Primary motor cortex activation by transcranial direct current stimulation in the human brain.
Transcranial direct current stimulation (tDCS) can modulate motor cortex excitability in the human brain. We attempted to demonstrate the cortical stimulation effect of tDCS on the primary motor cortex (M1) using functional MRI (fMRI). An fMRI study was performed for 11 right-handed healthy subjects at 1.5 T. Anodal tDCS was applied to the scalp over the central knob of the M1 in the left hemisphere. A constant current with an intensity of 1.0 mA was applied. The total fMRI paradigm consisted of three sessions with a 5-min resting period between each session. Each session consisted of five successive phases (resting-tDCS-tDCS-tDCS-tDCS), and each of the phases was performed for 21s. Our findings revealed that no cortical activation was detected in any of the stimulation phases except the fourth tDCS phase. In the result of group analysis for the fourth tDCS phase, the average map indicated that the central knob of the left primary motor cortex was activated. In addition, there were activations on the left supplementary motor cortex and the right posterior parietal cortex. We demonstrated that tDCS has a direct stimulation effect on the underlying cortex. It seems that tDCS is a useful modality for stimulating a target cortical region.


[Prospects for measuring the rheologic characteristics of human soft tissues based on the recording of their transverse rigidity].
It is shown by an example of a forearm that to determine objective characteristics of rheological properties of soft human tissues by measuring their transverse stiffness (K) one should first investigate the relation between K and the diameter of the used indentor (d). The nonlinearity of the dependence K(d) for indentor diameters from 2 to 8 mm is demonstrated and it is assumed that this nonlinearity is due to heterogeneity of tissue properties in the directions normal to the axis of force action.


Production of the Anticarsia gemmatalis multiple nucleopolyhedrovirus in serum-free suspension cultures of the saUFL-AG-286 cell line in stirred reactor and airlift reactor.
The velvetbean caterpillar, Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae), is one of the main plagues for soybean crops. Velvetbean caterpillar larvae are susceptible to be infected by occlusion bodies of the baculovirus Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV), a biological insecticide. The insect cell line saUFL-AG-286 produces very high yields of occlusion bodies of AgMNPV in suspension cultures done in the low-cost serum-free medium UNL-10 in shake-flasks. However, its ability to adapt to conditions of industrial production in bioreactors was unknown. The aim of this study was to characterize the growth of saUFL-AG-286 cell cultures in UNL-10 medium, as well as its capability to replicate AgMNPV in two different bio-reactors at laboratory scale. The cell line was able to adapt to conditions that can be used at industrial scale, both in an airlift reactor and a stirred reactor, although the former was better than the last to support the cell growth. The infection with AgMNPV in the airlift reactor produced a high yield of occlusion bodies, with very low production of budded virus, the progeny used as inoculums. On the other hand, infection in the stirred reactor yielded high titers of budded virus. These results suggest that a feasible strategy for scaling-up the production of AgMNPV might involve the use of airlift reactors for the scaling-up of cell suspension cultures and the final production of occlusion bodies, while the scaling-up of the viral inoculums being carried out under conditions as those existing in stirred reactors.


Social networking site (SNS) use by adolescent mothers: Can social support and social capital be enhanced by online social networks? - A structured review of the literature.
to critically appraise the available literature and summarise the evidence relating to adolescent mothers' use of social networking sites in terms of any social support and social capital they may provide and to identify areas for future exploration. social networking sites have been demonstrated to provide social support to marginalised individuals and provide psycho-social benefits to members of such groups. Adolescent mothers are at risk of; social marginalisation; anxiety disorders and depressive symptoms; and poorer health and educational outcomes for their children. Social support has been shown to benefit adolescent mothers thus online mechanisms require consideration. a review of original research articles METHOD: key terms and Boolean operators identified research reports across a 20-year timeframe pertaining to the area of enquiry in: CINAHL, Cochrane Library, Medline, Scopus, ERIC, ProQuest, PsychINFO, Web of Science, Health Collection (Informit) and Google Scholar databases. Eight original research articles met the inclusion criteria for this review. studies demonstrate that adolescent mothers actively search for health information using the Internet and social networking sites, and that social support and social capital can be attributed to their use of specifically created online groups from within targeted health interventions. Use of a message board forum for pregnant and parenting adolescents also demonstrates elements of social support. There are no studies to date pertaining to adolescent mothers' use of globally accessible social networking sites in terms of social support provision and related outcomes. further investigation is warranted to explore the potential benefits of adolescent mothers' use of globally accessible social networking sites in terms of any social support provision and social capital they may provide.


A comparison of preoperative radiotherapy regimens for bladder carcinoma. The University of Pennsylvania experience.
Between 1976 and 1985, 155 patients from the Hospital of the University of Pennsylvania, the Philadelphia Veterans Administration Hospital, and the Fox Chase Cancer Center were divided into groups, each of which was treated with one of three preoperative radiotherapy regimens to be followed by cystectomy. Patients initially were treated with 4000 cGy during 4 weeks followed by cystectomy (16 patients). Beginning in 1978, patients received 2000 cGy in 1 week prior to surgery (70 patients). Since 1982, 40 patients were treated with 500 cGy on the day prior to surgery with postoperative radiation therapy reserved for patients with either involved margins of resection, advanced stage or high grade. A fourth group of 20 patients was either not offered or refused preoperative radiation. Nine patients received only postoperative radiation therapy. The 5-year actuarial disease-free survival for pathologic Stages B2, C, and D lesions (T3-4, N0-2), was 63% for those who had received high-dose radiation versus 21% for those that had low-dose or no radiation. Patients with advanced pathologic stage disease who had received greater than 2000 cGy had a reduced rate of local failure (11% versus 27% for those who had received less treatment). Patients with abnormal upper tracts as shown on the intravenous pyelograms (IVP) had a reduced 5-year determinate survival of 23% versus 65% for patients with normal upper tracts. This condition did not independently affect survival, but rather reflected advanced stage. Patients with abnormal creatinine levels had a decreased survival that was independent of stage. Computed tomography was found to have low sensitivity for determining extravesical extension (39%) and metastatic lymphadenopathy (12%). Patients with clinical Stage B2 and C disease (T3) that were downstaged had a 63% 5-year survival versus 18% of those that were not downstaged. The incidence of both ureteroenteral strictures and stomal complications was found to be higher in the 2000 cGy group than in those patients treated with the other regimens. The overall incidence of complications in that group was also significantly greater. We conclude that there is a continuing role for adjuvant radiotherapy in invasive bladder carcinoma to improve both pelvic control and survival. The 500 cGy radiotherapy "sandwich" regimen was equal in terms of pelvic control and survival to the other regimens and showed less overall morbidity. The 2000 cGy regimen was associated with the greatest incidence of morbidity and did not substantially improve pelvic control.


Polysaccharide from Strongylocentrotus nudus eggs regulates intestinal epithelial autophagy through CD36/PI3K-Akt pathway to ameliorate inflammatory bowel disease.
Sea urchin is a popular food all over the world, of which eggs are main edible part. Previous studies suggested that polysaccharides from eggs of Strongylocentrotus nudus (SEP) exhibited immunomodulatory activities during anti-tumor therapy, nevertheless, effects of SEP on inflammatory bowel disease and its underlying mechanisms have never been reported. In the present study, we showed that the SEP inhibited dextran sodium sulfate-induced ulcerative colitis characterized by decreased disease activity index, restored colon length and body weight, improved histopathological changes, down-regulation of inflammatory cytokines levels and Th17/Treg ratios in C57BL/6 J mice. Moreover, immunofluorescence analysis suggested that SEP repaired gut barrier in UC mice, while 16S rDNA sequencing exhibited improved intestinal flora. Mechanistically, we found SEP significantly modulated autophagy-related factors in intestinal epithelial cells (IECs), while might contributed to pathogenesis of UC. Furthermore, we demonstrated PI3K/Akt pathway was involved in regulatory effect of SEP on lipopolysaccharide-induced autophagy of HT-29 cells. Besides, among possible polysaccharide binding receptors, change of the CD36 expression was most significant, which was associated with PI3K/Akt signals. Collectively, our study showed for the first time that the SEP might be used a prebiotic agent to improve IBD through regulating CD36-PI3K/Akt mediated autophagy of IECs.


