Potential of breastmilk in stem cell research.
Breastmilk is a dynamic, multi-faceted, and complex fluid containing a plethora of biochemical and cellular components that execute developmental effects or differentiation program, providing nourishment and immunity to newborns. Recently, it was reported that breastmilk contains a heterogeneous population of naïve cells, including pluripotent stem cells, multipotent stem cells, immune cells, and non-immune cells. The stem cells derived from breastmilk possess immune privilege and non-tumorigenic properties. Thus, breastmilk may represent an ideal source of stem cells collected by non-perceive procedure than other available sources. Thus, this "maternally originating natural regenerative medicine" may have innumerable applications in clinical biology, cosmetics, and pharmacokinetics. This review describes the efficient integrated cellular system of mammary glands, the impressive stem cell hierarchy of breastmilk, and their possible implications in translational research and therapeutics.


Dexamethasone inhibits IL-9 production by human T cells.
Interleukin 9 (IL-9) is produced by activated CD4+ T cells. Its effects include stimulation of mucus production, enhanced mast cell proliferation, enhanced eosinophil function, and IgE production. These effects are consistent with a role in allergic diseases. Glucocorticoids have potent anti-inflammatory effects, including suppression of cytokine synthesis, and are widely used in the treatment of allergic conditions. We examined the effect of the glucocorticoid dexamethasone (Dex) on IL-9 mRNA expression and protein secretion with real-time RT-PCR and ELISA. Peripheral blood mononuclear cells (PBMC) were prepared from human volunteers and activated with OKT3. CD4+ T cells were purified from PBMC and activated with OKT3 plus PMA. IL-9 mRNA abundance and protein secretion were both markedly reduced following treatment of activated PBMC with Dex. mRNA levels were reduced to 0.7% of control values and protein secretion was reduced to 2.8% of controls. In CD4+ T cells, Dex reduced protein secretion to a similar extent. The IC50 value of Dex on mRNA expression was 4 nM. These results indicate that IL-9 production is very markedly inhibited by Dex. The findings raise the possibility that the beneficial effects of glucocorticoids in the treatment of allergic diseases are in part mediated by inhibition of IL-9 production.


Conjugates of 5-isoquinolinesulfonylamides and oligo-D-arginine possess high affinity and selectivity towards Rho kinase (ROCK).
In the present work, conjugates of 5-isoquinolinesulfonylamides and D-arginine-rich peptides were developed into highly potent inhibitors for basophilic protein kinases. Based on Hidaka's inhibitor H9, a generic fluorescent probe ARC-1083 was constructed possessing subnanomolar dissociation constant towards several kinases of the AGC-group. Thereafter, Hidaka's inhibitor HA1077 or Fasudil was conjugated with oligo-D-arginine resulting in the compound ARC-3002 revealing high affinity towards ROCK-II (K(d)=20 pM) and over 160-fold selectivity compared to PKAc.


Why does caloric restriction increase life and healthspan? The 'clean cupboards' hypothesis.
The disposable soma hypothesis explanation of the effects of caloric restriction (CR) on lifespan fails to explain why CR generates negative impacts alongside the positive effects and does not work in all species. I propose here a novel idea called the clean cupboards hypothesis which overcomes these problems.


Bioequivalence Study of 2 Formulations of Rivaroxaban, a Narrow-Therapeutic-Index Drug, in Healthy Chinese Subjects Under Fasting and Fed Conditions.
This study aimed to evaluate the bioequivalence (BE) of 2 formulations of the 10-mg rivaroxaban tablet. The study was a randomized, open-label, 4-period, crossover study that included 28 healthy subjects in fasting or fed conditions. The pharmacokinetic parameters were determined based on the concentrations of rivaroxaban using high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the 4 study periods with fasting or fed conditions, a single dose of test or reference product was administered. Rivaroxaban concentrations in plasma were determined using a validated liquid chromatography with a tandem mass spectrometer detector method. The pharmacokinetic parameters assessed were the area under the plasma concentration-time curve (AUC0-t , AUC0-∞ ), the peak plasma concentration of the drug (Cmax ), time to achieve Cmax , elimination half-life, within-subject variability of test drug, and within-subject variability of reference drug. The geometric mean ratio (90%CI) of the test drug/reference drug for rivaroxaban was 90.38% to 103.60% for AUC0-t in fasting conditions and 90.13% to 100.42% in fed conditions. The AUC0-∞ s were 89.94% to 102.50% and 90.14% to 100.45% under fasting and fed conditions, respectively. The Cmax values were 90.58% to 105.01% and 96.36% to 108.07% in these 2 conditions, respectively. All 90%CIs for test drug/reference drug geometric mean ratio were ≤2.5. The 90%CIs for test/reference AUC ratio and Cmax ratio were within the acceptable range for BE. There were no adverse events encountered during this BE study. The study's results indicated that the 2 formulations of the rivaroxaban tablet were bioequivalent.


A case of Nd:YAG laser-induced traumatic macular hole with good visual prognosis after vitrectomy with inverted internal limiting membrane technique.
To report an accidental case of traumatic macular hole caused by Nd:YAG laser in a dermatology clinic. A 24-year-old woman sustained a laser injury to her right eye while practicing a dermatologic treatment using a Nd:YAG laser without wearing protective goggles. She noticed sudden-onset and progressing visual loss in her right eye and consulted an ophthalmologist 2 days after injury. The best-corrected visual acuity (BCVA) of her right eye decreased to 20/133. Fundus examination showed white parafoveal flecks with a central retinal hemorrhage and underlying serous retinal detachment. The retinal sensitivity in this lesion deteriorated. Two weeks later, a full-thickness macular hole (FTMH) developed in the affected eye. She was referred to Nagoya City University Hospital where the laser damage described was observed. The BCVA was 20/67. She underwent pars plana vitrectomy performed using the inverted internal limiting membrane (ILM) flap technique and gas tamponade. One week postoperatively, the FTMH closed, the BCVA in her right eye improved to 20/50, and the retinal sensitivity in the macular area mostly improved. The BCVA gradually improved and reached 20/25 9 months after the injury. Protective goggles must be worn when using an Nd:YAG laser in the laboratory or clinical setting. In the unfortunate event of a FTMH, early vitrectomy with an inverted ILM flap technique can be helpful to achieve a good visual prognosis.


Subcellular localization of RNA and proteins in prokaryotes.
The field of bacterial cell biology has been revolutionized in the last decade by improvements in imaging capabilities which have revealed that bacterial cells, previously thought to be non-compartmentalized, possess an intricate higher-order organization. Many bacterial proteins localize to specific subcellular domains and regulate the spatial deployment of other proteins, DNA and lipids. Recently, the surprising discovery was made that bacterial RNA molecules are also specifically localized. However, the mechanisms that underlie bacterial cell architecture are just starting to be unraveled. The limited number of distribution patterns observed thus far for bacterial proteins and RNAs, and the similarity between the patterns exhibited by these macromolecules, suggest that the processes that underlie their localization are inextricably linked. We discuss these spatial arrangements and the insights that they provide on processes, such as localized translation, protein complex formation, and crosstalk between bacterial machineries.


Exploring palliative treatment outcomes in women with advanced or recurrent ovarian clear cell carcinoma.
Clear cell carcinoma (CCC) of the ovary is increasingly recognized as responding poorly to chemotherapy (CT). This review examines the outcomes achieved with a variety of CT regimens, looking for evidence of activity that might guide the development of more effective treatments. A retrospective chart review of all cases of CCC referred to the BC Cancer Agency (BCCA) between 2000 and 2008 was conducted. Data were collected from those with primarily advanced disease and from those who recurred after adjuvant treatment. Outcomes were measured using broad definitions of treatment benefit (any objective or subjective evidence of disease control) in order to reflect the real-life use of palliative therapy. There were 158 women with pure CCC. First-line therapy for advanced disease was delivered to 33 patients. Second- and third-line treatment was delivered to 47 and 25 patients, respectively. The total number of treatment courses was 105: 88 CT-alone courses, 14 radiation therapy (RT)-alone and 3 combined modality. Treatment benefit was recorded in 24% of patients receiving CT, 64% of patients receiving RT, and each who received combined modality treatment. There was no CT drug class identified as obviously efficacious. Most patients with advanced or recurrent CCC have a low benefit-to-failure ratio from palliative CT. The role of RT and targeted agents must be explored to improve clinical outcomes for such patients.


Association of glomerular filtration rate slope with timely creation of vascular access in incident hemodialysis.
The factors associated with the timely creation of distal vascular access for hemodialysis initiation are unclear. We aimed to explore the association between the slope of estimated glomerular filtration rate (eGFR) and the successful usage of vascular access upon hemodialysis initiation. This single center retrospective cohort study enrolled chronic kidney disease patients who undertook a multidisciplinary care program from 2003 to 2016. Using eGFR slope as predictor, we evaluated the vascular access created timely upon hemodialysis initiation. Among the 987 patients, vascular access was created at a median eGFR of 5.8 min/ml/1.73 m2, with a median duration of 3.1 months before hemodialysis. The proportions of vascular access created timely, created not timely (vascular access immature), and not created were 68.5%, 8.8%, and 22.7%, respectively. There was a significant negative association of eGFR upon vascular access creation with eGFR slope (r = - 0.182, P < 0.001). The fastest eGFR slope patients (the first quartile or < - 10 min/ml/1.73 m2/year) had the lowest percentage of vascular access created timely. In the multivariable logistic regression analysis, only higher eGFR upon vascular access creation (P = 0.001) and eGFR slope (P = 0.009) were significantly associated with vascular access created timely. The adjusted odds ratios of each quartile of eGFR slopes for vascular access created timely were 0.46 (95% confidence interval 0.27-0.86), 1.30 (0.62, 2.72), 1.00 (reference), and 0.95 (0.48-1.87), respectively. eGFR slope is associated with the timely creation of vascular access for the initiation of hemodialysis in a reverse-J-shaped pattern and may help determine the time of vascular access creation.


