade and stage. Basal/parabasal staining expanded to the tumor layers in homogeneous "laminate" pattern used to be of better prognosis, compared to the heterogeneous "islets" or "dispersed" pattern. Our results highlighted the prognostic value of CD44 expression in UBT. Focusing especially on staining pattern offers a better understanding of bladder carcinogenesis mechanisms.


Associations of Dietary Intake with Cardiovascular Disease, Blood Pressure, and Lipid Profile in the Korean Population: a Systematic Review and Meta-Analysis.
Previous studies have separately reported the contributions of dietary factors to the risk of cardiovascular disease (CVD) and its markers, including blood pressure (BP) and lipid profile. This study systematically reviewed the current evidence on this issue in the Korean population. Sixty-two studies from PubMed and Embase were included in this meta-analysis. We performed a random-effects model to analyze pooled odds ratios (ORs) and hazard ratios (HRs) and their 95% confidence intervals (CIs) for the consumption of 14 food items, three macro- and eight micro-nutrients, two dietary patterns, and three dietary indices. An analysis of pooled effect sizes from at least four individual study populations showed significant associations between coffee consumption and CVD (OR/HR, 0.71; 95% CI, 0.52-0.97) and elevated/high triglycerides (TG) (OR, 0.84; 95% CI, 0.78-0.90), sugar-sweetened beverage intake and elevated BP (OR/HR, 1.20; 95% CI, 1.09-1.33), and milk and dairy intake and elevated/high TG and low high-density lipoprotein cholesterol (HDL-C) (OR/HR, 0.82; 95% CI, 0.76-0.89 for both). Carbohydrate consumption and the low-carbohydrate-diet score were consistently related to an approximately 25% risk reduction for elevated TG and low HDL-C. A lower risk of elevated total cholesterol, but not low-density lipoprotein, was additionally observed for those with a higher low-carbohydrate-diet score. A healthy dietary pattern was only associated with a reduced risk of elevated TG in the Korea National Cancer Screenee Cohort (OR, 0.81; 95% CI, 0.67-0.98). This study showed that milk and dairy and coffee had protective effects for CVD and its risk factors, such as BP and lipid profile, while sugar-sweetened beverages exerted harmful effects.


Enteric neuro-immune interactions in intestinal health and disease.
The enteric nervous system is an autonomous neuronal circuit that regulates many processes far beyond the peristalsis in the gastro-intestinal tract. This circuit, consisting of enteric neurons and enteric glial cells, can engage in many intercellular interactions shaping the homeostatic microenvironment in the gut. Perhaps the most well documented interactions taking place, are the intestinal neuro-immune interactions which are essential for the fine-tuning of oral tolerance. In the context of intestinal disease, compelling evidence demonstrates both protective and detrimental roles for this bidirectional neuro-immune signaling. This review discusses the different immune cell types that are recognized to engage in neuronal crosstalk during intestinal health and disease. Highlighting the molecular pathways involved in the neuro-immune interactions might inspire novel strategies to target intestinal disease.


Effects of Polymyxin B Hemoperfusion on Mortality in Patients With Severe Sepsis and Septic Shock: A Systemic Review, Meta-Analysis Update, and Disease Severity Subgroup Meta-Analysis.
Several studies have reported a survival benefit for polymyxin B hemoperfusion treatment in patients with severe sepsis and septic shock. However, recently, a propensity-matched analysis and a randomized controlled trial reported no survival benefit for polymyxin B hemoperfusion treatment. We performed an up-to-date meta-analysis to determine the effect of polymyxin B hemoperfusion treatment on mortality in patients with severe sepsis and septic shock. PubMed, Embase, and Cochrane Library were searched from inception to May 2016. Studies investigating the effect of polymyxin B hemoperfusion on mortality were considered eligible. We searched for terms related to severe sepsis and septic shock and terms related to polymyxin B hemoperfusion. The following data were extracted from the original articles: the name of the first author and publication year, subjects and setting, inclusion and exclusion criteria, mean age and size of the study population, male percentage, mortality, blood pressure, Sequential Organ Failure Assessment score, pulmonary oxygenation, and levels of endotoxin and humoral cytokines. A total of 17 trials were included. The pooled risk ratio for overall mortality was 0.81 (95% CI, 0.70-0.95), favoring polymyxin B hemoperfusion (p = 0.007). Disease severity subgroup meta-analysis revealed a significant reduction of mortality in the intermediate- and high-risk groups (risk ratio, 0.84; 95% CI, 0.77-0.92 and risk ratio, 0.64; 95% CI, 0.52-0.78, respectively), but not in the low-risk group (risk ratio, 1.278; 95% CI, 0.888-1.839). The nonlinear meta-regression with restricted cubic spline showed an almost linear inverse association between the baseline mortality rate and reduction in the risk of mortality. The present study demonstrated that polymyxin B hemoperfusion treatment may reduce mortality in patients with severe sepsis and septic shock in specific disease severity subgroups.


