Analgesic Effect of Intrathecal Melissa officinalis in the Rat Model of Hot-Water and Formalin-Induced Pain.
Melissa officinalis (MO) is one of the oldest herbal medicines commonly used in traditional medicine, which some studies have investigated for its analgesic effect. This study is an attempt to investigate the effects of intrathecal administration of Melissa officinalis on the pain induced by heat and formalin. In this experimental study, 70 male Wistar rats with an average weight of 270-320 g were randomly divided into five groups: control; sham that received 25 μl of saline through the spinal catheter; and three experimental groups that received 5, 10 or 20 mg/kg M. officinalis via the spinal catheter respectively. Five days after catheterization of the spinal cord from the lumbar region under anesthesia, the effects of Intrathecal administration of M. officinalis on heat- and formalin-induced pain were evaluated. Data were analyzed by using one-way ANOVA. Intrathecal injection of M. officinalis blocked heat-induced pain compared to sham group (p = 0.001). Maximum analgesia was observed 30 min after the injection. Furthermore, intrathecal administration of MO alleviated both acute (p = 0.007) and chronic (p = 0.001) phases of formalin-induced pain. Motor block was not observed in any of the above mentioned groups. The results showed that intrathecal administration of MO could significantly improve hot-water and formalin-induced pain in male Wistar rats.


Effect of Impaired T Cell Receptor Signaling on the Gut Microbiota in a Mouse Model of Systemic Autoimmunity.
T cell receptor (TCR) signaling abnormalities and gut dysbiosis are thought to be involved in the development of systemic lupus erythematosus (SLE). However, it is not known whether these mechanisms are interrelated. This study was undertaken to explore the impact of defective TCR signaling on microbiota-driven immune responses and the consequent triggering of systemic autoimmunity. The responses of B6SKG mice harboring a mutation in ZAP-70 leading to spontaneous development of SLE were evaluated under specific pathogen-free (SPF) and germ-free (GF) conditions. The gut microbiome was analyzed using 16S ribosomal RNA sequencing. Secretory IgA production in the gut and follicular helper T (Tfh) cell development in the spleen and Peyer's patches were analyzed. Interleukin-17 (IL-17)-deficient mice and segmented filamentous bacteria (SFB)-specific TCR-transgenic mice were used to examine the role of IL-17 and thymic selection. SLE development in B6SKG mice was significantly more attenuated under GF conditions than under SPF conditions. The gut microbiota in B6SKG mice was altered, which was associated with the expansion of SFB and consequent development of SLE by driving Th17 cell differentiation, which was in turn blunted by IL-17 deficiency. Notably, although systemic Tfh development and autoantibody IgG response were enhanced, local gut Tfh and IgA responses were impaired. Moreover, experiments in SFB-specific TCR-transgenic mice revealed that this differential response was caused by altered thymic selection of self- and microbiota-reactive TCR because of defective TCR signaling. Our findings indicate that defective TCR signaling alters the gut microbiota and promotes systemic autoimmunity by driving Th17 cell differentiation.


Comparation of quality of life in Chinese patients undergoing leadless versus conventional pacemaker implantation.
Leadless pacemakers are widely used, but the quality of life assessment of patients with leadless pacemakers is still unclear. Assume that leadless pacemakers can improve the patients' quality of life. Total of 119 patients who received pacemaker implantation at Beijing Anzhen Hospital from January 2020 to March 2022 were selected, including 35 leadless pacemakers and 84 conventional pacemakers. The SF-36 questionnaire was used to evaluate quality of life at baseline, 1 month and 3 months after surgery. We also used a questionnaire consisted of 4 specific questions related to the implant procedure to assess the surgery. There were no differences in baseline characteristics between the two groups, except for age and oral anticoagulant treatment. There was no difference in baseline SF-36 scores. At the 3-month follow-up, patients in leadless pacemakers group were significantly better at physical function (63.63 vs 47.50, p = .000), role physical (60.20 vs 40.23, p = .000), bodily pain (65.57 vs. 61.69, p = .042), physical component summary (61.25 vs. 50.57, p = .000), vitality (56.26 vs 49.57, p = .001), social function (80.14 vs 74.70, p = .004), role emotional (76.14 vs. 71.42, p = .015), mental health (75.46 vs. 68.18, p = .000), mental component summary (72.00 vs. 65.97, p = .000), even after adjusting for clinical baseline and SF-36 baseline. Pacemaker-related discomfort and mobility limitations were significantly reduced in leadless pacemakers group. Leadless pacemakers is associated with better quality of life with less activity limitations due to surgical discomfort and less emotional distress. However, current use of leadless pacemakers in China is limited due to the high cost.


[Quantifying the inflammatory activity in Crohn's disease using CE dynamic MRI].
Evaluation of dynamic contrast enhanced MRI in patients with Crohn's disease to assess local inflammatory activity. Prospective study of 13 patients with histologically proven Crohn's disease. Axial and coronal slices were acquired by a 1.5 T MR (Magnetom Vision, Siemens, Germany): T1 flash 2 D (TR 72.5 ms, TE 4.1 ms), T2 (TR 2730 ms, TE 138 ms), turbo-flash sequences T1 (TR 94.2 ms, TE 4.1 ms) post contrast media fat saturated (Magnevist, 0.2 ml/kg, flow 4 ml/s). In area of maximal thickening of terminal ileal wall, axial dynamic T1 sequences (TR 11 ms, TE 4.2 ms) were acquired every 1.5 s post contrast media application for a total duration of 1 min. Contrast uptake was subjectively measured by semiquantitative score and computed assisted ROI evaluation. MR parameters were correlated with CDAI (Crohn's disease activity index) and SAI (severe activity index). Contrast uptake in the intestinal wall occurred after 18.5 s (range: 3.0 - 28.0), contrast upslope until plateau phase lasted for 16.1 s (range: 8.0 - 50.0). Maximum contrast enhancement into the bowel wall was 266 % (105 - 450 %) of baseline. After maximum contrast uptake, we observed a plateau phase in all cases for the total duration of measurement. A significant correlation existed for maximum contrast uptake to CDAI (r = 0.591; p = 0.033), for beginning of contrast upslope to the time until plateau phase (r = 0.822; p = 0.001), and for the time until plateau phase to CDAI (r = 0.562; p = 0.046). CDAI was on average 108, median 106; SAI was on average 114, median 115. SAI correlated significantly to CDAI (r = 0.874). Maximum contrast uptake, beginning of contrast upslope, and time until plateau phase were independent to creeping fat, local lymphadenitis, laboratory parameters, temperature, body mass index, heart frequency and systolic blood pressure. Dynamic MRI enables to quantify local inflammatory activity of bowel wall in patients with Crohn's disease. Larger studies are necessary to establish this method in clinical routine.


Lactiplantibacillus plantarum L47 and inulin alleviate enterotoxigenic Escherichia coli induced ileal inflammation in piglets by upregulating the levels of α-linolenic acid and 12,13-epoxyoctadecenoic acid.
Alternatives to antibiotics for preventing bacteria-induced inflammation in early-weaned farm animals are sorely needed. Our previous study showed that Lactiplantibacillus plantarum L47 and inulin could alleviate dextran sulfate sodium (DSS)-induced colitis in mice. To explore the protective effects of L. plantarum L47 and inulin on the ileal inflammatory response in weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC), 28 weaned piglets were assigned into four groups, namely, CON group-orally given 10 mL/d phosphate buffer saline (PBS), LI47 group-orally given a mixture of 10 mL/d L. plantarum L47 and inulin, ECON group-orally given 10 mL/d PBS and challenged by ETEC, and ELI47 group-orally given 10 mL/d L. plantarum L47 and inulin mixture and challenged by ETEC. The results demonstrated that the combination of L. plantarum L47 and inulin reduced inflammatory responses and relieved the inflammatory damage caused by ETEC, including ileal morphological damage, reduced protein expression of ileal tight junction, decreased antioxidant capacity, and decreased anti-inflammatory factors. Transcriptome analysis revealed that L. plantarum L47 and inulin up-regulated the gene expression of phospholipase A2 group IIA (PLA2G2A) (P < 0.05) as well as affected alpha-linolenic acid (ALA) metabolism and linoleic acid metabolism. Moreover, L. plantarum L47 and inulin increased the levels of ALA (P < 0.05), lipoteichoic acid (LTA) (P < 0.05), and 12,13-epoxyoctadecenoic acid (12,13-EpOME) (P < 0.05) and the protein expression of Toll-like receptor 2 (TLR2) (P = 0.05) in the ileal mucosa. In conclusion, L. plantarum L47 and inulin together alleviated ETEC-induced ileal inflammation in piglets by up-regulating the levels of ALA and 12,13-EpOME via the LTA/TLR2/PLA2G2A pathway.


Computed tomography of the paranasal sinuses, nasopharynx, and soft tissues of the neck.
A number of cases are presented illustrating the value of computed tomography in the investigation of mass lesions involving the paranasal sinuses, nasopharynx, and soft tissues of the neck. Rapid advances in CT technology now underway will alter our approach to the investigation of certain diseases in these locations.


Catching As and Zs: poor sleep quality predicts failures to increase studying time.
We examined the association between sleep quality and academic performance by attending to university students' self-defined goals to increase studying behaviors over a four-week period. We evaluated this association in 100 undergraduates, who self-elected to change their studying behaviors and were randomly assigned to one of three interventions (action planning, dissonance-based, or reflection). We found a negative association between the Pittsburgh Sleep Quality Index (PSQI) at baseline and subsequent studying time over the next four weeks, reflecting a small to medium effect size (partial r = .21). Depressive symptoms did not mediate the predictive influence of sleep quality on studying behavior. Intervention type did not influence the association between sleep quality and studying time. The predictive significance of sleep quality, in the context of the failure of effects for the randomized interventions, underscores the potential for intervening with sleep as part of efforts to improve academic behaviors.


The effect of thymosin α1 on mortality of critical COVID-19 patients: A multicenter retrospective study.
Thymosin α1 therapy was commonly used in patients with coronavirus disease 2019 (COVID-19), while its impact on outcomes and which patients could benefit from thymosin α1 therapy were uncertain. Patients with COVID-19 from 19 designated hospitals between January 1 to February 29, 2020 were included, and the main exposure of interest was administration of thymosin α1. The primary outcome was 28-day mortality. Propensity score matching (PSM) was used to account for baseline confounders, cluster analysis and Cox proportional hazard model was used to account for subgroup analysis. A total of 771 patients were included, and 327/771 (42.4%) patients received thymosin α1 therapy. The 28-day mortality in thymosin group was significantly lower than that in control group (41.3% vs. 60.6%, p < 0.001). After PSM 522 patients were included in analysis and the 28-day mortality in thymosin α1 group and control group were 51.0% and 52.9% respectively, with no significant difference. In subgroup analyses, the association between thymosin α1 therapy and 28-day mortality appeared to be stronger among male patients (HR 0.673, 95% CI 0.454-0.998; p = 0.049). There were no benefits of thymosin α1 in 28-day mortality in other subgroups. There were two phenotypes after cluster analysis, but no benefits of thymosin α1 were shown in phenotype 1 (HR 0.823 95% CI 0.581-1.166; p = 0.273) and phenotype 2 (HR 1.148 95% CI 0.710-1.895; p = 0.442). There was no association between use of thymosin α1 and decreased mortality in critically ill COVID-19 patients. Subgroups analysis and phenotype analysis also showed no differences on mortality after thymosin α1 therapy.