Irritable bowel syndrome in inflammatory bowel disease. Synergy in alterations of the gut-brain axis?
The presence of digestive symptoms associated with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in remission is a topic of growing interest. Although there is heterogeneity in clinical studies regarding the use of IBD remission criteria and the diagnosis of IBS, the available data indicate that the IBD-IBS overlap would affect up to one third of patients in remission, and they agree on the finding of a negative impact on the mental health and quality of life of the individuals who suffer from it. The pathophysiological bases that would explain this potential overlap are not completely elucidated; however, an alteration in the gut-brain axis associated with an increase in intestinal permeability, neuroimmune activation and dysbiosis would be common to both conditions. The hypothesis of a new clinical entity or syndrome of "Irritable Inflammatory Bowel Disease" or "Post-inflammatory IBS" is the subject of intense investigation. The clinical approach is based on certifying the remission of IBD activity and ruling out other non-inflammatory causes of potentially treatable persistent functional digestive symptoms. In the case of symptoms associated with IBS and in the absence of sufficient evidence, comprehensive and personalized management of the clinical picture (dietary, pharmacological and psychotherapeutic measures) should be carried out, similar to a genuine IBS.


Differences in COPD-related readmissions to primary and secondary care hospitals.
To study differences in readmissions to primary and secondary care hospitals for exacerbations of chronic obstructive pulmonary disease (COPD). A register-based study. The data were gathered from the hospital admissions register of the Finnish National Research and Development Centre for Welfare and Health. The data included all acute periods of treatment received by COPD patients aged over 44 years in 1996-2004 who had a principal or subsidiary diagnosis of COPD (ICD 10: J41-J44), respiratory infection (ICD 10: J00-J39, J85-J86) or cardiac insufficiency (ICD 10: I50), followed by an emergency readmission. Treatment had to have taken place in either a primary care hospital or a specialized ward for respiratory diseases or internal medicine in a secondary care hospital. The risk of readmission within a week of discharge, analysed by site of care. The risk of readmission within seven days of discharge is 1.74-fold for a patient treated in primary care compared with a patient treated in secondary care. COPD patients discharged from primary care hospitals have a greater risk of readmission, particularly within a week, than those discharged from secondary care. This risk may be attributed to differences in treatment procedures and arrangement of subsequent care. Thus, in the future, more attention should be paid to primary healthcare resources and staff training.


Reconstitution and biochemical characterization of the RNA-guided helicase-nuclease protein Cas3 from type I-A CRISPR-Cas system.
Type I is the most prevalent CRISPR system found in nature. It can be further defined into six subtypes, from I-A to I-G. Among them, the Type I-A CRISPR-Cas systems are almost exclusively found in hyperthermophilic archaeal organisms. The system achieves RNA-guided DNA degradation through the concerted action of a CRISPR RNA containing complex Cascade and a helicase-nuclease fusion enzyme Cas3. Here, we summarize assays to characterize the biochemical behavior of Cas3. A steep temperature-dependency was found for the helicase component of Cas3HEL, but not the nuclease component HD. This finding enabled us to establish the correct experimental condition to carry out I-A CRISPR-Cas based genome editing in human cells with extremely high efficiency.


Negative binomial additive model for RNA-Seq data analysis.
High-throughput sequencing experiments followed by differential expression analysis is a widely used approach for detecting genomic biomarkers. A fundamental step in differential expression analysis is to model the association between gene counts and covariates of interest. Existing models assume linear effect of covariates, which is restrictive and may not be sufficient for certain phenotypes. We introduce NBAMSeq, a flexible statistical model based on the generalized additive model and allows for information sharing across genes in variance estimation. Specifically, we model the logarithm of mean gene counts as sums of smooth functions with the smoothing parameters and coefficients estimated simultaneously within a nested iterative method. The variance is estimated by the Bayesian shrinkage approach to fully exploit the information across all genes. Based on extensive simulations and case studies of RNA-Seq data, we show that NBAMSeq offers improved performance in detecting nonlinear effect and maintains equivalent performance in detecting linear effect compared to existing methods. The vignette and source code of NBAMSeq are available at http://bioconductor.org/packages/release/bioc/html/NBAMSeq.html.


Sinapic acid and 3,3'-diindolylmethane potentiate cyclophosphamide antitumor activity through induction of apoptosis and inhibition of metastasis.
New therapeutic strategies are required to enhance the anticancer efficacy of chemotherapeutic drugs and to reduce their cytotoxicity. The purpose of this study was to assess the anti-tumor, antimetastatic and anti-apoptotic activities of sinapic acid (SA) and 3,3'-diindolylmethane (DIM) in solid Ehrlich carcinoma (SEC) induced in mice and combining SA or DIM compounds with cyclophosphamide (CYP). For induction of solid tumor, the right hind limbs of mice were inoculated subcutaneously with Ehrlich carcinoma cells. After 5 days of tumor inoculation, mice were treated with SA (56 mg/kg), DIM (40 mg/kg), CYP (10 mg/kg), and their combinations (SA/CYP) and (SA/DIM) for 21 days. The mRNA levels of Elabela, Serpina3, caspase-3, MMP-2 and MMP-9 were assessed by qPCR. Tumor and liver tissues were stained with hematoxylin and eosin for histological examination. Serum was investigated for ALT and AST activities. Treatment of SEC mice with SA and DIM significantly reduced solid tumor weight by 45.6% and 33.2%, respectively. They also reduced tumor size and increased life span of SEC mice. SA and DIM diminished area of metastatic nodules of tumor cells in the liver by 54.1% and 47.4%, respectively. They also reduced serum aminotransferases activities. Both SA and DIM were found to upregulate caspase 3 and downregulate MMP-2 and MMP-9. Furthermore, SA and DIM reduced gene expression of Elabela by (44.8% and 35.1%) and Serpina3 by (30.7% and 23.5%), respectively. SA and DIM were also shown to potentiate the anti-tumor activity CYP. SA and DIM showed promising antitumor effects and enhanced CYP antitumor activity mostly through upregulation of apoptotic caspase 3 and suppressing metastatic enzymes MMP-2 and MMP-9. Additionally, SA and DIM exhibited a hepatoprotective effect. Our results suggest that these natural compounds may be used to improve the efficacy and reduce the adverse effects of chemotherapeutic drugs in the treatment of solid malignancies.


Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors.
The endogenous cannabinoid system is an important regulatory system involved in physiological homeostasis. Endocannabinoid signaling is known to modulate neural development, immune function, metabolism, synaptic plasticity and emotional state. Accumulating evidence also implicates brain endocannabinoid signaling in the etiology of drug addiction which is characterized by compulsive drug seeking, loss of control in limiting drug intake, emergence of a negative emotional state in the absence of drug use and a persistent vulnerability toward relapse to drug use during protracted abstinence. In this review we discuss the effects of drug intake on brain endocannabinoid signaling, evidence implicating the endocannabinoid system in the motivation for drug consumption, and drug-induced alterations in endocannabinoid function that may contribute to various aspects of addiction including dysregulated synaptic plasticity, increased stress responsivity, negative affective states, drug craving and relapse to drug taking. Current knowledge of genetic variants in endocannabinoid signaling associated with addiction is also discussed.


Densitometric measurement of renal echogenicity in infants and naked eye evaluation: a comparison.
The sonograms of 115 infants with normal renal function ranging in age from 1 to 120 days used to determine renal parenchymal echogenicity by densitometry. The measured values were contrasted with the evaluations of 4 independent examiners who rated renal echogenicity as "less than", "equal to" or "greater than" that of the liver. The results revealed that naked eye evaluation does not permit a clear distinction between the categories of echogenicity and also that the assessments of the individual examiners differed considerably. Contrary to the previously held view the present findings indicate that the initially increased renal parenchymal echogenicity in neonates has developed into the normal hypoechoic condition after 1 month. One should take these findings into account when evaluating renal sonograms of infants, especially if no densitometric data are available.


Fitting integrated enzyme rate equations to progress curves with the use of a weighting matrix.
A method is presented for fitting the pairs of values product formed-time taken from progress curves to the integrated rate equation. The procedure is applied to the estimation of the kinetic parameters of the adenosine deaminase system. Simulation studies demonstrate the capabilities of this strategy. A copy of the FORTRAN77 program used can be obtained from the authors by request.


Instructive roles of extracellular matrix on autophagy.
Autophagy plays an essential role in maintaining an intricate balance between nutrient demands and energetic requirements during normal homeostasis. Autophagy recycles metabolic substrates from nonspecific bulk degradation of proteins and excess or damaged organelles. Recent work posits an active and dynamic signaling role for extracellular matrix-evoked autophagic regulation, that is, allosteric and independent of prevailing nutrient conditions. Several candidates, representing a diverse repertoire of matrix constituents (decorin, collagen VI, laminin α2, endostatin, endorepellin, and kringle V), can modulate autophagic signaling pathways. Importantly, a novel principle indicates that matrix constituents can differentially modulate autophagic induction and repression via interaction with specific receptors. Most of the matrix-derived factors described here appear to control autophagy in a canonical manner but independent of nutrient deprivation. Because the molecular composition and structure of the extracellular matrix are dynamically remodeled during various physiological and pathological conditions, we propose that matrix-regulated autophagy is key for maintaining proper tissue homeostasis and disease prevention, such as cancer progression and muscular dystrophies.


Electron beam-induced radiation damage: the bubbling response in amorphous dried sodium phosphate buffer.
Irradiation of an amorphous layer of dried sodium phosphate buffer (pH = 7.0) by transmission electron microscopy (100-120 kV) causes rapid formation of numerous small spherical bubbles [10-100 A (= 1-10 nm)] containing an unknown gas. Bubbling is detected even with the first low-dose exposure. In a thin layer (ca. 100-150 A), bubbling typically goes through nucleation, growth, possible fusion, and end-state, after which further changes are not apparent; co-irradiated adjacent areas having a slightly smaller thickness never develop bubbles. In moderately thicker regions (ca. over 200 A), there is no end-state. Instead, a complex sequence of microstructural changes is elicited during continued intermittent high-dose irradiation: nucleation, growth, early simple fusions, a second round of extensive multiple fusions, general reduction of matrix thickness (producing flattening and expansion of larger bubbles, occasional bubble fission, and formation of very large irregularly-shaped bubbles by a third round of compound fusion events), and slow shrinkage of all bubbles. The ongoing lighter appearance of bubble lumens, maintenance of their rounded shape, and extensive changes in size and form indicate that gas content continues throughout their surprisingly long lifetime; the thin dense boundary layer surrounding all bubbles is proposed to be the main mechanism for their long lifetime.


