Environmental characteristics, field water relations, and photosynthetic responses of C4 Hawaiian Euphorbia species from contrasting habitats.
Four endemic Hawaiian Euphorbia species range in habitat from open arid coastal strand to shaded mesic forest and in growth-form from small prostrate shrubs to trees. As shown in the present study, these large differences in habitat and growth-form are paralleled by equally large differences in maximal photosynthetic rate (13.7 to 37.1 μmol CO2 m-2s-1), dark respiration rate (0.7 to 4.1 μmol CO2 m-2s-1), light level for saturation of photosynthesis (0.9 to over 2.0 mmol m-2s-1), light compensation point (0.01 to 0.11 mmol m-2s-1), leaf conductance to CO2 (1.7 to 4.9 mm s-1), and mesophyll conductance to CO2 (3.7 to 8.5 mm s-1). A principal consequence of this differentiation is that the capacity for photosynthesis at high light levels is higher in open site species, such as E. celastroides and E. degeneri, and at low light levels is higher in shade species, such as E. forbesii. E. hillebrandii, a species from intermediate semiopen habitats, exhibits an intermediate photosynthetic capacity at both high and low light levels. Despite this remarkable diversity, all four species exhibit the distinguishing physiological features of C4 photosynthesis.


Comparison of clinical and biologic features between myeloid and lymphoid transformation of Philadelphia chromosome positive chronic myeloid leukemia.
Analysis of clinical and biologic features of chronic myeloid leukemia (CML) in blast crisis (BC) was performed on 36 patients: 25 had myeloid and 11 had lymphoid transformation. The median duration from diagnosis to onset of BC was significantly shorter in patients with lymphoid BC (6 months) than in those with myeloid BC (41 months). Patients in lymphoid transformation showed better response to therapy and had a significantly longer median survival time after BC than patients with myeloid transformation (56% vs 0% and 10 months vs 4 months, respectively). The leukemic cells from all the patients with lymphoid BC showed B-cell immunophenotype, confirmed by the presence of immunoglobulin (Ig) heavy chain gene rearrangements in the five patients studied. Two of the eight patients with complete marker study expressed myeloid-associated antigens on the blasts. A high incidence of CD7 expression (7/17 or 41%) was found in patients with myeloid BC, but none of the patients who had DNA analysis showed rearrangement of T-cell receptor beta chain gene. Chromosomal abnormalities +8, +19, +21, and i(17q) were detected only in the patients with myeloid BC but not in those with lymphoid BC. Combined analysis of the patients in this series and those reported previously has revealed a statistically significant difference in the distribution of bcr breakpoints between myeloid and lymphoid BC: the bcr breakpoints in more than half of the patients with myeloid crisis were mapped to Zone 2 while those in patients with lymphoid crisis occurred most frequently in Zone 3.


Identification of a novel ferroptosis-related gene signature associated with prognosis, the immune landscape, and biomarkers for immunotherapy in ovarian cancer.
Ferroptosis has been implicated in tumor progression and immunoregulation. Identification of ferroptosis-related prognostic gene is important for immunotherapy and prognosis in ovarian cancer (OV). We assessed the potential predictive power of a novel ferroptosis-related gene (FRG) signature for prognosis and immunotherapy in Asian and Caucasian OV populations. We collected gene expression profiles and clinicopathological data from public databases. The least absolute shrinkage and selection operator Cox regression algorithm was used to construct the FRG signature. Receiver operating characteristic (ROC) curve, Kaplan-Meier method, Cox regression model were used to evaluate the clinical benefits of FRG signature. Gene functional and gene set enrichment analyses were used for functional annotation and immune landscape analysis. A 15-FRG signature was constructed and used to stratify patients into two risk groups. Patients in the high-risk group had significantly worse survival. The risk score was a significant independent risk factor for OS. The area under the ROC curve indicated the good prediction performance of the FRG signature. Notably, the low-risk group showed a significant enrichment in immune-related pathways and a "hot" immune status. The risk score was found to be an efficient and robust predictor of response to immunotherapy. In conclusion, our study identified a novel 15-FRG prognostic signature that can be used for prognostic prediction and precision immunotherapy in Asian and Caucasian OV populations.


Microcomputed Tomography to Visualize and Quantify Fungal Infection Burden and Inflammation in the Mouse Lung Over Time.
Pulmonary mycoses are an important threat for immunocompromised patients, and although current treatments are effective, they suffer from multiple limitations and fail to further reduce mortality. With the increasing immunocompromised population and increased antifungal resistance, fungal infection research is more relevant than ever. In preclinical respiratory fungal infection research, animal models are indispensable. However, too often researchers still rely on endpoint measurements to assess fungal burden while the dynamics of disease progression are left undiscovered. To open up this "black box", microcomputed tomography (μCT) can be implemented to longitudinally visualize lung pathology in a noninvasive way and to quantify μCT-image derived biomarkers. That way, disease onset, progression, and responsiveness to treatment can be followed up with high resolution spatially and temporally in individual mice, increasing statistical power. Here, we describe a general method for the use of low-dose high-resolution μCT to longitudinally visualize and quantify lung pathology in mouse models of respiratory fungal infections, applied to mouse models of aspergillosis and cryptococcosis.


[Determination of cholesteryl palmitate in Oviductus Ranae by HPLC].
To develop a new method for the determination of cholesteryl palmitate in Oviductus Ranae. A HPLC method was set up, using Zorbax Silica column and cyclohexane-diethyl ether (40:1) as mobile phase with a flow rate of 1.0 mL x min(-1), and the UV detection wavelength was 203 nm. The calibration curve was linear over the range of 0.60-8.92 microg (r = 0.9997), the average recovery of the method was 98.4%. RSD 1.8% (n = 6). The results showed that method was reliable and accurate.


Laser-scanned agarose gel sections for radiation field mapping.
A dedicated laser scanning system has been applied to the measurement of optical density change in ferrous sulphate-xylenol orange dye-agarose gel mixtures for applications in radiation field mapping. The gels were poured, irradiated, and optically scanned in Lucite casts providing a uniform gel section thickness of 1 cm. The gel sections were optically scanned both pre- and postirradiation to determine the optical density change in the gel and consequently the absorbed dose. Irradiations of the gel sections were performed with an orthovoltage unit and a linear accelerator. For linear dose response up to 10 Gy, an appropriate gel mixture was found to be 0.4 mM Fe2+, 0.2mM xylenol orange dye, 25 mM sulphuric acid, and 1% by weight agarose gel with a mixing temperature of 60 degrees C. In dosimetry of a 20 x 10 cm 6 MV wedged x-ray field, good agreement in terms of relative dose was found between the gel values and ionization chamber readings. However, in repeated experiments with the gel dosimeter involving calculation of absolute dose at various points in the wedged field, variations in absolute dose measurements of up to +/- 5% were observed. The dosimetry technique involving laser scanning of agarose gel sections has potential for further applications in radiotherapy dosimetry.


Transesophageal echocardiographic evaluation of left ventricular function during intraaortic balloon pump counterpulsation.
Transesophageal echocardiography was used to study the effects of intraaortic balloon pump counter pulsation (IABP) on left ventricular dimensions and function in 16 hypotensive patients after cardiac surgery. The short-axis cross section at midpapillary muscle level was used to determine systolic and diastolic dimensions. We found a significant decrease in end-systolic and end-diastolic area and increase in fractional area change during IABP-supported circulation. Regional area ejection fraction analysis demonstrated an improvement during IABP of impaired (particularly severely impaired) function at baseline. We conclude that both regional and global left ventricular function improve by the use of IABP in conjunction with a decrease of left ventricular size.


Targeting polyketide synthase 13 for the treatment of tuberculosis.
Tuberculosis (TB) is one of the most threatening diseases for humans, however, the drug treatment strategy for TB has been stagnant and inadequate, which could not meet current treatment needs. TB is caused by Mycobacterial tuberculosis, which has a unique cell wall that plays a crucial role in its growth, virulence, and drug resistance. Polyketide synthase 13 (Pks13) is an essential enzyme that catalyzes the biosynthesis of the cell wall and its critical role is only found in Mycobacteria. Therefore, Pks13 is a promising target for developing novel anti-TB drugs. In this review, we first introduced the mechanism of targeting Pks13 for TB treatment. Subsequently, we focused on summarizing the recent advance of Pks13 inhibitors, including the challenges encountered during their discovery and the rational design strategies employed to overcome these obstacles, which could be helpful for the development of novel Pks13 inhibitors in the future.


Molecular characterization, expression, and functional analysis of two thioredoxins in the black rockfish (Sebastes schlegelii).
Thioredoxins (TRxs) are a family of small evolutionarily conserved proteins that are essential for the maintenance of cellular homeostasis. Two TRx homologue cDNAs were isolated from a black rockfish concanavalin A (Con A)/phorbol myristate acetate (PMA)-stimulated leucocyte cDNA library and named BrTPx1-1 and BrTPx1-2. As compared with other known TRx peptide sequences, the most conserved regions of both BrTRx1-1 and BrTRx1-2 peptides were found to be the redox-active site Trp-Cys-X-X-Cys (WCXXC). The TRx present in most species is a TRx1-2 protein with a Cys-Pro-Gly-Cys (CPGC) active site. However, in the larger 13 kDa BrTRx1-1 protein, a Cys-Pro-Pro-Cys (CPPC) active site was identified. Here, we report the identification of a new member of the TRx protein family from the teleost black rockfish, which defines a new subclass of 13-kDa TRx1-1 proteins. Phylogenetic analysis indicated that both BrTRx1-1 and BrTRx1-2 were grouped with other vertebrate TRx1 peptides. BrTRx1-1 expression was strongly induced in peripheral blood leucocytes (PBLs) 12-24 h following Con A/PMA stimulation, with peak expression at 24 h post-stimulation. BrTRx1-2 was induced in PBLs after stimulation with lipopolysaccharide (LPS), Con A/PMA, or poly I:C at 24 h. The BrTRx1-1 gene was predominantly expressed in the liver and gills, while BrTRx1-2 was expressed in PBLs and gills. After treatment with a high concentration (10 μg/mL) of rBrTRx1-1 or rBrTRx1-2, kidney leucocytes exhibited increased cell proliferation and viability under oxidative stress.