The effect of chlorpromazine on the function of colonic and ileal mucosa in the anaesthetized rat.
1 The effect of chlorpromazine (Cpz) on the net fluxes of water and sodium in the ileum and colon has been studied in the anaesthetized rat. 2 Under control conditions both the ileum and colon absorbed water and sodium. Cpz (100 mumol/kg, s.c.) had no significant effect on these basal rates of absorption. 3 Intestinal secretion was stimulated by a combination of intra-arterial prostaglandin E1 (PGE1; 10 nmol kg-1 min-1) and intraluminal theophylline (25 mM). A marked potentiation occurred between PGE1 and theophylline in the stimulation of colonic and ileal secretion. 4 In the ileum, a dose-related inhibition of the PGE 1/theophylline-induced changes in the net fluxes of water and sodium was produced by Cpz (0.1 to 100 mumol/kg, s.c.). Under these conditions the inhibition of the secretagogue-induced changes was significant using Cpz at 1 mumol/kg (s.c.) and a dose of Cpz of 100 mumol/kg (s.c.) returned the net fluxes of both water and sodium to basal levels. 5 In the colon, Cpz, at doses of 0.1 and 1 mumol/kg subcutaneously did not inhibit the PGE1/theophylline-induced changes in the net fluxes of water and sodium, and, in contrast with the ileum, significant changes were only obtained with Cpz at 10 mumol/kg. Increasing the dose of Cpz to 100 mumol/kg further inhibited the net flux of sodium, but not that of water in the colon, and in each case the secretagogue-induced changes were not returned to basal levels.


Aliphatic polyesters for medical imaging and theranostic applications.
Medical imaging is a cornerstone of modern medicine. In that context the development of innovative imaging systems combining biomaterials and contrast agents (CAs)/imaging probes (IPs) for improved diagnostic and theranostic applications focuses intense research efforts. In particular, the classical aliphatic (co)polyesters poly(lactide) (PLA), poly(lactide-co-glycolide) (PLGA) and poly(ɛ-caprolactone) (PCL), attract much attention due to their long track record in the medical field. This review aims therefore at providing a state-of-the-art of polyester-based imaging systems. In a first section a rapid description of the various imaging modalities, including magnetic resonance imaging (MRI), optical imaging, computed tomography (CT), ultrasound (US) and radionuclide imaging (SPECT, PET) will be given. Then, the two main strategies used to combine the CAs/IPs and the polyesters will be discussed. In more detail we will first present the strategies relying on CAs/IPs encapsulation in nanoparticles, micelles, dendrimers or capsules. We will then present chemical modifications of polyesters backbones and/or polyester surfaces to yield macromolecular imaging agents. Finally, opportunities offered by these innovative systems will be illustrated with some recent examples in the fields of cell labeling, diagnostic or theranostic applications and medical devices.


Spontaneous and cyclophosphamide-induced sister-chromatid exchanges in diploid and endoreduplicated tetraploid metaphases of preimplantation mouse embryos.
Endoreduplicated tetraploid metaphases could for the first time be induced in preimplantation mouse embryos by culture in the suboptimum medium MEM. In such endomitoses sister-chromatid exchange (SCE) frequency was approximately the same during the first and the second cell cycle. However, when morulae and blastocysts were cultured in the presence of cyclophosphamide metabolites SCE frequency was increased predominantly during the second cell cycle. Compared to diploid metaphases a decreased SCE frequency was found under both conditions of endomitoses induction, which may be related to DNA-repair processes.


Genomic aberrations of BRCA1-mutated fallopian tube carcinomas.
Intraepithelial carcinomas of the fallopian tube are putative precursors to high-grade serous carcinomas of the ovary and peritoneum. Molecular characterization of these early precursors is limited but could be the key to identifying tumor biomarkers for early detection. This study presents a genome-wide copy number analysis of occult fallopian tube carcinomas identified through risk-reducing prophylactic oophorectomy from three women with germline BRCA1 mutations, demonstrating that extensive genomic aberrations are already established at this early stage. We found no indication of a difference in the level of genomic aberration observed in fallopian tube carcinomas compared with high-grade serous ovarian carcinomas. These findings suggest that spread to the peritoneal cavity may require no or very little further tumor evolution, which raises the question of what is the real window of opportunity to detect high-grade serous peritoneal carcinoma arising from the fallopian tube before it spreads. Nonetheless, the similarity of the genomic aberrations to those observed in high-grade serous ovarian carcinomas suggests that genetic biomarkers identified in late-stage disease may be relevant for early detection.


Improving nursing school diversity through use of a group admission interview.
Nursing student diversity is a priority of the University of North Florida School of Nursing, but faculty members found that the prelicensure track admission process favored students with high grade point averages (GPAs) and eliminated many potentially good students, including minorities. Adding an interview to the admission process resulted in acceptance of highly qualified students while giving deserving students, including minority students with good but lower GPAs, the opportunity to enter the program. The change in the admission process increased minority admissions from a low of 2% to as high as 25%. Neither the overall attrition rate nor the licensure examination pass rate has been adversely affected.


Electrochemical nutrient removal from natural wastewater sources and its impact on water quality.
In this study, a suite of natural wastewater sources is tested to understand the effects of wastewater composition and source on electrochemically driven nitrogen and phosphorus nutrient removal. Kinetics, electrode behavior, and removal efficiency were evaluated during electrochemical precipitation, whereby a sacrificial magnesium (Mg) anode was used to drive precipitation of ammonium and phosphate. The electrochemical reactor demonstrated fast kinetics in the natural wastewater matrices, removing up to 54% of the phosphate present in natural wastewater within 1 min, with an energy input of only 0.04 kWh.m-3. After 1 min, phosphate removal followed a zero-order rate law in the 1 min - 30 min range. The zero-order rate constant (k) appears to depend upon differences in wastewater composition, where a faster rate constant is associated with higher Cl- and NH4+ concentrations, lower Ca2+ concentrations, and higher organic carbon content. The sacrificial Mg anode showed the lowest corrosion resistance in the natural industrial wastewater source, with an increased corrosion rate (vcorr) of 15.8 mm.y-1 compared to 1.9-3.5 mm.y-1 in municipal wastewater sources, while the Tafel slopes (β) showed a direct correlation with the natural wastewater composition and origin. An overall improvement of water quality was observed where important water quality parameters such as total organic carbon (TOC), total suspended solids (TSS), and turbidity showed a significant decrease. An economic analysis revealed costs based upon experimental Mg consumption are estimated to range from 0.19 $.m-3 to 0.30 $.m-3, but costs based upon theoretical Mg consumption range from 0.09 $.m-3 to 0.18 $.m-3. Overall, this study highlights that water chemistry parameters control nutrient recovery, while electrochemical treatment does not directly produce potable water, and that economic analysis should be based upon experimentally-determined Mg consumption data. Synopsis Statement: Magnesium-driven electrochemical precipitation of natural wastewater sources enables fast kinetics for phosphate removal at low energy input.


Computational investigation of molecular mechanism and neuropathological implications in Huntington disease.
Huntington's disorder (HD), caused by mutations of the IT-15 gene, is an autosomal genetic disease that causes the breakdown of the nerve cells in the brain. The IT-15 gene encodes the huntingtin (Htt) protein. Htt, along with its interacting partners, are involved in maintaining proper communication among neurons. Our work is based on the interaction behavior between Htt (in three polyglutamine (polyQ) states that is Htt 0Q, 17Q and 36Q) and SH3GL3 interacting protein by using computational methods. We used the HADDOCK docking platform to find out the extent of interaction between Htt polyQ models and SH3GL3. The Htt36Q (mutated) showed higher interaction than Htt17Q (native) with SH3GL3. Molecular dynamics simulation was performed to uncover the structural fluctuations of polyQ models and their complexes. RMSD, Rg, SASA, and total interaction energy graph showed significant results, where as mutant Htt showed higher fluctuations and flexibility than native Htt. The increase in the length of polyQ was found to affect the stability, flexibility, and compactness of the protein and its complex. Our research provided a propitious approach to understand the consequence of polyglutamination in Htt and its relation with HD.


Single-session treatment of benign cystic thyroid nodules with ethanol versus radiofrequency ablation: a prospective randomized study.
To compare volume reduction of single-session ethanol ablation (EA) and radiofrequency (RF) ablation for cystic thyroid nodule treatment. All patients gave written informed consent to participate in this prospective institutional review board-approved study. From May 6, 2010, to August 8, 2011, in this single-institutional, noninferiority trial, 50 patients, each with a single cystic thyroid nodule, were randomly assigned to EA (25 patients; mean age for women, 45.7 years, and for men, 37.5 years) or RF ablation (25 patients; mean age for women, 45.1 years, and for men, 43.7 years) treatment. Internal fluid was aspirated prior to EA or RF ablation. Primary end point was the volume reduction ratio (percentage) at 6-month follow-up; the noninferiority margin was chosen as -8% (EA minus RF ablation). Secondary end points included therapeutic success rate, improvement of symptoms and cosmetic problems, and number of major complications. Analysis was performed primarily in intention-to-treat manner. A one-sided 95% confidence interval (CI) for the mean difference in volume reduction ratio 6 months after treatment was calculated to test for noninferiority. Subsequent superiority comparison of EA with RF ablation on a condition of establishment of the noninferiority of EA to RF ablation was preplanned and used two-sided 95% CI of the outcome difference. The mean volume reduction was 96.9% in EA and 93.3% in RF ablation (n = 21 for each) (difference, 3.6%; lower bound of the one-sided 95% CI of the difference, 1.2%), thus demonstrating the noninferiority of EA to RF ablation. Two-sided 95% CI of the outcome difference was 0.7% to 6.5%, demonstrating significant superiority of EA to RF ablation. All patients demonstrated therapeutic success (P > .99). Mean symptom and cosmetic scores showed no significant difference in either group (P = .806 and P = .682, respectively). There were no major complications (P > .99). EA may be the first-line treatment modality for cystic thyroid nodules, which has comparable therapeutic efficacy to, but is less expensive than, RF ablation.