Comparative responsiveness and minimal change of the Knee Quality of Life 26-item (KQoL-26) questionnaire.
To assess the responsiveness of the KQoL-26 and demonstrate minimal change for this instrument in two different samples of patients with suspected internal derangement of the knee. Data were collected from two surveys conducted alongside a clinical trial: the arthroscopy sample and the general practitioner (GP) sample. The effect size (ES) was used to assess responsiveness. Anchor-based minimal change included minimal clinical important difference (MCID) and receiver operator characteristic curves; standardized error of measurement and minimal detectable change (MDC) was employed for distribution-based approaches. The KQoL-26 results are compared with those for the Lysholm Knee Score, EQ-5D and SF-36. The arthroscopy sample consisted of 121 participants and the GP sample of 218 participants at baseline. The largest ES was found for the KQoL-26 emotional functioning scale in both samples. The results were in favour of the condition-specific instrument. The MCID for KQoL-26 physical functioning, activities limitations and emotional functioning scales were 3, 15 and 18, respectively, in the arthroscopy sample; they were 11, 16 and 24 in the GP sample. The MDC 95 % was estimated as 18, 28 and 34, and 15, 24 and 30 in each sample, respectively. The KQoL-26 emotional functional scale was the most responsive of all scales. It is recommended that an instrument such as the KQoL-26 that includes emotional functioning should be included rather than the Lysholm in future clinical trials of patients with suspected internal derangement of the knee.


A range of complex probabilistic models for RNA secondary structure prediction that includes the nearest-neighbor model and more.
The standard approach for single-sequence RNA secondary structure prediction uses a nearest-neighbor thermodynamic model with several thousand experimentally determined energy parameters. An attractive alternative is to use statistical approaches with parameters estimated from growing databases of structural RNAs. Good results have been reported for discriminative statistical methods using complex nearest-neighbor models, including CONTRAfold, Simfold, and ContextFold. Little work has been reported on generative probabilistic models (stochastic context-free grammars [SCFGs]) of comparable complexity, although probabilistic models are generally easier to train and to use. To explore a range of probabilistic models of increasing complexity, and to directly compare probabilistic, thermodynamic, and discriminative approaches, we created TORNADO, a computational tool that can parse a wide spectrum of RNA grammar architectures (including the standard nearest-neighbor model and more) using a generalized super-grammar that can be parameterized with probabilities, energies, or arbitrary scores. By using TORNADO, we find that probabilistic nearest-neighbor models perform comparably to (but not significantly better than) discriminative methods. We find that complex statistical models are prone to overfitting RNA structure and that evaluations should use structurally nonhomologous training and test data sets. Overfitting has affected at least one published method (ContextFold). The most important barrier to improving statistical approaches for RNA secondary structure prediction is the lack of diversity of well-curated single-sequence RNA secondary structures in current RNA databases.


Telomere Abnormalities in the Pathobiology of Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) occurs primarily in older adults and the incidence is clearly associated with aging. This disease seems to be associated with several hallmarks of aging, including telomere attrition and cellular senescence. Increasing evidence suggests that abnormalities involving telomeres and their proteome play a significant role in the pathobiology of IPF. The aim of this study is to summarize present knowledge in the field, as well as to discuss its possible clinical implications. Numerous mutations in genes associated with telomere functioning were studied in the context of IPF, mainly for Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC). Such mutations may lead to telomere shortening, which seems to increase the risk of IPF, negatively influence disease progression, and contribute to worse prognosis after lung transplantation. Some evidence indicates the possibility for the use of telomerase activators as potential therapeutic agents in pulmonary fibrosis. To sum up, increasing evidence suggests the role of telomere abnormalities in the pathobiology of IPF, natural history and prognosis of the disease. There are also possibilities for telomerase targeting in the potential development of new treatment agents. However, all these aspects require further research.


[Reconstruction of tumor defects in the oral cavity and mesopharynx].
A superiorly based cervical skin flap (eventually including the sternocleido-mastoid muscle) has been used in combination with a deltopectoral flap for the one-stage reconstruction of large defects of the oral cavity and mesopharynx. The results obtained in 17 patients show that the presented method is of particular value in cases presenting with unfavorable tissue conditions resulting from heavy irradiation.


miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14.
Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3'-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan-Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.


Controlling Quantum Interference between Virtual and Dipole Two-Photon Optical Excitation Pathways Using Phase-Shaped Laser Pulses.
Two-photon excitation (TPE) proceeds via a "virtual" pathway, which depends on the accessibility of one or more intermediate states, and, in the case of non-centrosymmetric molecules, an additional "dipole" pathway involving the off-resonance dipole-allowed one-photon transitions and the change in the permanent dipole moment between the initial and final states. Here, we control the quantum interference between these two optical excitation pathways by using phase-shaped femtosecond laser pulses. We find enhancements by a factor of up to 1.75 in the two-photon-excited fluorescence of the photobase FR0-SB in methanol after taking into account the longer pulse duration of the shaped laser pulses. Simulations taking into account the different responses of the virtual and dipole pathways to external fields and the effect of pulse shaping on two-photon transitions are found to be in good agreement with our experimental measurements. The observed quantum control of TPE in the condensed phase may lead to an enhanced signal at a lower intensity in two-photon microscopy, multiphoton-excited photoreagents, and novel spectroscopic techniques that are sensitive to the magnitude of the contributions from the virtual and dipole pathways to multiphoton excitations.