Positive Correlation between Pesticide Consumption and Longevity in Solitary Bees: Are We Overlooking Fitness Trade-Offs?
The ubiquitous use of pesticides is one major driver for the current loss of biodiversity, and the common practice of simultaneously applying multiple agrochemicals may further contribute. Insect toxicology currently has a strong focus on survival to determine the potential hazards of a chemical routinely used in risk evaluations. However, studies revealing no effect on survival or even indicating enhanced survival are likely to be misleading, if potential trade-offs between survival and other physiological factors are overlooked. Here, we used standard laboratory experiments to investigate the sublethal (i.e., food consumption) and lethal (i.e., survival) effects of two common agricultural pesticides (Roundup® and clothianidin) on adult female solitary bees, Osmia bicornis. The data showed no significant effect of the treatment on cumulative survival; however, a significant positive correlation between herbicide and insecticide exposure and age was revealed, i.e., bees exposed to higher dosages lived longer. As no significant differences in daily food consumption were observed across treatment groups, increased food intake can be excluded as a factor leading to the prolonged survival. While this study does not provide data on fitness effects, two previous studies using solitary bees observed significant negative effects of neonicotinoid insecticides on fitness, yet not on survival. Thus, we conjecture that the observed non-significant effects on longevity may result from a trade-off between survival and reproduction. The data suggest that a focus on survival can lead to false-negative results and it appears inevitable to include fitness or at least tokens of fitness at the earliest stage in future risk assessments.


[Impact of serum epidermal growth factor on progressive psoriasis vulgaris and regulation of Chinese herbal medicine for cleaving heat, cooling blood, and detoxicating on it].
To investigate the impact of serum epidermal growth factor (EGF) on progressive psoriasis vulgaris and the regulatory effect of Chinese herbal medicine on it. Serum level of EGF was measured in 31 patients with progressive psoriasis vulgaris (the tested group) and 17 healthy subjects (the control group) by ELISA. The changes in EGF level and condition of illness were observed before and after patients orally administered Chinese composite recipe for clearing heat, cooling blood and removing toxic substances for 10 weeks, and the severity of illness was assessed by psoriasis area and severity index (PASI) as well. Serum level of EGF in patients was 175.35 +/- 179.86 ng/L before treatment, markedly higher than that in healthy subjects (72.05 +/- 63.01 ng/L), showing significant difference between them (t = - 2.888, P = 0.006); it reduced to 121.67 +/- 94.74 ng/L after treatment, significantly different to that before treatment (t = 2.155, P = 0.04), but still higher than that in the control (t = - 2.146, P = 0.037). Average PASI was 9.65 +/- 5.82 before treatment and 5.74 +/- 4.69 after treatment, displaying a significant reduction (t = 7.740, P < 0.01). Linear regression analysis showed no apparent correlation between serum EGF level and PASI (r = 0.030, P = 0.872; r = 0.050, P = 0.793). Serum level of EGF might be an important factor related to the progress of psoriasis. Chinese herbal medicine for clearing heat, cooling blood and removing toxic substances can lessen the severity of psoriasis, its action in reducing serum EGF is possibly one of the mechanisms for these kinds of herbs in treating psoriasis.


Comparison of the dynamics of n-hexane in ZSM-5 and 5A zeolite structures.
The translational and rotational dynamics of n-hexane adsorbed in ZSM-5 and 5A zeolites has been studied by neutron scattering and deuterium solid-state NMR, at various temperatures. The dynamics of n-hexane is quite different in the two zeolites. In the ZSM-5 structure, the molecule sits in channel segments, the energy barrier between adjacent adsorption sites is small and fast anisotropic motions are observed. In the 5A zeolite, the molecule is adsorbed in alpha-cages; the barrier between adjacent cages is larger so that the molecule spends a longer time exploring the volume of an alpha-cage, leading to a more isotropic motion. The diffusion coefficient of the molecule is reduced by more than 4 orders of magnitude in 5A zeolite compared with ZSM-5.


Quantification of gluten in wheat flour by FT-Raman spectroscopy.
A procedure for the quantitative determination of gluten in wheat flour based on partial least squares (PLS) treatment of FT-Raman data is described. Results of similar quality were found using a PLS model derived from NIR (near infrared) spectra obtained in DRIFTS (diffuse reflectance infrared Fourier transform spectroscopy) mode and of slightly worse quality from the model constructed based on IR (infrared) spectra registered using a single reflection ATR (attenuated total reflection) diamond accessory. The relative standard errors of prediction (RSEP) were calculated for the calibration, validation and analysed data sets. These errors amounted to 3.2-3.6%, 3.5-3.8% and 4.8-5.7% for the three techniques applied, respectively. The proposed procedures can be used as simple, fast and accurate methods for the quantitative analysis of gluten in flour.


Development of a tetrameric streptavidin mutein with reversible biotin binding capability: engineering a mobile loop as an exit door for biotin.
A novel form of tetrameric streptavidin has been engineered to have reversible biotin binding capability. In wild-type streptavidin, loop(3-4) functions as a lid for the entry and exit of biotin. When biotin is bound, interactions between biotin and key residues in loop(3-4) keep this lid in the closed state. In the engineered mutein, a second biotin exit door is created by changing the amino acid sequence of loop(7-8). This door is mobile even in the presence of the bound biotin and can facilitate the release of biotin from the mutein. Since loop(7-8) is involved in subunit interactions, alteration of this loop in the engineered mutein results in an 11° rotation between the two dimers in reference to wild-type streptavidin. The tetrameric state of the engineered mutein is stabilized by a H127C mutation, which leads to the formation of inter-subunit disulfide bonds. The biotin binding kinetic parameters (k(off) of 4.28×10(-4) s(-1) and K(d) of 1.9×10(-8) M) make this engineered mutein a superb affinity agent for the purification of biotinylated biomolecules. Affinity matrices can be regenerated using gentle procedures, and regenerated matrices can be reused at least ten times without any observable reduction in binding capacity. With the combination of both the engineered mutein and wild-type streptavidin, biotinylated biomolecules can easily be affinity purified to high purity and immobilized to desirable platforms without any leakage concerns. Other potential biotechnological applications, such as development of an automated high-throughput protein purification system, are feasible.


Adult human bone marrow-derived mesenchymal progenitor cells are capable of adhesion-independent survival and expansion.
We show the existence of adult human mesenchymal progenitor cells (hMPCs) that can proliferate, in a cytokine-dependent manner, as individual cells in stirred suspension cultures (SSC) while maintaining their ability to form functional differentiated mesenchymal cell types. Ficolled human bone marrow (BM)-derived cells were grown in SSC (and adherent controls) in the presence and absence of exogenously added cytokines. Phenotypic, gene expression, and functional assays for hematopoietic and nonhematopoietic cell populations were used to kinetically track cell production. Limiting-dilution analysis was used to relate culture-produced cells to input cell populations. Cytokine cocktail influenced total and progenitor cell expansion, as well as the types of cells generated upon plating. Flow cytometric analysis of CD117, CD123, and CD45 expression showed that cytokine supplementation influenced SSC output. The concomitant growth of CD45(+) and CD45(-) cells in the cultures that exhibited the greatest hMPC expansions suggests that the growth of these cells may benefit from interactions with hematopoietic cells. Functional assays demonstrated that the SSC-derived cells (input CFU-O number: 1990+/-377) grown in the presence of SCF+IL-3 resulted, after 21 days, in the generation of a significantly greater number (p<0.05) of bone progenitors (33,700+/-8763 CFU-O) than similarly initiated adherent cultures (214+/-75 CFU-O). RT-PCR analysis confirmed that the SSC-derived cells grown in osteogenic conditions express bone-specific genes (Cbfa1/Runx2, bone sialoprotein, and osteocalcin). Our approach not only provides an alternative strategy to expand adult BM-derived nonhematopoietic progenitor cell numbers in a scalable and controllable bioprocess, but also questions established biological paradigms concerning the properties of connective-tissue stem and progenitor cells.


Anxiety and heart rate in a real-life class test in undergraduates choosing real-time or prerecorded oral presentations.
Most studies on acute stress stem from works conducted under artificial laboratory conditions. Inducing stress for experimental scrutiny is problematic and can be unethical. In this study, a 'research methods' course's curriculum included a demonstration study testing anxiety and heart rate responses to the midterm test. Fifty-four university students (35 males and 19 females) presented a research topic in-person (n = 14) or prerecorded while being present (n = 40). Students selected a test format they could change until the week before the midterm test. The measures were trait anxiety, test anxiety, state anxiety, heart rate (HR), the last two being measured before and after examination, and grades. All students manifested decreased state anxiety and increased HR from before to after the test. Females exhibited higher HR and state anxiety than males. Real-time presentations were associated with higher HRs but not higher state anxiety. Those who changed their planned presentation mode from in-person to prerecorded exhibited higher test anxiety but not trait anxiety than those who presented as planned. Students who presented in-person obtained lower grades than those who prerecorded their presentations. Grades were negatively correlated with state anxiety after the test, but test anxiety did not significantly mediate the grades. Pre-test state anxiety was positively associated with both trait anxiety and test anxiety. The findings suggest that test anxiety is unlikely to affect grades, but test-anxious students need more control over academic evaluation. A choice in test format could be helpful in this regard.


Murine and human T cell factors that induce the differentiation of normal mouse lymphocytes into cytotoxic cells copurify with interleukin 2.
Fetal calf serum (FCS)-specific T promoter cell lines (line 12), clones, or lymphomas produce lymphocyte promoter factors (LPF). These factors are defined as T-cell supernatant activities that induce polyclonal differentiation of normal experimentally unprimed mouse lymphocytes into antibody-forming cells (B-LPF) or into cytotoxic cells (T-LPF). The cytotoxic cells thus induced lysed a broad range of target cells including syngeneic and allogeneic tumour cells and lymphoblasts. We have investigated whether T cell tumours (mouse or human) other than FCS-specific T promoter cell lines (line 12), clones, or lymphomas produce T-LPF activity, and whether T-LPF activity is related to interleukin 2 (IL-2) activity. We found that the EL4 thymoma cells were high producers of T-LPF and IL-2 activity. When EL4 cells and T-LPF+ line 12 lymphomas were cloned, all T-LPF high-producer clones were also high IL-2 producers. In addition, the human Jurkat T tumour cells produced both T-LPF and IL-2 activity which could be detected on both mouse and human lymphocytes. By using biochemical fractionation (size fractionation or chromatofocusing fractionation) and absorption techniques, we could not separate T-LPF and IL-2 activity. Thus, the present data may indicate that the T-LPF and IL-2 activities studied in the present systems are borne by the same molecule(s) (= IL-2?). These results are discussed in relation to current hypotheses on the cellular and molecular requirements for the generation of cytotoxic T cells.