Robotic-Extended Rethymectomy for Refractory Myasthenia Gravis: A Case Series.
To assess the safety and efficacy of robotic-extended rethymectomy in selected refractory myasthenia gravis (MG) patients with suspected residual thymic tissue. Robotic-extended rethymectomy was performed in 6 MG patients with seropositive acetylcholine receptors (AChR) antibody who had undergone a previous thymectomy (1 cervicotomy, 2 video-assisted thoracoscopic surgeries, and 3 sternotomies). The median observation time before robotic rethymectomy was 108 (24-171) months. The main outcomes were perioperative morbidity, mortality, conversion to open surgery, and clinical outcomes according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS). Before rethymectomy, all patients required immunosuppressants and 5 patients (83.3%) required intravenous immune globulin and/or plasma exchange to control the symptoms. The median specimen weight was 24.5 (14-144) g after rethymectomy, and residual thymic tissue was found in 5 patients (83.3%). No conversion to open surgery or perioperative morbidity and mortality was observed. With a median follow-up time of 46.5 (13-155) months, 3 patients (50%) achieved "improved" and 3 (50%) were "unchanged" according to the MGFA-PIS. Compared with preoperative use, the median daily dose of corticosteroids statistically decreased (25 [7.5-60] vs 0 [0-5] mg, P = 0.002) without significant change in azathioprine use (100 [0-200] vs 50 [0-150] mg, P = 0.360). AChR antibody positive MG patients with a treatment refractory long-term course after thymectomy might have remaining thymic tissue with the 2 commonly associated thymus pathologies, thymoma, and follicular hyperplasia. Robotic-extended rethymectomy might be considered as a safe and beneficial treatment option in these patients.


Immunotoxicity of bis(tri-n-butyltin)oxide in the rat: effects on thymus-dependent immunity and on nonspecific resistance following long-term exposure in young versus aged rats.
To investigate whether immune function suppression observed in an earlier study after short-term bis(tri-n-butyltin)oxide (TBTO) exposure also occurred after long-term treatment, function studies for specific and nonspecific resistance were performed after exposure of weaned male rats to diets containing 0, 0.5, 5, or 50 mg TBTO/kg for 4-6 and 15-17 months. Treatment for 4.5 months had no effect on body weight but reduced thymus weight at 50 mg/kg. Regarding the thymus-dependent immunity, delayed-type hypersensitivity reactions to ovalbumin and tuberculin were not depressed, in contrast to the results of the short-term study. The resistance to the nematode Trichinella spiralis was dose-relatedly suppressed at the 5 and 50 mg/kg levels, in both experiments (5.5 and 16.5 months exposure), as shown by increased counts of muscle larvae and depressed serum IgE titers. Also the inflammatory reaction around cysts in parasitized musculature was reduced. No significant reduction was found in IgM and IgG titers to T. spiralis, ovalbumin, and sheep red blood cells as determined by enzyme-linked immunosorbent assay. TBTO exposure at 50 mg/kg for 4.5 months significantly reduced thymus weight, but the response of thymocytes to T-cell mitogens was unaltered. TBTO treatment for 4.5 or 16 months did not influence the response of spleen cells to T-and B-cell mitogens and neither influenced spleen weight. A dose-related shift was observed in T- and B- cell numbers in mesenteric lymph nodes as shown by flow cytometry using monoclonal antibodies: treatment for 6 and 18 months reduced the relative count of T-lymphocytes and consequently increased the percentage of B-lymphocytes. As a result, the T:B ratio was reduced in the 5 and 50 mg/kg groups. Concerning the nonspecific resistance, TBTO exposure for 5 and 17 months reduced macrophage function at 50 mg/kg as shown by impaired splenic clearance of Listeria monocytogenes bacteria. Natural cell-mediated cytotoxicity of spleen and peritoneal cells was investigated in a 51Cr-release assay with YAC-lymphoma target cells. TBTO treatment significantly suppressed natural killer (NK) activity in spleen cells. Significant suppression was noted in all treatment groups following 16 months TBTO exposure; in contrast to treatment for 4.5 months. No significant alterations were observed in the spontaneous cytotoxicity of nonadherent and adherent peritoneal cells following 4.5 months treatment. Treatment of aged (i.e., 1-year-old) male rats for 5 months with the 50 mg/kg diet reduced thymus weight but had no effect on body or spleen weight.(ABSTRACT TRUNCATED AT 400 WORDS)


A Comparative study of microwave-induced pyrolysis of lignocellulosic and algal biomass.
Microwave (MW) pyrolysis of algal and lignocellulosic biomass samples were studied using a modified domestic oven. The pyrolysis temperature was recorded continuously by inserting a thermocouple into the samples. Temperatures as high as 1170 and 1015°C were achieved for peanut shell and Chlorella vulgaris. The activation energy for MW pyrolysis was calculated by Coats-Redfern method and the values were 221.96 and 214.27kJ/mol for peanut shell and C. vulgaris, respectively. Bio-oil yields reached to 27.7wt.% and 11.0wt.% during pyrolysis of C. vulgaris and peanut shell, respectively. The bio-oil samples from pyrolysis were analyzed by a gas chromatography-mass spectrometry (GC-MS). Bio-oil from lignocellulosic biomass pyrolysis contained more phenolic compounds while that from microalgae pyrolysis contained more nitrogen-containing species. Fourier transform infrared spectroscopy (FTIR) analysis results showed that concentration of OH, CH, CO, OCH3, and CO functional groups in char samples decreased significantly after pyrolysis.


Application of novel copolymer-TiO(2) membranes for some textile dyes adsorptive removal from aqueous solution and photocatalytic decolorization.
Novel low density polyethylene-grafted-poly(4-vinylpyridine-co-acrylamide) (LDPE-g-P(4-VP/AAm)) films were prepared by means of gamma-radiation-induced graft copolymerization as support for photocatalytic application. Nanometer-sized TiO(2) particles were immobilized to the grafted LDPE via dip coating technique. The efficiency of immobilized photocatalyst is tested on two target pollutants (textile azo dyes: Remazol red RB-133 (RR RB 133) and reactive blue 2 (RB2)). The efficient photocatalytic ability as reflected in determined photobleaching rate of both dyes was observed and is comparable to that for the non-supported TiO(2) used in a typical slurry photoreactor. The LDPE-g-(4-VP/AAm) copolymers supported TiO(2) photocatalyst has the practical advantages of easy separation and removal from the polluted environment. It could be a viable technique for the safe disposal of textile wastewater into the water streams.


[Smoking habits, attitudes and smoking cessation among sixth-year medical students of Kaunas University of Medicine].
The aim of the study was to assess trends of smoking and the relation between smoking behavior of undergraduate medical students and their attitudes towards smoking and treatment of tobacco dependence. Data were collected from sixth-year medical students of Kaunas University of Medicine during ten consecutive years. A total of 1518 students completed the anonymous questionnaire; response rate was 83.5%. The daily smoking rate was 19.4% in males and 4.2% in females; 15.9% and 10.4% respectively were irregular smokers, never smoked 41.6% of males and 64% of females. 70% of smokers and 83% of nonsmokers agreed that tobacco smoking is one of the greatest health hazards of modern times; 97.1% of all students considered passive smoking as harmful. More nonsmokers (70%) than smokers (5l%) were aware of addictive nature of tobacco, but there was a little difference in their opinion about support to smokers for quitting: 83.2% of smokers and 87.1% of nonsmokers stated that medical doctors should help smokers to give up smoking and 68% of them thought that doctors had not enough knowledge how to help. Less smokers (55%) than nonsmokers (87%) believed that smoking should be banned in hospitals. Prevalence of smoking was significantly lower among medical students than in general population. There were no significant changes in smoking prevalence among male medical students during the period of 1995-2004. At the same time smoking prevalence among female medical students increased more than twice. Attitudes of smokers and nonsmokers were significantly different on most items of tobacco, but knowledge of tobacco problem in the undergraduate students was not sufficient. Teaching about tobacco and related issues remains essential in the undergraduate medical course.


Sodium alginate/carboxymethyl starch/κ-carrageenan enteric soft capsule: Processing, characterization, and rupture time evaluation.
Although gelatin has good characteristics in preparing soft capsules, its noticeable shortcomings force researchers to further develop substitutes for gelatin soft capsules. In this paper, sodium alginate (SA), carboxymethyl starch (CMS) and κ-carrageenan (κ-C) were used as matrix materials, and the formula of the co-blended solutions was screened through rheological method. In addition, films of the different blends were characterized by thermogravimetry analysis, SEM, FTIR, X-ray, water contact angle and mechanical properties. The results showed that κ-C had strong interaction with CMS and SA, and the mechanical properties of capsule shell were greatly improved by the addition of κ-C. When the ratio of CMS/SA/κ-C was 2:0.5:1.5, the microstructure of the films was more dense and uniform. In addition, this formula had the best mechanical properties and adhesion properties, and was more suitable for the production of soft capsules. Finally, a novel plant soft capsule was successfully prepared by dropping method, and its appearance and rupture properties met the requirements of enteric soft capsules. In simulated intestinal fluid, the soft capsules were almost completely degraded within 15 min, and they were superior to the gelatin soft capsules. Therefore, this study provides an alternative formula for preparing enteric soft capsules.


Aggregation of alpha-synuclein induced by the Cu,Zn-superoxide dismutase and hydrogen peroxide system.
Alpha-synuclein is a major component of the abnormal protein aggregation in Lewy bodies of Parkinson's disease (PD) and senile plaques of Alzheimer's disease (AD). Previous studies have shown that the aggregation of alpha-synuclein was induced by copper (II) and H(2)O(2) system. Since copper ions could be released from oxidatively damaged Cu,Zn-superoxide dismutase (SOD), we investigated the role of Cu,Zn-SOD in the aggregation of alpha-synuclein. When alpha-synuclein was incubated with both Cu,Zn-SOD and H(2)O(2), alpha-synuclein was induced to be aggregated. This process was inhibited by radical scavengers and spin trapping agents such as 5,5'-dimethyl 1-pyrolline N-oxide and tert-butyl-alpha-phenylnitrone. Copper chelators, diethyldithiocarbamate and penicillamine, also inhibited the Cu,Zn-SOD/H(2)O(2) system-induced alpha-synuclein aggregation. These results suggest that the aggregation of alpha-synuclein is mediated by the Cu,Zn-SOD/H(2)O(2) system via the generation of hydroxyl radical by the free radical-generating function of the enzyme. The Cu,Zn-SOD/H(2)O(2)-induced alpha-synuclein aggregates displayed strong thioflavin-S reactivity, reminiscent of amyloid. These results suggest that the Cu,Zn-SOD/H(2)O(2) system might be related to abnormal aggregation of alpha-synuclein, which may be involved in the pathogenesis of PD and related disorders.