Lack of deuterium isotope effects in the antidepressant effects of (R)-ketamine in a chronic social defeat stress model.
(R,S)-ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exhibits rapid and long-lasting antidepressant effects and anti-suicidal ideation in treatment-resistant patients with depression. However, the precise mechanisms underlying the antidepressant actions of (R,S)-ketamine are unknown. Although the previous report demonstrated the deuterium isotope effects in the antidepressant actions of (R,S)-ketamine, the deuterium isotope effects in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, are unknown. We examined whether deuterium substitution at the C6 position could affect antidepressant effects of (R)-ketamine in a chronic social defeat stress (CSDS) model. Pharmacokinetic studies showed that levels of (2R,6R)-d1-hydroxynorketamine [(2R,6R)-d1-HNK], a final metabolite of (R)-d2-ketamine, in the plasma and brain after administration of (R)-d2-ketamine (10 mg/kg) were lower than those of (2R,6R)-HNK from (R)-ketamine (10 mg/kg), indicating deuterium isotope effects in the production of (2R,6R)-HNK. In contrast, levels of (R)-ketamine and its metabolite (R)-norketamine in the plasma and brain were the same for both compounds. In a CSDS model, both (R)-ketamine (10 mg/kg) and (R)-d2-ketamine (10 mg/kg) showed rapid and long-lasting (7 days) antidepressant effects, indicating no deuterium isotope effect in the antidepressant effects of (R)-ketamine. The present study suggests that deuterium substitution of hydrogen at the C6 position slows the metabolism from (R)-ketamine to (2R,6R)-HNK in mice. In contrast, we did not find the deuterium isotope effects in terms of the rapid and long-lasting antidepressant effects of (R)-ketamine in a CSDS model. Therefore, it is unlikely that (2R,6R)-HNK is essential for antidepressant effects of (R)-ketamine.


Identification of possible sources of atmospheric PM10 using particle size, SEM-EDS and XRD analysis, Jharia Coalfield Dhanbad, India.
Identification of responsible sources of pollution using physical parameter particulate matter (PM)10 in a critically polluted area is discussed in this paper. Database was generated by Ambient Air Quality Monitoring (AAQM) with respect to PM10 and PM2.5 in 18 monitoring stations at Jharia coalfield as per the siting criteria (IS: 5182, Part XIV) during 2011 to 2012. Identification of the probable sources of PM10 was carried out through particle size, shape, morphology analysis (scanning electron microscopy (SEM)), suitable compounds (X-ray diffraction (XRD)) and elements (energy-dispersive spectroscopy (EDS)). Monitoring stations nearby opencast mine were affected by the big-sized and irregular-shaped particles; on the other hand, monitoring stations nearby city were affected by the small-sized and regular-shaped particles. In a city area, additional sources like diesel generator (DG) set, construction activities, coal burning, etc., were identified. Blistering effects were also observed in the particles from mine fire-affected areas. Using the X-ray diffraction technique, presence of FeS2, CuO, FeSO4 and CuSO4 compounds was observed, which indicates the effects of mine fire on particulate emission due to presence of SO4(2-) and S2- ions.


Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus.
Feline infectious peritonitis (FIP), caused by feline coronavirus (FcoV), is considered one of the most enigmatic diseases in cats. Developing effective drugs for FIP is crucial due to its global prevalence and severity. In this study, six antiviral drugs were tested for their cytotoxicity, cell viability, and antiviral efficacies in Crandell-Reese feline kidney cells. A cytotoxicity assay demonstrated that these drugs were safe to be used with essentially no cytotoxicity with concentrations as high as 250 µM for ruxolitinib; 125 µM for GS441524; 63 µM for teriflunomide, molnupiravir, and nirmatrelvir; and 16 µM for ritonavir. GS441524 and nirmatrelvir exhibited the least detrimental effects on the CRFK cells, with 50% cytotoxic concentration (CC50) values of 260.0 µM and 279.1 µM, respectively, while ritonavir showed high toxicity (CC50 = 39.9 µM). In the dose-response analysis, GS441524, nirmatrelvir, and molnupiravir demonstrated promising results with selectivity index values of 165.54, 113.67, and 29.27, respectively, against FIPV. Our study suggests that nirmatrelvir and molnupiravir hold potential for FIPV treatment and could serve as alternatives to GS441524. Continued research and development of antiviral drugs are essential to ensure the well-being of companion animals and improve our preparedness for future outbreaks of coronaviruses affecting animals and humans alike.


The efficacy of a combination non-thermal focused ultrasound and radiofrequency device for noninvasive body contouring in Asians.
Several studies have been published on the first generation non-thermal focused ultrasound with an average improvement of 0-3.95 cm reported. We aim to investigate the efficacy of the second-generation non-thermal focused ultrasound device with a combined radiofrequency hand piece. With the addition of radiofrequency energy, the temperature of the adipose tissue is raised before focused ultrasound is applied. This facilitates the mechanical disruption of fat cells by focused ultrasound. Twenty subjects were recruited and underwent three treatments biweekly. Caliper reading, abdominal circumference, and standardized photographs were taken with the Vectra(®) system at all visits. We aim to have the subjects stand and hold the same position and the photograph taken after exhalation. Caliper and circumference measurements carry uncertainty. It is impossible to eliminate all uncertainties but can be improved by having the same trained physician assistant perform the measurement at the same site and taking an average of three readings. Pain score and satisfaction were recorded by means of the visual analogue scale. The efficacy is defined by a statistically significant improvement in circumferential improvement based on intention-to-treat analysis. Seventeen subjects completed the treatment schedule. Abdominal circumference showed statistically significant improvement at 2 weeks post-second treatment (P = 0.023) and almost all subsequent follow-ups. Caliper readings were statistically significant at 2 weeks post-second treatment (P = 0.013) and almost all follow-ups. The mean pain score reported was 2.3 on the visual analog scale and 6% were unsatisfied with the overall treatments. Six incidents of wheal formation appeared immediately after treatment all of which subsided spontaneously within several hours. The combination non-thermal focused ultrasound and radiofrequency device is effective for improving body contour in Asians.


Analytical toxicology of fluorinated inhalation anaesthetics.
The chemical and pharmacological properties of the current fluorinated inhalation anaesthetics, halothane, enflurane, isoflurane, sevoflurane and desflurane, are surveyed with implications to toxicity. Analytical methods, especially gas chromatography with head space, purge and trap, or pulse heating extraction, are reviewed in forensic toxicological and occupational/therapeutic monitoring contexts.