Brain-derived neurotrophic factor selectively enhances allergen-specific IgE production.
We studied the effect of brain-derived neurotrophic factor (BDNF) on in vitro Japanese cedar pollen (JCP)-specific IgE production by mononuclear cells from atopic keratoconjunctivitis patients with JCP allergy. BDNF enhanced JCP-specific IgE production in a dose-dependent fashion in cultures of mononuclear cells stimulated with JCP, and maximal enhancement was achieved at 10 ng/ml. In contrast, BDNF had no effect on JCP-specific IgA or IgG4 production. On the other hand, other neurotrophins, NGF, NT-3, or NGF failed to enhance JCP-specific IgE production. Moreover, anti-BDNF mAb specifically blocked BDNF-induced enhancement of JCP-specific IgE production. Study for cytokine production revealed that BDNF decreased production of Th1 cytokines, IFN-gamma and IL-12, while it had no effect on production of TH2 cytokines, IL-4, IL-10 and IL-13, in cultures of mononuclear cells stimulated with JCP. These results indicate that BDNF relatively skews cytokine pattern toward Th2 type. Collectively, BDNF may increase allergen-specific IgE production, which may in turn aggravate allergic symptoms.


Paroxysmal episodic central thermoregulatory failure.
A 51-year-old man presenting with paroxysmal attacks of unilateral sweating for 1 year was studied. Clinical and laboratory findings made the diagnosis of Shapiro or Harlequin syndrome unlikely. The onset of the sweating "crisis" was immediately followed by a progressive decrease in rectal and skin temperature, lasting for about 2 hours. This indicated that hypothermia was related to an abnormal downward shift of the thermoregulatory set point and a delayed effect of mechanisms blocking heat dissipation.


Studies on Ca(II) binding to gamma-carboxyglutamic acid. Use of thermal decarboxylation to probe metal ion/gamma-carboxyglutamic acid interactions.
The thermal decarboxylation of N-benzyloxycarbonyl-L-gamma-carboxyglutamic acid alpha-methyl ester [Z)-L-Gla-OMe) has been studied. In the presence of increasing amounts of calcium or magnesium ions, lyophilized powders of (Z)-L-Gla-OMe exhibit a corresponding increase in thermal stability. Both magnesium and calcium form relatively tight, thermally stable complexes with (Z)-L-Gla-OMe at high metal ion concentrations. Differences between Ca(II) and Mg(II) binding are noted at low metal ion concentrations, where (Z)-L-Gla-OMe is in excess. Under these conditions, complex formation with Mg(II) apparently favors a 2:1 Gla-magnesium ion complex in which both Gla residues are unstable to thermal decarboxylation. Calcium ion complexes, however, are found to favor a 3:1 Gla-calcium ion complex in which 1 of the 3 Gla residues is thermally stable.


The effect of an iron chelating agent on protoporphyrin IX levels and phototoxicity in topical 5-aminolaevulinic acid photodynamic therapy.
In 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT), the prodrug ALA is endogenously converted to the active sensitizer protoporphyrin IX (PpIX), while further conversion of PpIX to haem requires iron. To explore the potential of the iron chelator desferrioxamine (DFO) to enhance PpIX levels and phototoxicity in ALA-PDT. A series of six doses of 2% ALA solution was iontophoresed into the healthy skin of each ventral forearm of 10 volunteers. One arm was pretreated with 20% DFO in aqueous cream, while the control arm received aqueous cream alone, for 16 h. At 5 h following iontophoresis, skin-surface PpIX fluorescence was measured, following which the forearms were simultaneously irradiated with 100 J cm-2 broadband red light. The phototoxic reaction was assessed at 24 h postirradiation as the minimal phototoxic dose (MPD) and with quantification of erythema. Next, eight patients with two superficial basal cell carcinomas or two plaques of Bowen's disease of similar appearance received 20% ALA topically to one lesion and 20% ALA with 20% DFO to the other, for 3 h. Skin-surface PpIX fluorescence was measured at 5 h, following which lesions were irradiated with 100 J cm-2 broadband red light. In healthy skin, PpIX fluorescence increased with increasing ALA dose at DFO-treated and untreated sites (P < 0.0005); PpIX fluorescence peak values were consistently higher in DFO-treated compared with control sites (P < 0.02). Erythema also correlated with ALA dose (P < 0.0005), but a significant difference between active and control sites occurred only at low ALA dose (P < 0.05). The median MPD appeared lower at the DFO-treated sites, at 6 mC vs. 12 mC (P = 0.06). In contrast, in lesional skin there was no consistent difference in PpIX fluorescence levels between those treated with and without DFO. While iron chelation augmented ALA-PDT phototoxicity in normal skin, this occurred only at low ALA dose. Addition of DFO does not appear to confer additional benefit in ALA-PDT of nonmelanoma skin cancers.


Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion.
Endometrial cancer is the most frequent malignancy of the female genital tract in western countries. Our group has previously characterized the upregulation of the transcription factor ETV5 in endometrial cancer with a specific and significant increase in those tumor stages associated with myometrial invasion. We have shown that ETV5 overexpression in Hec1A endometrial cancer cells induces epithelial to mesenchymal transition resulting in the acquisition of migratory and invasive capabilities. In the present work, we have identified Nidogen 1 (NID1) and Nuclear Protein 1 (NUPR1) as direct transcriptional targets of ETV5 in endometrial cancer cells. Inhibition of NID1 and NUPR1 in ETV5 overexpressing cells reduced cell migration and invasion in vitro and reduced tumor growth and dissemination in an orthotopic endometrial cancer model. Importantly, we confirmed a significant increase of NUPR1 and NID1 protein expression in the invasion front of the tumor compared to their paired superficial zone, concomitant to ETV5 overexpression. Altogether, we conclude that NID1 and NUPR1 are novel targets of ETV5 and are actively cooperating with ETV5 at the invasion front of the tumor in the acquisition of an invasive phenotype to jointly drive endometrial cancer invasion.


Exploring the relevance of localization in anti-drinking and driving PSAs: factors that may influence college students' behaviors.
This article generalizes the results of a qualitative study, which suggested that localization of consequences in PSAs may have a impact on reducing the incidence of drunk driving among college students. The results of the current study suggest that this implication may be true. The results also suggest that frequency of binge drinking, gender, and age are factors that influence perceptions of drunk driving risk, and that PSAs need to take these factors into account in order to be effective.


Roles of histidine charge and cardiolipin in membrane disruption by antimicrobial peptides Gaduscidin-1 and Gaduscidin-2.
Gad-1 and Gad-2 are helical, histidine-rich antimicrobial peptides (AMPs) from paralogous genes in cod. 15N and 2H solid state nuclear magnetic resonance (NMR) were used to characterize their lipid-bound structures and lipid interactions. Gad-1 was found to position in-plane in POPC: POPG bilayers. Gad-1 displayed greater effects than Gad-2 on lipid acyl chain order of POPE: POPG and POPE: POPG: CL bilayers, in keeping with its greater activity against E. coli. The effect of Gad-1 and Gad-2 on lipid bilayer order was only weakly affected by changes in pH, and hence changes in histidine charge. This was somewhat surprising for Gad-2 as this peptide's biological activity has been shown to be greater at low pH and thus the finding may point to the existence of functional interactions with non-lipid components of bacteria. The incorporation of cardiolipin into POPE: POPG bilayers in such a way as to preserve the overall charge of the bilayers did not alter Gad-1's effects on lipid acyl chain order parameters, which report on motions on the 10-5 s timescale. When cardiolipin and Gad-1 were both present, there were subtle changes on membrane dynamics at other timescales.


3-Methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester: an exploration of the C-2 position. Part I.
Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester, a potent and selective mGluR1 non-competitive antagonist, we report here a detailed exploration of the C-2 position of this scaffold with the preparation of differently substituted amides. Great improvement of the pharmacokinetic properties has been achieved through this exercise.


Comparative effects of antithrombitic and antimycotic N-substituted imidazoles on rat hepatic microsomal steroid and xenobiotic hydroxylases in vitro.
N-Substituted imidazoles have been shown to be potent inhibitors of microsomal mixed-function oxidase activities in vitro and in vivo. In the present study the effects of two antithrombitic (dazmegrel and dazoxiben) and four antimycotic (ketoconazole, econazole, miconazole and clotrimazole) imidazoles on microsomal cytochrome P-450-mediated steroid and xenobiotic hydroxylases were studied in vitro. Despite the presence of the N-substituted imidazole moiety, the antithrombitic agents were essentially non-potent as inhibitors of all of the oxidase activities evaluated. In contrast, the antimycotic drugs were potent inhibitory compounds. Binding studies revealed that all six imidazoles elicited type II optical difference spectra and exhibited relatively high affinity for ferricytochrome P-450 in microsomal suspensions (Ks range 0.26-0.73 microM for the antimycotic agents and 6.5 microM and 21 microM for dazmegrel and dazoxiben, respectively). The structural feature that the antithrombitic compounds share is a carboxylate function so that, at physiological pH, less than 1% of the drug would be present in the unionised form. This functionality is absent from the structures of the antimycotic agents which possess much greater hydrophobic character. Even though the antithrombitic imidazoles elicit type II binding interactions of quite high affinity it would appear from this study that significant inhibition potency does not necessarily follow. The present findings also suggest that interesting differences exist between the active site binding regions in the cytochrome P-450 that catalyse thromboxane synthetase activity and those involved in microsomal drug oxidation. Inhibitor hydrophobicity is clearly an important factor in the inhibition of microsomal cytochromes P-450 whereas effective thromboxane synthetase inhibitors may be quite hydrophilic at physiological pH.


Platelet-activating factor-mediated synthesis of prostaglandins in rat Kupffer cells.
Synthesis of prostaglandins was stimulated in rat Kupffer cells upon challenge with platelet-activating factor (PAF). PAF-mediated synthesis of prostaglandins was inhibited by the Ca2+ ion chelator (EGTA), the Ca2+ channel antagonist (nifedipine) and U66985, a structural analogue and antagonist of the biological effects of PAF in other cellular systems. Inhibitors of protein kinase C, staurosporine and polymixin B, did not affect PAF-induced prostaglandin synthesis. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, stimulated synthesis of prostaglandins in Kupffer cells; PAF and PMA exerted additive actions on this process. Both PAF- and PMA-stimulated prostaglandin production was inhibited by TMB-8. PAF-stimulated synthesis of prostaglandins also was inhibited upon treatment of Kupffer cells with pertussis toxin. Cholera toxin, in contrast, stimulated the production of prostaglandins in a concentration-dependent manner; cholera toxin and PAF together had an additive effect. These results suggest that PAF-induced synthesis of prostaglandins is stimulated via a specific receptor coupled to a pertussis toxin-sensitive G-protein, is dependent upon extracellular Ca2+ and is not influenced by protein Kinase C activation. Since PAF and prostaglandins are produced in the liver under conditions such as endotoxemia, PAF-mediated synthesis of these lipid autacoids may be of importance in the regulation of hepatic function during pathophysiological episodes.