Comparison of matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry platforms for the identification of gram-negative rods from patients with cystic fibrosis.
We evaluated the performance of the Bruker Biotyper and the bioMérieux Vitek MS with both the SARAMIS v4.09 and Knowledge Base v2.0 databases for the identification of 203 non-glucose-fermenting Gram-negative rods that had previously been identified by 16S rRNA gene sequencing. Including those that underwent repeat testing, 96.6%, 90.1%, and 93.6% of isolates, respectively, had identifications that agreed with the previous identification.


Characterization of the 5' flanking region of the rat Na+/K(+)-ATPase beta 1 subunit gene.
We have isolated the 5' end of the rat Na+/K(+)-ATPase beta 1 subunit gene. A genomic fragment containing 817 bp of the 5' flanking sequence, exon 1 and 479 bp of intron 1 was sequenced. The 5' flanking region contains a potential TATA box and several putative CAAT and GC boxes. Potential binding sites for thyroid and glucocorticoid receptors were identified together with multiple sequence motifs which exhibit homology to calcium and serum responsive elements.


A case of diabetic muscle infarction in Japan.
Diabetic muscle infarction (DMI) is a rare complication of diabetes mellitus. We report the first recorded case in Japan. A 45-year-old Japanese woman presented with severe pain in the left antero-medial thigh. She had a 14-year history of Type 2 diabetes mellitus (DM). She had first noticed pain in her left thigh after a walk 2 weeks prior to presentation. The pain worsened progressively. She noticed a firm mass in her left thigh. T2-weighted magnetic resonance imaging (MRI) demonstrated a high-intensity signal in the muscle bulk of the anterior component of the left thigh. A needle biopsy of the mass showed necrosis. She was treated with bedrest and an antiplatelet agent. The mass disappeared 8 weeks after admission. DMI is a rare complication of poorly controlled diabetes mellitus. Twenty-seven cases with DMI have been reported in the English literature but we believe this is the first Japanese case with DMI.


Fracture of the proximal pole of the bipartite carpal scaphoid: a probable Holt-Oram-like syndrome.
Bipartite scaphoid has been debated, and is of a traumatic origin for some authors and congenital for others. The aim of study is to distinguish clinical, radiographic and MR criteria for the diagnosis of congenital bipartite scaphoid. I describe a case of a patient with bilateral bipartite scaphoid admitted at my clinic following a traumatic accident which produced a fracture of the proximal pole of the right carpal scaphoid. The patient had a history of bipartite scaphoid. In conclusion, I believe that congenital origin is more probable and this rare pathology is a sporadic form of Holt-Oram-like syndrome.


Alzheimer's disease proteins in cerebellar and hippocampal synapses during postnatal development and aging of the rat.
Alzheimer's dementia may be considered a synaptic disease of central neurons: the loss of synapses, reflected by early cognitive impairments, precedes the appearance of extra cellular focal deposits of beta-amyloid peptide in the brain of patients. Distinct immunocytochemical patterns of amyloid precursor proteins (APPs) have previously been demonstrated in the synapses by ultrastructural analysis in the cerebellum and hippocampus of adult rats and mice. Now we show that during postnatal development and during aging in these structures, the immunocytochemical expression of APPs increases in the synapses in parallel with the known up-regulation of total APPs brain levels. Interestingly, as shown previously in the adult rodents, the presenilins (PSs) 1 and 2, which intervene in APPs metabolism, exhibit a synaptic distribution pattern similar to that of APPs with parallel quantitative changes throughout life. In the brain tissue, single and double immunocytochemistry at the ultrastructural level shows co-localisation of APPs and PSs in axonal and dendritic synaptic compartments during postnatal synaptogenesis, adulthood and aging. In addition, double-labelling immunocytofluorescence detects these proteins close to synaptophysin at the growth cones of developing cultured neurons. Thusly, the brain expression of APPs and PSs appears to be regulated synchronously during lifespan in the synaptic compartments where the proteins are colocated. This suggests that PS-dependent processing of important synaptic proteins such as APPs could intervene in age-induced adjustments of synaptic relationships between specific types of neurons.


Use of focal radiotherapy boost for prostate cancer and perceived barriers toward its implementation: a survey.
In a recent phase III randomized control trial (FLAME), delivering a focal radiotherapy (RT) boost to tumors visible on MRI was shown to improve outcomes for prostate cancer patients without increasing toxicity. The aim of this study was to assess how widely this technique is being applied in current practice as well as physicians' perceived barriers toward its implementation. An online survey assessing the use of intraprostatic focal boost was conducted in December 2022 and February 2023. The survey link was distributed to radiation oncologists worldwide via email list, group text platform, and social media. The survey initially collected 205 responses from various countries over a two-week period in December 2022. The survey was then reopened for one week in February 2023 to allow for more participation, leading to a total of 263 responses. The highest-represented countries were the United States (42%), Mexico (13%), and the United Kingdom (8%). The majority of participants worked at an academic medical center (52%) and considered their practice to be at least partially genitourinary (GU)-subspecialized (74%). 57% of participants reported not routinely using intraprostatic focal boost. Even among complete subspecialists, a substantial proportion (39%) do not routinely use focal boost. Less than half of participants in both high-income and low-to-middle-income countries were shown to routinely use focal boost. The most commonly cited barriers were concerns about registration accuracy between MRI and CT (37%), concerns about risk of additional toxicity (35%), and challenges to accessing high-quality MRI (29%). Despite level 1 evidence from the FLAME trial, most radiation oncologists surveyed are not routinely offering focal RT boost. Adoption of this technique might be accelerated by increased access to high-quality MRI, better registration algorithms of MRI to CT simulation images, physician education on benefit-to-harm ratio, and training on contouring prostate lesions on MRI.


Psychometric evaluation of the Swedish version of the 30-item endometriosis health profile (EHP-30).
The 30-Item Endometriosis Health Profile (EHP-30) is a specific instrument measuring quality of life among women with endometriosis. Although the Swedish version of EHP-30 is widely used in research and clinical settings, it has not yet been evaluated psychometrically. Ensuring validity and reliability is of most importance when using translated instruments. Therefore, the aim of the study was to evaluate the psychometric properties of the Swedish version of the EHP-30. This study was conducted at a Swedish referral university hospital specializing in endometriosis. Data collection was performed in January 2013. The EHP-30 was sent to 369 randomly selected women with a laparoscopy-verified endometriosis diagnosis. The psychometric evaluation included evaluation of data completeness, score distributions, floor and ceiling effects, internal consistency, factor analysis and test-retest reliability. Out of the 211 women with endometriosis who answered the questionnaire, 128 were native Swedish speakers who had experienced symptoms of endometriosis during the past 4 weeks, and were included in the psychometric evaluation. Data completeness was 99.5%. The highest median score was found in the Control and Powerlessness subscale, and lowest in Pain. Distributions towards ill health were found in all subscales except for the pain subscale, but there were no noteworthy floor or ceiling effects. Internal consistency was good (Cronbach's α 0.83-0.96). Factor analysis could roughly confirm three of the five subscales. The test-rest analysis showed good reliability. Scores were systematically lower during the second measurement. We conclude that the Swedish version of EHP-30 is a valid and reliable instrument to measure health-related quality of life in women with endometriosis. It is understandable, acceptable and usable and can be recommended for use in clinical daily routines and for research purposes.


Combined hormonal contraception.
This article discusses the different combined hormonal contraception methods. Combined methods, delivering both estrogen and a progestin simultaneously, are among the most effective, widely used hormonal contraceptive options. They also have the best noncontraceptive benefit profile for young women of all hormonal contraceptive options. Oral contraceptive pills (OCPs) are described as the standard combined hormonal method and are discussed in detail. Newer combined hormonal contraceptive delivery systems, the transdermal patch, vaginal ring, and injectable form, are compared with OCPs in terms of pharmacology, efficacy, and adverse events. Advantages and disadvantages of all methods are emphasized, with particular attention to adolescent development and acceptability.


A preferential inhibition by Zn2+ on platelet activating factor- and thrombin-induced serotonin secretion from washed rabbit platelets.
Zinc ions at micromolar levels exhibited a significant inhibitory activity toward platelet activating factor (AGEPC)- and thrombin-induced serotonin release from washed rabbit platelets. In the ranges from 25 to 30 microM and 10 to 50 microM, respectively, zinc essentially prevented any serotonin release from 1.25 X 10(8) cells/microliter by 1 X 10(-10) M AGEPC and by 0.2 unit thrombin/ml. This inhibition by zinc ions, in micromolar range, occurred in the presence of 1.0 mM Ca2+. The amount of zinc needed for inhibition was inversely proportional to the amount of AGEPC present and further zinc must be added prior to or at the same time as the AGEPC to be effective. Introduction of zinc ions after the AGEPC essentially abolished the inhibitory properties of this divalent cation. Other cations such as Cu2+, La3+, Cd2+, and Mg2+ were ineffective as inhibitors at concentrations where zinc showed its maximal effects. Under conditions similar to those noted above, aggregation induced by AGEPC was blocked only to the extent of 25% of a control. No inhibitory action by zinc on thrombin-induced aggregation was noted. It is apparent that zinc ions influence a site(s) on the rabbit platelet of considerable importance to the activation (or signaling) process by AGEPC and thrombin in these cells, as expressed by serotonin release. Zinc should provide a suitable probe to explore the mechanism of action of these agonists in their interaction with sensitive cells and to define in more specific biochemical terms the putative receptor for these molecules.


Who's paying for new drugs?
Direct payment by patients for treatment with drugs still in development is the subject of controversy. The matter goes deeper than it might first appear.


Utilization of microbial biofilms as monitors of bioremediation.
A down-well aquifer microbial sampling system was developed using glass wool or Bio-Sep beads as a solid-phase support matrix. Here we describe the use of these devices to monitor the groundwater microbial community dynamics during field bioremediation experiments at the U.S. Department of Energy Natural and Accelerated Bioremediation Research Program's Field Research Center at the Oak Ridge National Laboratory. During the 6-week deployment, microbial biofilms colonized glass wool and bead internal surfaces. Changes in viable biomass, community composition, metabolic status, and respiratory state were reflected in sampler composition, type of donor, and groundwater pH. Biofilms that formed on Bio-Sep beads had 2-13 times greater viable biomass; however, the bead communities were less metabolically active [higher cyclopropane/monoenoic phospholipid fatty acid (PLFA) ratios] and had a lower aerobic respiratory state (lower total respiratory quinone/ PLFA ratio and ubiquinone/menaquinone ratio) than the biofilms formed on glass wool. Anaerobic growth in these systems was characterized by plasmalogen phospholipids and was greater in the wells that received electron donor additions. Partial 16S rDNA sequences indicated that Geobacter and nitrate-reducing organisms were induced by the acetate, ethanol, or glucose additions. DNA and lipid biomarkers were extracted and recovered without the complications that commonly plague sediment samples due to the presence of clay or dissolved organic matter. Although microbial community composition in the groundwater or adjacent sediments may differ from those formed on down-well biofilm samplers, the metabolic activity responses of the biofilms to modifications in groundwater geochemistry record the responses of the microbial community to biostimulation while providing integrative sampling and ease of recovery for biomarker analysis.