Implications of the COVID19 pandemic on the need and timing of second transurethral bladder tumour resection in high-grade non-muscle invasive bladder cancer.
Due to the COVID19 pandemic, the EAU has recommended to, if needed, postpone second transurethral resection of bladder tumour (TURBT) after BCG induction in selected patients. We aimed to evaluate the oncological outcomes of postponed TURBT and the potential to replace second TURBT by routine cystoscopy and cytology. A single-center, retrospective analysis of patients with TaG3/high grade (HG) or T1HG urothelial bladder cancer was performed. All patients underwent a complete TURBT between 2000 and 2013 with presence of detrusor muscle, full BCG induction and routine cystoscopy and cytology, followed by a second TURBT. Results of the cystoscopy, cytology and pathology reports of the TURBT were analyzed by descriptive characteristics, sensitivity, specificity, negative and positive predictive values, as well as survival analyses. 112 patients were included. Residual tumour was present at second TURBT in 21.4%. Upstaging rate from pTaHG to pT1HG and pT1HG to pT2 was 0% and 2.7%, respectively. pT0 was confirmed in 79% of patients, but in 98% of patients with combined negative cytology and cystoscopy after BCG. With a median follow-up of 109 months, the 3-year OS was 85%, RFS 74% and PFS 89%. Sensitivity, specificity, negative predictive value and positive predictive value of cystoscopy and urinary cytology for the presence of residual tumour were 92%, 97%, 98% and 85%, respectively. This study underpins the recommendation of the EAU NMIBC guideline panel that, if needed and in selected patients, second TURBT may be postponed until after BCG induction treatment in pT1HG disease. Also, routine second TURBT can be omitted in pTaHG disease. Data on replacing second TURBT after BCG treatment by routine cystoscopy and cytology appear promising but require further confirmation in prospective studies.


Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice.
Growth hormone receptor/binding protein knockout (GHR-KO) mice are characterized by resistance to growth hormone (GH), reduced insulin like growth factor 1 (IGF1) levels and enhanced insulin sensitivity and markedly increased lifespan. Findings in these and other long-lived mutant mice, and in normal animals subjected to caloric restriction (CR) indicate that insulin signaling is importantly involved in the control of longevity. We have examined the mRNA expression level of genes involved in insulin/IGF1 action in the skeletal muscle and liver of normal and GHR-KO mice fed ad libitum or subjected to long term 30% CR. The levels of IR, IRS1, IRS2, GLUT4 and IGF1 message in the skeletal muscle were reduced by CR in both normal and GHR-KO mice. In the liver, the results indicate that in GHR-KO mice mRNA expression of genes related to early steps of insulin signaling is up-regulated in the liver but not in the muscle. The results also show that improved insulin sensitivity in response to CR is not due to increased mRNA expression of the above genes in either normal or GHR-KO animals.


The Efficacy of Conservative Treatment of Bone Marrow Edema Syndrome: A Scoping Review of the Last Ten Years of Literature.
The purpose of this review was to conduct a literature search assessing the efficacy of various conservative treatments of BMES. According to the PRISMA guidelines, a literature search was conducted in April 2021 in MEDLINE database via PubMed and Embase to identify original articles describing the results of conservative treatments for BMES of hip and knee published in the last ten years. For each study, information regarding study characteristics, description of the treatment, patient's demographic and clinical data, length of follow-up, clinical outcome measure, disability, adverse events, classification, and extent and of edema on MRI, were extracted. A total of 12 studies were identified. Two studies described treatment with iloprost, three with hyperbaric oxygen (HBO), two with bisphosphonates, five with extracorporeal shockwave therapy (ESWT). The total number of patients was 351: 34 treated with iloprost, 64 with hyperbaric oxygen, 37 with bisphosphonates, 216 with ESWT. In ESWT studies, treatment with a higher flux density and a higher number of therapy sessions lead to better clinical and radiological scores. In iloprost studies, a more remarkable improvement in the VAS scale was observed in the study on hip patients. The treatment of idiopathic bone marrow edema is currently not standardized, making it difficult to find data that can be compared in a highly reliable way. The studies available in the literature show promising results as for the possibility to cure bone marrow edema efficiently. Standardized radiological scores for evaluating bone marrow edema area are needed in future studies.


Crystallographic Wet Chemical Etching of Semipolar GaN (11-22) Grown on m-Plane Sapphire Substrates.
This paper reports the etch rates and etched surface morphology of semipolar GaN using a potassium hydroxide (KOH) solution. Semipolar (11-22) GaN could be etched easily using a KOH solution and the etch rate was higher than that of Ga-polar c-plane GaN (0001). The etch rate was anisotropic and the highest etch rate was measured to be approximately 116 nm/min for the (1011) plane and 62 nm/min for the (11-20) plane GaN using a 4 M KOH solution at 100 °C, resulting in specific surface features, such as inclined trigonal cells.


Methods used for prevention of white spot lesion development during orthodontic treatment with fixed appliances.
The aim of this study was to survey methods that Dutch orthodontists use to prevent development or progression of enamel decalcifications during orthodontic treatment. A pre-tested questionnaire was sent by post to all orthodontists in the Netherlands with a private practice (n = 189). The response rate was 81%. At the start of orthodontic treatment a basic practice protocol for prevention of enamel demineralization was used by 93% of the orthodontists. This included oral hygiene instructions (92%) and the advice for additional use of a fluoride mouth rinse (64%). Other preventive measures were rarely prescribed. About 85% of those who prescribed a fluoride mouth rinse advised to rinse once a day, directly after evening tooth brushing. The results suggest that the commonly used practice of fluoride mouth rinsing directly after evening tooth brushing by orthodontic patients during fixed appliance treatment ignores actual evidence of preventive advices. This study recommends mouth rinsing at another moment than after evening tooth brushing, thus increasing the frequency of fluoride intakes, which might enhance the effectiveness in preventing WSL development or progression during orthodontic treatment.


[Aerobic capacity, weight status and self-concept in schoolchildren].
To analyze the relationship between self-concept, aerobic capacity and weight status in schoolchildren. Relational descriptive design in which was assessed the weight status and aerobic capacity of 256 schoolchildren among 8-11 years. Aerobic capacity (low vs high) and the body mass index (normal-weight vs overweight-obesity) were categorized using standard criteria. The self-concept was assessed through the Piers Harris self-concept scale for children. Schoolchildren with normal-weight and high fitness level showed better levels of conductual self-concept (P=.030), physical (P<.001), lack of anxiety (P=.048), and global self-concept (P=.002). The schoolchildren with normal-weight show higher levels of conductual self-concpt (P=.016), intellectual (P=.050), physical (P<.001), life satisfaction (P=.036), and global self-concept (P=.001). The schoolchildren with a higher fitness level showed better conductual self-concept (P=.024), physical (P=.004), lack of anxiety (P=.011), social (P=.024), and global (P=.003). The results of the study strengthen the importance to transmit to the educative community the knowledge of the relationship between the variables analyzed aiming to improve the schoolchildren self-concept.


Three old and one new: protein import into red algal-derived plastids surrounded by four membranes.
Engulfment of a red or green alga by another eukaryote and subsequent reduction of the symbiont to an organelle, termed a complex plastid, is a process known as secondary endosymbiosis and is shown in a diverse group of eukaryotic organisms. Important members are heterokontophytes, haptophytes, cryptophytes, and apicomplexan parasites, all of them with complex plastids of red algal origin surrounded by four membranes. Although the evolutionary relationship between these organisms is still debated, they share common mechanisms for plastid protein import. In this review, we describe recent findings and current models on preprotein import into complex plastids with a special focus on the second outermost plastid membrane. Derived from the plasma membrane of the former endosymbiont, the evolution of protein transport across this so-called periplastidal membrane most likely represented the challenge in the transition from an endosymbiont to a host-dependent organelle. Here, remodeling and relocation of the symbiont endoplasmic reticulum-associated degradation (ERAD) machinery gave rise to a translocon complex termed symbiont-specific ERAD-like machinery and provides a fascinating insight into complex cellular evolution.