A portable wireless intelligent electrochemical sensor based on layer-by-layer sandwiched nanohybrid for terbutaline in meat products.
The aim of this study is to develop a portable wireless intelligent nanosensor (PWIN) for rapid cost-effective on-site determination of terbutaline (TRA) residue in meat products outdoors in comparison with traditional nanosensor and high-performance liquid chromatography (HPLC). The layer-by-layer sandwiched nanohybrid fabricated by platinum-palladium nanoparticles, carboxylated graphene and graphene-like molybdenum disulfide displayed a wide linear range of 0.55-14.9 μmol/L using the portable potentiostat with smartphone, and the result was almost close to the linear range (0.4-14 μmol/L) using the traditional potentiostat with desktop computer for TRA. The limit of detections were identified as 0.44 μmol/L and 0.18 μmol/L, respectively. PWIN displayed satisfactory recovery (91%-98.43%) of TRA in samples by the standard addition method and in comparison with both traditional sensor (93.79%-98%) and HPLC (93.4%-98.6%), revealing that PWIN for rapid cost-effective on-site analysis in the food safety field is feasible.


Confirmation of Aortic Stenosis Severity in Case of Discordance Between Aortic Valve Area and Gradient.
In this report, we illustrate the different flow-gradient patterns of aortic stenosis associated with discordant grading of stenosis severity at transthoracic echocardiography (TTE). The discordance among TTE parameters (mean gradient and aortic area) can be reconciled and true severity can be confirmed by ruling out potential measurements errors and by using multimodality imaging. (Level of Difficulty: Advanced.).


Activation and active sites of nickel-containing hydrogenases.
Hydrogenases that contain nickel and iron-sulphur clusters also have a regulatory mechanism, by which exposure to oxidants such as oxygen prevents their reaction with hydrogen. Treatment with reducing agents then causes reactivation. In some hydrogenases from Desulfovibrio species, there is evidence that there are at least two different deactivated states, which differ in their rates of reductive reactivation. The membrane-bound hydrogenase of D. desulfuricans, Norway strain, the periplasmic hydrogenase of D. gigas and the membrane-bound hydrogenase of Alcaligenes eutrophus can be isolated in a state (termed "Unready") which requires up to several hours for full activation by hydrogen. By contrast the soluble hydrogenases of D. desulfuricans and A. eutrophus can be reactivated relatively rapidly. In all of these enzymes, with the exception of the latter one, the existence of the activated and deactivated states can be correlated with different ESR-detectable forms of nickel. The possible functions of nickel and [Fe-4S] clusters in catalysis are discussed.


Ascorbic acid in the brain.
Ascorbic acid is highly concentrated in the central nervous system. Measurement of the extracellular concentration of ascorbate in animals, mainly by the technique of voltammetry in vivo, has demonstrated fluctuation in release from neuropil, both spontaneously and in response to physical stimulation of the animal and to certain drugs. Although in the adrenal medulla ascorbate is co-released with catecholamines, release of ascorbate from brain cells is associated principally with the activity of glutamatergic neurones, mainly by glutamate-ascorbate heteroexchange across cell membranes of neurones or glia. This phenomenon is discussed in relation to a possible role of ascorbate as a neuromodulator or neuroprotective agent in the brain.


Fractional order uncertainty estimator based hierarchical sliding mode design for a class of fractional order non-holonomic chained system.
This paper proposes a novel fractional order sliding mode control approach to address the issues of stabilization as well as tracking of an N-dimensional extended chained form of fractional order non-holonomic system. Firstly, the hierarchical fractional order terminal sliding manifolds are selected to procure the desired objectives in finite time. Then, a sliding mode control law is formulated which provides robustness against various system uncertainties or external disturbances. In addition, a novel fractional order uncertainty estimator is deduced mathematically to estimate and mitigate the effects of uncertainties, which also excludes the requirement of their upper bounds. Due to the omission of discontinuous control action, the proposed algorithm ensures a chatter-free control input. Moreover, the finite time stability of the closed loop system has been proved analytically through well known Mittag-Leffler and Fractional Lyapunov theorems. Finally, the proposed methodology is validated with MATLAB simulations on two examples including an application of fractional order non-holonomic wheeled mobile robot and its performances are also compared with the existing control approach.


A Positive Regulatory Feedback Loop between EKLF/KLF1 and TAL1/SCL Sustaining the Erythropoiesis.
The erythroid Krüppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to the CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and the promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf-/-) mouse embryos, we identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with the molecular/cellular analysis of the mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF is Tal1/Scl. Tal1/Scl encodes another DNA-binding hematopoietic transcription factor TAL1/SCL, known to be an Eklf activator and essential for definitive erythroid differentiation. Further identification of the authentic Tal gene promoter in combination with the in vivo genomic footprinting approach and DNA reporter assay demonstrate that EKLF activates the Tal gene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors, which sustains mammalian erythropoiesis.


V. R. Khanolkar and the Indian Cancer Research Centre, 1952-1962.
This note presents a brief account of the ideas and efforts of V.R. Khanolkar in the period 1952-1962 to develop the Indian Cancer Research Centre into a "center of excellence". Khanolkar, who is recognized as a pioneer in cancer research in India, focused on developing multidisciplinary medical research and mentored and trained young medical researchers. He sought and received aid from the Rockefeller Foundation, which was keen to support him in this task.


Behavioral fingerprints predict insecticide and anthelmintic mode of action.
Novel invertebrate-killing compounds are required in agriculture and medicine to overcome resistance to existing treatments. Because insecticides and anthelmintics are discovered in phenotypic screens, a crucial step in the discovery process is determining the mode of action of hits. Visible whole-organism symptoms are combined with molecular and physiological data to determine mode of action. However, manual symptomology is laborious and requires symptoms that are strong enough to see by eye. Here, we use high-throughput imaging and quantitative phenotyping to measure Caenorhabditis elegans behavioral responses to compounds and train a classifier that predicts mode of action with an accuracy of 88% for a set of ten common modes of action. We also classify compounds within each mode of action to discover substructure that is not captured in broad mode-of-action labels. High-throughput imaging and automated phenotyping could therefore accelerate mode-of-action discovery in invertebrate-targeting compound development and help to refine mode-of-action categories.


Cost of Potentially Preventable Hospitalizations Among Adults With Chronic Kidney Disease: A Population-Based Cohort Study.
Prior studies report high hospitalization rates among patients with chronic kidney disease (CKD) and approximately 10% to 20.9% of hospitalizations are potentially preventable. To determine the rate, proportion, and cost of potentially preventable hospitalizations and whether this varied by CKD category. Retrospective cohort study using population-based data. Alberta, Canada. All adults with an outpatient serum creatinine measurement between January 1 and December 31, 2017 in the Alberta Kidney Disease Network data repository. CKD risk categories were based on measures of proteinuria (where available), eGFR, and use of dialysis. Patients were linked to administrative data to capture frequency and cost of hospital encounters and followed until death or end of study (December 31, 2018). The outcomes of interest were the rate and cost of potentially preventable hospitalizations, as identified using the Canadian Institute for Health Information (CIHI)-defined ambulatory care sensitive condition (ACSC) algorithm and a CKD-related ACSC algorithm. Unadjusted and adjusted rates per 1000-patient years, proportions, and cost attributable to preventable hospitalizations were identified for the cohort as a whole and for patients within each CKD risk category. Of the 1,110,895 adults with eGFR and proteinuria measurements, 181,422 had CKD. During a median follow-up of 1 year, there were 62,023 hospitalizations among patients with CKD resulting in a total cost of $946 million CAD; 6907 (11.1%) of these hospitalizations were for CIHI-defined ACSCs while 4323 (7.0%) were for CKD-related ACSCs. Adjusted rates of hospitalization for ACSCs increased with CKD risk category and were highest among patients treated with dialysis. Among CKD patients, the total cost of potentially preventable hospitalizations was $79 million and $58 million CAD for CIHI-defined and CKD-related ACSCs (8.4% and 6.2% of total hospitalization cost, respectively). Based on the ACSC construct, we were unable to determine if these hospitalizations were truly preventable. Potentially preventable hospitalizations have a substantial cost and burden on the health care system among people with CKD. Effective strategies that reduce preventable admissions among CKD patients may lead to significant cost savings. Not applicable-observational study design.


The Wrb antigen, a receptor for Plasmodium falciparum malaria, is located on a helical region of the major membrane sialoglycoprotein of human red blood cells.
1. Immunoprecipitation of periodate/NaB3H4-labelled human erythrocytes using anti-Wrightb (Wrb) monoclonal antibodies showed that these antibodies specifically react with the major erythrocyte sialoglycoprotein alpha (glycophorin A). 2. Similar experiments on erythrocytes from the only known individual lacking the Wrb antigen but with otherwise normal sialoglycoproteins did not result in the immunoprecipitation of any sialoglycoprotein. 3. We suggest that the Wrb antigen is located on an alpha-helical region between residues 55 and 70 of sialoglycoprotein alpha.


Understanding modes of moderate sedation during gastrointestinal procedures: a current review of the literature.
Recommendations for routine screening for colorectal cancer with colonoscopy are likely to substantially increase the demand for provision of sedation for these procedures. Because of this burgeoning caseload and associated economic constraints, it is unlikely that anesthesiologists will be available for all such procedures, particularly those involving average-risk patients. Thus, sedative agents that can be safely administered by nonanesthesiologists, appropriately trained in monitoring and managing the patient's airway, are desperately needed. New concepts in sedation for colonoscopy include enhanced mechanisms for drug delivery such as patient-controlled sedation/analgesia and target-controlled infusion, along with the development of new drugs such as a modified cyclodextrin-based formulation of propofol and fospropofol disodium (Aquavan Injection), a water-soluble prodrug of propofol.


The Effect of Alkyl Terminal Chain Length of Schiff-Based Cyclotriphosphazene Derivatives towards Epoxy Resins on Flame Retardancy and Mechanical Properties.
A series of Schiff-based cyclotriphosphazenes with different alkyl chain length terminal ends, 4a (dodecyl) and 4b (tetradecyl), were synthesized and the structures were characterized using Fourier-transform infrared spectroscopy (FT-IR), and 1H, 13C, and 31P nuclear magnetic resonance (NMR) and carbon, hydrogen, and nitrogen (CHN) elemental analysis. The flame-retardant and mechanical properties of the epoxy resin (EP) matrix were examined. The limiting oxygen index (LOI) of 4a (26.55%) and 4b (26.71%) revealed a good increment compared to pure EP (22.75%). The LOI results corresponded to their thermal behavior studied using thermogravimetric analysis (TGA) and the char residue analyzed under field emission scanning electron microscopy (FESEM). The mechanical properties of EP showed a positive impact on tensile strength with a trend of EP < 4a < 4b. The tensile strength went from 8.06 N/mm2 (pure EP) to 14.36 and 20.37 N/mm2, indicating that the additives were compatible with epoxy resin.