A retrospective analysis of the effect of human milk on prevention of necrotizing enterocolitis and postnatal growth.
The objective of this study is to determine whether the use of donor human milk (DHM) in very low birth weight (VLBW, ⩽1500 g) neonates in a large neonatal intensive care unit (NICU) affected the rate of necrotizing enterocolitis (NEC) or impacted growth. This was a retrospective chart review of 550 VLBW neonates following the introduction of DHM as the preferred diet if maternal breast milk (MBM) was not available. Demographics, growth parameters, incidence of NEC or death and days of DHM or MBM were extracted from charts. Compared with infants who received human milk (HM) on fewer than 50% of hospital days, neonates who received HM on ⩾50% of hospital days had equivalent growth outcomes but lower rates of NEC (NEC 3.4 vs 13.5%, P<0.001) and mortality (1.0 vs 4.2%, P=0.017). Growth and NEC rates were inversely correlated with the duration of exposure to HM. HM should always be the diet of choice in preterm infants. DHM is a safe alternative, if MBM is not available. Although the use of HM is associated with lower rates of NEC, growth rates were significantly lower in infants with significant HM intake. The decline in growth rates following the introduction of DHM should draw attention to optimize fortification of all HM feedings.


Transverse relaxation optimized HCN experiment for nucleic acids: combining the advantages of TROSY and MQ spin evolution.
A three-dimensional MQ-TROSY-HCN pulse sequence is presented which provides intra-base and sugar-to-base correlations for 13C, 15N labeled nucleic acids (RNA, DNA). The experiment simultaneously exploits the favorable relaxation properties of 1H-13C multiple quantum coherence for sugar carbons and of 13C TROSY-type spin evolution for base carbons. MQ-TROSY-HCN thus combines the advantages of MQ-HCN for sugar-to-base and TROSY-HCN for intra-base correlations in a single experiment. In addition, two slightly different implementations of the MQ-TROSY-HCN experiment ensure optimal performance for small and larger oligonucleotides, respectively. The advantages of the MQ-TROSY-HCN experiment compared to the best previous implementations of HCN are demonstrated for a 33 nucleotide RNA aptamer.


The assessment of the spatial and seasonal variability of chromophoric dissolved organic matter in the Southern Yellow Sea and the East China Sea.
Samples of chromophoric dissolved organic matter (CDOM) from the Southern Yellow Sea (SYS) and the East China Sea (ECS) were evaluated by fluorescent Excitation Emission Matrix (EEM) combined with Parallel Factorial Analysis (PARAFAC). Three terrestrial humic-like components (C1, C2 and C3) and one autochthonous protein-like component (C4) were identified. As for seasonal variations, CDOM displayed the following order on the whole: summer>spring>autumn. The C1, C2 and C3 components were mainly dominated by terrestrial inputs and their spatial distributions and temporal variations also can be influenced by primary productivity of phytoplankton, microbial activities and photobleaching. C4 was produced by phytoplankton and microorganisms and consumed by marine bacteria, and besides its distribution was attributed to the influence of riverine inputs. Terrestrial inputs were the dominant sources of CDOM in the SYS and ECS.


Changes in the prevalence of nonnutritive sucking patterns in the first 8 years of life.
The purposes of the study were to determine prospectively the duration of nonnutritive sucking behaviors of children between 1 and 8 years of age and the effect of persistent habits on selected occlusal characteristics in the late deciduous dentition. Sucking behavior data were initially collected from 797 children who were followed longitudinally from birth; the data came from periodic questionnaires completed by the parents. In addition, study models were obtained for 372 children at 4 to 5 years of age and assessed for posterior crossbite, anterior open bite, and overjet. The subjects were grouped according to the duration and type of habit (pacifier or digit, for less than 12 months or more than 48 months). Children with nonnutritive sucking of less than 12 months were further grouped according to the duration of breast-feeding. The McNemar nonparametric test was used to compare the changes in the incidence and effect of the habits with time. There was a significant (P = .001) decrease in the incidence of pacifier habits between 1 and 5 years of age, from 40% to 1%. There was a significant (P = .01) decrease in the incidence of digit habits between 1 and 4 years of age, from 31% to 12%. Between 4 and 7 years of age, the decrease in the incidence reached a plateau--ie, the decrease continued but at a slower rate. Between 7 and 8 years of age, there was an additional significant (P = .008) decrease in the incidence of digit habits, but 4% of the children were, to various extents, still sucking fingers. Children who had pacifier or digit habits lasting less than 12 months did not have significantly different occlusal characteristics than children who were breast-fed for 6 to 12 months. Prolonged pacifier and digit habits caused significant changes in the occlusal characteristics in the late deciduous dentition, and the effects of pacifier habits were different from those of digit sucking. To intercept the development of crossbites and functional shifts, the developing occlusion should be observed in the deciduous dentition in children with prolonged digit or pacifier habits. The transverse occlusal relationship, particularly in pacifier-sucking children, should be evaluated between 2 and 3 years of age. If there are interfering contacts of the deciduous canines, the parents should be instructed to reduce pacifier-sucking time, and appropriate treatment should be rendered, if required.


Hypothalamic amenorrhea: clinical perspectives, pathophysiology, and management.
The development of functional hypothalamic amenorrhea reflects an individual's response to environmental stressors and life-style variables. In this disorder there are no detectable anatomic abnormalities with respect to the hypothalamic-pituitary-ovarian-endometrial axis. Current evidence suggests that the common underlying defect is a decrease in the activity of the hypothalamic gonadotropin-releasing hormone pulse generator. Of the neuroendocrine factors that appear to regulate gonadotropin-releasing hormone activity, the opiate and dopamine neuronal systems have been implicated as factors that are responsible in part for the decreased secretion of gonadotropin-releasing hormone. Because of the functional nature of this disorder, reactivation of the hypothalamic-pituitary unit would be expected to take place in most women after accommodation to environmental stressors or modification in life-style. For women with persistent anovulation, treatment with estrogen-replacement therapy should be offered. In those desiring fertility, ovulation induction with pulsatile gonadotropin-releasing hormone would be the most effective modality.


Molecular dynamics simulations of RDX and RDX-based plastic-bonded explosives.
Molecular dynamics simulations have been performed to investigate well-known energetic material cyclotrimethylene trinitramine (RDX) crystal and RDX-based plastic-bonded explosives (PBXs) with four typical fluorine-polymers, polyvinylidenedifluoride (PVDF), polychlorotri-fluoroethylene (PCTFE), fluorine rubber (F(2311)), and fluorine resin (F(2314)). The elastic coefficients, mechanical properties, binding energies, and detonation performances are obtained for the RDX crystal and RDX-based PBXs. The results indicate that the mechanical properties of RDX can be effectively improved by blending with a small amount of fluorine polymers and the overall effect of fluorine polymers on the mechanical properties of the PBXs along three crystalline surfaces is (001)>(010) approximately (100) and PVDF is regarded to best improve the mechanical properties of the PBXs on three surfaces. The order of the improvement in the ductibility made by the fluorine polymers on different surfaces is (001) approximately (010)>(100). The average binding energies between different RDX crystalline surfaces and different polymer binders are obtained, and the sequence of the binding energies of the PBXs with the four fluorine polymers on the three different surfaces is varied. Among the polymer binders, PVDF is considered as best one for RDX-based PBXs. The detonation performances of the PBXs decrease in comparison with the pure crystal but are superior to those of TNT.


Prevalence and clinical correlates of dementia among COVID-19-related deaths in Italy.
We aimed at exploring the proportion of patients dying with COVID-19 and concomitant dementia in Italy, as well as their clinical characteristics and trajectories of care. The proportion of COVID-19-related deaths occurring in people with dementia and the clinical characteristics of deceased individuals according to their dementia status were explored by considering the medical charts of a representative sample of patients deceased in Italian hospitals (n = 2621). A total of 415 individuals with dementia were identified in the study population, accounting for 15.8% of overall COVID-19-related deaths. Patients with dementia less frequently presented with cough, had lower chance of receiving supportive therapies and intensive care approaches, and showed a faster clinical worsening as compared with individuals with intact cognition. Dementia confers a relevant risk of adverse outcomes in case of SARS-CoV-2 infection and influences the clinical presentation, course and management of affected individuals.


What next? A Bayesian hierarchical modeling re-examination of treatments for adolescents with selective serotonin reuptake inhibitor-resistant depression.
Psychiatrists frequently struggle with how to sequence treatment for depressed adolescents who do not respond to an adequate trial of a selective serotonin reuptake inhibitor (SSRI). This study leveraged recent statistical and computational advances to create Bayesian hierarchal models (BHMs) of response in the treatment of SSRI-resistant depression in adolescents study to inform treatment planning. BHMs of individual treatment trajectories were developed and estimated using Hamiltonian Monte Carlo no u-turn sampling. From the Monte Carlo pseudorandom sample, 95% credible intervals, means, posterior tail probabilities, and so forth, were determined. Then, for the random effects model, posterior tail probabilities were used to create Bayesian two-tailed p values to evaluate the null hypotheses: no difference in efficacy between SSRIs and venlafaxine. The robustness of the results was examined using the fixed effects model of treatment comparisons. In patients not receiving cognitive behavioral therapy (CBT; n = 168), SSRIs produced greater and faster improvement in depressive symptoms compared to venlafaxine (p = .015). No differences in response or trajectory of response for symptoms of anxiety were detected between SSRIs and venlafaxine (p = .168). For patients receiving CBT (n = 162), SSRIs and venlafaxine produced similar improvements in symptoms of anxiety and depression. Findings from this novel computational approach suggest that a second trial of an SSRI is warranted for depressed adolescents who fail to respond to initial SSRI treatment.