Spectroscopic studies on histone-DNA interactions. II. Three transitions in nucleosomes resolved by salt-titration.
The multiple-step transitions in DNA-histone interactions in chicken erythrocyte nucleosomes with increasing ionic strength are resolved by salt-titration spectroscopy. Both the circular dichroism of the DNA and the fluorescence of the histones in nucleosomes change during the titration process with concentrations of NaCl from 0.1 M to 2.5 M. By differentiating the titration curves, three distinct peaks corresponding to three structural transitions are observed. The two peaks near 0.95 M and 1.45 M-NaCl are common to the circular dichroism and fluorescence curves. The circular dichroism curve has another peak near 0.55 M-NaCl. Because the derivative of the fluorescence titration curve for the DNA-(H3, H4) complex has only one peak near 1.45 M-NaCl, that peak is attributed to the dissociation of the histone dimer (H3, H4). The peak near 0.95 M-NaCl corresponds to the dissociation of the dimer (H2A, H2B) from the DNA-(H3, H4) complex, as shown by binding experiments of (H2A, H2B) to the DNA-(H3, H4) complex at the salt concentration near this peak. The peak near 0.55 M-NaCl reflects some inner-core structural change. As the change of the circular dichroism signal is reversible, salt-titration spectroscopy is applicable to equilibrium studies of the physical chemical properties of DNA-histone interactions. By the assumption of a non-co-operative model, the binding constant for the chicken erythrocyte (H2A, H2B) dimer to the DNA-(H3, H4) complex is calculated as 2.8 X 10(6) M-1 at 1.0 M-NaCl (20 degrees C, pH 7.6). The DNA sequence dependence of the stability of the DNA-(H3, H4) interaction is observed in the salt-titration profiles of reconstituted material. Decreasing stability of the interaction of (H3, H4) is observed following the order: poly[(dG)-(dC)] much greater than chicken erythrocyte DNA greater than poly[(dA)-(dT)]. It is concluded that histones (H3, H4) have a different DNA sequence dependence from histones (H2A, H2B).


The role of macrophages and giant cells in loosening of joint replacement.
Macrophages and foreign-body giant cells from the bone-cement interface of loosened joint replacement were assayed for direct bone resorption in an in vitro experimental model. Human osteoclasts from giant cell tumors and experimental animal osteoclasts were not capable of resorbing the bone under experimental conditions, but osteoclasts are. It is suggested that macrophages and giant cells in loosened implants may initiate bone resorption, removing the extra-cellular barrier that normally protects mineral crystals from osteoclastic recognition.


Advanced experimental techniques for the sensitive detection of a toxic bisphenol A using UiO-66-NDC/GO-based electrochemical sensor.
In the present study, a simple and sensitive method for detecting bisphenol A (BPA) in various environments, including groundwater, was described using a widespread electrochemical method. BPA is well-known for its endocrine-disrupting properties, which may cause potential toxicological effects oon the nervous, reproductive, and immune systems. A novel metal-organic framework (UiO-66-NDC/GO) was synthesized, and its existence was confirmed by several characterization techniques like FTIR, UV-visible, XRD, SEM-EDX, Raman spectroscopy, and TGA. Due to the excellent electrocatalytic nature, UiO-66-NDC/GO was chosen as the sensor material and integrated on the surface of the bare carbon paste electrode (BCPE). The UiO-66-NDC/GO modified carbon paste electrode (MCPE) was engaged for the detection of BPA using techniques like cyclic Voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The applied sensor exhibited an astonishing outcome for BPA detection with high sensitivity and selectivity. The lower detection limit (LLOD) of 0.025 μM was achieved at the modified sensor with a linear concentration range of 10-70 μM. Moreover, the practical applicability of the sensor was tested on tap water, drinking water, and fresh liquid milk, giving an excellent recovery of BPA in the range of 94.8-99.3 (v.%). The proposed method could be employed for electrochemical device or a solid state device fabrication for the onsite monitoring of BPA.


Heat-induced dissociation of human erythrocyte spectrin dimer into monomers.
Human erythrocyte spectrin heated above 49 degrees C could be separated into two fractions by DEAE-Toyopearl column chromatography at room temperature. The first fraction eluting with the salt gradient was predominantly the alpha subunit, indicating a heat-induced dissociation of the spectrin alpha beta dimer into monomers. The second fraction, obtained with 0.5 M NaOH after salt elution, consisted of high-molecular-weight proteins in addition to alpha and beta subunits, which were visualized by gel electrophoresis with sodium dodecyl sulfate. The isolated beta subunit when heated above 48 degrees C could also be separated into two fractions by column chromatography. About 30% of the protein eluted with the salt solution and the rest of the proteins were in the alkali eluate in which high molecular weight protein bands also appeared, indicating a heat-induced aggregation of the beta subunits. Almost all the isolated alpha subunit, however, eluted out with the salt solution, even though the subunit was heated at 52 degrees C. Studies of the binding of subunits to inside-out vesicles indicate that the isolated beta subunit was denatured irreversibly by heating; on the other hand, the alpha subunit kept its binding ability after heating above 50 degrees C. These findings are attributed to the heat-induced dissociation of the spectrin molecules into alpha and beta subunits at 49-50 degrees C, and eventual aggregation of the denatured beta subunits.


Sporotrichosis in Sudan.
Two cases of lymphocutaneous sporotrichosis are reported from Sudan in a boy aged four and a half years and a girl aged 16 years respectively. Diagnosis was based mainly on the clinical findings and the dramatic response to treatment with oral potassium iodine, as well as the histological finding of yeasts compatible with the yeast phase Sporothrix schenkii.


The Cyberchondria Severity Scale (CSS): German Validation and Development of a Short Form.
'Cyberchondria' describes a pattern of researching health information online motivated by distress or anxiety about health, which becomes excessive and in turn increases distress. The Cyberchondria Severity Scale (CSS) assesses this construct. The aims of the present study were to validate a German version of the CSS and to propose a short form. The CSS was translated and posted online. Inclusion criteria were fulfilled by n = 500 participants (age 29.1 ± 10.4 years, 73.6 % women). Item analyses, an exploratory factor analysis and correlations with health anxiety, somatic symptoms, health-care utilization and depression were calculated. A brief version with 15 items was developed (CSS-15) and validated in a second sample (n = 292; age 24.2 ± 4.1 years, 76.4 % women). The internal consistency of the CSS was α = .93 and its split-half reliability α = .95. The mean item-total correlation was r itc = .51, the mean inter-item correlation r = .29 and the mean item difficulty p i = .36. The principal component analysis extracted five factors. The CSS score correlated highly with health anxiety and moderately with somatic symptoms and health-care utilization. The CSS-15 still had an internal consistency of α = .82 and the confirmatory factor analysis confirmed the five factors. The correlation coefficients with health-related measures were unaffected. The German version of the CSS possesses very good psychometric characteristics, which were preserved in a short version. The factorial structure was replicated. The correlations with health anxiety and depression for both scales underscore their validity and clinical relevance.