Ultrafine fibrous gelatin scaffolds with deep cell infiltration mimicking 3D ECMs for soft tissue repair.
In this research, ultrafine fibrous scaffolds with deep cell infiltration and sufficient water stability have been developed from gelatin, aiming to mimic the extracellular matrices (ECMs) as three dimensional (3D) stromas for soft tissue repair. The ultrafine fibrous scaffolds produced from the current technologies of electrospinning and phase separation are either lack of 3D oriented fibrous structure or too compact to be penetrated by cells. Whilst electrospun scaffolds are able to emulate two dimensional (2D) ECMs, they cannot mimic the 3D ECM stroma. In this work, ultralow concentration phase separation (ULCPS) has been developed to fabricate gelatin scaffolds with 3D randomly oriented ultrafine fibers and loose structures. Besides, a non-toxic citric acid crosslinking system has been established for the ULCPS method. This system could endow the scaffolds with sufficient water stability, while maintain the fibrous structures of scaffolds. Comparing with electrospun scaffolds, the ULCPS scaffolds showed improved cytocompatibility and more importantly, cell infiltration. This research has proved the possibility of using gelatin ULCPS scaffolds as the substitutes of 3D ECMs.


Correlation between estimated fetal weight and weight at birth in infants with gastroschisis and omphalocele.
An accurate estimated fetal weight (EFW) calculated with traditional formulae in cases of abdominal wall defects (AWDs) can be challenging. As a result of reduced abdominal circumference, fetal weight may be underestimated, which could affect prenatal management. Siemer et al. proposed a formula without the use of abdominal circumference, but it is not used in our protocols yet. Our aim was to evaluate the correlation of EFW and birth weight in fetuses with AWD by using Hadlock 1, Hadlock 2, and Siemer et al.'s formulae. Our secondary goal was to evaluate how often fetuses classified as small for gestational age (SGA) were in fact SGA at birth. This was a retrospective cohort study of gestations complicated by gastroschisis and omphalocele at two tertiary-care centers in Brazil and Italy during an 8-year period. Of a total of 114 cases, 85 (44 cases of gastroschisis and 41 cases of omphalocele) met our criteria. The last prenatal scan was performed 5.2 (±4.1) days before birth. The mean gestational age at birth was 37.2 (±1.8) weeks. Correlation of EFW with birth weight was calculated with the three formulae with and without adjustment for weight gain between scan and birth, with the use of the Spearman coefficient. The correlation between EFW and weight at birth was positive according to all three formulae for the infants with gastroschisis. This finding was not confirmed in the infants with omphalocele. All formulae overestimated the number of SGA cases: although only 17.6% of fetuses were actually SGA at birth, the Hadlock formulae had classified nearly 35% of them as SGA, and Siemer et al.'s formula, 15.3%. All three formulae yielded a good correlation between EFW in the last scan and birth weight in the infants with gastroschisis but not for those with omphalocele. Cases of SGA were overestimated.


Automated finite element modeling of the lumbar spine: Using a statistical shape model to generate a virtual population of models.
Population-based modeling of the lumbar spine has the potential to be a powerful clinical tool. However, developing a fully parameterized model of the lumbar spine with accurate geometry has remained a challenge. The current study used automated methods for landmark identification to create a statistical shape model of the lumbar spine. The shape model was evaluated using compactness, generalization ability, and specificity. The primary shape modes were analyzed visually, quantitatively, and biomechanically. The biomechanical analysis was performed by using the statistical shape model with an automated method for finite element model generation to create a fully parameterized finite element model of the lumbar spine. Functional finite element models of the mean shape and the extreme shapes (±3 standard deviations) of all 17 shape modes were created demonstrating the robust nature of the methods. This study represents an advancement in finite element modeling of the lumbar spine and will allow population-based modeling in the future.


Natural history of aortic root dilatation and pathologic aortic regurgitation in tetralogy of Fallot and its morphological variants.
We sought to characterize the natural history of aortic root dilatation and aortic regurgitation in tetralogy of Fallot (TOF). A single-center review of patients who underwent TOF repair from January 1960 to December 2022 was performed. Morphology was categorized as TOF-pulmonary stenosis or TOF-variant (including TOF-pulmonary atresia and TOF-pulmonary atresia-major aortopulmonary collateral arteries). Echocardiographically determined diameters and derived z scores were measured at the annulus, sinus of Valsalva, and sinotubular junction immediately before TOF repair and throughout follow-up. Linear mixed-effects models assessed trends in dimensions over time. Of 2205 patients who underwent primary repair of TOF at a median age of 4.9 months (interquartile range, 2.3-20.5 months) and survived to discharge, 1608 (72.9%) patients had TOF-pulmonary stenosis and 597 (27.1%) patients had TOF-variant. At a median postoperative follow-up of 14.4 years (interquartile range, 3.3-27.6 years; range, 0.1-62.6 years), 313 (14.2%) patients had mild or greater aortic regurgitation and 34 (1.5%) patients required an aortic valve or root intervention. The overall mean rates of annular, sinus of Valsalva, and sinotubular junction growth were 0.5 ± 0.2, 0.6 ± 0.3, and 0.7 ± 0.5 mm/year, respectively. Root z scores remained stable with time. At baseline, patients with TOF-variant had larger diameters and z scores at the annulus, sinus of Valsalva, and sinotubular junction, compared with patients with TOF-pulmonary stenosis (all P values < .05). Over time, patients with TOF-variant demonstrated relatively greater annular (P = .020), sinus of Valsalva (P < .001), and sinotubular junction (P < .001) dilatation. Patients with ≥75th percentile root growth rates had a higher incidence of mild or greater aortic regurgitation (P < .001), moderate or greater aortic regurgitation (P < .001), and aortic valve repair or replacement (P = .045). Patients with TOF-variant are at comparatively greater risk of pathologic root dilatation over time, warranting closer longitudinal follow-up.


Mucositis prevention by improved dental care in acute leukemia patients.
The aim of the present study was to evaluate the effects of the intensive dental care protocol in preventing oral complications in acute leukemia patients. Thirty-four patients hospitalized for induction remission therapy for acute leukemia were randomly assigned to one of two groups, whether to receive intensive dental care protocol or not. The intensive dental care group of patients received dental treatment and plaque and calculus removal prior to chemotherapy and supervised oral hygiene measures during chemotherapy. The limited dental care group of patients did not receive prechemotherapy dental care. Groups were comparable in age, sex, and antineoplastic treatment received. Patients were examined after admission to the hospital; at the initiation of the chemotherapy; and 7, 14, 21, and 28 days after initiation of therapy. Positive data about subjective difficulties were taken by anamnesis. Oral hygiene index (OHI) and gingival index (GI) were used to assess the periodontal status of the patients. The severity of mucositis was evaluated according to WHO classification. The results of this study pointed out lower mean values of GI and lower mean values of mucositis score in the intensive dental care group of patients during the whole period of examination. Although the differences in mean values were not statistically significant on most of the examination days, intensive dental care group of patients developed less severe and less painful oral complications compared to the limited dental care group of patients. We conclude that proper dental care and preventive measures both before and during chemotherapy can be beneficial to these patients.


Survey of attitudes regarding the use of siblings for gamete donation.
We conclude that the acceptability of using a sister for gamete donation is high among couples desiring ovum donation. On the contrary, couples undergoing AID generally rejected the concept of using the husband's brother as a known donor. Thus, although similar in concept, disparity exists regarding the use of siblings for gamete donation. Though the use of sibling gamete donation may provide a short-term solution to the dwindling supply of acceptable gamete donors, the long-term acceptability of such practice remains unknown.


Neuropeptide derivatives to regulate the reproductive axis: Kisspeptin receptor (KISS1R) ligands and neurokinin-3 receptor (NK3R) ligands.
Recent research has indicated pivotal roles for neuropeptides and their cognate receptors in reproductive physiology. Kisspeptins are RF-amide neuropeptides that stimulate gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides and positively regulates pulsatile GnRH secretion. These peptides are coexpressed in kisspeptin/NKB/Dyn (KNDy) neurons of the arcuate nucleus, where they contribute to the regulation of puberty onset and other reproductive functions. In this review, the design of peptide ligands for the kisspeptin (KISS1R) and neurokinin-3 (NK3R) receptors are described. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 588-597, 2016.


Real-world patient data: Can they support decision making and patient engagement?
Patient-reported outcomes (PROs) capture data related to patients' perception of their health status and aspects of health care delivery. In parallel, digital innovations have advanced the administration, storage, processing, and accessibility of PROs, allowing these data to become actively incorporated in day-to-day clinical practice along the entire patient care pathway. Further, the emergence of shared decision making, where patients are engaged in informed treatment selection aligned with their preferences, values, and needs, can be realized by PROs and technology. This technology-enabled, data-driven approach provides insights which, when actioned, can enhance musculoskeletal care of patients and populations, while enriching the clinician-patient experience of decision making. In this review, we provide an overview of the opportunities enabled by PROs and technology for the cycle of orthopedic care.


Phase II trial of amonafide in advanced pancreas cancer. A Southwest Oncology Group study.
Amonafide is a new synthetic anticancer agent whose mechanism of action is through inhibition of macromolecular synthesis as well as DNA intercalation. The Southwest Oncology Group (SWOG) has investigated this drug in a phase II study of pancreas cancer. Thirty-six patients were registered on this study: of these 29 were eligible for response evaluation, and 20 received the two cycles required for making a response assessment. Patients met the standard phase II criteria of no prior chemotherapy, measurable disease and a SWOG performance status of 2 or less. Toxicity, predominantly hematologic with significant neutropenia and thrombocytopenia, was quite severe. Four treatment related deaths were encountered. No responses were seen in thirty-six patients studied. We conclude that this drug is not active against adenocarcinoma of the pancreas.