Inferior vena cava diameter measurements and BUN/creatinine values to determine dehydration in patients with hip fractures preoperatively: A prospective observational study.
Dehydration is a common problem in patients undergoing hip fracture surgery. Sonographic inferior vena cava (IVC) diameter measurement evaluates to estimate volume status. The aim of the study to evaluate the relationship between IVC measurements (expiratory diameter of IVC, collabsibility index [CI], inspiratory diameter of IVC) and blood urea nitrogen (BUN)/creatinine ratio in patients undergoing hip fracture surgery. Ultrasonography of IVC was performed on 35 patients underwent hip fracture surgery. The end-expiratory diameter of IVC, end-inspiratory diameter of IVC, and CI were assessed preoperatively. The patients were classified as group 1 for BUN/Cr ratio <20, group 2 for BUN/Cr ratio of >20. Sonographic IVC measurement was not successful in 14.2% of patients and 30 patients remained. The mean age was 80.43 ± 11.10 (58-95) years. The IVC diameter values had no discriminatory value for the prediction of dehydration according to BUN/creatinine ratio (P > .05). Receiver operating characteristic curve indicated that area under the curve (AUC) for CI: 49.5%, (95% CI 26.5-72.5) P > .05; for IVC inspiratory diameter: AUC: 43.3%, (95% CI, 19.9-66.6) P > .05; for IVC expiratory diameter: AUC: 45.5%, (95% CI, 26.6-65.4) P > .05. No correlations of BUN/creatinine ratio with CI and IVC expiratory diameter were found (as r = -0.262 [P = .163]; [r = 0.206, P = .274]; respectively). There were not any correlation in linear regression analysis model between BUN/Cr ratio according to independent variables (Age, CI, IVCmax, IVCmin) (P = .108, P = .419, P = .282, P = .257; respectively). No discriminatory relationship was found between the bedside ultrasonographic measurement of IVC parameters and BUN/creatinine ratio in patients underwent hip fracture surgery to predict the preoperative dehydration.


The association between serum 25-hydroxyvitamin D level and subclinical atherosclerosis in healthy population.
Background: Subclinical atherosclerosis is the asymptomatic phase of carotid atherosclerosis, and its early diagnosis is important to prevent cerebrovascular diseases. Although the vitamin D plays a role in the structure of vessels, the association between the serum level of vitamin D and subclinical atherosclerosis has not been well-studied. We aimed to investigate the association between serum vitamin D level and carotid artery intima-media thickness (CIMT) in Iranian population. Methods: One hundred individuals with the age range from 20 to 50 years with no history of cardiovascular risk factors were selected for the analysis. Measurements of serum 25-hydroxyvitamin D3 [25(OH) D3] concentration and CIMT were made. Confounding factors such as diabetes, hypertension (HTN), smoking, alcohol, tobacco, dyslipidemia, cardiovascular disease (CVD), high body mass index (BMI), history of drug intake especially calcium, vitamin D, statins, and anti-hypertensive drugs were considered and then excluded from our study. Results: The mean serum vitamin D level was 15.55 ± 0.42 ng/ml, whereas in the increased intima-media thickness (IMT), it was 12.50 ± 9.50 ng/ml. 55% of the subjects were diagnosed with subclinical atherosclerosis (IMT ≥ 0.75 mm). Mean IMT was 0.74 ± 0.12 mm; however, it was higher (0.86 ± 0.30) in severe vitamin D deficiency group. The analysis showed an association between serum 25(OH) D3 level and CIMT (P = 0.002). 44% of those participants with subclinical atherosclerosis had also a severe vitamin D deficiency, while only 13% of normal people had a severe vitamin D deficiency. Also, a correlation was observed between severe vitamin D deficiency and the presence of plaque or higher IMT. Conclusion: Serum 25(OH) D3 level was inversely correlated with CIMT in our investigated subjects with no cardiovascular risk factor.