The Impact of the COVID-19 Pandemic on Patients With CKD: Systematic Review of Qualitative Studies.
COVID-19 disproportionately affects people with comorbidities, including chronic kidney disease (CKD). We describe the impact of COVID-19 on people with CKD and their caregivers. A systematic review of qualitative studies. Primary studies that reported the experiences and perspectives of adults with CKD and/or caregivers were eligible. MEDLINE, Embase, PsycINFO, CINAHL searched from database inception to October 2022. Two authors independently screened the search results. Full texts of potentially relevant studies were assessed for eligibility. Any discrepancies were resolved by discussion with another author. A thematic synthesis was used to analyze the data. Thirty-four studies involving 1,962 participants were included. Four themes were identified: exacerbating vulnerability and distress (looming threat of COVID-19 infection, intensifying isolation, aggravating pressure on families); uncertainty in accessing health care (overwhelmed by disruption of care, confused by lack of reliable information, challenged by adapting to telehealth, skeptical about vaccine efficacy and safety); coping with self-management (waning fitness due to decreasing physical activity, diminishing ability to manage diet, difficulty managing fluid restrictions, minimized burden with telehealth, motivating confidence and autonomy); and strengthening sense of safety and support (protection from lockdown restrictions, increasing trust in care, strengthened family connection). Non-English studies were excluded, and inability to delineate themes based on stage of kidney and treatment modality. Uncertainty in accessing health care during the COVID-19 pandemic exacerbated vulnerability, emotional distress, and burden, and led to reduced capacity to self-manage among patients with CKD and their caregivers. Optimizing telehealth and access to educational and psychosocial support may improve self-management and the quality and effectiveness of care during a pandemic, mitigating potentially catastrophic consequences for people with CKD. During the COVID-19 pandemic, patients with chronic kidney disease (CKD) faced barriers and challenges to accessing care and were at an increased risk of worsened health outcomes. To understand the perspectives about the impact of COVID-19 among patients with CKD and their caregivers, we conducted a systematic review of 34 studies involving 1,962 participants. Our findings demonstrated that uncertainty in accessing care during the COVID-19 pandemic exacerbated the vulnerability, distress, and burden of patients and impaired their abilities for self-management. Optimizing the use of telehealth and providing education and psychosocial services may mitigate the potential consequences for people with CKD during a pandemic.


Deconstructing the Growth Hormone Receptor(GHR): Physical and Metabolic Phenotypes of Tissue-Specific GHR Gene-Disrupted Mice.
Growth hormone (GH)-induced signaling results in numerous effects in multiple tissues throughout the body. Elucidation of several of these effects has come from studies observing the various phenotypes of the GH receptor (GHR) gene-disrupted (GHR-/-) mouse. These mice are dwarf and obese with increased insulin sensitivity, are resistant to cancer and diabetes, and have an extended lifespan. While these mice have proven to be a valuable tool for understanding the pleiotropic effects of GH, we and others have generated novel tissue-specific GHR gene-disrupted mouse lines that are now helping to further dissect the actions of GH on specific cells/tissues. In this chapter, we summarize the various phenotypes observed in these mice.


Denitrogenative Suzuki and carbonylative Suzuki coupling reactions of benzotriazoles with boronic acids.
Unprecedented palladium-catalyzed denitrogenative Suzuki and carbonylative Suzuki coupling reactions of benzotriazoles with boronic acids have been realized, which afforded structurally diverse ortho-amino-substituted biaryl and biaryl ketone derivatives. The key to this success is due to the development of a rationally designed strategy to achieve the ring opening of benzotriazoles with a synergistic activating-stabilizing effect, which enables the in situ generation of the corresponding ortho-amino-arenediazonium species. The present work opens up a new avenue to utilize benzotriazoles as synthetic equivalents of ortho-amino-arenediazoniums, which otherwise could not be directly accessed by existing synthetic methods.


End-stage renal disease: incidence and prediction by coronary heart disease, and educational level. Follow-up from diagnosis of childhood-onset type 1 diabetes throughout Norway 1973-2017.
To investigate incidence of end-stage renal disease (ESRD), and the association of education and coronary heart disease (CHD) with ESRD, in subjects throughout Norway followed from the diagnosis of childhood-onset type 1 diabetes. All new onset cases of type 1 diabetes 1973-2016 were followed for CHD and ESRD in nation-wide registries through 2017. Ten matched controls per case were selected from the National Population Register. Cox regression was used to estimate hazard ratios, and probabilities were estimated by the cumulative incidence function accounting for competing risk. Among 9311 patients with type 1 diabetes, 130 developed ESRD with a probability of ESRD after 40 years of 5.5%. The rate was 35-fold higher than in controls (aHR = 35.5, 95% CI 23.1 - 54.6). Higher education was associated with lower risk of ESRD compared to low education (aHR = 0.14, 95% CI 0.07 - 0.27). Diagnosed CHD was associated with 14-fold increased rate of ESRD (aHR = 14.3, 95% CI 9.2 - 22.2). The hazard rate of ESRD was 35-fold higher in cases compared to controls. CHD was associated with a 14-fold increased rate of subsequent ESRD, while higher education was associated with substantially lower rate of ESRD.


Overcoming biological barriers to improve treatment of a Staphylococcus aureus wound infection.
Chronic wounds frequently become infected with bacterial biofilms which respond poorly to antibiotic therapy. Aminoglycoside antibiotics are ineffective at treating deep-seated wound infections due to poor drug penetration, poor drug uptake into persister cells, and widespread antibiotic resistance. In this study, we combat the two major barriers to successful aminoglycoside treatment against a biofilm-infected wound: limited antibiotic uptake and limited biofilm penetration. To combat the limited antibiotic uptake, we employ palmitoleic acid, a host-produced monounsaturated fatty acid that perturbs the membrane of gram-positive pathogens and induces gentamicin uptake. This novel drug combination overcomes gentamicin tolerance and resistance in multiple gram-positive wound pathogens. To combat biofilm penetration, we examined the ability of sonobactericide, a non-invasive ultrasound-mediated-drug delivery technology to improve antibiotic efficacy using an in vivo biofilm model. This dual approach dramatically improved antibiotic efficacy against a methicillin-resistant Staphylococcus aureus (MRSA) wound infection in diabetic mice.


Stepwise bioprocess for exopolysaccharide production using potato starch as carbon source.
Xanthan gum is a biopolymer produced by Xanthomonas sp. XC6. In this study, xanthan gum is produced from potato starch using a stepwise bioprocess design. Potato starch is hydrolyzed using Bacillus sp. having amylase activity and 30.2 g/L reducing sugar was released, while Xanthomonas sp. XC6 can release only 14.5 g/L. Bacillus sp. hydrolyzed potato starch extract was further used as a carbon source for xanthan gum biosynthesis using Xanthomonas sp. XC6. Yeast extract acts as the best nitrogen source, and 10.0 g/L xanthan gum was recovered. Downstreaming process after stepwise bioprocess resulted in 17.4 g/L xanthan gum production, which is 2.8 times higher as compared to single step process.


New approaches to insect tissue culture.
Current methods of insect cell culture have produced a limited variety of cell types in an ever expanding list of insect cell lines. In developing midgut epithelial cell lines, we found that traditional methods in insect cell culture failed to provide healthy cells from mature tissues. Examination of mammalian cell culture literature for this particular cell type provided the insight required to successfully develop a cell-specific line (Baines et al., 1994). The potential applications for cell-specific lines from insects are numerous. This paper is a compilation of ideas that will hopefully enable other researchers to develop additional cell-specific lines.


[The effect of iodized mineral substance mixtures for cattle and swine on iodine requirements and struma prevention].
In the southern districts of the GDR the calculated iodine uptake of adults was 80 micrograms/day before the iodine supplementation of the mixtures of mineral substances and the packet kitchen salt. The iodine supplementation of the mixtures of mineral substances for cattle and pig tripled the iodine content of the milk or increased it fivefold in the county of Erfurt and doubled the proportion of iodine of the meat, the inner parts and the sausage produced from them. In a daily consumption of 0.31 of milk and 250 g of meat and sausage a surplus supply of 35 micrograms of iodine for adults was calculated in the southern counties of the GDR. The 35 micrograms of iodine for the future necessary for covering the demand of iodine are certainly delivered by the iodized kitchen salt.