Young Women's Experiences Obtaining Judicial Bypass for Abortion in Texas.
Like many states, Texas requires parental consent for adolescents under 18 to access abortion care. Adolescents who cannot obtain parental consent can try to obtain a judicial bypass of parental consent through the court system. Little is known about adolescents' experiences with the judicial bypass process. Working with Jane's Due Process, an organization providing legal representation for adolescents, we explored adolescents' experiences with the judicial bypass process. We conducted phone interviews with 20 adolescents, 16-19 years old in Texas between September and December 2016 about their experiences trying to obtain a judicial bypass. Data analysis included inductive and deductive coding based on theories about engaging with the court system and stigma regarding abortion and adolescent sexuality. In addition to unpredictability and logistic burdens such as finding time away from school and arranging transportation, participants described the bypass process as "intimidating" and "scary" and described judges and guardians-ad-litem who shamed them, "preached" at them, and discredited evidence of their maturity. Data suggest adolescents internalize stigma and trauma they experienced through rationalizing both the need for the bypass process and disrespectful treatment by authority figures. We found the bypass process functions as a form of punishment and allows state actors to humiliate adolescents for their personal decisions. The bypass process was implemented to protect adolescents from alleged negative emotional consequences of abortion, yet our results suggest the bypass process itself causes emotional harm through unpredictability and humiliation. Despite participants' resilience, the process may have negative consequences for adolescent health.


A case of nosocomial transmission of Crimean-Congo hemorrhagic fever from patient to patient.
Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick-borne viral disease, with the potential for human to human transmission. Infection often has severe hemorrhagic manifestations and considerable mortality. Healthcare workers (HCWs) caring for patients with CCHF constitute a major risk group for infection. Although nosocomial transmission from patients to HCWs accounts for a significant proportion of CCHF cases and outbreaks worldwide, transmission of CCHF from patient to patient has not previously been reported. A case of nosocomial transmission of CCHF from patient to patient at a hospital is described.


Planktonic microbial community and biological metabolism in a subtropical drinking water river-reservoir system.
To understand the dynamics of planktonic microbial community and its metabolism processes in subtropical drinking water river-reservoir system with lower man-made pollution loading, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate spatial-temporal characteristics of community profile and functional genes involved in biological metabolism, and to analyze the influence of environmental factors. The results indicated that Proteobacteria and Actinobacteria were the most diverse phyla with proportion ranges of 9%-80% in target system, and carbohydrate metabolism (5.76-7.12 × 10-2), amino acid metabolism (5.78-7.21 × 10-2) and energy metabolism (4.07-5.17 × 10-2) were found to be the dominant pathways of biological metabolism. Although there were variations in biological properties both spatially and temporally, seasonal variation had a greater influence on microbial community and biological metabolism, than locational differences. Regarding the role of environmental factors, this study revealed that microbial diversity could be affected by multiple abiotic factors, with total organic carbon, total phosphorus and temperature being more influential (absolute value of standardized regression weights >2.13). Stochastic processes dominated the microbial community assembly (R2 of neutral community model = 0.645), while niche-based processes differences represented by nutrients, temperature and pH level played secondary roles (R > 0.388, P < 0.01). Notably, the synergistic influences among the environmental factors accounted for the higher percentages of community variation (maximum proportion up to 17.6%). Additionally, pH level, temperature, and concentrations of dissolved oxygen, carbon and nitrogen were found to be the significant factors affecting carbon metabolism pathways (P < 0.05), yet only total organic carbon significantly affected on nitrogen transformation (P < 0.05). In summary, the microbial profile in reservoir is not completely dominated by that in feeding river, and planktonic microbial community and its metabolism in subtropical drinking water river-reservoir system are shaped by multiple abiotic and biotic factors with underlying interactions.


Spatiotemporal patterns of Gem expression after rat spinal cord injury.
Gem is an atypical protein of the Ras superfamily that plays a role in regulating voltage-gated Ca(2+) channels and cytoskeletal reorganization. To elucidate the certain expression and biological function in central nervous system (CNS), we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis showed a marked up-regulation of Gem after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of Gem in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen (PCNA) and phenotype-specific markers indicated increases of Gem expression in proliferating microglia and astrocytes. Our data suggest that Gem may be implicated in the proliferation of microglia and astrocytes after SCI.


Characterization of the novel HLA-B*44:544N allele by sequencing-based typing.
HLA-B*44:544N differs from HLA-B*44:02:01:01 by one nucleotide substitution in codon 147 in exon 3.


Optical biosensor analysis in studying herpes simplex virus glycoprotein D binding to target nectin1 receptor.
Studies on molecular interactions between cellular receptors of herpes simplex virus (HSV) and the viral glycoproteins showing receptor-binding activity are of great relevance for understanding the molecular basis of virus entry. Information on such interactions further provides the basis for a rational design of antiviral drugs. A variety of biochemical and biophysical methodologies are used for determining the binding parameters of interacting biomolecules. Most of them require relatively high amounts of the analyzed compounds, or the use of labeled target molecules. Here, we report the study of the binding of two recombinant forms of HSV glycoprotein D, gD(Delta 290-299t) and gD(305t), and a recombinant form of the human cellular receptor for HSV, nectin1-Fc, by using an optical biosensor (IAsys Plus, Affinity Sensors, UK). This device detects and quantifies the changes in refractive index in the vicinity of the surface of sensor chips to which ligands are immobilized. The changes in the refractive index are proportional to the change in the absorbed mass, thus the analysis allows the monitoring of the interaction process in real-time and the determination of the binding parameters. HSV cellular receptor has been immobilized on the surface of the biosensor cuvette, bearing a carboxymethyl dextran layer. The immobilized receptor cuvette was then used for the binding experiments of the two glycoproteins. A significant difference in their dissociation constants was determined, showing for the gD(Delta 290-299t) protein a much higher affinity (K(D), 2.8 x 10(-7) M) with respect to gD(305t) (K(D), 2.8 x 10(-6) M). The active ligand concentration decreased on time, however the binding properties of the immobilized receptor were maintained over 5 weeks.


Visual acuity testing in diabetic subjects: the decimal progression chart versus the Freiburg visual acuity test.
To study reproducibility and biological variation of visual acuity in diabetic maculopathy, using two different visual acuity tests, the decimal progression chart and the Freiburg visual acuity test. Twenty-two eyes in 11 diabetic subjects were examined several times within a 12-month period using both visual acuity tests. The most commonly used visual acuity test in Denmark (the decimal progression chart) was compared to the Freiburg visual acuity test (automated testing) in a paired study. Correlation analysis revealed agreement between the two methods (r(2)=0.79; slope=0.82; y-axis intercept=0.01). The mean visual acuity was found to be 15% higher (P<0.0001) with the decimal progression chart than with the Freiburg visual acuity test. The reproducibility was the same in both tests (coefficient of variation: 12% for each test); however, the variation within the 12-month examination period differed significantly. The coefficient of variation was 17% using the decimal progression chart, 35% with the Freiburg visual acuity test. The reproducibility of the two visual acuity tests is comparable under optimal testing conditions in diabetic subjects with macular oedema. However, it appears that the Freiburg visual acuity test is significantly better for detection of biological variation.


Peanut lectin stimulates proliferation in colonic explants from patients with inflammatory bowel disease and colon polyps.
The TF antigen (galactose-beta 1,3-N-acetylgalactosamine alpha) is overexpressed in malignant and premalignant colonic epithelium. Previous studies have shown that peanut lectin (PNA), which binds TF, is mitogenic for normal human colonic epithelium. This study aimed to determine its effect on abnormal colonic epithelium. Crypt cell proliferation rate (CCPR) was measured using vincristine arrest and mucus synthesis by incorporation of radiolabeled N-acetyl glucosamine in colonoscopic biopsy specimens cultured with and without PNA. Unstimulated CCPR was greater in patients with ulcerative colitis than in patients with histologically normal colon. PNA (25 micrograms/mL) produced a 25% average increase in CCPR in tissues from patients with ulcerative colitis, Crohn's disease, and colonic polyps. In ulcerative colitic biopsy specimens incubated with PNA, CCPR increased to more than double that of unstimulated normal colonic epithelium. In controls, the response to PNA was greater when adjacent specimens were positive for PNA (avidin-biotin) histochemistry than when they were negative. Mucus synthesis was increased by an average 75% over 24 hours by PNA. Increased TF expression by premalignant epithelia may allow stimulation of proliferation by dietary galactose N-acetylgalactosamine-binding lectins. If the hyperplasia-dysplasia cancer hypothesis is correct, this could explain the increased colon cancer risk in ulcerative colitis.


COVID-19 in a patient with end-stage renal disease on chronic in-center hemodialysis after evidence of SARS-CoV-2 IgG antibodies. Reinfection or inaccuracy of antibody testing.
A patient with end-stage renal disease on hemodialysis with a previous positive SARS-CoV-2 IgG antibody was diagnosed with severe COVID-19. Issues regarding reinfection, the potential lack of antibody protection after asymptomatic infection, the possibility of antibody dependent enhancement and careful interpretation of antibody test results are discussed.


Unilateral renal artery revascularization can salvage renal function and terminate dialysis in selected patients with uremia.
Revascularization of renal arteries to salvage glomerular function in patients with chronic renal failure is performed infrequently. However, during the past 12 months we have encountered three patients over 60 years of age known to have chronic renal failure who were on dialysis for 2 weeks, 3 weeks, and 2 months, respectively. All three patients were hypertensive, requiring between four and five antihypertensive medications. One patient was ventilator dependent in intractable cardiac failure with pulmonary artery systolic pressures ranging from 60 to 70 mm Hg. Standard biplanar arteriography revealed occlusion of the left renal artery with distal reconstitution in two patients and a 99% stenosis of the right renal artery in the remaining patient. The contralateral renal artery was totally occluded in two patients and diffusely stenotic in one. The recipient kidneys measured 8, 10, and 11 cm in length. Kidney function was assessed by renal scintigraphy and creatinine clearance. Two splenorenal bypasses and one hepatorenal bypass with 6 mm polytetrafluoroethylene graft were performed successfully. After surgery, renal function improved in all patients with two of three patients resuming normal function as evidenced by reduction of serum creatinine levels to 0.9 and 1.3 mg/dl. The third patient recovered to have a creatinine level of 3.2 mg/dl. All patients were discharged home within 1 month with a daily urine output greater than 1500 ml. At discharge, each patient required only two antihypertensive medications to control blood pressure. Duplex scanning 3, 6, and 12 months after surgery confirmed patency of all reconstructions.(ABSTRACT TRUNCATED AT 250 WORDS)


Endocrine manifestations of Erdheim-Chester disease (a distinct form of histiocytosis).
Erdheim-Chester disease (ECD) is a disorder of unclear aetiology, characterized by exuberant histiocyte proliferation and a variable clinical course. We report the case of a woman with multi-organ involvement secondary to ECD. Central diabetes insipidus (CDI), hyperprolactinaemia, gonadotropin insufficiency and decreased insulin-like growth factor I levels were present, suggesting hypothalamic-pituitary dysfunction. The high-intensity signal of the posterior pituitary on T1-weighted images was absent on magnetic resonance imaging, but no sellar mass lesions or stalk thickening were apparent. Additionally, our patient had bilateral adrenal enlargement. Even though ECD is a rare cause of neuroendocrine dysfunction or adrenal enlargement, it should be considered in patients with these disorders in the setting of multiorgan disease.