Nuclear transport in vitro.
In this paper, progress towards the goal of understanding communication between the nucleus and cytoplasm using an in vitro system is reviewed. To probe the mechanism of nuclear targeting, we developed an in vitro transport system and have begun to dissect the highly selective process of nuclear transport. The basic parameters of transport were defined using an easily isolated nuclear protein, nucleoplasmin. To study the interaction of nuclear targeting signals with the pore, an artificial nuclear transport substrate was constructed, which consists of human serum albumin coupled to the signal sequence of the SV40 T-antigen. A similar peptide-protein conjugate was made using a mutant signal sequence. These conjugates were fluorescently labeled and/or tagged with gold and tested for transport in the in vitro system. High levels of nuclear transport of the wild-type signal sequence-containing protein were observed, while no transport of the mutant signal sequence-containing protein was seen. Thus, the in vitro system correctly recognizes the single amino acid change between the wild-type and mutant signal sequences. We found that the observed nuclear transport was completely dependent on the presence of ATP. Using the in vitro system we identified a specific inhibitor of nuclear transport, the lectin wheat germ agglutinin (WGA), which we find binds directly to the nuclear pore. Probing blots of nuclear proteins with 125I-WGA identified a family of nuclear pore glycoproteins, including one major glycoprotein of 62K (K = 10(3)Mr) molecular weight. With the inhibitor and the in vitro assay, it has been possible to experimentally separate nuclear transport into two steps: (1) a step in which the signal sequence-bearing protein binds to the pore, followed by (2) a step in which the protein translocates through the pore. It is this second step which is the ATP-dependent step of transport, since pore binding but not translocation was seen to occur in the absence of ATP.


Slit/Robo Signaling Regulates Multiple Stages of the Development of the Drosophila Motion Detection System.
Neurogenesis is achieved through a sequence of steps that include specification and differentiation of progenitors into mature neurons. Frequently, precursors migrate to distinct positions before terminal differentiation. The Slit-Robo pathway, formed by the secreted ligand Slit and its membrane bound receptor Robo, was first discovered as a regulator of axonal growth. However, today, it is accepted that this pathway can regulate different cellular processes even outside the nervous system. Since most of the studies performed in the nervous system have been focused on axonal and dendritic growth, it is less clear how versatile is this signaling pathway in the developing nervous system. Here we describe the participation of the Slit-Robo pathway in the development of motion sensitive neurons of the Drosophila visual system. We show that Slit and Robo receptors are expressed in different stages during the neurogenesis of motion sensitive neurons. Furthermore, we find that Slit and Robo regulate multiple aspects of their development including neuronal precursor migration, cell segregation between neural stem cells and daughter cells and formation of their connectivity pattern. Specifically, loss of function of slit or robo receptors in differentiated motion sensitive neurons impairs dendritic targeting, while knocking down robo receptors in migratory progenitors or neural stem cells leads to structural defects in the adult optic lobe neuropil, caused by migration and cell segregation defects during larval development. Thus, our work reveals the co-option of the Slit-Robo signaling pathway in distinct developmental stages of a neural lineage.


[Short-term results of treatment of tennis elbow with anti-inflammatory drugs alone or in combination with local injection of a corticosteroid and anesthetic mixture].
We compared the short-term results of anti-inflammatory drugs alone or in combination with local injection of a corticosteroid and anesthetic mixture in the treatment of tennis elbow. The study included 21 patients (12 males, 9 females; mean age 45 years; range 19 to 72 years) with tennis elbow. The patients were randomized to oral and topical anti-inflammatory drugs alone (group 1, n=10) or combined with a single local injection of a corticosteroid and anesthetic mixture (group 2, n=11). The patients were evaluated with a pain score (0 to 10 points) and clinical examination before and one month after treatment. Complete or near-complete relief of pain and unlimited function were obtained in four patients (40%) in group 1, and in 10 patients (90.9%) in group 2. On physical examination, two patients (20%) in group 1 and eight patients (72.7%) in group 2 were pain-free upon pressure on the lateral epicondyle or dorsiflexion of the wrist. Pain scores differed significantly in both groups after treatment (p=0.026 and p=0.003, respectively); however, combination treatment was associated with a significantly higher efficacy (p=0.036). It was concluded that significantly enhanced efficacy of the combination treatment used in this study might be limited to the short-term and that adverse effects of steroids on the tendons should be taken into consideration.


[Supply, metabolism and biological effects of trans-isomeric fatty acids in infants].
Consumption of trans-fatty acids increased markedly during this century due to the widespread use of partially hydrogenated fats. A sensitive analytical method was developed which enables the precise determination of 7 trans-isomers in small sample volumes. With this method we documented the materno-fetal transfer of trans-fatty acids across the human placenta. The content in human milk depends on maternal diet and is lower in Germany than in the Sudan. The distribution in fore- and hind-milk, in milk fat fractions and within the triglyceride molecule was determined. The content of trans-fatty acids is lower in commercial and home-made infant formulae than in human milk, although there is a certain batch to batch variation in formulae. Infants absorb dietary trans-isomers and incorporate them into endogenous lipids, subcutaneous tissue and cell membranes. Trans-fatty acids in plasma lipids are significantly higher in infants fed human milk than in those fed formulae. African children have a lower exposure than Germans. The relative contribution of trans-octadecenoic acid is lower in plasma sterol esters than in triglycerides and phospholipids, pointing to a negative selectivity of plasmatic cholesterol esterification with this fatty acid. Thus, a high supply of trans-octadecenoic acid might have negative effects on the cholesterol levels. In premature infants we found an inverse correlation between trans-fatty acid exposure and birthweight, thus interference with intrauterine growth appears possible. A possible causative factor could be impaired biosynthesis of long-chain polyunsaturated fatty acids by trans-isomers, for which we found strong indications. The results of our investigations the question whether the consumption of trans-fatty acids in pregnant and lactating women and in infants is nutritionally safe.