The influence of epidural analgesia on the splanchnic exchange of amino acids during upper abdominal surgery.
Splanchnic turnover of plasma amino acids was studied in 10 patients given thoracic epidural analgesia combined with general anaesthesia for elective cholecystectomy. Ten other patients given only general anaesthesia for cholecystectomy served as a control group. All patients received an infusion of glucose during the investigation. The total concentration of amino acids in arterial plasma did not change in the patients given epidural analgesia but decreased by approximately 15% in the non-epidural group. In both groups splanchnic uptake of amino acids increased during surgery and was found to be more than doubled in the early postoperative period. The addition of epidural analgesia to general anaesthesia did not modify the splanchnic uptake of amino acids during surgery and in the immediate (2 h) postoperative period.


Upregulation of long non-coding RNA RAB1A-2 induces FGF1 expression worsening lung cancer prognosis.
The chromosomal locations of lncRNAs (long non-coding RNAs, lncRNAs) infer their biological functions in cancer. Lnc-RAB1A-2, a Ras-related protein Rab-1A (RAB1A) upstream lncRNA, was chosen for assessment of its impact on lung cancer prognosis in a case-based analysis and investigation of its biological function though a series of functional assays. Lnc-RAB1A-2 was significantly upregulated in 276 lung cancer tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with clinical stage and metastasis status in lung cancer patients. Patients with high expression levels of this lncRNA had a shorter median survival time (16.0 months vs. 23.0 months, P = 0.011 in southern samples; 8.0 months vs. 19.0 months, P = 0.020 in eastern samples; 13.0 months vs. 19.0 months, P = 0.002 in merged samples) and a higher risk of death than those with lower levels (HR = 1.52; 95% CI = 1.01-2.26, in merged samples). Additionally, overexpression of lnc-RAB1A-2 significantly promoted lung cancer cell proliferation in vitro and in vivo. Further analyses using digital gene expression tag profiling revealed that lnc-RAB1A-2 could affect the expression of fibroblast growth factor 1 (FGF1), a gene involved in the PI3K/AKT/mTOR pathway that is largely activated by RAB1A. FGF1 was confirmed to be a down-stream gene of lnc-RAB1A-2. Collectively, our study demonstrated that lnc-RAB1A-2 is associated with poor lung cancer prognosis by promoting lung cancer development.


Development and evaluation of a pediatric hospital medicine board review course.
The American Board of Medical Specialties recognized Pediatric Hospital Medicine (PHM) for subspecialty certification in 2016, with the first certification exam in 2019. To address the need for exam preparatory materials, we designed and evaluated a novel PHM board review course that was offered both in-person and online. Course content was based on the American Board of Pediatrics (ABP) PHM certifying exam outline. Course objectives were developed from published PHM core competencies and the 2012 ABP general pediatrics content objectives. National experts served as faculty, presenting didactic sessions, and contributing to a question bank for high-yield review. For program evaluation, we applied the Kirkpatrick Model, evaluating estimated exam pass rates (Level 4), participant learning (Level 2) via post-presentation practice questions, and participants' ratings of presenters (via five-point Likert scale) and satisfaction (Level 1). There were 112 in-person and 144 online participants with estimated pass rates of 89 and 93%, respectively. The mean correct response for the post-presentation knowledge questions was 84%. Faculty effectiveness ratings ranged from 3.81 to 4.96 (median score 4.60). Strengths included the pace of the course, question bank, and printed syllabus. Suggestions for improvement included question bank expansion, focus on "testable" points rather than general information, and challenges with long days of didactic presentations. This novel PHM board review course demonstrated effectiveness. Hospitalists preferred focused "testable" information, an active learning environment, and a robust question bank. Future preparatory courses should consider including more opportunities for practice questions, focused content review, and learner engagement.


14-Membered macrocyclic ring-derived toolbox: the identification of small molecule inhibitors of angiogenesis and early embryo development in zebrafish assay.
A highly practical and modular synthesis to obtain a diverse 14-membered ring-based macrocyclic toolbox is achieved. These compounds were further tested in zebrafish assays related to early embryonic development, angiogenesis, and neurogenesis, respectively. 1.4c was identified as an antiangiogenesis agent.


CNT-Intertwined Polymer Electrode toward the Practical Application of Wearable Devices.
One of the greatest challenges for wearable electronics is the lack of virtually flexible electrodes with satisfactory electrochemical performance, and there is always a "softness vs effective capacity" dilemma. Herein, a polymer electrode is proposed. The carefully chosen and partially conjugated polyimide realizes the dual function of a flexible agent and an active agent. The softness of the electrode is rendered by the polymer, while the carbon nanotube ensures electron transfer (ET) within the polymer. A modified electrospinning method has been used in the preparation of a carbon nanotube (CNT)-intertwined polyimide (PI) film. The binder-free and current collector-free polymer electrode has as high as 80% active phase and releases near-theoretical capacity accompanied by very stable cycling up to 200 cycles. Owing to the dual role of the polymer component, the softness vs effective capacity dilemma has been well addressed. Aiming at the practical application, a fatigue test has been first conducted in a practical mode and the well-reserved electrochemical activity under extreme stress change as well as in plenty of electrolyte has been revealed. The work realizes that the flexible electrode well fulfills the requirement and sheds more light on the application of the polymer electrode materials.


Cardiac Sarcoidosis: A Literature Review of Current Recommendations on Diagnosis and Management.
Cardiac sarcoidosis (CS) is a rare multisystem disorder characterized by granulomatous infiltration of the myocardium, which can lead to significant morbidity and mortality. Its clinical manifestations range from asymptomatic conduction abnormalities to severe heart failure (HF) and sudden cardiac death. This comprehensive review aims to provide an overview of the diagnosis, clinical features, and current medical management strategies for CS. Additionally, the role of implantable cardioverter-defibrillators (ICDs) and the potential use of positron emission tomography in guiding management decisions are explored. A comprehensive understanding of the medical management of CS is essential for improving patient outcomes and guiding future research endeavors.


Role of autologous bone marrow transplantation as consolidation therapy in acute promyelocytic leukemia patients in complete remission.
Autologous bone marrow transplantation (ABMT), which consents a low mortality rate, has been proposed as an alternative approach to maintenance chemotherapy in patients with acute promyelocytic leukemia (APL) in first complete remission irrespective of the patients' molecular status. Sixteen patients with acute APL in complete remission were submitted to ABMT and were analyzed for the presence of the PML-RARa fusion gene by reverse transcription-polymerase chain reaction (RT-PCR). Our study demonstrated that continued positivity of PCR analysis before ABMT could predict subsequent relapse in patients who undergo un-purged ABMT procedures.


Bursoscopy of the trochanteric bursa.
We report two cases in a single patient with severe, refractory trochanteric bursitis, treated successfully with bursoscopy and bursectomy. The symptoms, clinical findings, surgical technique, and short-term results are described.


Photogenerated charges transfer across the interface between NiO and TiO2 nanotube arrays for photocatalytic degradation: A surface photovoltage study.
To better understand the behavior of photogenerated charges in the composite photocatalyst interface is beneficial to the designing of effective photocatalyst for photocatalytic reaction. In our work, the separation and transfer process of photogenerated charges in NiO/TiO2 nanotube arrays (NiO/TiO2 NTAs) has been studied by surface photovoltage (SPV) spectroscopy and transient photovoltage (TPV) measurement. Through the experimental results analysis, we find that an interfacial electric field is formed at NiO/TiO2 NTAs interface, which is attributed to the work function difference between NiO and TiO2 NTAs. The photogenerated holes in TiO2 can transfer to the NiO layer along the interface electric field under the ultraviolet irradiation. A large amount of photogenerated holes can be separated effectively and then prolonged the holes lifetime to participate in the photocatalytic oxidation reaction. The above results show that the favorable hole-collecting process of NiO in the surface of TiO2 NTAs is the main factor being responsible for the increase the photocatalytic efficiency.