[Research advance on mechanism and application of HATs and HDACs in epithelial-mesenchymal transition of lung cancer].
Lung cancer is one of the most common diseases that endanger health and life of people domestically. A number of recurrence and death of lung cancer originated from metastasis. As a key step in metastasis of lung cancer, epithelial to mesenchymal transition involved down-regulation of E-cadherin, as well as regulated by EMT transcription factors. HATs and HDACs is a protein family that catalyzes acetylation and deacetylation of histones. Not only they have vital functions in tumor pathogenesis, but also participate in the EMT of lung cancer. HATs and HDACs interact with certain EMT transcription factors. Moreover, the function of these EMT transcription factors may be regulated by acetylation, which has influence on EMT program in lung cancer. Therefore, this review introduces the event of HATs and HDACs function in EMT of lung cancer, and investigate the molecular mechanism of their interaction. Then, the potential of HDAC inhibitor utilization in the inhibition of EMT and lung cancer therapy were discussed, as to pave the way for the related basic research and clinical practice.


The Burden of Irritable Bowel Syndrome in Medical and Nurse Italian University Student Population: The VANVITELLI-IBS Survey.
The increased prevalence of irritable bowel syndrome (IBS) among medical and nursing students is a global challenge. Unfortunately, data on the Italian medical and nurse student population are scarce. Therefore, this study was designed to assess the prevalence of IBS in this setting and to evaluate the demographic, university, Mediterranean diet adherence, and anxiety factors associated with its increased presence. To assess the prevalence of IBS, anxiety levels, and adherence to the Mediterranean diet in medical and nursing university students. An anonymous online questionnaire was sent to participants. Several demographic and educational variables were assayed, and the presence of symptoms associated with the definition of IBS (according to Rome IV criteria). In addition, anxiety levels and adherence to the Mediterranean diet were also assessed. Of 161 students, 21.11% met the Rome IV criteria for IBS. Some subgroups, the out-ofcourse students or no scholarship recipients, were found to have a higher percentage of IBS (p < 0.05). Being out-of-course was shown to be associated with an increased and unreported risk of presenting IBS (OR: 8.403, p < 0.001). Levels of anxiety and adherence to the Mediterranean diet were significantly worse in the IBS group (p < 0.01). Adherence to the Mediterranean diet was associated with a reduced risk of presenting IBS in our setting (OR 0.258, p = 0.002). Our sample of Italian medical and nursing students recorded a non-negligible percentage of IBS. Therefore, screening and awareness campaigns could be suggested.


Covalent modifications of aminophospholipids by 4-hydroxynonenal.
Lipid oxidation is implicated in a wide range of pathophysiological disorders, which leads to reactive compounds such as aldehydes. Among them 4-hydroxynonenal (4-HNE) reacts strongly with the NH2 groups of amino acids and forms mainly Michael adducts and minor Schiff-base adducts. Such reactions occur also with compounds containing thiol groups. No data are available describing 4-HNE interactions with amino-phospholipids. To investigate such a possibility, 4-HNE was incubated with either phosphatidylethanolamine (PE) or phosphatidylserine (PS) in an aqueous-organic biphasic system and the resulting products were identified by liquid chromatography-mass spectrometry (LC-MS). Our study points out the potential capacity of 4-HNE to react with phospholipids containing amino groups and particularly PE. The main resulting compounds found were a Michael adduct plus a minor Schiff base adduct, which was partly cyclized as a pyrrole derivative via a loss of water. Its stabilization as a pyrrole derivative allows to differentiate 4-HNE from the other aldehydes generated via lipid oxidation (e.g., malondialdehyde, 2-nonenal) that lack the 4-hydroxyl group. Their formation seems not to be affected when the pH varies from 6.5 to 8.5. Surprisingly, PS reacted poorly producing only a small amount of Michael adduct, the Schiff-base adduct being nondetectable. We conclude that such adducts, if they are formed in cell membranes, could alter the phospholipase-dependent cell signaling.


Biodegradable magnesium fuel-based Janus micromotors with surfactant induced motion direction reversal.
The speed and motion directionality of bubble-propelled micromotors is dependent on bubble lifetime, bubble formation frequency and bubble stabilization. Absence and presence of bubble stabilizing agents should significantly influence speed and propulsion pattern of a micromotor, especially for fast-diffusing molecules like hydrogen. This study demonstrates a fully biodegradable Janus structured micromotor, propelled by hydrogen bubbles generated by the chemical reaction between hydrochloric acid and magnesium. Six different concentrations of hydrochloric acid and five different concentrations of the surfactant Triton X-100 were tested, which also cover the critical micelle concentration at a pH corresponding to an empty stomach. The Janus micromotor reverses its propulsion direction depending on the availability and concentration of a surfactant. Upon surfactant-free condition, the Janus micromotor is propelled by bubble cavitation, causing the micromotor to be pulled at high speed for short time intervals into the direction of the imploding bubble and thus backwards. In case of available surfactant above the critical micelle concentration, the Janus micromotor is pushed forward by the generated bubbles, which emerge at high frequency and form a bubble trail. The finding of the propulsion direction reversal effect demonstrates the importance to investigate the motion properties of artificial micromotors in a variety of different environments prior to application, especially with surfactants, since biological media often contain large amounts of surface-active components.


Lysing of fresh human tumor by a cytotoxic factor derived from autologous large granular lymphocytes independently of other known cytokines.
During interaction with autologous tumor cells large granular lymphocytes (LGL) of cancer patients released a soluble cytotoxic factor, termed LGL-derived cytotoxic factor, which mediated lysing of autologous fresh tumor cells. The cytotoxic factor was compared with purified human recombinant cytotoxic cytokines, including tumor necrosis factor (TNF), lymphotoxin (LT), interferon (IFN) alpha, IFN gamma, interleukin-1 alpha (IL-1 alpha) and IL-2. The LGL cytotoxic factor exhibited cytotoxicity against autologous and allogeneic fresh human tumor cells in an 18-h 51Cr-release assay, while these target cells were resistant to lysing by any of the recombinant cytokines. Mixtures of recombinant(r) TNF, rLT, rIFN alpha, rIFN gamma, rIL-1 alpha and rIL-2 were still unable to produce cytotoxic effects on fresh human tumor cells. Treatment with monoclonal and polyclonal antibodies directed against rTNF, rLT, rIFN alpha, rIFN gamma, or rIL-1 alpha did not inhibit the cytotoxic activity of LGL-derived cytotoxic factor against fresh human tumor cells. Even a mixture of all the antibodies was incapable of blocking the cytolytic activity of the factor to fresh human tumor cells. Furthermore, intact LGL-mediated lysing of autologous tumor cells was not inhibited by any of the antibodies. These results may indicate that a cytotoxic factor produced by LGL in response to autologous tumor cells mediates lysing of fresh human tumor cells independently of TNF, LT, IFN, IL-1 and IL-2.


Discovery of piperidin-4-yl-aminopyrimidine derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
A novel series of piperidin-4-yl-aminopyrimidine derivatives were designed fusing the pharmacophore templates of etravirine-VRX-480773 hybrids our group previously described and piperidine-linked aminopyrimidines. Most compounds displayed significantly improved activity against wild-type HIV-1 with EC50 values in single-digit nanomolar concentrations compared to etravirine-VRX-480773 hybrids. Selected compounds were also evaluated for activity against reverse transcriptase, and had lower IC50 values than that of nevirapine. The improved potency observed in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits reverse transcriptase, and represents a remarkable step forward in the development of AIDS therapeutics.


Modelling of ultrasonic assisted osmotic dehydration of cape gooseberry using adaptive neuro-fuzzy inference system (ANFIS).
In the present investigation, the cape gooseberry (Physalis peruviana L.) was preserved by the application of osmotic dehydration (sugar solution) with ultrasonication. The experiments were planned based on central composite circumscribed design with four independent variables and four dependent variables, which yielded 30 experimental runs. The four independent variables used were ultrasonication power (XP) with a range of 100-500 W, immersion time (XT) in the range of 30-55 min, solvent concentration (XC) of 45-65 % and solid to solvent ratio (XS) with range 1:6-1:14 w/w. The effect of these process parameters on the responses weight loss (YW), solid gain (YS), change in color (YC) and water activity (YA) of ultrasound assisted osmotic dehydration (UOD) cape gooseberry was studied by using response surface methodology (RSM) and adaptive neuro-fuzzy inference system (ANFIS). The second order polynomial equation successfully modeled the data with an average coefficient of determination (R2) was found to be 0.964 for RSM. While for the ANFIS modeling, Gaussian type membership function (MF) and linear type MF was used for the input and output, respectively. The ANFIS model formed after 500 epochs and trained by hybrid model was found to have average R2 value of 0.998. On comparing the R2 value the ANFIS model found to be superior over RSM in predicting the responses of the UOD cape gooseberry process. So, the ANFIS was integrated with a genetic algorithm (GA) for optimization with the aim of maximum YW and minimum YS, YC and YA. Depending on the higher fitness value of 3.4, the integrated ANFIS-GA picked the ideal combination of independent variables and was found to be XP of 282.434 W, XT of 50.280 min, XC of 55.836 % and XS of 9.250 w/w. The predicted and experimental values of response at optimum condition predicted by integrated ANN-GA were in close agreement, which was evident by the relative deviation less than 7%.