The effect of the introduction of the national lung cancer screening program on short-term mortality in Korea.
South Korea introduced the National Lung Cancer Screening Program (NLCSP) in 2019. This study investigated the effect of the NLCSP on one-year mortality in individuals with a history of lung cancer. This study used the 2018-2020 National Health Insurance Service claims data. The difference-in-differences approach was used to investigate the effect of participating in the NLCSP between the case and control groups before and after the intervention period. The case group included individuals aged between 54 and 74 years with a smoking history of ≥ 30 pack-years and the control group those aged between 54 and 74 years with a history of smoking of <30 pack-years and non-smokers. The pre-intervention period was from January 2018 to June 2019 and the post-intervention period from July 2019 to December 2020. The introduction of the NLCSP was related to an overall decrease in one-year mortality (-3.21 % points, 95 % Confidence Interval (CI) -4.84 to -1.58). Specifically, this reduction was significant for lung cancer related mortality (lung cancer: -2.69 % points, 95 % CI -4.24 to -1.13). Furthermore, stronger associations were found in individuals of older age, residing in non-metropolitan areas, and who visited healthcare institutions in non-metropolitan areas. The findings confirm a relationship between implementation of the NLCSP and one-year mortality in eligible individuals with a history of lung cancer, which is noteworthy considering that Korea is one of the first countries to include lung cancer into the national cancer screening program.


Solid-phase extraction of multi-class pharmaceuticals from environmental water samples onto modified multi-walled carbon nanotubes followed by LC-MS/MS.
In this paper, pristine and chemically treated multi-walled carbon nanotubes (MWCNTs) were employed as solid-phase extraction sorbents for the isolation and enrichment of multi-class pharmaceuticals from the surface water and groundwater, prior to liquid chromatography-tandem mass spectrometry analysis. Thirteen pharmaceuticals that belong to different therapeutical classes (erythromycin, azithromycin, sulfamethoxazole, diazepam, lorazepam, carbamazepine, metoprolol, bisoprolol, enalapril, cilazapril, simvastatin, clopidogrel, diclofenac) and two metabolites of metamizole (4-acetylaminoantipyrine and 4-formylaminoantipyrine) were selected for this study. The influence of chemical treatment on MWCNT surface characteristics and extraction efficiency was studied, and it was shown that HCl treatment of MWCNT leads to a decrease in the amount of surface oxygen groups and at the same time favorably affects the efficiency toward extraction of selected pharmaceuticals. After the optimization of the SPE procedure, the following conditions were chosen: 50 mg of HCl-treated MCWNT as a sorbent, 100 mL of water sample at pH 6, and 15 mL of the methanol-dichloromethane mixture (1:1, v/v) as eluent. Under optimal conditions, high recoveries (79-119%), as well as low detection (0.2 to 103 ng L-1) and quantitation (0.5-345 ng L-1) limits, were obtained. The optimized method was applied to the analysis of five surface water and two groundwater samples, and three pharmaceuticals were detected, the antiepileptic drug carbamazepine and two metabolites of antipyretic metamizole.


Interleukin-17A Deficiency Attenuated Emphysema and Bone Loss in Mice Exposed to Cigarette Smoke.
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease, which is associated with various comorbidities including osteoporosis. Interleukin(IL)-17 has been reported to play important roles in the pathogenesis of COPD and also associated with bone destruction in inflammatory diseases. However, the role of IL-17A in COPD-related osteoporosis is yet unknown. The purpose of our study was to investigate the potential contribution of IL-17A in COPD-related bone loss. We examined the bone mass and bone microarchitecture in wild-type and IL-17A-/- mice exposed to long-term cigarette smoke (CS). Osteoclast activities and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in bone tissues were assessed, and the blood levels of inflammatory cytokines were measured. Less bone loss as well as attenuated emphysema were shown in IL-17A-/- mice compared with wild-type mice. CS-exposed IL-17A-/- mice had decreased TRAP+ osteoclast numbers and lower RANKL expression compared with CS-exposed wild-type mice. Inflammatory cytokines including IL-6 and IL-1β in circulation were decreased in IL-17A-/- mice exposed to CS compared with wild-type mice. This study indicates that IL-17A is involved in CS-induced bone loss and may be a common link between COPD and osteoporosis.


Rearrangement of the Fermi Surface of Dense Neutron Matter and the Direct Urca Cooling of Neutron Stars.
It is proposed that a rearrangement of single-particle degrees of freedom may occur in a portion of the quantum-fluid interior of a neutron star. Such a rearrangement is associated with the pronounced softening of the spin-isospin collective mode which, under increasing density, leads to pion condensation. Arguments and estimates based on fundamental relations of many-body theory show that one realization of this phenomenon could produce very rapid cooling of the star via a direct nucleon Urca process displaying a T5 dependence on temperature.