Dizziness in the elderly.
Vertigo, unsteadiness, and other balance-related symptoms are common among older adults. These complaints should be taken seriously because they can lead to falls, injuries, loss of independence, and even death. This article provides a review of the underlying causes for the increased prevalence of dizziness with age, and discusses how specific test procedures may need to be modified for older individuals. Issues related to the management of these symptoms in the aging population are also considered.


Pan-cancer characterization of long non-coding RNA and DNA methylation mediated transcriptional dysregulation.
Disruption of DNA methylation (DNAm) is one of the key signatures of cancer, however, detailed mechanisms that alter the DNA methylome in cancer remain to be elucidated. Here we present a novel integrative analysis framework, called MeLncTRN (Methylation mediated LncRNA Transcriptional Regulatory Network), that integrates genome-wide transcriptome, DNA methylome and copy number variation profiles, to systematically identify the epigenetically-driven lncRNA-gene regulation circuits across 18 cancer types. We show that a significant fraction of the aberrant DNAm and gene expression landscape in cancer is associated with long noncoding RNAs (lncRNAs). We reveal distinct types of regulation between lncRNA modulators and target genes that are operative in either only specific cancers or across cancers. Functional studies identified a common theme of cancer hallmarks that lncRNA modulators may participate in. The coupled lncRNA gene interactions via DNAm also serve as markers for classifications of cancer subtypes with different prognoses. Our study reveals a vital layer of DNAm and associated expression regulation for many cancer-related genes and we also provide a valuable database resource for interrogating epigenetically mediated lncRNA-gene interactions in cancer. National Natural Science Foundation of China [91959106, 31871255].


Influence of valvular insufficiency and recurrent airway obstruction on haemodynamics and therapy in warmblood horses with atrial fibrillation.
The aim of this study was to investigate the potential haemodynamic effects of valvular insufficiency and recurrent airway obstruction (RAO) in horses with atrial fibrillation (AF). Therefore in ten healthy horses (group 1) and 40 horses with AF a clinical examination, a lung examination, echocardiography and right heart catheterization for measurement of intracardic and pulmonary pressures were performed. According to the clinical findings the horses with AF were subdivided into 4 groups (group 2: AF; group 3: AF/valvular insufficiency; group 4: AF/RAO; group 5: AF/valvular insufficiency/RAO). Most of the horses of group 3 and 5 suffered from two valvular insufficiencies (mitral and tricuspid valve insufficiency: n=11, mitral and aortic valve insufficiency: n=2). The remaining horses showed a single mitral (n=6), tricuspid (n=2) or aortic valve insufficiency (n=1) or more than two valvular insufficiencies (n=4). In group 2 right ventricular mean pressure (RVPm) was higher than in group 1 and 4 (P<0.025); diastolic right ventricular pressure was higher than in group 1; PWP was higher than in group 1 and group 4; PDP was lower compared to group1. Compared to group1 in group 3 left atrial diameter (LA) was greater; the PAPs was higher and the PDP lower (P<0.05). In group 4 RVPm and PWP was lower compared to group 2. In group 5 LA, fractional shortening and diastolic left ventricular diameter were greater, PWP and PAPs were higher and PDP lower compared to group1. Twenty six of the 40 horses with AF (65%) were treated. Successful cardioversion to sinus rhythm occurred in 15 horses (58%). Therapy was successful in 50% of the treated horses of group 2 and 3, in 67% of the treated horses of group 4 and in 63% of the treated horses in group 5. In conclusion the presence of valvular insufficiency or RAO influences the haemodynamics of horses with AF.


Hair Transplantation and Follicular Unit Extraction.
This article introduces the reader to the key components of hair transplantation, including evaluating the surgical patient, deciding whether to perform follicular unit transplantation (FUT) or follicular unit extraction (FUE), understanding the key components of these procedures, and establishing practical preoperative and postoperative protocols.


Pregnancy-induced changes in resistance blood vessels.
This study was designed to examine the effect of reproductive status on the basic mechanical properties of resistance size blood vessels. The hypothesis to be tested was that pregnancy is associated with alterations in both the passive and active properties of blood vessels small enough to be major determinants of peripheral vasculature resistance. Third-order arteries (165 microns in diameter) from the mesenteric arcade of the rat were removed at all three stages of gestation and the four stages of the estrous cycle. These were placed in a specially designed myograph system in which their active and passive tension-internal circumference characteristics were measured. Pregnancy was found to be associated with a decrease in stiffness of these vessels and a reduction in contractile ability by 20 days' gestation.


Endoscopic endonasal odontoidectomy for basilar invagination in children: Literature review and case report.
Basilar invagination (BI) is an uncommon clinical condition of the craniocervical junction (CCJ). Surgical management depends on 2 factors: mobility and reducibility; in cases of irreducible dislocation or persistent compression, odontoidectomy should be considered. We present the case of a 13-year-old boy with severe BI, causing cervical myelopathy with progressive gait disorder. The patient underwent cervical traction followed by posterior decompression and occipitocervical fusion. Postoperatively, symptoms initially improved, until new neurological deterioraton set in 4 months later. Follow-up neuroimaging showed compression of the bulbo-medullary junction, with severe brainstem kinking and appearance of a cervical syrinx. Secondary surgery via an endoscopic endonasal approach (EEA) was deemed necessary to relieve the compression. Postoperative course was unremarkable, with steady clinical improvement and a return to independent activities of daily living within 6 months. A systematic literature review indicated that EEA conserves the palate and oropharynx mucosae, thus causing less airway and swallowing complications than the transoral approach. In selected cases with persistent anterior compression, odontoidectomy on EEA is a safe, effective and valid alternative for managing CCJ pathology.


Quantum mechanical study of antioxidative ability and antioxidative mechanism of rutin (vitamin P) in solution.
A quantum mechanical approach has been used to shed light on the antioxidative mechanism for scavenging hydroxyl radicals (()OH) and superoxide radicals (O2-) by rutin in the solution phase. Density-functional theory (DFT) using B(3)LYP and UB(3)LYP functional and split-valance 6-311+G(∗∗) basis sets were used to optimize rutin and its different radical forms. Analysis of the theoretical bond dissociation enthalpy (BDE) values for all OH sites of rutin in solution clearly shows the importance of the B-ring and the 3'-OH and 4'-OH groups in the antioxidant activity. We have also investigated the spin density of the radicals to determine the delocalization possibilities. The results of the calculations showed that the oxidation of rutin by both the hydroxyl radical and superoxide radical is an exothermic reaction. In all calculations solvent effects were considered using a polarized continuum model (PCM).


Sexual differences in root growth and antioxidant characteristics in Salix viminalis exposed to cadmium stress.
Salix viminalis, a dioecious shrub willow, has been widely used in phytoremediation, yet sexually differences in tolerance to cadmium of which remained unclear. This study focused on different responses to cadmium stress between roots of male and female S. viminalis. Results show that male plants of S. viminalis have stronger cadmium tolerance than female plants, which indicates male S. viminalis should be more considered to be applied for phytoremediation and ecological restoration of cadmium-accumulated soil considering cadmium tolerance characteristics. The findings can provide valuable evidence and insights for researches focused on phytoremediation with dioecious woody plants and sexual dimorphism under abiotic stress.


Decision making in a life-threatening cerebral condition: a comparative study of the ethical reasoning of intensive care unit physicians and neurosurgeons.
To study the support for the arguments of neurosurgeons and intensive care unit (ICU) physicians for and against life-sustaining treatment of critically ill patients, and whether neurosurgeons are less inclined to emphasize quality-of-life aspects than ICU physicians. A postal questionnaire was sent to a random sample of ICU physicians in Sweden (n= 298) and all neurosurgeons in Sweden (n= 112). The respondents evaluated and prioritized different arguments for and against withholding neurosurgery, withdrawing life-sustaining treatment and providing drugs which may hasten death. The response rate was 62.5% for neurosurgeons and 73.5% for ICU physicians. Quality-of-life aspects were stressed as an important argument by the majority of both neurosurgeons and ICU physicians (76.8% vs. 54.0%); however, significantly more neurosurgeons regarded this argument as the most important (P < 0.001). A minority in both groups, although more ICU physicians (P < 0.001), supported a patient's previously expressed wish of not ending in a persistent vegetative state as the most important argument. As the case clinically progressed, a consensus regarding the arguments for decision making evolved. No support was found for the hypothesis that ICU physicians care more about the quality of life of a severely ill patient. Indeed, significantly more neurosurgeons emphasized the quality-of-life aspects in this particular setting. Compared with neurosurgeons, significantly more ICU physicians considered the patient's own wishes to be important.


Immediate Vitrectomy vs Tap and Inject in eyes with Acute Post-cataract endophthalmitis and visual acuity ≥HM: A Randomized Clinical Trial.
To compare outcomes of immediate vitrectomy (PPV) vs tap and inject (T&I) in eyes with post-cataract surgery endophthalmitis (PCE). Patients presenting with acute PCE and visual acuity (VA) between ≥ hand movement and <6/18 were randomized to receive either PPV (Group A) or T&I (Group B). There were 26 and 31 eyes in Group A and B respectively. The final mean VA at 6 weeks (0.14 (Snellen's equivalent 6/7.5) vs 0.22 (Snellen's equivalent 6/9.5) LogMAR in groups A & B respectively; p = 0.2) was similar. However, eyes in Group A had significantly greater mean letter gain in vision compared to Group B (66.36 vs 43.36, p=0.02), and more eyes in group A (88%) than in group B (65%) attained a VA of ≥ 6/18 (p=0.06). Eyes in group B needed more re-interventions including delayed vitrectomy after T&I. than those in Group A (39% vs 8%; p = 0.09) On subgroup analysis, the mean visual acuity at the final follow-up was significantly better in the immediate PPV group compared to the delayed PPV group. (p=0.04). PPV resulted in earlier recovery, lesser interventions, and greater change in visual acuity than T&I in eyes with PCE presenting with visual acuity of ≥ HM.