The impact of social exclusion vs. inclusion on subjective and hormonal reactions in females and males.
The experience of social exclusion represents an extremely aversive and threatening situation in daily life. The present study examined the impact of social exclusion compared to inclusion on steroid hormone concentrations as well as on subjective affect ratings. Eighty subjects (40 females) participated in two independent behavioral experiments. They engaged in a computerized ball tossing game in which they ostensibly played with two other players who deliberately excluded or included them, respectively. Hormone samples as well as mood ratings were taken before and after the game. Social exclusion led to a decrease in positive mood ratings and increased anger ratings. In contrast, social inclusion did not affect positive mood ratings, but decreased sadness ratings. Both conditions did not affect cortisol levels. Testosterone significantly decreased after being excluded in both genders, and increased after inclusion, but only in males. Interestingly, progesterone showed an increase after both conditions only in females. Our results suggest that social exclusion does not trigger a classical stress response but gender-specific changes in sex hormone levels. The testosterone decrease after being excluded in both genders, as well as the increase after inclusion in males can be interpreted within the framework of the biosocial status hypothesis. The progesterone increase might reflect a generalized affiliative response during social interaction in females.


Integrated transcriptome and metabolome provide insight into flavonoid variation in goji berries (Lycium barbarum L.) from different areas in China.
Goji berries (Lycium barbarum L.) were rich in flavonoids, showing high nutritional and medicinal value. However, a thorough evaluation and comparison of the flavonoids in goji berries from various regions and the possible biological regulation pathways with differences are scanty. Here, we investigated the flavonoid metabolites and gene expression levels of goji berries from three major production areas in China using transcriptomics sequencing and metabolomics. The total flavonoid content and total polyphenol content of goji berry in Ningxia (57.87 μg/g and 183.41 μg/g, respectively) were higher than in Qinghai (50.77 μg/g and 156.81 μg/g) and Gansu (47.86 μg/g and 111.17 μg/g). We identified the 105 differentially accumulated flavonoids (DAFs) and 1858 differentially expressed genes (DEGs) from the goji berries in three habitats. Interestingly, gossypetin-3-O-rutinoside and isorhamnetin were significantly expressed between Ningxia and Qinghai berries. The chalcone isomerase (CHI), chalcone synthase (CHS), and flavonol synthase (FLS) genes also played key roles in the regulation of flavonoid synthesis. In addition, MYB1 positively regulated the expression of quercetin-3-O-glucoside, quercetin-7-O-glucoside and isohyperoside. As a result, we speculated that CHI, CHS, FLS genes, and related transcription factors jointly controlled the variation of flavone accumulation in goji berries. These findings may provide a new perspective for understanding the accumulation and molecular mechanisms of goji flavonoids.


Endometrial polyps in 2 African pygmy hedgehogs.
Reports of spontaneously occurring endometrial polyps in animals are rare and have only involved a few species. This report is intended to advise veterinarians that older African pygmy hedgehogs may develop endometrial polyps and that these lesions can be a cause of bloody vaginal discharge, sometimes interpreted as hematuria.


Subtalar joint position during gastrocnemius stretching and ankle dorsiflexion range of motion.
Gastrocnemius stretching exercises often are prescribed as part of the treatment program for patients with overuse injuries associated with limited ankle dorsiflexion. However, little is known about how the position of the subtalar joint during gastrocnemius stretching affects ankle dorsiflexion range of motion (ROM). To determine the effect of subtalar joint position during gastrocnemius stretching on ankle dorsiflexion ROM. This study was a 3-way mixed-model design. The 3 factors were subtalar joint position (supinated, pronated), lower extremity (experimental, control), and time (pretest, posttest). Lower extremity and time were the repeated measures. University research laboratory. Thirty-three healthy volunteers (29 women, 4 men). Participants performed a gastrocnemius stretching exercise 2 times daily for 3 weeks with the subtalar joint of the randomly assigned experimental side (dominant or nondominant) in the randomly assigned position (supination or pronation). The contralateral lower extremity served as the control. Before and after the 3-week gastrocnemius stretching program, we used goniometers to measure ankle dorsiflexion ROM in weight-bearing and non-weight-bearing positions with the subtalar joint positioned in anatomic 0 degrees . Ankle dorsiflexion ROM measured in weight-bearing and non-weight-bearing positions increased after the gastrocnemius stretching program (P = .034 and .003, respectively), but the increase in ROM did not differ based on subtalar joint position (P = .775 and .831, respectively). Subtalar joint position did not appear to influence gains in ankle dorsiflexion ROM after a gastrocnemius stretching program in healthy volunteers.


Randomized clinical trial comparing primary closure with the Limberg flap in the treatment of primary sacrococcygeal pilonidal disease.
The purpose of the study was to compare the outcome of excision and primary closure with that of rhomboid excision and the Limberg flap procedure in patients with primary sacrococcygeal pilonidal disease (SPD). Two hundred consecutive patients with SPD were randomly allocated to undergo either excision and primary closure (group 1, n = 100) or rhomboid excision and the Limberg flap procedure (group 2, n = 100). Duration of operation, postoperative pain, time to first mobilization, length of hospital stay, postoperative complications, time to resumption of work, recurrence and time to recurrence were recorded for all patients. : Duration of operation was longer in group 2 than in group 1 (P = 0.001). However, postoperative pain was less (P < 0.001), mobilization earlier (P < 0.001), duration of hospital stay shorter (P < 0.001), time to resumption of work shorter (P < 0.001) and postoperative complications fewer (P < 0.001) in group 2. During a median follow-up of 28 months, no recurrence was detected in patients in group 2 versus 11 patients in group 1 (P = 0.001). Because of its low complication rate and acceptable long-term results, rhomboid excision and the Limberg flap procedure is preferable to simple excision and primary closure in the treatment of SPD.


In vitro pharmacological purging of human bone marrow is enhanced by the use of lonidamine.
Lonidamine (LND), previously reported as a useful antitumor substance in combination with physical or chemical agents, has been studied for its capacity in increasing pharmacological elimination in vitro of residual tumor cells from human bone marrow. Different drugs were tested in association with LND against mixtures of human bone marrow and a tumor cell line, clonogenic human leukemic blast progenitors, and normal human bone marrow precursors. The results demonstrated that LND increased the efficacy of anthracycline derivatives (Adriamycin, Mitoxantrone) both on the tumor cell line and on the leukemic blast progenitors, while VP-16 or ASTA-Z 7654 was not affected by the same substance. The toxicity on normal stem cells reflected that of each drug and was not modified by the addition of LND. While a consistent dose-dependent CFU-GM reduction was observed immediately after treatment with the different drugs, a complete recovery was reached after 7 and 14 days of long-term marrow cultures. Because of the low toxicity and the efficacy demonstrated in association with certain agents in increasing tumor cell elimination in vitro, LND could play an important role in in vitro purging prior to autologous bone marrow transplantation.


Modification of the prolonged mechanical ventilation prognostic model score to predict short-term and 1-year mortalities.
We aimed to validate the use of the Prolonged Mechanical Ventilation Prognostic Model (ProVent) score in medically ill patients with co-morbidities and to modify the score to improve the prediction power of 1-year mortality. We conducted a retrospective study of all patients who required at least 14 days of mechanical ventilation (MV) and established two groups (14-20 and ≥21 days of MV) based on the MV duration. We performed external validation of the present ProVent Model in our patients on Day 14 (or Day 21 for the ≥21-day MV group) of MV, and established the extended ProVent model, while considering the albumin and bilirubin levels and co-morbidities (chronic obstructive pulmonary disease and cancer). A total of 1288 patients (666 and 622 with 14-20 and ≥21 days of MV, respectively) with at least 14 days of MV were enrolled. The 1-year mortality was 79.9% and 78.7% in the ≥21- and 14-20-day groups, respectively. Most of the observed mortality rates in all groups were within the 95% CI of predicted mortality as per the ProVent Model, except for the ProVent scores of 0 and 5. In the ProVent model, the area under the curve for the prediction of 1-year mortality was 0.69 in all patients with ≥14 days of MV, whereas in the extended ProVent model, the area under the curve was 0.89. The extended ProVent model, which considers co-morbidities and laboratory data, increases the prediction power of 1-year mortality in patients who require prolonged MV.


Sites of interaction in the complex between beta- and gamma-subunits of transducin.
Transducin, the guanine nucleotide-binding regulatory protein in rod outer segments, is a heterotrimer consisting of alpha-, beta-, and gamma-subunits. Activation of the photoreceptor, rhodopsin, by light, results in activation of transducin which cleaves to form transducin alpha. GTP and a complex of beta gamma-subunits. We have investigated the point(s) of contact between the subunits of transducin by analyzing for the formation of intersubunit disulfide bond(s) in the presence of copper phenanthroline. The formation of a new species with an apparent molecular mass of 43 kDa was observed which had resulted from the formation of a disulfide bond between the beta- and gamma-subunits. The amino acid residues participating in the disulfide bond were identified as Cys-25 in the beta-subunit and Cys-36 and/or Cys-37 in the gamma-subunit. Thus, these cysteine residues and, probably, some of the adjacent amino acid residues form a point of contact between the beta- and gamma-subunits of transducin in the stable complex.


[Initial presentation of the Pentafecta score as a quality instrument for outcome evaluation of primary surgical treatment in patients with penile cancer].
Recently, the Tetrafecta score has been published as the first instrument for assessing the quality of primary surgical treatment for penile cancer (PECa). An external scientific discussion about the defining criteria is still pending and forms the study objective. An international working group consisting of 12 urologists and an oncologist with clinical and academic-scientific expertise in penile cancer was established. In a modified four-stage Delphi process, a total of 13 criteria for PECa patients in clinical AJCC stages 1-4 (T1-3N0-3, but M0) were defined, incorporating the Tetrafecta criteria. Each expert had to select five of these criteria in a secret ballot to generate an individual Pentafecta score. Subsequently, the experts' ratings were aggregated and a final Pentafecta score was formed. None of the original Tetrafecta criteria were included in the final Pentafecta score, which consisted of the following criteria: 1) organ preservation, if possible (≤T2), but always with negative surgical margins, 2) bilateral inguinal lymph node dissection (ILND) from ≥pT1G2N0, 3) perioperative chemotherapy if indicated by guidelines, 4) ILND, if indicated, within a maximum of three months after primary tumour resection, and 5) the treating clinic should perform at least 15 primary surgical treatments in PECa patients. Only in seven out of the 13 experts (54%), a strong correlation was found between individual Pentafecta scores and the final Pentafecta score (rsp >0.60). Based on a moderated voting process among international PECa experts, a Pentafecta score was developed as a quality assurance instrument for primary surgical treatment, which now needs to be validated using patient-relevant and patient-reported endpoints.