Plasma levels of neurotrophin 4/5, NGF and pro-BDNF influence transition to mental disorders in a sample of individuals at ultra-high risk for psychosis.
Neurotrophins (NTs) and their precursors (pro-NTs) are polypeptides with important roles in neuronal development, differentiation, growth, survival and plasticity, as well as apoptosis and neuronal death. Imbalance in NT levels were observed in schizophrenia spectrum disorders, but evidence in ultra-high risk for psychosis (UHR) samples is scarce. A naturalistic sample of 87 non-help-seeking UHR subjects and 55 healthy controls was drawn from the general population. Blood samples were collected and NT-3, NT-4/5, BDNF, pro-BDNF, NGF, pro-NGF were analyzed through enzyme linked immunosorbent assay (ELISA). Information on cannabis and tobacco use was also collected. Logistic regression models and path analysis were used to control for confounders (tobacco, age, cannabis use). NT-4/5 was significantly decreased, and pro-BDNF was significantly increased in UHR individuals compared to controls. Cannabis use and higher NGF levels were significantly related to transition to psychiatric disorders among UHR subjects. Increased pro-BDNF and decreased NT-4/5 influenced transition by the mediation of perceptual abnormalities. Our study shows for the first time that NTs are altered in UHR compared to healthy control individuals, and that they can be a predictor of transition to psychiatric illnesses in this population. Future studies should employ larger naturalistic samples to confirm the findings.


Optimizing Care in Kidney Transplantation.
This article provides fundamental information to health care providers on kidney transplant. It reviews some of the preoperative testing, postoperative complications, and treatments. It is to help those who help assist with postoperative care of kidney transplants ensure care is optimal. This article will help educate and inform caregivers of guidelines and suggested plans of care to follow for best outcomes for transplant recipients. The short- and long-term care of these patients are extremely important, and health care providers need to follow practice guidelines to achieve optimal outcomes. This discussion will benefit anyone who has direct care to transplant recipients including, but not limited to: nursing staff, nurses aids, training physicians, general practitioners, and mid-level providers.


Human glioma associated and related antigens, identified by monoclonal antibodies.
Tumour specific and various tumour-associated antigens expressed on human glioma cells were reported from many laboratories. These have been identified by xeno-, allo-, or auto-sera and more recently by utilizing monoclonal antibodies produced by hybridoma technique. In this article, the results of reports are summarized comparing the studies with conventional antisera and monoclonal antibodies. The present and future clinical applications of these monoclonal antibodies are described.


Young man presenting with chest pain.
This is a case report of a young man, who had an acute coronary event followed by angioplasty. On further workup he was found out to have hyper-homocysteinemia.


Anti-PD-L1 antibodies promote cellular proliferation by activating the PD-L1-AXL signal relay in liver cancer cells.
Immune checkpoint inhibitors (ICIs) are emerging treatments for advanced hepatocellular carcinoma (HCC); however, evidence has shown they may induce hyperprogressive disease via unexplained mechanisms. In this study, we investigated the possible stimulative effect of ICIs on programmed cell death-ligand 1 (PD-L1)-harboring liver cancer cells under immunocompetent cell-free conditions. The sarcomatous HAK-5 cell line displayed the highest expression of PD-L1 among 11 human liver cancer cell lines used in this study. HLF showed moderate expression, while HepG2, Hep3B, and HuH-7 did not show any. Moreover, sarcomatous HCC tissues expressed high levels of PD-L1. We observed approximately 20% increase in cell proliferation in HAK-5 cells treated with anti-PD-L1 antibodies, such as durvalumab and atezolizumab, for 48 h compared with that of those treated with the control IgG and the anti-PD-1 antibody pembrolizumab. No response to durvalumab or atezolizumab was shown in PD-L1-nonexpressing cells. Loss-of-function and gain-of-function experiments for PD-L1 in HAK-5 and HepG2 cells resulted in a significant decrease and increase in cell proliferation, respectively. Phosphorylated receptor tyrosine kinase array and immunoprecipitation revealed direct interactions between PD-L1 and AXL in tumor cells. This was stabilized by extrinsic anti-PD-L1 antibodies in a glycosylated PD-L1-dependent manner. Activation of AXL, triggering signal relay to the Akt and Erk pathways, boosted tumor cell proliferation both in vitro and in xenografted tumors in NOD/SCID mice. Collectively, this suggests that anti-PD-L1 antibodies stimulate cell proliferation via stabilization of the PD-L1-AXL complex in specific types of liver cancer, including in HCC with mesenchymal components. Therapeutic anti-PD-L1 antibodies promote cell proliferation by stabilizing the PD-L1-AXL complex in PD-L1-abundant neoplasms, including in HCC with mesenchymal components. Such a mechanism may contribute to the development of hyperprogressive disease.


Physical exercise and its effects on coronary artery disease.
The beneficial effects of physical exercise on stable coronary artery disease (CAD) have been shown by an increasing number of studies. Exercise training leads to an improved bioavailability of the endothelial nitric oxide and partially attenuates endothelial dysfunction. Further effects are an economization of ventricular function and a reduction of cardiovascular risk factors. In clinical studies exercise training was associated with a decreased total and cardiovascular mortality and a reduced angina pectoris threshold. Thus exercise training has developed to an evidence-based therapeutic option of stable CAD with a Class Ia recommendation in the guidelines.


Functional characterization of rice metallothionein OsMT-I-Id: Insights into metal binding and heavy metal tolerance mechanisms.
Metallothioneins (MTs) are cysteine-rich proteins known for their strong metal-binding capabilities, making them effective in detoxifying heavy metals (HMs). This study focuses on characterizing the functional properties of OsMT-I-Id, a type-I Metallothionein found in rice. Using a HM-responsive yeast cup1Δ (DTY4), ycf1∆ (for cadmium), and acr3∆ mutants (for trivalent arsenic), we assessed the impact of OsMT-I-Id on metal accumulation and cellular resilience. Our results demonstrated that yeast cells expressing OsMT-I-Id showed increased tolerance and accumulated higher levels of copper (Cu), arsenic (As), and cadmium (Cd), compared to control cells. This can be attributed to the protein's ability to chelate and bind HMs. Site-directed mutagenesis was employed to investigate the specific contributions of cysteine residues. The study revealed that yeast cells with a mutated C-domain displayed heightened HM sensitivity, while cells with a mutated N-domain exhibited reduced sensitivity. This underscores the critical role of C-cysteine-rich domains in metal binding and tolerance of type-I rice MTs. Furthermore, the study identified the significance of the 12th cysteine position at the N-domain and the 68th and 72nd cysteine positions at the C-domain in influencing OsMT-I-Id metal-binding capacity. This research provides novel insights into the structure-function relationship and metal binding properties of type-I plant MTs.