Aortic Stenosis Progression, Cardiac Damage, and Survival: Comparison Between Bicuspid and Tricuspid Aortic Valves.
This study sought to compare aortic stenosis (AS) progression rates, AS-related cardiac damage (AS-CD) indicator incidence and determinants, and survival between patients with tricuspid aortic valve (TAV)-AS and those with bicuspid aortic valve (BAV)-AS. Differences in AS progression and AS-CD between patients with BAV and patients with TAV are unknown. We retrospectively studied consecutive patients with baseline peak aortic valve velocity (peakV) ≥2.5 m/s and left ventricular ejection fraction ≥50%. Follow-up echocardiograms (n = 4,818) provided multiparametric AS progression rates and AS-CD. The study included 330 BAV (age 54 ± 14 years) and 581 patients with TAV (age 72 ± 11 years). At last echocardiogram (median: 5.9 years; interquartile range: 3.9 to 8.5 years), BAV-AS exhibited similar peakV and mean pressure gradient (MPG) as TAV-AS, but larger calculated aortic valve area due to larger aortic annulus (p < 0.0001). Multiparametric progression rates were similar between BAV-AS and TAV-AS (all p ≥ 0.08) and did not predict age-/sex-adjusted survival (p ≥ 0.45). Independent determinants of rapid progression were male sex and baseline AS severity for TAV (all p ≤ 0.024), and age, baseline AS severity, and cardiac risk factors (age interaction: p = 0.02) for BAV (all p ≤ 0.005). At 12 years, patients with TAV-AS had a higher incidence of AS-CD than BAV-AS patients (p < 0.0001), resulting in significantly worse survival compared to BAV-AS (p < 0.0001). AS-CD were independently determined by multiple factors (MPG, age, sex, comorbidities, cardiac function; all p ≤ 0.039), and BAV was independently protective of most AS-CD (all p ≤ 0.05). In this cohort, TAV-AS and BAV-AS progression rates were similar. Rapid progression did not affect survival and was determined by cardiac risk factors for BAV-AS (particularly in patients with BAV <60 years of age) and unmodifiable factors for TAV-AS. AS-CD and mortality were significantly higher in TAV-AS. Independent determinants of AS-CD were multifactorial, and BAV morphology was AS-CD protective. Therefore, the totality of AS burden (cardiac damage) is clinically crucial for TAV-AS, whereas attention to modifiable risk factors may be preventive for BAV-AS.


Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide exchange factor for Rab5a and Rab22.
RIN proteins serve as guanine nucleotide exchange factors for Rab5a. They are characterized by the presence of a RIN homology domain and a C-terminal Vps9 domain. Currently three family members have been described and analyzed. Here we report the identification of a novel RIN family member, Rin-like (Rinl), that represents a new interaction partner of the receptor tyrosine kinase MuSK, which is an essential key regulator of neuromuscular synapse development. Rinl is localized to neuromuscular synapses but shows the highest expression in thymus and spleen. Rinl preferentially binds to nucleotide-free Rab5a and catalyzes the exchange of GDP for GTP. Moreover, Rinl also binds GDP-bound Rab22 and increases the GDP/GTP exchange implicating Rinl in endocytotic processes regulated by Rab5a and Rab22. Interestingly, Rinl shows a higher catalytic rate for Rab22 compared to Rab5a. Rinl is closely associated with the cytoskeleton and thus contributes to the spatial control of Rab5a and Rab22 signaling at actin-positive compartments. Most importantly, overexpression of Rinl affects fluid-phase as well as EGFR endocytosis.


Science education reforms in the UK.
As children return to school at the end of the summer in the UK, planned reforms aim to increase their science and maths literacy. A comprehensive foundation in these essential subjects is necessary to ensure that the UK remains at the forefront of science and technology for decades to come.


'Hot gall bladder service' by emergency general surgeons: Is this safe and feasible?
Despite NICE/AUGIS recommendations, the practice of early laparoscopic cholecystectomy (ELC) has been particularly poor in the UK offered only by 11%-20% surgeons as compared to 33%-67% internationally, possibly due to financial constraints, logistical difficulties and shortage of expertise, thus, reflecting the varied provision of emergency general surgical care. To assess whether emergency general surgeons (EGS) could provide a 'Hot Gall Bladder Service' (HGS) with an acceptable outcome. This was a prospective HGS observational study that was protocol driven with strict inclusion/exclusion criteria and secure online data collection in a district general hospital between July 2018 and June 2019. A weekly dedicated theatre slot was allocated for this list. Of the 143 referred for HGS, 86 (60%) underwent ELC which included 60 (70%) women. Age, ASA and body mass index was 54* (18-85) years, II* (I-III) and 27* (20-54), respectively. 86 included 46 (53%), 19 (22%), 19 (22%) and 2 (3%) patients presenting with acute calculus cholecystitis, gallstone pancreatitis, biliary colic, and acalculus cholecystitis, respectively. 85 (99%) underwent LC with a single conversion. Grade of surgical difficulty, duration of surgery and post-operative stay was 2* (1-4) 68* (30-240) min and 0* (0-13) day, respectively. Eight (9%) required senior surgical input with no intra-operative complications and 2 (2%) 30-day readmissions. One was post-operative subhepatic collection that recovered uneventfully and the second was pancreatitis, imaging was clear requiring no further intervention. In the current climate of NHS financial crunch, COVID pandemic and significant pressure on inpatient beds: Safe and cost-effective HGS can be provided by the EGS with input from upper GI/HPB surgeons (when required) with acceptable morbidity and a satisfactory outcome. *Median.


[The laser photocoagulation and electrical excision of gastric polyps].
The paper deals with results of endoscopic removal of gastric polyps using r. f. current or laser photocoagulation obtained by the author. Merits and demerits of those methods are discussed. Certain advantages of endoscopic polypectomy using r. f. current are emphasized.


Sigmoid colon perforation induced by the vascular type of Ehlers-Danlos syndrome: report of a case.
The vascular type of Ehlers-Danlos syndrome (vEDS) is a rare inherited disease of the connective tissues, and is caused by abnormal type III collagen resulting from heterogeneous mutations of the type III collagen COL3A1 gene. We herein report the case of a vEDS patient who developed a sigmoid colon perforation and was given a definitive diagnosis by a genetic and biomolecular assay. The patient demonstrated clinical manifestations caused by tissue weakness such as frequent pneumothorax events and a detached retina. During the operation, we noticed easy bruising and thin skin with visible veins on the patient's abdominal wall. Finally, a diagnosis was confirmed by the reduction of type III collagen synthesis and by the identification of a mutation in the gene for type III collagen. We conclude that it is difficult to diagnose a vEDS patient without clinical experiences and specialized genetic methods. Furthermore, all organs must be treated gently during therapy, because the tissues of vEDS patients are extremely fragile.


Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor.
Microarray analysis was used to characterize the labor-selective transcriptome of the human myometrium during labor. One highly up-regulated transcript, monocyte chemotactic protein-1 (MCP-1), was further characterized. Expression of MCP-1 was evaluated in the myometrium, the placenta, the gestational membranes (GM) and the amniotic fluid (AF) by real time RT-PCR, Northern blot analysis and ELISA. The level of immunoreactive (IR) MCP-1 content of primary myometrial cultures treated with inflammatory cytokines was quantified by ELISA. Up-regulation of the myometrial MCP-1 transcript in term laboring patients was demonstrated by microarray and confirmed by real time (RT)-PCR and Northern blot analysis. Increased MCP-1 transcripts were demonstrated in GM during term labor. The IR content of myometrial MCP-1 was increased during term labor and in the AF from patients experiencing preterm delivery. Levels of IR MCP-1 increased in myometrial cultures in response to interleukin 1-beta. The expression of myometrial MCP-1 was significantly increased during term labor and was similarly increased in vitro in response to interleukin 1-beta, a pro-inflammatory substance known to play a role in preterm birth. The increased IR content of MCP-1 within the AF preceding preterm delivery may render this protein a useful predictor of preterm birth.


[Prevalence of genital anomalies in young football players].
The purpose of genital examination (GE) during the Pre-participation Physical Examination (PPE) is to identify the state of maturity, and rule out any genital pathology. To describe genital anomalies (GA) and estimate the awareness of GE in young football players. A descriptive, cross-sectional study was conducted in 280 elite football players from the results of PPE over two seasons. There was a detection rate of 5.4% GA, with varicocele being 3.2%, and of which only 13% were aware of their condition. Although this study shows a low incidence of genital abnormality in the study population, only 13% were aware of the GE prior to assessment. These findings demonstrate a low incidence of GA in this population. While GE is recommended during PPE, it is not a routine practice performed by family doctors or sports medicine specialists. This article attempts to raise awareness of the importance of GE in PPE as a preventive health strategy.


Bone marrow infiltration by a parietal lobe grade III oligodendroglioma.
We report a patient with oligodendroglioma metastases 1 year after tumour debulking and postoperative radiotherapy to the parietal lobe primary. This treatment controlled the patient's tumour locally. Distant recurrence was manifest by back pain, weight loss and malaise. The serum alkaline phosphatase was raised and a bone scan showed generalized increased uptake. Bone marrow trephine revealed infiltration by oligodendroglioma. Bone marrow infiltration by gliomas is very rare. If the trephine had not been performed it might have been assumed that he had a disseminated second primary tumour.


Enrichment of Persister Cells Through Β-Lactam-Induced Filamentation and Size Separation.
Analyzing persisters at the single-cell level is crucial to properly define their phenotypic traits. However, single-cell analyses are challenging due to the rare and temporary nature of persister cells, thus requiring their rapid and efficient enrichment in a culture. Existing methods to isolate persisters from a bacterial population show important shortcomings, including contamination with susceptible cells and/or cell debris, which complicate subsequent microscopic analyses. We here describe a protocol to enrich persisters in a culture using β-lactam-induced filamentation followed by size separation. This protocol minimizes the amount of cell debris in the final sample, facilitating single-cell studies of persister cells.