Incidence of occult uterine sarcoma and other unexpected pathologies in patients having surgery for presumed myomas: A retrospective observational study.
To determine the incidence of occult uterine sarcomas and other unexpected pathologies in patients undergoing hysterectomies or myomectomies with a pre-operative diagnosis of uterine leiomyomas. Retrospective study. Tertiary hospital in Santiago, Chile. 921 women who underwent surgery for presumed myomas. Database analysis of surgical and pathological notes, from January 2007 to December 2017 with a preoperative diagnosis of uterine leiomyoma. number of patients with uterine sarcoma confirmed on histology. During this period, a total of 921 gynecological surgeries were performed for benign uterine fibroids of which 787 were hysterectomies and 134 were myomectomies. We found four cases of malignant neoplasms (0,43 %). Two were uterine leiomyosarcoma (LMS), one mixed epithelial and mesenchymal tumor, and one case of incidental cervical cancer. This gives an LMS incidence of 1 in 460 and 1 in 921 of mixed epithelial and mesenchymal tumor. There were seven cases of unexpected benign pathology. This included six atypical myomas and one leiomyoblastoma epithelioid myoma. If we combine the malignant and benign cases, we would have an incidence of 1.2 % of unexpected pathology. In our series of patients undergoing myomectomies or hysterectomies for presumed myomas the incidence of LMS was 1 in 460. The incidence of any unexpected pathology including benign ones in presumed myomas was 1 in 83 (six atypical myomas, one leiomyoblastoma epithelioid myoma, two LMS, one mixed epithelial and mesenchymal tumor, one incidental cervical cancer).


The electrophysiology of the motor neuron diseases.
The motor neuron diseases are a set of disorders associated with the selective degeneration of motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common and confers the gravest prognosis. Although ALS occurs with known genetic causes in a small minority, other motor neuron disorders have well-defined genetic mutations. Electrodiagnostic testing is important to distinguish these various disorders. Electrodiagnostic testing is also crucial for distinguishing potential mimic syndromes, such as multifocal motor neuropathy and inclusion body myositis. Newer neurophysiology techniques have been developed in the past several years. What role these techniques will play in clinical practice is currently unknown.


Evaluation of the ecological impacts of short- and long-chain perfluoroalkyl acids on constructed wetland systems: Perfluorobutyric acid and perfluorooctanoic acid.
Perfluoroalkyl substances (PFASs) contamination of aquatic system has attracted widespread attention in recent years. From both plant and microbial perspectives, the ecological risk of CWs by comparing PFASs with different chain lengths have not been fully understood. In this study, the influences of perfluorobutyric acid (PFBA) and perfluorooctanoic acid (PFOA) as typical of short- and long-chains on the ecological effect of CWs have been specifically studied. The results showed that plants produced oxidative stress response and the activities of superoxide dismutase (SOD) and peroxidase (POD) in leaves were stimulated by 17.23-28.13% and 10.49-14.17% upon 10 mg/L PFBA and PFOA exposure. Under the high level of PFBA and PFOA stress, the chlorophyll content was reduced by 15.20-39.40% and lipid peroxidation was observed in leaves with the accumulation of malondialdehyde (MDA) at 1.20-1.22 times of the control. Dehydrogenase (DHA) exhibited the most sensitivity in the presence of PFBA and PFOA with an inhibition ratio of over 90%. The biotoxicity of PFOA was higher than that of PFBA in terms of the inhibition degree of several substrate enzymes. The information of Illumina Miseq sequencing indicated that the diversity and structure of microbial community in CWs were significantly altered by PFBA and PFOA addition and led to an enrichment of more PFASs-tolerant bacteria.


Hospitalized prenatal and childhood infections and obesity in Danish male conscripts.
We examined the relation between early life infections and adult obesity. A cohort of Danish males who underwent mandatory army fitness examinations was studied. Hospitalizations for childhood infections and their mothers' hospitalization for infection during pregnancy were identified via the Danish National Registry of Patients. The outcome was obesity (body mass index ≥ 30 kg/m(2)) at conscription. We calculated prevalence odds ratios (OR) and 95% confidence intervals (CI) associating the obesity with whether the conscript had a hospitalization for infection up to age 5, and separately, whether the conscript's mother was hospitalized for an infection prenatally. Of the 17,456 men, 13% had a childhood infection (8.2% of whom were obese, compared with 7.4% without childhood infection); 1.2% of conscripts were exposed to a prenatal infection (10% of whom were obese, compared with 7.4% without prenatal infection). For childhood infection, the adjusted OR was 1.21 (95% CI, 1.01-1.44); stratified analyses suggested the association may be greater among conscripts born preterm (adjusted OR, 2.08; 95% CI, 1.06-4.09), whereas among the conscripts who were full term, the adjusted OR was 1.15 (95% CI, 0.96-1.38). For prenatal infection, the adjusted OR was 1.34 (95% CI, 0.82-2.19). We found a small association between both prenatal and childhood infections and prevalent obesity in early adulthood, although the results may be partly explained by unmeasured confounders.


Nutritional regulation of host resistance and predictive value of immunologic tests in assessment of outcome.
In this review, the authors describe the current information on nutrition modulation of immunity, enumerate the various immunologic tests that are potentially useful in nutritional assessment, examine the reliability of tests predicting disease and complications, and discuss how immunologic evaluation may help in the decision process regarding nutritional support.


Heterogeneous biocatalytic system for effective decolorization of textile dye effluent.
The current physicochemical methods for decolorizing toxic synthetic dyes are not sustainable to halt the environmental damage as they are expensive and often produce concentrated sludge, which may lead to secondary disposal problems. Biocatalysis (microbes and/or their enzymes) is a cost-effective, versatile, energy-saving and clean alternative. The most common enzymes involved in dye degradation are laccases, azoreductases and peroxidases. Toxic dyes could be converted into less harmful byproducts through the combined action of many enzymes or the utilization of whole cells. The action of whole cells to treat dye effluents is either by biosorption or degradation (aerobic or anaerobic). Using immobilized cells or enzymes will offer advantages such as superior stability, persistence against harsh environmental conditions, reusability and longer half-lives. This review envisages the recent strategies of immobilization and bioreactor considerations with the immobilized system as the effective treatment of textile dye effluents. Packed bed reactors are the most popular heterogeneous biocatalytic reactors for dye decolorization due to their efficiency and cost-effectiveness.


Managing occupational safety and health in aluminum production: case study of aluminum production factory, Mostar, Bosnia and Herzegovina.
To assess the effect of modernization of the aluminium production on physical and chemical health hazards at work environment in the Aluminium Mostar factory. The modernization included introduction of automatic equipment, computerized management, and rationalized coke manipulation in Anoda, Electrolysis, and Cast House plants. Periodical measurements of chemical (gas concentrations and aerosols) and physical (microclimatic factors, noise, and illumination) factors were performed at the same workplaces by the same methods of measurements before (1982-1988) and after the modernization (2004). The measured values were compared with the recommended Occupational Safety and Health Standards of Bosnia and Herzegovina. The number of workplaces with a high noise level was reduced from 65.0% (89/137) in 1982-1988 to 28.7% (51/178) in 2004. The best results were achieved in Cast House plant. The illumination of the workplace was partly improved. Values of microclimatic factors did not considerably change; they deviated from the recommended values at nearly all the workplaces in the factory. The concentrations of chemical agents were above the recommended standards in 56.3% (196/348) of the samples in 1982-1988, and in only 15.4% (99/645) of the samples tested in 2004. High concentrations of hydrogen fluoride have remained the primary pollutant in Electrolysis plant. The modernization of the factory has considerably reduced the amount of harmful substances at work environment in the Aluminum Mostar. However, the exposure to unfavorable physical factors has been only partly reduced.


A sensitive quantitative analysis of abiotically synthesized short homopeptides using ultraperformance liquid chromatography and time-of-flight mass spectrometry.
In the origins of life field understanding the abiotic polymerization of simple organic monomers (e.g., amino acids) into larger biomolecules (e.g., oligopeptides), remains a seminal challenge. Recently, preliminary observations showed a limited set of peptides formed in the presence of the plausible prebiotic phosphorylating agent, diamidophosphate (DAP), highlighting the need for an analytical tool to critically evaluate the ability of DAP to induce oligomerization of simple organics under aqueous conditions. However, performing accurate and precise, targeted analyses of short oligopeptides remains a distinct challenge in the analytical chemistry field. Here, we developed a new technique to detect and quantitate amino acids and their homopeptides in a single run using ultraperformance liquid chromatography-fluorescence detection/time of flight mass spectrometry. Over an 8-minute retention time window, 18 target analytes were identified and quantitated, 16 of which were chromatographically separated at, or near baseline resolution. Compound identity was confirmed by accurate mass analysis using a 10 ppm mass tolerance window. This method featured limits of detection < 5 nM (< 1 fmol on column) and limits of quantitation (LOQs) <15 nM (< 3 fmol on column). The LODs and LOQs were upwards of ∼28x and ∼788x lower, respectively, than previous methods for the same analytes, highlighting the quantifiable advantages of this new method. Both detectors provided good quantitative linearity (R2 > 0.985) for all analytes spanning concentration ranges ∼3 - 4 orders of magnitude. We performed a series of laboratory experiments to investigate DAP-mediated oligomerization of amino acids and peptides and analyzed experimental products with the new method. DAP readily polymerized amino acids and peptides under a range of simulated environmental conditions. This research underscores the potential of DAP to have generated oligopeptides on the primordial Earth, enhancing prebiotic chemical diversity and complexity at or near the origin of life.


Synthesis and anti-histaminic activity of some novel pyrimidines.
Novel pyrimidines were prepared by the condensation of chalcones of 4'-piperazine acetophenone with guanidine HCl. The structures of the synthesized compounds RP 1-5 were assigned on the basis of elemental analysis, IR, (1)H NMR and mass spectroscopy. These compounds were also screened for anti-histaminic activity. The recorded percentage of histamine inhibition showed a significant anti-histaminic activity when compared to the reference anti-histaminic drug mepiramine.


Liver function and structure in survivors of acetaminophen poisoning. A follow-up study of serum bile acids and liver histology.
A series of 30 patients, hospitalized with acetaminophen overdose, were studied during initial admission and again three months later. The quantity of acetaminophen ingested varied from 5 to 50 g and 19 patients developed raised transaminase levels in the serum during the initial period. Liver damage, on the basis of needle biopsy findings, was categorized as severe in 5, moderate in 7, and mild or minimal in 18 patients. At three months' follow-up all but one of the biochemical indicants of liver damage had reverted to normal in all patients. The exception was the serum total bile acids. Residual changes found on liver biopsy at three months were minimal and nonspecific, apart from one previously severely affected patient in whom there was evidence of scarring. It is concluded that in the usual spectrum of acetaminophen poisoning requiring hospitalization there is no evidence of lasting liver damage.