False positive abdominal aortic aneurysm on bedside emergency ultrasound.
Bedside ultrasound is the diagnostic method of choice for unstable patients with suspected abdominal aortic aneurysm. Its ability to provide rapid and accurate diagnosis is critical in an emergency setting. Previous studies have documented the ability of Emergency Physicians to accurately diagnose abdominal aortic aneurysms, thus potentially saving lives. A search of the medical literature did not reveal any reports of false positive abdominal aortic aneurysm diagnosis with ultrasound use. We report a case of a false positive abdominal aortic aneurysm diagnosed in a patient with a previously unknown large malignant para-aortic lymph node.


Systematic analysis of critical genes and pathways identified a signature of neuropathic pain after spinal cord injury.
Spinal cord injury (SCI) damages sensory systems, producing chronic neuropathic pain that is resistant to medical treatment. The specific mechanisms underlying SCI-induced neuropathic pain (SCI-NP) remain unclear, and protein biomarkers have not yet been integrated into diagnostic screening. To better understand the host molecular pathways involved in SCI-NP, we used the bioinformatics method, the PubMed database and bioinformatics methods to identify target genes and their associated pathways. We reviewed 2504 articles on the regulation of SCI-NP and used the text mining of PubMed database abstracts to determine associations among 12 pathways and networks. Based on this method, we identified two central genes in SCI-NP: interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Adult male Sprague-Dawley rats were used to build the SCI-NP models. The threshold for paw withdrawal was significantly reduced in the SCI group, and TLR4 was activated in microglia after SCI. Enzyme-linked immunosorbent assay(ELISA) analysis of TNF-α and IL-6 levels was significantly higher in the SCI group than in the sham group. Western blot showed that expressions of the TLR4/MyD88/NF-κB inflammatory pathway protein increased dramatically in the SCI group. Using the TLR4 inhibitor TAK-242, the pain threshold and expressions of inflammatory factors and proteins of the proteins of the inflammatory signal pathway were reversed, TLR4 in microglia was suppressed, suggesting that SCI-NP was related to neuroinflammation mediated by the TLR4 signalling pathway. In conclusion, we found that TNF-α and IL-6 were the neuroinflammation-related genes involved in SCI-NP that can be alleviated by inhibiting the inflammatory pathway upstream of the TLR4/MyD88/NF-κB inflammatory pathway.


[Universal broadband ultrasonic apparatus for use with biological objects].
To obtain bacterial and medicinal aerosols and to study the action of an ultrasonic field on various biological objects an all-purpose broad-band ultrasonic set-up, operating within a frequency range of 0.2-5.0 MHz has been constructed.


Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives.
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer. Akkermansia muciniphila (A. muciniphila) is a next-generation probiotic that has been reported to improve metabolic disorders. Emerging evidence indicates the therapeutic potential of A. muciniphila for NAFLD, especially in the inflammatory stage, nonalcoholic steatohepatitis. Here, the current knowledge on the role of A. muciniphila in the progression of NAFLD was summarized. A. muciniphila abundancy is decreased in animals and humans with NAFLD. The recovery of A. muciniphila presented benefits in preventing hepatic fat accumulation and inflammation in NAFLD. The details of how microbes regulate hepatic immunity and lipid accumulation in NAFLD were further discussed. The modulation mechanisms by which A. muciniphila acts to improve hepatic inflammation are mainly attributed to the alleviation of inflammatory cytokines and LPS signals and the downregulation of microbiota-related innate immune cells (such as macrophages). This review provides insights into the roles of A. muciniphila in NAFLD, thereby providing a blueprint to facilitate clinical therapeutic applications.


Analysis of mPygo2 mutant mice suggests a requirement for mesenchymal Wnt signaling in pancreatic growth and differentiation.
Pygopus has recently been identified in Drosophila as an essential component of the nuclear complex required for canonical Wnt signaling. Here, we have investigated the role of the mammalian pygopus ortholog, mPygo2, in pancreas development. We show that a null mutation of mPygo2 in mice causes pancreas hypoplasia due to decreased progenitor cell proliferation after embryonic day (e) 12.5. During the same time window, mPygo2-deficient embryos begin to display a reduction in endocrine progenitors and consequently a decrease in islet endocrine cell mass. Consistent with its function after e12.5, late-developing endocrine cell types, such as beta, delta and PP cells, are specifically reduced, while the earlier-forming alpha cells develop normally. We find canonical Wnt signaling to be predominantly active in the mesenchyme at the time when mPygo2 is required and demonstrate the dependence of Wnt signal transduction on mPygo2. Furthermore, conditional deletion of mPygo2(flox) allele in the pancreatic epithelium does not phenocopy the defects in mPygo2-null mutants. Since mPygo2 is expressed in the pancreatic mesenchyme and the role of the mesenchyme in epithelial progenitor cell expansion is well documented, our findings suggest an indirect role for mPygo2 in epithelial growth and differentiation through regulation of mesenchymal signals. Together, our data suggest a previously unappreciated role for mesenchymal Wnt signaling in regulating pancreatic organ growth and cell differentiation.


Amyand's hernia with scrotal abscess presenting as acute scrotum.
Amyand's hernia is a rare form of inguinal hernia in which an inflamed appendix is incarcerated in a hernial sac. The clinical presentation of Amyand's hernia varies, depending on the extent of inflammation involved in the hernial sac and the presence or absence of a scrotal abscess. If a scrotal abscess is present, this usually indicates that the appendix in the hernial sac is perforated. However, without the availability of computed tomography (CT) scans, the condition is often preoperatively misdiagnosed as a strangulated inguinal hernia. We describe a rare case of a 64-year-old man who presented at our emergency room complaining of scrotal swelling and pain. Diagnosis of Amyand's hernia with a scrotal abscess was confirmed preoperatively by CT scan.


Complete necrotization of hepatocellular carcinoma by chemotherapy and subsequent intravascular coagulation: a case report.
A 45-year-old man with hepatocellular carcinoma who developed intravascular coagulation following complete tumor regression by chemotherapy is described. After 2 doses of 10 mg of Mitomycin C given into the hepatic artery at the time of selective angiography, and 16 intravenous doses of 5-fluorouracil and Mitomycin C, 2 doses per week, subjective symptoms and hepatomegaly disappeared. Alpha-fetoprotein became negative and a remarkable change in tumor size and vasculature was noted in the arteriogram. Three months after chemotherapy, the patient developed thrombocytopenia, intravascular hemolysis, and acute renal failure. Autopsy disclosed a 8 X 7 X 5 cm solitary, encapsulated hepatocellular carcinoma in the right lobe. The tumor was surrounded by a thick capsule and completely necrotized. Neither intrahepatic invasion nor extrahepatic metastasis was observed. In the kidney, generalized fibrin thrombi were seen in the afferent arterioles of glomeruli as accounted for by intravascular coagulation.


The Pampulha reservoir remains a potential urban focus of schistosomiasis mansoni in Brazil: changes in the occurrence patterns of Biomphalaria species and a new record of the parasite.
The Pampulha reservoir has long been a focus of schistosomiasis transmission in Belo Horizonte, State of Minas Gerais, Brazil. The last malacological study conducted in this urban reservoir was more than two decades ago, and thus, an update on the distribution of the species of Biomphalaria as well as new data on the presence of Schistosoma mansoni in this water body are required. The current distribution of Biomphalaria spp. in the Pampulha reservoir and their infection with S. mansoni was evaluated during 55 malacological surveys conducted between 2009 and 2012. Biomphalaria straminea displayed a high population density and distribution, and 13.7% (2,233/16,235) of the specimens collected were infected with larval trematodes other than Schistosoma mansoni. Biomphalaria tenagophila and Biomphalaria glabrata, species currently presenting a restricted distribution and small populations, displayed trematode infection rates of 15.2% (98/644) and 13% (83/640), respectively. Thirteen (2%) specimens of B. glabrata were found to be infected with S. mansoni. In addition, a historical review based on previous and new data on the occurrence patterns of Biomphalaria species in this reservoir is presented. The results indicate that the Pampulha reservoir remains a potential focus of urban schistosomiasis in Brazil, and significant changes in the occurrence patterns of Biomphalaria species were verified.


Common allergens in shoe dermatitis: our experience in Lahore, Pakistan.
Shoe dermatitis is a form of contact dermatitis resulting from exposure to shoes. Different chemicals, in conjunction with a hot and humid environment within the shoe, give rise to allergic or irritant dermatitis. Allergic shoe dermatitis is commonly caused by constituents of rubber, leather, adhesives, and rarely by linings and dyes. To determine the frequency of various allergens in shoe dermatitis in our patients. One hundred and nine patients suspected of having contact dermatitis due to shoe allergens were included. All patients were patch tested with the Shoe series and European Standard series. Patches were applied on the upper back and removed after 48 h. Results were read at 48, 72, and 120 h and interpreted according to International Contact Dermatitis Research Group (ICDRG) criteria. Of the 119 patients, 87 (73%) reacted positively to various allergens, 48% of whom showed polysensitivity. Glues (33.6%), particularly para-tert-butylphenol formaldehyde resin (PTBP-FR) (26.9%), were the leading cause of shoe dermatitis. Other allergens were leather chemicals (26.4%), potassium dichromate (16.18%), rubber allergens (7.6%), and dyes (7.6%). Shoe scrapings tested positive in 26.3% of patients. Other common allergens were nickel sulfate (22.7%), neomycin sulfate (10.1%), and cobalt chloride (8.4%). Considering the diversity of allergens, all patients presenting with shoe dermatitis should be patch tested with the Shoe series and a standard series to determine the etiologic allergens.


Cancer: ADT and acute kidney injury-causal or casual relationship?
A recent observational study has reported that androgen deprivation therapy for prostate cancer is associated with an increased risk of acute kidney injury. As a result of limited biological plausibility and critical measured and unmeasured confounders, the reported link is more likely to be casual than causal.


Deep Immunophenotyping of Human Whole Blood by Standardized Multi-parametric Flow Cytometry Analyses.
Immunophenotyping is proving crucial to understanding the role of the immune system in health and disease. High-throughput flow cytometry has been used extensively to reveal changes in immune cell composition and function at the single-cell level. Here, we describe six optimized 11-color flow cytometry panels for deep immunophenotyping of human whole blood. A total of 51 surface antibodies, which are readily available and validated, were selected to identify the key immune cell populations and evaluate their functional state in a single assay. The gating strategies for effective flow cytometry data analysis are included in the protocol. To ensure data reproducibility, we provide detailed procedures in three parts, including (1) instrument characterization and detector gain optimization, (2) antibody titration and sample staining, and (3) data acquisition and quality checks. This standardized approach has been applied to a variety of donors for a better understanding of the complexity of the human immune system. The online version contains supplementary material available at 10.1007/s43657-022-00092-9.