Radiomics for the Prediction of Treatment Outcome and Survival in Patients With Colorectal Cancer: A Systematic Review.
Prediction of outcome in patients with colorectal cancer (CRC) is challenging as a result of lack of a robust biomarker and heterogeneity between and within tumors. The aim of this review was to assess the current possibilities and limitations of radiomics (on computed tomography [CT], magnetic resonance imaging [MRI], and positron emission tomography [PET]) for the prediction of treatment outcome and long-term outcome in CRC. Medline/PubMed was searched up to August 2020 for studies that used radiomics for the prediction of response to treatment and survival in patients with CRC (based on pretreatment imaging). The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and Radiomics Quality Score (RQS) were used for quality assessment. A total of 76 studies met the inclusion criteria and were included for further analysis. Radiomics analyses were performed on MRI in 41 studies, on CT in 30 studies, and on 18F-FDG-PET/CT in 10 studies. Heterogeneous results were reported regarding radiomics methods and included features. High-quality studies (n = 13), consisting mainly of MRI-based radiomics to predict response in rectal cancer, were able to predict response with good performance. Radiomics literature in CRC is highly heterogeneous, but it nonetheless holds promise for the prediction of outcome. The most evidence is available for MRI-based radiomics in rectal cancer. Future radiomics research in CRC should focus on independent validation of existing models rather than on developing new models.


Agreement and reproducibility of gray-scale intravascular ultrasound and optical coherence tomography for the analysis of the bioresorbable vascular scaffold.
To report the agreement between gray-scale intravascular ultrasound (GS-IVUS) and optical coherence tomography (OCT) in assessing the bioresorbable vascular scaffolds (BVS) structures and their respective reproducibility. BVS are composed of an erodible polymer. Ultrasound and light signals backscattered from polymeric material differs from metallic stents using GS-IVUS and OCT. Forty-five patients included in the ABSORB trial were treated with a 3.0 × 18 mm BVS and imaged with GS-IVUS 20 MHz and OCT post-implantation. Qualitative (ISA, side-branch struts, protrusion, and dissections) and quantitative (number of struts, lumen, and scaffold area) measurements were assessed by two investigators. The agreement and the inter- and intraobserver reproducibility were investigated using the kappa (κ) and the interclass correlation coefficient (ICC). GS-IVUS and OCT agreement was predominantly poor at a lesion, frame, and strut level analysis (κ and ICC <0.4) for qualitative measurements. GS-IVUS demonstrated a reduced ability to detect cross-sections with ISA (4.5% vs. 20.6%), side-branch (SB) struts (6.3% vs. 7.8%), protrusions (3.2% vs. 9.6%), and dissections (0.2% vs. 9.0%) compared with OCT. GS-IVUS reproducibility was poor-moderate (κ and ICC <0.6) except for ISA and SB-struts (κ and ICC between 0.2 and 0.75). OCT showed an excellent reproducibility (κ and ICC > 0.75) except for the assessment of tissue protrusion (κ and ICC between 0.47 and 0.94). GS-IVUS reproducibility was poor-moderate (ICC ≤ 0.5) in assessing the number of struts but excellent with OCT (ICC > 0.85). The reproducibility to assess lumen and scaffold areas was excellent using both techniques (ICC > 0.85). GS-IVUS has a poor capacity to detect qualitative findings post-BVS implantation and its reproducibility is low compared with OCT. The use of GS-IVUS should be limited when assessing lumen and scaffold areas.


Critical care ultrasonography.
Resuscitative ultrasonography provides rapid, repeatable, and multisystem assessment to guide diagnosis and management of critically ill patients in the emergency department (ED). Cardiac ultrasonography offers new anatomic and hemodynamic information, previously unavailable in an ED setting, whereas other applications match or exceed the speed and utility of existing tests such as chest radiograph (thoracic ultrasonography) or central venous pressure determination (inferior vena cava ultrasonography). Evolving areas of resuscitative ultrasonography include neurologic applications and transesophageal echocardiography, which promise to further enhance the role of ultrasonography in managing critical illness in the ED.


Exclusion of BRAFV599E as a melanoma susceptibility mutation.
Very recently, BRAF mutations were found in about 2/3 of malignant melanomas and at lower frequencies in other human cancers. The BRAF gene codes for a protein in the mitogen-activated protein kinase (MAPK) pathway. All mutations identified to date are within the kinase domain, with a single missense mutation (V599E) accounting for 80%. We investigated the hypothesis that this common somatic BRAF mutation (V599E) would contribute to melanoma predisposition in familial and polygenic malignant melanoma if occurring as a germ-line mutation. We performed comprehensive mutational screening of exon 15 of BRAF using DHPLC (denaturing high-performance liquid chromatography) and DNA sequencing techniques. No V599E mutation could be detected in 172 melanoma patients comprising 46 familial cases, 21 multiple melanoma patients and 106 cases with at least one first-degree relative suffering from other cancers. We therefore conclude that the common somatic BRAF mutation V599E does not contribute to polygenic and familial melanoma predisposition.


Total coronary occlusion: a different animal?
Provided collateralization is adequate, a chronic total coronary occlusion clinically imitates a 90% stenosis but is exempt from the risk of myocardial infarction. For angioplasty of vessels with chronic total coronary occlusion, technical difficulties and clinical risks are balanced against projected subjective benefit and amount of viable myocardium concerned. The primary success rate is approximately 65% and complications are rare because abrupt vessel reclosure may be common but is harmless. New Q wave infarction in that context has not been reported. The duration of occlusion is the most important predictor of success. The length of the occluded segment is also important. Recurrence averages 68% (21% reocclusion and 47% restenosis) and happens typically within 6 months. The high recurrence rate is due to competitive pressure exerted by collateral vessels and an often suboptimal local result. Even if the primary success rate of angioplasty in vessels with chronic total coronary occlusion can be improved by advanced technology and skill, the clinical yield will remain low compared with that of angioplasty of stenoses. Because low yield procedures must be low risk and low cost, there are definite limits to how sophisticated, risky and expensive new techniques can become. Derivatives of conventional balloon systems are likely to remain the equipment of first choice, perhaps complemented by mechanical drills. Although chronic total coronary occlusions are no clinical menace in contrast to stenoses, they frequently deserve revascularization and are the reason to select bypass surgery over angioplasty. These factors justify endeavors to improve recanalization techniques that help to refine coronary angioplasty of nontotal lesions, because total occlusion, albeit a different animal, is of the same species.


Inherited Arterial Calcification Syndromes: Etiologies and Treatment Concepts.
We give an update on the etiology and potential treatment options of rare inherited monogenic disorders associated with arterial calcification and calcific cardiac valve disease. Genetic studies of rare inherited syndromes have identified key regulators of ectopic calcification. Based on the pathogenic principles causing the diseases, these can be classified into three groups: (1) disorders of an increased extracellular inorganic phosphate/inorganic pyrophosphate ratio (generalized arterial calcification of infancy, pseudoxanthoma elasticum, arterial calcification and distal joint calcification, progeria, idiopathic basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; (2) interferonopathies (Singleton-Merten syndrome); and (3) others, including Keutel syndrome and Gaucher disease type IIIC. Although some of the identified causative mechanisms are not easy to target for treatment, it has become clear that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering arterial and cardiac valve calcification. Further studies will focus on targeting the phosphate/pyrophosphate ratio to effectively prevent and treat these calcific disease phenotypes.


The AP2/ERF transcription factor WIND1 controls cell dedifferentiation in Arabidopsis.
Many multicellular organisms have remarkable capability to regenerate new organs after wounding. As a first step of organ regeneration, adult somatic cells often dedifferentiate to reacquire cell proliferation potential, but mechanisms underlying this process remain unknown in plants. Here we show that an AP2/ERF transcription factor, WOUND INDUCED DEDIFFERENTIATION 1 (WIND1), is involved in the control of cell dedifferentiation in Arabidopsis. WIND1 is rapidly induced at the wound site, and it promotes cell dedifferentiation and subsequent cell proliferation to form a mass of pluripotent cells termed callus. We further demonstrate that ectopic overexpression of WIND1 is sufficient to establish and maintain the dedifferentiated status of somatic cells without exogenous auxin and cytokinin, two plant hormones that are normally required for cell dedifferentiation. In vivo imaging of a synthetic cytokinin reporter reveals that wounding upregulates the B-type ARABIDOPSIS RESPONSE REGULATOR (ARR)-mediated cytokinin response and that WIND1 acts via the ARR-dependent signaling pathway to promote cell dedifferentiation. This study provides novel molecular insights into how plants control cell dedifferentiation in response to wounding.


Dysregulated luminal bacterial antigen-specific T-cell responses and antigen-presenting cell function in HLA-B27 transgenic rats with chronic colitis.
HLA-B27/beta2 microglobulin transgenic (TG) rats spontaneously develop T-cell-mediated colitis when colonized with normal commensal bacteria, but remain disease-free under germ-free conditions. We investigated regulation of in vitro T-cell responses to enteric bacterial components. Bacterial lysates prepared from the caecal contents of specific pathogen-free (SPF) rats stimulated interferon-gamma (IFN-gamma) production by TG but not non-TG mesenteric lymph node (MLN) cells. In contrast, essentially equivalent amounts of interleukin-10 (IL-10) were produced by TG and non-TG cells. However, when cells from MLNs of non-TG rats were cocultured with TG MLN cells, no suppression of IFN-gamma production was noted. Both non-TG and TG antigen-presenting cells (APC) pulsed with caecal bacterial lysate were able to induce IFN-gamma production by TG CD4+ cells, although non-TG APC were more efficient than TG APC. Interestingly, the addition of exogenous IL-10 inhibited non-TG APC but not TG APC stimulation of IFN-gamma production by cocultured TG CD4+ lymphocytes. Conversely, in the presence of exogenous IFN-gamma, production of IL-10 was significantly lower in the supernatants of TG compared to non-TG APC cultures. We conclude that commensal luminal bacterial components induce exaggerated in vitro IFN-gamma responses in HLA-B27 TG T cells, which may in turn inhibit the production of regulatory molecules, such as IL-10. Alterations in the production of IFN-gamma, and in responses to this cytokine, as well as possible resistance of TG cells to suppressive regulation could together contribute to the development of chronic colitis in TG rats.


In vitro construction of bacteriophage lambda and plasmid DNA molecules containing DNA fragments from bacteriophage T4.
Restriction endonucleases EcoRI and HindIII generated fragments of T4 cytosine-containing DNA were inserted into bacteriophage vector lambdagtSuIII and plasmid vectors pMB9 and pBR313. Resulting clones were screened for hybridization with 32P labeled T4 tRNA. Recombinant bacteriophages and plasmids were isolated which contained a T4 fragment coding for T4 RNA species 1 and 2 and T4 tRNA Arg. Selected lambda-T4 hybrid bacteriophages were grown to high titer and their DNA analyzed by gel electrophoresis.