Seven naphtho-γ-pyrones from the marine-derived fungus Alternaria alternata: structure elucidation and biological properties.
Eight bioactive pyrone derivatives were identified from the culture of Alternaria alternata strain D2006, isolated from the marine soft coral Denderonephthya hemprichi, which was selected as its profound antimicrobial activities. The compounds were assigned as pyrophen (1), rubrofusarin B (2), fonsecin (3), and fonsecin B (5) beside to the four dimeric naphtho-γ-pyrones; aurasperone A (6), aurasperone B (7), aurasperone C (8), and aurasperone F (9). Structures of the isolated compounds were identified on the basis of 1D and 2D NMR spectroscopy and mass (EI, ESI, HRESI) data, and by comparison with the literature. Configuration of the four dimeric naphtho-γ-pyrones 6-9 was analyzed by CD spectra, exhibiting an identical stereochemistry.


Prevalence and impact of bilateral vestibular hypofunction: results from the 2008 US National Health Interview Survey.
Profound bilateral vestibular hypofunction (BVH) causes disabling oscillopsia, chronic disequilibrium, and postural instability, but little is known about its epidemiology and impact. To assess prevalence and functional impact of BVH in the US adult population. National cross-sectional survey using a national database and corollary validation study. Adult respondents to the 2008 Balance and Dizziness Supplement to the US National Health Interview Survey (N = 21 782). Prevalence of BVH, socioeconomic and quality-of-life impact of BVH, and fall risk. Criteria for the survey-based diagnosis of BVH included all of the following: presence of visual blurring with head movement; unsteadiness; difficulty walking in darkness or unsteady surfaces and in a straight path; and symptoms being at least "a big problem" and present for at least 1 year, in the absence of other neurologic conditions or eye pathologic conditions affecting vision. Adjusted national estimates from this survey indicate the prevalence of BVH in 2008 was 28 per 100 000 US adults (64 046 Americans). Of the participants with BVH, 44% reported changing their driving habits because of their symptoms, 56% reported reduced participation in social activities, and 58% reported difficulties with activities of daily living. Respondents with BVH had a 31-fold increase in the odds of falling in multivariate analyses compared with all respondents, with 25% reporting a recent fall-related injury. As estimated by the presence of specific symptoms in a nationally representative survey, BVH has considerable socioeconomic and quality-of-life impacts and significantly increases fall risk. These data support the need for new therapeutic strategies for BVH, including vestibular rehabilitation and implantable vestibular prostheses.


Laboratory characteristics of acute encephalopathy with multiple organ dysfunctions.
To clarify the laboratory characteristics and deduce the pathogenesis of acute encephalopathy associated with multiple organ dysfunctions in Japan. We measured cytokine levels [tumor necrosis factor alpha (TNF-alpha), soluble tumor necrosis factor-receptor 1 (sTNF-R1), and interleukin-6 (IL-6)] in serum and cerebrospinal fluid (CSF) as well as general laboratory examinations in 27 patients with acute encephalopathy. Urea nitrogen (UN), creatinine (Cr), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and C-reactive protein (CRP) levels in blood, and CSF protein levels at the initial stage were significantly higher in patients with an unfavorable outcome. TNF-alpha, sTNF-R1, and IL-6 levels at the initial stage were higher in the serum than in the CSF of patients with acute encephalopathy. Serum cytokine levels correlated well with patient outcome. The high CSF protein level and the high UN, Cr, AST, LDH, and CRP levels in the blood represent the severity of vascular leakage through the blood-brain barrier and multiple organ dysfunctions, respectively, and thus suggest an unfavorable prognosis. The high serum inflammatory cytokine levels at the initial stage and the good correlation of those levels with the outcome suggest that intravascular inflammation has a significant role in vascular leakage and multiple organ dysfunctions in acute encephalopathy.


Development and Preliminary Validation of the Physical Education-Study Process Questionnaire : Insights for Physical Education University Students.
The Revised Two Factor Study Process Questionnaire (R-SPQ-2F) is used to examine students' study approaches in higher education. The questionnaire is designed to measure two factors: deep and surface approaches. In order to measure these approaches for students in physical education and sport, a new measurement instrument should take into consideration the practical context of this field of education that makes it specific to other fields. The present study aims (a) to develop and empirical test of a new instrument for measuring the study process in physical education and sports students, and (b) to test psychometric properties of the tool. Two exploratory and confirmatory samples of physical education students enrolled in a bachelor's degree program in physical education at the High Institute of Physical Education and Sports of Kef-Tunisia, aged 19-26 years, were recruited online among female students (n = 414) and male students (n = 393). The participants filled in Google Form survey including Physical Education-Study Process Questionnaire (PE-SPQ) and the Arabic version of the Revised Study Process Questionnaire-2 Factors (R-SPQ-2F). Exploratory factor analysis showed a suitable four factors solution, which is approved by confirmatory factor analysis indices [χ2 = 466.47, TLI = 0.94, CFI = 0.95; RMSEA = 0.56 IC 90% (0.050-0.062)]. Internal consistency of the PE-SPQ simultaneously checked by McDonald's ω, Cronbach's α and Gutmann's λ6 showed good reliability of the PE-SPQ. Convergent validity examined by Average variance extracted (AVE) was good. The comparison between the AVE root mean square and Pearson correlation coefficients of each factor with his indicators reveals the discriminant validity of the PE-SPQ. Furthermore, Pearson's correlation between the PE-SPQ factors and the R-SPQ-2F establishes the concurrent validity of the new scale. The PE-SPQ scale is valid and reliable and can be used to assess study process factors in physical education students.


Tailoring vapor film beneath a Leidenfrost drop.
For a drop on a very hot solid surface, a vapor film will form beneath the drop, which has been discovered by Leidenfrost in 1756. The vapor escaping from the Leidenfrost film causes uncontrollable flows, and actuates the drop to move around. Recently, although numerous strategies have been used to regulate the Leidenfrost vapor, the understanding of surface chemistry for modulating the phase-change vapor dynamics remains incomplete. Here, we report how to rectify vapor by "cutting" the Leidenfrost film using chemically heterogeneous surfaces. We demonstrate that the segmented film cut by a Z-shaped pattern can spin a drop, since the superhydrophilic region directly contacts the drop and vaporizes the water, while a vapor film is formed on the superhydrophobic surrounding to jet vapor and reduce heat transfer. Furthermore, we reveal the general principle between the pattern symmetry design and the drop dynamics. This finding provides new insights into the Leidenfrost dynamics modulation, and opens a promising avenue for vapor-driven miniature devices.


Commercial AI solutions in detecting COVID-19 pneumonia in chest CT: not yet ready for clinical implementation?
In response to the COVID-19 pandemic, many researchers have developed artificial intelligence (AI) tools to differentiate COVID-19 pneumonia from other conditions in chest CT. However, in many cases, performance has not been clinically validated. The aim of this study was to evaluate the performance of commercial AI solutions in differentiating COVID-19 pneumonia from other lung conditions. Four commercial AI solutions were evaluated on a dual-center clinical dataset consisting of 500 CT studies; COVID-19 pneumonia was microbiologically proven in 50 of these. Sensitivity, specificity, positive and negative predictive values, and AUC were calculated. In a subgroup analysis, the performance of the AI solutions in differentiating COVID-19 pneumonia from other conditions was evaluated in CT studies with ground-glass opacities (GGOs). Sensitivity and specificity ranges were 62-96% and 31-80%, respectively. Negative and positive predictive values ranged between 82-99% and 19-25%, respectively. AUC was in the range 0.54-0.79. In CT studies with GGO, sensitivity remained unchanged. However, specificity was lower, and ranged between 15 and 53%. AUC for studies with GGO was in the range 0.54-0.69. This study highlights the variable specificity and low positive predictive value of AI solutions in diagnosing COVID-19 pneumonia in chest CT. However, one solution yielded acceptable values for sensitivity. Thus, with further improvement, commercial AI solutions currently under development have the potential to be integrated as alert tools in clinical routine workflow. Randomized trials are needed to assess the true benefits and also potential harms of the use of AI in image analysis. • Commercial AI solutions achieved a sensitivity and specificity ranging from 62 to 96% and from 31 to 80%, respectively, in identifying patients suspicious for COVID-19 in a clinical dataset. • Sensitivity remained within the same range, while specificity was even lower in subgroup analysis of CT studies with ground-glass opacities, and interrater agreement between the commercial AI solutions was minimal to nonexistent. • Thus, commercial AI solutions have the potential to be integrated as alert tools for the detection of patients with lung changes suspicious for COVID-19 pneumonia in a clinical routine workflow, if further improvement is made.


Different IncI1 plasmids from Escherichia coli carry ISEcp1-blaCTX-M-15 associated with different Tn2-derived elements.
The bla(CTX-M-15) gene, encoding the globally dominant CTX-M-15 extended-spectrum β-lactamase, has generally been found in a 2.971-kb ISEcp1-bla(CTX-M-15)-orf477Δ transposition unit, with ISEcp1 providing a promoter. In available IncF plasmid sequences from Escherichia coli, this transposition unit interrupts a truncated copy of transposon Tn2 that lies within larger multiresistance regions. In E. coli, bla(CTX-M-15) is also commonly associated with IncI1 plasmids and here three such plasmids from E. coli clinical isolates from western Sydney 2006-2007 have been sequenced. The plasmid backbones are organised similarly to those of other IncI1 plasmids, but have insertions and/or deletions and sequence differences. Each plasmid also has a different insertion carrying bla(CTX-M-15). pJIE113 (IncI1 sequence type ST31) is almost identical to plasmids isolated from the 2011 E. coli O104:H4 outbreak in Europe, where the typical bla(CTX-M-15) transposition unit interrupts a complete Tn2 inserted directly in the plasmid backbone. In the novel plasmid pJIE139 (ST88), ISEcp1-blaC(TX-M-15)-orf477Δ lies within a Tn2/3 hybrid transposon. Homologous recombination could explain movement of ISEcp1-bla(CTX-M-15)-orf477Δ between copies of Tn2 on IncF and IncI1 plasmids and generation of the Tn2/3 hybrid. pJIE174 (ST37) is almost identical to pESBL-12 from the Netherlands and in these plasmids bla(CTX-M-15) is flanked by two copies of IS26 that truncate the transposition unit within a larger region bounded by the ends of Tn2. bla(CTX-M-15) and the associated ISEcp1-derived promoter may be able to move from this structure by the actions of IS26, independently of both ISEcp1 and Tn2.