No need for disease: testing extinction hypotheses for the thylacine using multi-species metamodels.
Population viability analysis (PVA) is widely used to assess the extinction risk of threatened species and to evaluate different management strategies. However, conventional PVA neglects important biotic interactions and therefore can fail to identify important threatening processes. We designed a new PVA approach that includes species interactions explicitly by networking species models within a single 'metamodel'. We demonstrate the utility of PVA metamodels by employing them to reinterpret the extinction of the carnivorous, marsupial thylacine Thylacinus cynocephalus in Tasmania. In particular, we test the claim that well-documented impacts of European settlement cannot account for this extinction and that an unknown disease must have been an additional and necessary cause. We first constructed a classical, single-species PVA model for thylacines, which was then extended by incorporation within a dynamic predator-herbivore-vegetation metamodel that accounted for the influence of Europeans on the thylacine's prey base. Given obvious parameter uncertainties, we explored both modelling approaches with rigorous sensitivity analyses. Single-species PVA models were unable to recreate the thylacine's extinction unless a high human harvest, small starting population size or low maximum population growth rate was assumed, even if disease effects were included from 1906 to 1909. In contrast, we readily recreated the thylacine's demise using disease-free multi-species metamodels that simulated declines in native prey populations (particularly due to competition with introduced sheep). Dynamic, multi-species metamodels provide a simple, flexible framework for studying current species declines and historical extinctions caused by complex, interacting factors.


[Study of the binding between bacterial lipopolysaccharides and polymyxin by a bioluminescent method].
For rating the interaction of lipopolysaccharides (LPS) with polymixin B (PmB) a bacterial bioluminescence is offered to be used. Bioluminescence level of bacteria decreases under free antibiotic amounts action. It is shown, that as a result of interaction with LPS antibiotic properties of PmB are reduced, and the intensity of bacterial bioluminescence is restored. The bioluminescence level in such system characterizes the LPS quantity. Kinetic properties of bacterial light emission at the presence of LPS and PmB are investigated as well as equilibrium state of the system. Kinetic and equilibrium constants describing this reaction are determined. The conditions of quantitative bioluminescent definition of LPS in an interval of concentration 0.166-10 micrograms/ml have been chosen and calibration curves are presented.


Continuous versus interrupted skin sutures for non-obstetric surgery.
Most surgical procedures involve a cut in the skin, allowing the surgeon to gain access to the surgical site. Most surgical wounds are closed fully at the end of the procedure; this review focuses on these closed wounds. There are many ways to close the surgical incision, for example, using sutures (stitches), staples, tissue adhesives or tapes. Skin sutures can be continuous or interrupted. In general, continuous sutures are usually subcuticular and can be absorbable or non-absorbable, while interrupted sutures are usually non-absorbable and involve the full thickness of the skin - although some surgeons do use absorbable interrupted sutures. To compare the benefits and harms of continuous compared with interrupted skin closure techniques in participants undergoing non-obstetric surgery. In August 2013 we searched the following databases: Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase; and EBSCO CINAHL. We included only randomised controlled trials (RCTs) that compared skin closure using continuous sutures with skin closure using interrupted sutures, irrespective of whether there were differences in the nature of the suture materials used in the two groups. We included all relevant RCTs in the analysis, irrespective of language of publication, publication status, publication year or sample size. Two review authors independently identified the trials and extracted data. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing binary outcomes between the groups, and calculated the mean difference (MD) with 95% CI for comparing continuous outcomes. We performed meta-analysis using a fixed-effect model and a random-effects model. We performed intention-to-treat analysis whenever possible. We included five RCTs with a total of 827 participants. Outcomes were available for 730 participants (384 participants randomised to continuous sutures and 346 participants to interrupted sutures). All the trials were of unclear or high risk of bias. The participants underwent abdominal or groin operations. The only outcomes reported in the trials were superficial surgical site infection, superficial wound dehiscence (breakdown) and length of hospital stay. Other important outcomes such as quality of life, long-term patient outcomes and use of healthcare resources were not reported in these trials.Overall, 6.5% (39/602 participants, four trials) developed superficial surgical site infections. There was no significant difference between the groups in the proportion of participants who developed superficial surgical site infections (RR 0.73; 95% CI 0.40 to 1.33). A total of 23 participants (23/625 (3.7%), four trials) developed superficial wound dehiscence. Twenty-two of the 23 participants belonged to the interrupted suture group.The proportion of participants who developed superficial wound dehiscence was statistically significantly lower in the continuous suture group compared to the interrupted suture group (RR 0.08; 95% CI 0.02 to 0.35). Most of these wound dehiscences were reported in two recent trials in which the continuous skin suture groups received absorbable subcuticular sutures while the interrupted skin suture groups received non-absorbable transcutaneous sutures. The non-absorbable sutures were removed seven to nine days after surgery in the interrupted sutures groups whilst sutures in the comparator groups were not removed, being absorbable. The continuous suture technique with absorbable suture does not require suture removal and provides support for the wound for a longer period of time. This may have contributed to the difference between the two groups in the proportion of participants who developed superficial wound dehiscence. There was no significant difference in the length of the hospital stay between the two groups (MD -1.40 days; 95% CI -7.14 to 4.34). Superficial wound dehiscence may be reduced by using continuous subcuticular sutures. However, there is uncertainty about this because of the quality of the evidence. Besides, the nature of the suture material used may have led to this observation, as the continuous suturing technique used suture material that did not need to be removed, whereas the comparator used interrupted (non-absorbable) sutures that did need to be removed. Differences in the methods of skin closure have the potential to affect patient outcomes and use of healthcare resources. Further well-designed trials at low risk of bias are necessary to determine which type of suturing is better.