Evidence for a primarily humoral rejection mechanism in concordant xenogeneic heart transplantation. A sequential immunohistological study in a hamster-to-rat model.
Heterotopic heart transplantations in an unmodified hamster-to-rat model were studied sequentially by immunohistochemical analysis. Monoclonal mouse anti-rat antibodies against B cells, T cells, macrophages and neutrophilic granulocytes (MRC OX-19, MRC OX-38, MRC OX-8, MRC OX-22, MRC OX-33, MRC OX-41 and MRC OX-42) were used in an indirect immunoperoxidase technique and monoclonal mouse anti-rat IgM and IgG were used for immunofluorescence. In grafts investigated after 6 h (N = 8) minimal infiltration of macrophages was demonstrated with MRC OX-41+ and MRC OX-42+ cells. No T- or B cells were seen. In a few cases, deposition of IgG and IgM was seen related to the endothelium of larger vessels. In grafts examined 24 h after transplantation (N = 10) the number of MRC OX-41+ and MRC OX-42+ cells had increased and in half of the cases IgM and IgG were located in relation to endothelial cells of larger vessels. In grafts investigated 48 h after transplantation (N = 8) the infiltration with MRC OX-41+ and MRC OX-42+ cells had further increased and a few scattered MRC OX-19+ and MRC OX-8+ cells appeared. At this time all but one heart had deposition of IgG and IgM in the vessel walls. Upon complete rejection (N = 8) diffuse infiltration of MRC OX-41+ and MRC OX-42+ cells was seen, but still only a few scattered T cells could be demonstrated. At this time IgG an IgM deposition appeared in all vessels and was also located in relation to the capillaries. These results further support our hypothesis that acute xenograft rejection in this animal model is primarily of the humoral type.


Characterization of the Complete Chloroplast Genome of Four Species in Callerya.
Callerya reticulata (Bentham) Schot, Callerya dielsiana (Harms) P.K. Loc ex Z. Wei & Pedley, Callerya nitida var. hirsutissima (Z. Wei) X.Y. Zhu, and Callerya nitida (Bentham) R. Geesink, which belongs to the Leguminosae family, are important medicinal plants in China. The genus Callerya includes 26 species, 18 species are distributed in China, and the vine stems of some species are used as traditional medicinal herbs because they have important pharmacological activity. Due to the high similarity of appearance, it is difficult to identify them in the market by appearance alone. Therefore, circulating of Callerya-related materia medica on the market is confusing, sometimes even leading to drug safety problems. It is urgent to develop molecular methods for their identification. To sequence and analyze the complete chloroplast (cp) genomes of C. reticulata, C. dielsiana, C. nitida var. hirsutissima, and C. nitida and to analyze their cp genome differences as a basis for seeking easier DNA barcoding for their identification. After using Illumina high-throughput sequencing and nanopore sequencing to obtain the genome data, some bioinformatics software was used to assembly and analyze the molecular structure of cp genomes. The complete cp genomes of the four species were circular molecules, which ranged from 130 435 to 132 546 bp, and GC contents ranged from 33.89% to 34.89%. Each of them includes a large single-copy region, a small single-copy region, and without large inverted repeat regions. These results suggested that highly variable regions of the four cp genomes would provide useful plastid markers, which could be used as a potential genomic resource to resolve phylogenetic questions and provide a reference for mining specific DNA barcodes of these species. Our study provided highly effective molecular markers for subsequent phylogenetic analysis, species identification, and biogeographic analysis of Callerya.


Establishment and performance evaluation of multiplex PCR-dipstick DNA chromatography assay for simultaneous diagnosis of four sexually transmitted pathogens.
Rapid, sensitive, and specific diagnostic methods are indispensable for sexually transmitted infections (STIs). In this study, a multiplex PCR-dipstick DNA chromatography assay for diagnosis of four STI pathogens, namely Neisseria gonorrhoeae (N. gonorrhoeae), Mycoplasma hominis (M. hominis), Ureaplasma (U. urealyticum and U. parvum), and Chlamydia trachomatis (C. trachomatis), was established and evaluated. Based on the hybridization of probes and interaction between streptavidin and biotin, PCR products were visualized through hybridization of specific probes and enzymatic color generation. The sensitivity and specificity of all four pathogens were evaluated. Clinical performance of the test was evaluated using 295 specimens, and comparisons among results were determined via culture or colloidal gold assay. No cross-reactions were observed, confirming the high specificity of this method. The limit of detection (LOD) of the four STI pathogens was 100 copies/μL. The sensitivity between PCR-dipstick DNA chromatography and culture or colloidal gold assay ranged from 84.6% to 100%. The specificity was between 93.5% and 96.6%, positive predictive value ranged from 53.6% to 86.7%, negative predictive value was over 98.3%, kappa value ranged from 0.676 to 0.864 (Cohen's kappa coefficient test), and the agreement rate was over 93.5%. In conclusion, PCR-dipstick DNA chromatography serves as a rapid, sensitive, and specific method for simultaneous diagnosis of four STI pathogens.


Quantitative characterization of food products by two-dimensional D-T2 and T1-T2 distribution functions in a static gradient.
We present new NMR techniques to characterize food products that are based on the measurement of two-dimensional diffusion-T2 relaxation and T1-T2 relaxation distribution functions. These measurements can be performed in magnets of modest strength and low homogeneity and do not require pulsed gradients. As an illustration, we present measurements on a range of dairy products that include milks, yogurt, cream, and cheeses. The two-dimensional distribution functions generally exhibit two distinct components that correspond to the aqueous phase and the liquid fat content. The aqueous phase exhibits a relatively sharp peak, characterized by a large T1/T2 ratio of around 4. The diffusion coefficient and relaxation times are reduced from the values for bulk water by an amount that is sample specific. The fat signal has a similar signature in all samples. It is characterized by a wide T2 distribution and a diffusion coefficient of 10(-11) m2/s for a diffusion time of 40 ms, determined by bounded diffusion in the fat globules of 3 microm diameter.


Resiliency and vulnerability in the HER2-HER3 tumorigenic driver.
About 25% of breast cancers harbor the amplified oncogene human epidermal growth factor receptor 2 (HER2) and are dependent on HER2 kinase function, identifying HER2 as a vulnerable target for therapy. However, HER2-HER3 signaling is buffered so that it is protected against a nearly two-log inhibition of HER2 catalytic activity; this buffering is driven by the negative regulation of HER3 by Akt. We have now further characterized HER2-HER3 signaling activity and have shown that the compensatory buffering prevents apoptotic tumor cell death from occurring as a result of the combined loss of mitogen-activated protein kinase (MAPK) and Akt signaling. To overcome the cancer cells' compensatory mechanisms, we coadministered a phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor and a HER2 tyrosine kinase inhibitor (TKI). This treatment strategy proved equivocal because it induced both TKI-sensitizing and TKI-desensitizing effects and robust cross-compensation of MAPK and Akt signaling pathways. Noting that HER2-HER3 activity was completely inhibited by higher, fully inactivating doses of TKI, we then attempted to overcome the cells' compensatory buffering with this higher dose. This treatment crippled all downstream signaling and induced tumor apoptosis. Although such high doses of TKI are toxic in vivo when given continuously, we found that intermittent doses of TKI administered to mice produced sequential cycles of tumor apoptosis and ultimately complete tumor regression in mouse models, with little toxicity. This strategy for inactivation of HER2-HER3 tumorigenic activity is proposed for clinical testing.


Biventricular pacing in a patient with ventilatory and inotropic dependant heart failure following coronary artery by-pass surgery.
Resynchronisation of intra- and interventricular conduction delay by biventricular pacing has become a proven therapy for selected heart failure patients. We present a case of biventricular pacing, used with great success, as a 'bail out' for a patient with refractory congestive heart failure following by-pass surgery.


Effects of Three Feed Additives on the Culturable Microbiota Composition and Histology of the Anterior and Posterior Intestines of Zebrafish (Danio rerio).
In this study, the effect of three promising feed additives (chelated compounds of trace elements, butyric acid, lycopene) on changes in the culturable microbiota and histological parameters of two sections of the intestines of Danio rerio (zebrafish) was studied. The use of these feed additives can help to eliminate the deficiency of trace elements, modulate the composition of the microbiota due to the postbiotic properties of butyric acid, and reduce oxidative stress when using lycopene. Incorporation of the investigated supplements in the feed resulted in a significant change in the relative abundance of certain groups of microorganisms. The taxonomic diversity of cultured microorganisms did not differ in the anterior and posterior intestines, while there were differences in the relative abundance of these microorganisms. The most sensitive groups of microorganisms were the genera Bacillus and Serratia. A significant effect on the composition of the cultured microbiota was caused by lycopene (in all studied concentrations), leading to a significant increase in the relative abundance of Firmicutes in the anterior gut. Studies of the histological structure of the anterior and posterior guts have shown the relationship between the barrier and secretory functions of the gut and the composition of the microbiota while using butyric acid (1 and 2 g kg-1) and trace element chelated compounds (2 mg kg-1). This culture-dependent method of studying the microbiome makes it possible to assess changes in some representatives of the main groups of microorganisms (Firmicutes and Proteobacteria). Despite the incompleteness of the data obtained by the culture-dependent method, its application makes it possible to assess the bioactive properties of feed and feed additives and their impact on the microbiota involved in digestive processes.


Early diastolic mitral regurgitation in left ventricular aneurysm.
Diastolic mitral regurgitation is a type of functional mitral regurgitation that develops via a reversal of the left atrioventricular pressure gradient during diastole. This study aimed to explore the mechanism underlying early diastolic mitral regurgitation (EDMR) in patients with left ventricular (LV) aneurysms after anterior myocardial infarction (AMI) by assessing the intraventricular pressure difference using vector flow mapping. We enrolled 23 consecutive patients with LV aneurysms (with and without EDMR) and 15 healthy men as controls. In the control group, LV suction began from the apex during early diastole. In contrast, the blood that pooled in the apical aneurysm during systole generated a relatively higher pressure at the apex than at the basal LV during early diastole; consequently, the pressure reversal phenomenon occurred in the LV. Compared to the EDMR- group, the EDMR + group (n = 7) exhibited a significantly higher diastolic time ratio ([time from the second heart sound to the pressure inversion point]/[total diastolic time]) (P < 0.001). The diastolic time ratio was significantly correlated with log BNP, but not with E/A, E/E', or the left atrial expansion index. In conclusion, EDMR in LV aneurysm may be due to a prolonged diastolic time ratio leading to prolonged pressure inversion in the LV during early diastole.