Assessing Accuracy of Wrist-Worn Wearable Devices in Measurement of Paroxysmal Supraventricular Tachycardia Heart Rate.
Wrist-worn wearable devices provide heart rate (HR) monitoring function via photoplethysmography technology. Recently, these devices have been used by patients to measure the HR when palpitation occurs, but few validation studies of these instruments have been conducted. We assessed the accuracy of these devices for measuring a HR. This study enrolled 51 consecutive patients with a history of paroxysmal supraventricular tachyarrhythmia (SVT) or paroxysmal palpitations who were scheduled to undergo an electrophysiological study (EPS). Three devices were assessed: Apple Watch Series 2 (Apple), Samsung Galaxy Gear S3 (Galaxy), and Fitbit Charge 2 (Fitbit). Patients were randomly assigned to wear 2 different devices. The HR at baseline and induced SVT were measured during the EPS. After successful ablation of SVT, HR measurements was also done during atrial and ventricular pacing study. The mean patient age was 44.4±16.6 years and 27 patients were male (53%). The accuracy (within ±5 beats per minute [bpm] of an electrocardiogram [ECG] measurement) of the baseline HR measurements was 100%, 100%, and 94%, for Apple, Galaxy, and Fitbit, respectively. The HR during induced SVT ranged from 108 bpm to 228 bpm and the accuracy (within ±10 bpm of an ECG) was 100%, 90%, and 87% for the Apple, Galaxy, and Fitbit, respectively. During pacing study, accuracy of these devices was also acceptable but tended to decrease as the HR increased, and showed differences between the devices. Wrist-worn wearable devices accurately measure baseline and induced SVT HR. Clinical Research Information Service Identifier: KCT0002282.


Microenvironment-Responsive Prodrug-Induced Pyroptosis Boosts Cancer Immunotherapy.
The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage-associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor-specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual-responsive nano-prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual-responsive system facilitates the nano-prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo-photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo-photodynamic therapy and control-release PTX synergistically induce gasdermin E (GSDME)-related pyroptosis. It is speculated that inspired chemo-photodynamic therapy using the presented nano-prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency.


Catastrophic reactions and other behaviors of Alzheimer's residents: special unit compared with traditional units.
Using a quasi-experimental pretest/posttest design, the effects of a Special Care Unit (SCU) on the incidence of catastrophic reactions and other behaviors of nursing home residents with Alzheimer's disease (AD) were examined. Findings indicate significantly fewer catastrophic reactions and other selected behavior changes occurred during the posttest period for subjects in the experimental group compared with the subjects in the control group. Implications for psychiatric consultation/liaison nurses (PCLNs) working with this vulnerable population are discussed.


Molecular Updates in Prostate Cancer.
A wide array of molecular markers and genomic signatures, reviewed in this article, may soon be used as adjuncts to currently established screening strategies, prognostic parameters, and early detection markers. Markers of genetic susceptibility to PCA, recurrent epigenetic and genetic alterations, including ETS gene fusions, PTEN alterations, and urine-based early detection marker PCA3, are discussed. Impact of recent genome-wide assessment on our understanding of key pathways of PCA development and progression and their potential clinical implications are highlighted.


Effect of Nitro-Substituted Ending Groups on the Photovoltaic Properties of Nonfullerene Acceptors.
Chemical modification of end groups has proved to be an effective way to design new acceptor-donor-acceptor (A-D-A)-structured nonfullerene acceptors (NFAs) for high-performance organic solar cells (OSCs). Herein, we designed and synthesized two nitro-substituted end groups, N1 and N2. Using the two end groups as A units, two A-D-A acceptors, F-N1 and F-N2, were obtained. It also has been found that the nitro substitution position on end groups affects not only the absorptions and energy levels of the resultant acceptor materials but also their molecular packing behavior and active layer morphologies. In addition, the devices based on the two acceptors showed different energy losses. Power-conversion efficiencies (PCEs) of 10.66 and 11.86% were achieved for F-N1- and F-N2-based devices, respectively. This work reveals that the nitration of end groups is one of the potential strategies for designing high-performance photovoltaic active layer materials.


The copper dependent-lysyl oxidases contribute to the pathogenesis of pulmonary emphysema in chronic obstructive pulmonary disease patients.
Abnormalities in the elastic fiber biology are seen in pulmonary emphysema (PE). The copper-dependent lysyl oxidases regulate the production and accumulation of elastic fibers in the connective tissue. This study focused on the relationship between lysyl oxidase (LOX), LOX-like protein 1 (LOXL1), and LOXL2 and PE pathogenesis. Lung samples with or without PE from patients with chronic obstructive lung disease (n=35) were used. Protein levels of elastin, LOX, LOXL1, LOXL2, hypoxia inducible factor 1-alpha (HIF-1α), copper metabolism domain containing-1 (COMMD1), and phosphatase and tensin homolog (PTEN) were assayed using microscopic and biochemical methods The emphysematous areas were characterized by enlargement of the alveoli, destruction of the alveolar structure, accumulation of macrophages in the alveolar lumens, and showed increased HIF-1α immunoreactivity. Additionally, the emphysematous areas had significantly lower elastin, LOX, LOXL1, LOXL2, HIF-1α, COMMD1, and PTEN protein levels than the non-emphysematous areas. We suppose that the reductions in the HIF-1α levels led to decreases in the protein levels of active LOX, LOXL1, and LOXL2. These decreases might cause abnormalities in the elastic fiber biology. HIF-1α activation induced by decreased COMMD1 and protease activation induced by decreased PTEN might contribute to the development of PE. Finally, methods aimed at increasing the protein levels of LOXs, COMMD1 and PTEN might be effective for treating PE.


Machine Learning Models Based on Molecular Fingerprints and an Extreme Gradient Boosting Method Lead to the Discovery of JAK2 Inhibitors.
Developing Janus kinase 2 (JAK2) inhibitors has become a significant focus for small-molecule drug discovery programs in recent years because the inhibition of JAK2 may be an effective approach for the treatment of myeloproliferative neoplasm. Here, based on three different types of fingerprints and Extreme Gradient Boosting (XGBoost) methods, we developed three groups of models in that each group contained a classification model and a regression model to accurately acquire highly potent JAK2 kinase inhibitors from the ZINC database. The three classification models resulted in Matthews correlation coefficients of 0.97, 0.94, and 0.97. Docking methods including Glide and AutoDock Vina were employed to evaluate the virtual screening effectiveness of our classification models. The R2 of three regression models were 0.80, 0.78, and 0.80. Finally, 13 compounds were biologically evaluated, and the results showed that the IC50 values of six compounds were identified to be less than 100 nM. Among them, compound 9 showed high activity and selectivity in that its IC50 value was less than 1 nM against JAK2 while 694 nM against JAK3. The strategy developed may be generally applicable in ligand-based virtual screening campaigns.


Characterisation of the arrestment responses of Trichogramma evanescens.
Contact kairomones and oviposition in a host egg stimulated arrestment behaviour in Trichogramma evanescens, characterised by a reduction in walking speed and increased turning. Previous oviposition experience did not influence a parasitoid's response to contact kairomones, but successive encounters with kairomone patches resulted in parasitoids habituating to the contact chemical. Oviposition on a kairomone patch did not reverse this habituation effect. It was concluded that contact kairomones and host eggs will both contribute independently to the duration of a patch visit. The selection of patches by T. evanescens will depend on its response to kairomones. Results from this study indicate that the application of contact kairomones to field crops will not necessarily increase the probability of parasitoids finding hosts.


Salvage arthrodesis for charcot arthropathy.
The principles of fusion of a Charcot joint arise from the assertion that successful fusion requires removal of all cartilage, debris, and sclerotic bone. The authors believe that reconstruction can prevent amputation in patients who have unbraceable or unstable deformities, or recurrent ulcerations. The goal with any Charcot reconstruction procedure is to achieve a plantigrade foot free of ulceration, and to prevent any future collapse, deformity, or ulcerations. The authors strongly believe arthrodesis of unstable joints of the Charcot neuropathic foot can lead to limb salvage and better quality of life.


[Second-look and third-look laparotomies in follow-up of ovarian cancer. A critical review of 6 years' experience].
The authors report about their experience during the years 1980-1985 with second-look and third-look laparotomies in the follow-up of ovarian carcinoma, after completed radical surgery and postoperative chemotherapy in 23 patients. Morbidity and mortality of the procedure in their series, together with survival rates after the operation, as well as its value as part of the general therapeutic approach to ovarian carcinoma, are discussed.


Comparison of the pulmonary vasculature in newborns and stillborns with congenital diaphragmatic hernia.
The purpose of this study was to compare structural changes in the pulmonary vasculature in newborns with congenital diaphragmatic hernia (CDH) complicated by persistent pulmonary hypertension (PPH) and stillborns with CDH. Victorian blue van Gieson (VVG) staining and immunostaining with anti-alpha smooth-muscle actin (ASMA) was performed on lung tissue obtained at autopsy from 23 newborns with CDH complicated by PPH, 7 stillborns with CDH, and 11 age-matched controls with sudden infant death syndrome (SIDS). The degrees of adventitial and medial thickness and area were measured in pulmonary arteries with an external diameter (ED) of <75 micrometers, 75-100 micrometers, 100-150 micrometers, 150-250 micrometers, 250-500 micrometers, and >500 micrometers by image analyzer and compared statistically. The degrees of adventitial and medial thickness and area were measured in pulmonary veins with an ED of <100 micrometers, 100-200 micrometers, and >200 micrometers by image analyzer and compared statistically. In order to determine whether the characteristic structural changes were size-related, each was related to ED. There was a significant increase in adventitial thickness and area in arteries of all sizes in both newborns and stillborns with CDH compared to SIDS patients (P < 0. 05). The degree of medial thickness in newborns and stillborns with CDH was significantly increased compared to SIDS patients (P < 0.01). The degree of medial area was significantly increased for arteries with ED less than 100 micrometers (P < 0.05) in newborns and stillborns with CDH compared with SIDS patients. There was a significant increase in adventitial thickness and area in veins of all sizes in newborns with CDH compared to stillborns with CDH and SIDS (P < 0. 05). The degree of adventitial thickness and area of pulmonary veins were similar in stillborns with CDH and SIDS. There were no significant differences in medial thickness of veins between the three groups. The presence of abnormally thick-walled pulmonary arteries in stillborns with CDH suggests that the intrapulmonary arteries in CDH may become excessively muscularized during fetal life, becoming unable to adapt normally at birth. The absence of structural changes in pulmonary veins in stillborns with CDH suggests that the pulmonary venous changes observed in newborns with CDH complicated by PPH occur after birth as a result of increases in transvascular pressure or a response to release of peptide growth factors.


Stereopsis: where depth is seen.
Disparity-selective cells appear to occur in all parts of the visual cortex, but a recent fMRI study finds that some cortical areas are more strongly associated with disparity than others. More sophisticated tests of binocular function may be needed to identify the properties of single neurons that support this specialization.