New technologies for CAS that might overcome the burden of microembolization.
Microembolization during carotid artery stenting (CAS) is the result of embolic events shown by intraprocedural transcranial Doppler (TCD) or postprocedure diffusion-weighted MRI that do not lead to acute neurological deficit. Although the long term clinical outcome of these silent infarcts is not yet well established, there is increasing evidence that these events could be associated with neurological impairments, such as cognitive decline. In order to prevent microembolization due to excessive catheter manipulation at the time of guiding catheter placement in patients with challenging anatomy, a cervical access system with flow reversal protection was developed. Other embolic events are often seen as the result of plaque protrusion through stent struts. A new type of stent, so-called "hybrid" stent, incorporates the flexibility and conformability of an open-cell stent as well as plaque coverage seen with a close-cell stent, with the goal of achieving better plaque stabilization reducing macro and microembolization, while maintaining original vessel anatomy and flow hemodynamic. At the present time there are three different stents under investigation or this application.


Induction of lymphomas and tumor antigen by Marek's disease virus in turkeys.
Pathogenic Marek's disease (MD) virus (MDV) induced a high incidence of mortality and gross and microscopic lesions in turkey poults. Inoculated turkey poults became persistently viremic with MDV, although the levels of detectable circulating MDV were generally lower in turkeys than in similarly inoculated chickens. The early lytic phase of MD characterized by lymphoid cell destruction and the appearance of viral antigen in lymphoid organ was not as prominent in turkeys as in chickens. Gross MD lesions in turkeys were most prevalent in liver and spleen; peripheral nerves were involved infrequently. MD tumors in turkeys contained cells that reacted with antiserum prepared against chicken MD-tumor-associated surface antigen (MATSA); this result indicated that MDV induced cellular transformation in turkeys and the tumor-associated antigen in chicken and turkeys cross-reacted. Several in vitro-propagating B-cell lines were developed from the turkey lymphomas. As in chickens, MD in turkeys also resulted in immunodepression. Circulating lymphocytes from turkeys that eventually died of MD or had gross tumors at the end of the experiment were deficient in mitogenic response to Concanavalin A.


Cropping practices modulate the impact of glyphosate on arbuscular mycorrhizal fungi and rhizosphere bacteria in agroecosystems of the semiarid prairie.
A growing body of evidence obtained from studies performed under controlled conditions suggests that glyphosate use can modify microbial community assemblages. However, few studies have examined the influence of glyphosate in agroecosystems. We examined 4 wheat-based production systems typical of the Canadian prairie over 2 years to answer the following question: Does preseeding of glyphosate impact soil rhizosphere microorganisms? If so, do cropping practices influence this impact? Glyphosate caused a shift in the species dominating the arbuscular mycorrhizal fungal community in the rhizosphere, possibly through the modification of host plant physiology. Glyphosate stimulated rhizobacterial growth while having no influence on saprotrophic fungi, suggesting a greater abundance of glyphosate-tolerant 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in bacteria than in fungi. Glyphosate stimulated rhizosphere bacteria in pea but not in urea-fertilized durum wheat, which is consistent with inhibition of EPSPS tolerance to residual glyphosate through high ammonium levels. Mitigation of the effects of glyphosate on rhizosphere bacteria through tillage suggests a reduction in residual glyphosate activity through increased adsorption to soil binding sites upon soil mixing. The influence of glyphosate on Gram-negative bacteria was mitigated under drought conditions in 2007. Our experiment suggests that interactions between soil fertility, tillage, and cropping practices shape the influence of glyphosate use on rhizosphere microorganisms.