Remote ischemic preconditioning improves spatial memory and sleep of young males during acute high-altitude exposure.
The high-altitude hypoxia environment will cause poor acclimatization in a portion of the population. Remote ischemic preconditioning(RIPC)has been demonstrated to prevent cardiovascular and cerebrovascular diseases under ischemic or hypoxic conditions. However, its role in improving acclimatization and preventing acute mountain sickness (AMS) at high altitude has been undetermined. This study aims to estimate the effect of RIPC on acclimatization of individuals exposed to high altitude. The project was designed as a randomized controlled trial with 82 healthy young males, who received RIPC training once a day for 7 consecutive days. Then they were transported by aircraft to a high altitude (3680 m) and examined for 6 days. Lake Louise Score(LLS) of AMS, physiological index, self-reported sleep pattern, and Pittsburgh Sleep Quality Index(PSQI)score were applied to assess the acclimatization to the high altitude. Five neurobehavioral tests were conducted to assess cognitive function. The result showed that the RIPC group had a significantly lower AMSscore than the control group (2.43 ± 1.58 vs 3.29 ± 2.03, respectively; adjusted mean difference-0.84, 95% confidence interval-1.61 to -0.06, P = 0.036). and there was no significant difference in AMS incidence between the two groups (25.0% vs 28.57%, P = 0.555). The RIPC group performed better than the control group in spatial memory span score (11[9-12] vs 10[7.5-11], P=0.025) and the passing digit (7[6-7.5] vs 6[5-7], P= 0.001). Spatial memory was significantly higher in the high-altitude RIPC group than in the low-altitude RIPC group (P<0.01). And the RIPC group obtained significantly lower self-reported sleep quality score (P = 0.024) and PSQI score (P = 0.031). The RIPC treatment improved spatial memory and sleep quality in subjects exposed to acute hypoxic exposure and this may lead to improved performance at high altitude.


Performance of basophil activation test and specific IgG4 as diagnostic tools in nonspecific lipid transfer protein allergy: Antwerp-Barcelona comparison.
Recent studies show that nsLTP sensitization is not limited to the Mediterranean basin and can present diverse clinical phenotypes. It remains challenging to predict clinical outcome when specific IgE antibodies (sIgE) to nsLTPs are present. This study compares both clinical and in vitro allergy characteristics but also diagnostic performance of a basophil activation test (BAT) and sIgG4 in nsLTP-sensitized patients from Antwerp (ANT, Belgium) and Barcelona (BCN, Spain). Adult subjects with positive sIgE rPru p 3 and/or rMal d 3 ≥ 0.10 kUA /L (n = 182) and healthy controls (n = 37) were included. NsLTP-sensitized individuals were stratified according to clinical symptoms with peach/apple, respectively. BAT rPru p 3 and rMal d 3 were performed and sIgG4 antibodies to both components quantified. In BCN, only ratios of sIgG4/sIgE rMal d 3 and BAT rMal d 3 (0.001 µg/mL) can identify clinically relevant Mal d 3 sensitization (sensitivity of 60%-63% and a specificity of 75%-67%, respectively). In ANT, only the sIgE/total IgE rPru p 3 ratio shows added value (sensitivity 60% and specificity 83%). Finally, it appears that symptomatic patients in BCN are more sensitive to lower allergen concentrations compared to ANT. In addition, it was shown that ANT patients were more often sensitized to pollen and that specific pollen sources differed between regions. NsLTP-related allergy profiles and diagnostic performance differ significantly between regions and are component-specific, which makes extrapolation of data difficult to do. In addition, it seems that basophil sensitivity might show geographical differences. Additional research is needed to confirm these findings.


Crystal structure and Hirshfeld surface analysis of (±)-N'-(2-hy-droxy-3-meth-oxy-benzyl-idene)-2-(4-iso-butyl-phen-yl)propionohydrazide.
The title mol-ecule, C21H26N2O3, adopts a V-shaped conformation and is chiral at the C atom with methyl group attached at the common cut of the edges of the V-conformation and crystallizes as a racemate. It also contains an intra-molecular O-H⋯N hydrogen bond. In the crystal, N-H⋯O hydrogen bonds form chains of mol-ecules extending along the c-axis direction, together with normal van der Waals contacts. The roles of the various inter-molecular inter-actions were clarified by Hirshfeld surface analysis, which reveals that the most important contributions to the crystal packing are from H⋯H (62.6%), C⋯H/H⋯C (15.8%) and O⋯H/H⋯O (15.3%) contacts.


Using sensitivity analysis to identify factors promoting higher versus lower infection prevalence in multi-host communities.
Relationships between host species richness and levels of disease in a focal host are likely to be context-dependent, depending on the characteristics of which particular host species are present in a community. I use a multi-host epidemiological model with environmental transmission to explore how the characteristics of the host species (e.g., competence and competitive ability), host density, and the pathogen transmission mechanism affect the proportion of infected individuals (i.e., infection prevalence) in a focal host. My sensitivity-based approach identifies the indirect pathways through which specific ecological and epidemiological processes affect focal host infection prevalence. This in turn yields predictions about the context-dependent rules governing whether increased host species richness increases (amplifies) or decreases (dilutes) infection prevalence in a focal host. For example, in many cases, amplification and dilution are predicted to occur when added host species are sources or sinks of infectious propagules, respectively. However, if the added host species have strong and asymmetric competitive effects on resident host species, then amplification and dilution are predicted to occur when the added host species have stronger competitive effects on resident host species that are sources or sinks of infectious propagules, respectively. My results also predict that greater dilution and less amplification is more likely to occur under frequency-dependent direct transmission than density-dependent direct transmission when (i) the added hosts have lower competence than resident host species and (ii) interspecific competition between the added host species and resident host species is lower; the opposite conditions promote greater amplification and less dilution under frequency-dependent direct transmission. This work helps identify and explain the mechanisms shaping the context-dependent relationships between host species richness and disease in multi-host communities.


Transcription of genes encoding enzymes involved in DNA synthesis during the cell cycle of Saccharomyces cerevisiae.
We have examined the pattern of transcription exhibited by four genes in the dTTP biosynthetic pathway of Saccharomyces cerevisiae. Consistent with the results reported previously by Storms et al. (1984), the TMP1 (or CDC21) gene encoding thymidylate synthase was found to be transcribed in a periodic manner during the cell cycle with maximal mRNA levels occurring just prior to the onset of DNA replication. Three other genes in this pathway DCD1, DUT1 and DFR1 encoding dCMP deaminase, dUTP pyrophosphatase and dihydrofolate reductase, respectively, exhibited relatively constant levels of transcription throughout the cell cycle. These results, particularly for DFR1, are in marked contrast with those obtained in other eukaryotic systems which have suggested that, in general, genes encoding enzymes involved in DNA precursor synthesis are subject to cell cycle regulation. Thus, periodic transcription is not a property common to all genes involved in DNA replication in this eukaryote.


Selenium uptake and simultaneous catalysis of sulfite oxidation in ammonia-based desulfurization.
Accelerating the (NH4)2SO3 oxidation gives rise to the reclaiming of byproduct, while there are secondary environmental risks from reduction of the coexisted selenium species by sulfite. In this study, a bi-functional Co-SBA-15-SH, were synthesized through Co impregnation and sulfhydryl (-SH) decoration, which can simultaneously uptake Se and accelerate sulfite oxidation efficiently. Meanwhile, the adsorption kinetics and migration mechanism of Se species were revealed through characterization and density functional calculations, with maximum adsorption capacity of 223 mg/g. The inhibition of Se0 re-emission and poisonous effect of Se on sulfite oxidation was also investigated. Using the findings of this study, the ammonia desulfurization can be improved by enabling purification of the byproduct and lowering the toxicity of effluent by removing toxic pollutants.


Developmental changes of the FAS and HSL mRNA expression and their effects on the content of intramuscular fat in Kazak and Xinjiang sheep.
Twenty-four male Kazak sheep and 30 Xinjiang fine wool sheep at different ages were selected to investigate the development-dependent expression levels of fatty acid synthase (FAS) gene and hormone-sensitive lipase (HSL) gene in muscle and their effects on the contents of intramuscular fat (IMF). Longissimus dorsal muscle was sampled to measure IMF and total RNA was extracted to determine FAS and HSL mRNA expression levels by real-time PCR. The results showed that: 1) The IMF content increased continuously with growth and showed significant differences (P < 0.05) between different age groups in male Kazak sheep, but in Xinjiang fine wool sheep there was no such difference observed. Furthermore, the IMF contents in Kazak were much higher (P < 0.01) than that of the other breed from day 30 to 90. 2) FAS mRNA expression level was the highest (P < 0.05) on day 0 in Kazak sheep and then declined with growth, in the other breed the gene showed a 'decline-rise-decline-rise' expression manner as the animals grew. HSL mRNA expression level had a similar model in two breeds, in Kazak sheep it was the highest on day 0 (P < 0.05) and in Xinjiang fine wool sheep on day 30 (P < 0.01), then both decreased after this term. 3) In male Kazak sheep, FAS and HSL mRNA expression level were both negatively related to IMF content (r = -0.485 (P = 0.02), r = -0.423 (P = 0.05)), and the ratio of FAS/HSL expression exhibited significantly negatively related IMF contents. In male Xinjiang sheep, there were no obvious relationship between FAS and HSL expression and IMF content (P > 0.05).


The Role of Facial Expression Analysis and Electrodermal Activity as an Objective Evaluation of Persistent Idiopathic Facial Pain.
Persistent idiopathic facial pain (PIFP) is an enigmatic condition presenting with variable features. Psychiatric comorbidities are speculated to influence PIFP.In this study, the authors evaluated patients with PIFP through the hospital anxiety and depression scale, facial expression analysis, and electrodermal activity.A total of 67 respondents enrolled as the experimental group and 28 participants as the control group. Pain scores were higher in the experimental group (5.24; SD 2.349) P < 0.001 depression (5.58 (SD 3.766) versus 3.07 (SD 2.418), P = 0.002) and anxiety scores (9.78 (SD 4.923) versus 6.75 (SD 4.097) P = 0.007) were higher in the experimental group. The experimental group expressed more negative episodes (P = 0.024); Electrodermal Activity data in terms of peaks/min (P = 0.872) and average peak amplitude (P = 0.168) were not significantly different between the groups.It may be concluded that pain levels may be influenced by psychiatric comorbidity as PIFP patients showed insignificant physiological response to pain.