Genome size evolution at the speciation level: the cryptic species complex Brachionus plicatilis (Rotifera).
Studies on genome size variation in animals are rarely done at lower taxonomic levels, e.g., slightly above/below the species level. Yet, such variation might provide important clues on the tempo and mode of genome size evolution. In this study we used the flow-cytometry method to study the evolution of genome size in the rotifer Brachionus plicatilis, a cryptic species complex consisting of at least 14 closely related species. We found an unexpectedly high variation in this species complex, with genome sizes ranging approximately seven-fold (haploid '1C' genome sizes: 0.056-0.416 pg). Most of this variation (67%) could be ascribed to the major clades of the species complex, i.e. clades that are well separated according to most species definitions. However, we also found substantial variation (32%) at lower taxonomic levels--within and among genealogical species--and, interestingly, among species pairs that are not completely reproductively isolated. In one genealogical species, called B. 'Austria', we found greatly enlarged genome sizes that could roughly be approximated as multiples of the genomes of its closest relatives, which suggests that whole-genome duplications have occurred early during separation of this lineage. Overall, genome size was significantly correlated to egg size and body size, even though the latter became non-significant after controlling for phylogenetic non-independence. Our study suggests that substantial genome size variation can build up early during speciation, potentially even among isolated populations. An alternative, but not mutually exclusive interpretation might be that reproductive isolation tends to build up unusually slow in this species complex.


Dielectrophoretically-assisted electroporation using light-activated virtual microelectrodes for multiple DNA transfection.
Gene transfection is an important technology for various biological applications. The exogenous DNA is commonly delivered into cells by using a strong electrical field to form transient pores in cellular membranes. However, the high voltage required in this electroporation process may cause cell damage. In this study, a dielectrophoretically-assisted electroporation was developed by using light-activated virtual microelectrodes in a new microfluidic platform. The DNA electrotransfection used a low applied voltage and an alternating current to enable electroporation and transfection. Single or triple fluorescence-carrying plasmids were effectively transfected into various types of mammalian cells, and the fluorescent proteins were successfully expressed in live transfected cells. Moreover, the multi-triangle optical pattern that was projected onto a photoconductive layer to generate localized non-uniform virtual electric fields was found to have high transfection efficiency. The developed dielectrophoretically-assisted electroporation platform may provide a simpler system for gene transfection and could be widely applied in many biotechnological fields.


Probucol, a new cholesterol lowering drug.
The purpose of this investigation was to determine the ability of Dh-581 (Procubol) (See Figure 1) to reduce the level of serum cholesterol for extended periods of time and to maintain the reduction without loss of effectiveness. The effects of DH-581 on triglycerides and the safety and tolerance of daily doses were also assessed.


Respiratory support status from EHR data for adult population: classification, heuristics, and usage in predictive modeling.
Respiratory support status is critical in understanding patient status, but electronic health record data are often scattered, incomplete, and contradictory. Further, there has been limited work on standardizing representations for respiratory support. The objective of this work was to (1) propose a practical terminology system for respiratory support methods; (2) develop (meta-)heuristics for constructing respiratory support episodes; and (3) evaluate the utility of respiratory support information for mortality prediction. All analyses were performed using electronic health record data of COVID-19-tested, emergency department-admit, adult patients at a large, Midwestern healthcare system between March 1, 2020 and April 1, 2021. Logistic regression and XGBoost models were trained with and without respiratory support information, and performance metrics were compared. Importance of respiratory-support-based features was explored using absolute coefficient values for logistic regression and SHapley Additive exPlanations values for the XGBoost model. The proposed terminology system for respiratory support methods is as follows: Low-Flow Oxygen Therapy (LFOT), High-Flow Oxygen Therapy (HFOT), Non-Invasive Mechanical Ventilation (NIMV), Invasive Mechanical Ventilation (IMV), and ExtraCorporeal Membrane Oxygenation (ECMO). The addition of respiratory support information significantly improved mortality prediction (logistic regression area under receiver operating characteristic curve, median [IQR] from 0.855 [0.852-0.855] to 0.881 [0.876-0.884]; area under precision recall curve from 0.262 [0.245-0.268] to 0.319 [0.313-0.325], both P < 0.01). The proposed generalizable, interpretable, and episodic representation had commensurate performance compared to alternate representations despite loss of granularity. Respiratory support features were among the most important in both models. Respiratory support information is critical in understanding patient status and can facilitate downstream analyses.


Complex structure of a maize Myb gene promoter: functional analysis in transgenic plants.
The maize P gene encodes a Myb-like transcription factor that regulates synthesis of red flavonoid pigments in floral organs. To study the transcriptional regulation of the P gene, candidate regulatory sequences of the P1-rr gene promoter were identified by Ac insertional mutagenesis and subjected to functional testing in transgenic maize plants. The results indicate that a 561 bp fragment (Pb) encompassing the transcription start site (-235 to +326) supports weak expression of a GUS reporter gene in floral organs, including husk, silk, kernel pericarp, cob and male inflorescence. Two other fragments, located approximately 1 and 5 kb 5' of the transcription start site, increased the levels of GUS activity in floral tissues and thus appear to contain enhancer elements. All of the tested constructs gave similar patterns of GUS expression, suggesting that the 561 bp Pb fragment that is common among the transgene constructs contains regulatory elements that promote activation in floral organs. The basal promoter and proximal enhancer fragments contain putative binding sites for bZip regulatory factors, and a complex arrangement of palindromes including a large inverted repeat of two tRNA-like genes. Possibly, interconversions between linear and cruciform conformations of the palindromes may affect protein/DNA interactions and thereby modulate P1-rr expression.