Modulation effect of the SORL1 gene on functional connectivity density in healthy young adults.
The sortilin-related receptor 1 (SORL1) gene has been associated with late-onset Alzheimer's disease (LOAD) and structural impairments in several ethnic populations. However, how this gene affects brain function properties remains unclear. We investigated associations of SORL1 rs2070045 with functional connectivity density (FCD) in healthy young adults. This single-nucleotide polymorphism was selected because it is the SORL1 variant that has been frequently associated with LOAD in several populations, including the Chinese Han population. A total of 275 healthy young Chinese Han subjects with successful genotyping and MRI examinations were included. The effect of SORL1 rs2070045 was explored using a voxel-wise FCD analysis. A significant effect of SORL1 rs2070045 on the FCD was found in the right inferior temporal gyrus. The risk G allele carriers of the rs2070045 exhibited a lower FCD than the protective TT carriers. This effect was independent of the status of apolipoprotein E. This study provides the first evidence that the SORL1 gene is associated with brain FCD differences in healthy young adults. In the genetic risk subjects, connectivity impairment already starts during young adulthood, which may predispose the risk allele carriers to be susceptible to LOAD after several decades.


Incorporating local researchers' and decision makers' preferences for groundwater resources management in a spatial multi-voiced decision model.
Water is a crucial and highly sensitive political issue. The overexploitation of groundwater resources and deterioration of water quality caused by pollution as well as the deficiencies of the existing infrastructure require immediate attention. The main goal of this paper is to carry out a multi-voiced multicriteria analysis that integrates the preferences of local researchers and decision makers in a process aimed at prioritizing watersheds that require the implementation of groundwater management instruments. Using the Criterium Decision Plus system, criteria and subcriteria were integrated into a spatial multi-voiced decision model for the prioritization of watersheds for groundwater resources management. The criteria chosen were Groundwater quality, Groundwater quantity, Land use with potential pollutant load, Equity and Intrinsic aquifer vulnerability. Criteria and subcriteria preferences analysis were derived from workshops with local researchers and decision makers. The spatial multi-voiced decision model identified five of the fourteen watersheds as high to very high priority and requiring groundwater resources management. Based on the local researchers' and decision makers' preferences and hierarchy scheme of the multi-voiced decision model the main criteria and subcriteria that contributed to the final model results were identified. Regarding the criteria, Groundwater quality, Equity and Groundwater quantity contributed extensively to the model. The subcriteria contributions to the groundwater resources management came mainly from High intrinsic aquifer vulnerability, Agrochemicals, Groundwater Storage and Groundwater for domestic supply. This proposed procedure showed that time and effort can be directed to using data and preferences to assist in planning and decision making for groundwater resources management.


HLA, complement C2, C4, properdin factor B and glyoxalase types in South Indian diabetics.
A series of diabetic patients from 3 centres in South India have been tested for HLA A, HLA B, BF, C2, C4A, C4B and GLO types. For insulin-dependent diabetes mellitus (IDDM) patients there was a significant increase in HLA B8, of BF F and decrease of C4 A6. No significant variation in HLA, BF, C2 or GLO frequencies was found in non-insulin-dependent diabetes mellitus (NIDDM) patients, but there was a significant decrease in C4B 1 and an increase in C4B 2. The HLA and BF association in South Indian IDDM patients is very different from that reported previously in North India.


Effects of chronic intraventricular nerve growth factor treatment on vasoactive intestinal peptide and neuropeptide Y levels in the hippocampal formation and cerebral cortex following fimbrial transections.
The present study determined whether chronic intracerebroventricular (i.c.v.) nerve growth factor (NGF) treatment alters the hippocampal content of vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) in rats with unilateral fimbrial transections. In addition, effects of chronic NGF treatment on cortical VIP and NPY levels were determined. Following partial and full fimbrial transections, hippocampal choline acetyltransferase (ChAT) activity was reduced by 41% and 60% ipsilateral to the lesioned side, respectively. Chronic NGF treatment partially attenuated (by 48%) the reduction of ChAT following partial lesions, but not full lesions. Neither the hippocampal contents of VIP or NPY were altered by partial or full fimbrial transections nor by chronic NGF treatment. However, in the NGF-treated rats, significant increases not only in cortical ChAT activity (by 28%), but also cortical VIP levels (by 68%) were observed. Cortical NPY levels remained unchanged following chronic NGF administration. In summary, the results suggest that the increases in cortical VIP levels observed in chronic NGF-treated rats may be specific to this tissue and consequent to the enhanced cholinergic tone exerted by this neurotrophin in the basalocortical pathway. Additionally, it appears that NGF when administered in pharmacological doses is not involved in the regulation of NPY synthesis in the hippocampus or cortex despite the presence of an NGF-responsive element associated with the rat NPY gene.


Characterization of phosphatidylserine synthesis and translocation in permeabilized animal cells.
The synthesis of phosphatidylserine and its translocation to the mitochondria were examined in permeabilized Chinese hamster ovary (CHO)-K1 cells by following the metabolism of a [3H]serine precursor to [3H] phosphatidylserine (PtdSer) and [3H]phosphatidylethanolamine (PtdEtn). In physiological salt solutions approximating the intracellular ionic composition, both the synthesis of PtdSer and its translocation required ATP. The ATP requirement for PtdSer synthesis could be completely bypassed, and that for translocation could be partially bypassed at Ca2+ concentrations 10(3)-10(4) times the intracellular physiological level (i.e. 1 mM). The ATP-dependent synthesis of PtdSer could be inhibited by chelation of Ca2+ with EGTA, inhibition of Ca2+ sequestration with 2,5-di(tert-butyl)hydroquinone, mobilization of sequestered Ca2+ with ionomycin, and competition for [3H]serine with ethanolamine. The inhibition of the ATP-dependent synthesis of PtdSer by the aforementioned inhibitors provided an efficient method to rapidly arrest the incorporation of [3H]serine into [3H]PtdSer. By pulse-labeling the [3H]PtdSer pool and arresting further synthesis with inhibitors, the translocation of nascent PtdSer could be uncoupled from synthesis. The results of these pulse-labeling-arrest experiments provide unambiguous evidence that PtdSer translocation to the mitochondria is not driven by PtdSer synthesis. The addition of apyrase to ATP-supplemented, permeabilized cells abruptly terminates [3H]serine incorporation into [3H]PtdSer and the decarboxylation of [3H]PtdSer to [3H]PtdEtn, thereby demonstrating that a specific ATP requirement exists for the translocation of nascent PtdSer to the mitochondria in permeabilized cells. The translocation of nascent PtdSer to the mitochondria was unaffected by 45-fold dilution of the standard reaction thus indicating that the translocation intermediate was unlikely to be a freely diffusible complex. The requirements for translocation of nascent phosphatidylserine are different from those for the vesicular movement of proteins insofar as the lipid movement does not require cytosol and is unaffected by the addition of Ca2+, GTP, or GTP gamma S. From these studies, we conclude that: 1) the synthesis and translocation of PtdSer can be readily studied in permeabilized cells, 2) the ATP-dependent synthesis of PtdSer is functionally coupled to the ATP-dependent sequestration of Ca2+ by the endoplasmic reticulum or closely related membranes, 3) PtdSer translocation is independent of its synthesis, and 4) there is a specific requirement for ATP in the translocation of PtdSer to the mitochondria.


Behavioral treatment of the speaking stomach syndrome.
The speaking stomach syndrome consists of persisting gurgling sounds in the gastric region, synchronous with breathing. A characteristic finding in patients suffering from this syndrome is an abnormal pattern of respiration, with extreme activity of the abdominal muscles and active involvement of the diaphragm. To teach the patient a different way of breathing using combined thoracic/abdominal respiration, with no, or hardly any, active contraction of the abdominal muscles, is an essential feature of treatment. This is accomplished in three steps. The treatment was successful in the three cases. Problems encountered in therapy are discussed.


The effect of dipyridamole on the thrombocyte count and bleeding tendency in open-heart surgery.
The effect of dipyridamole (Persantine) on the thrombocyte count and bleeding tendency in connection with open-heart surgery and perfusion was studied in 22 patients. A control series of 21 patients undergoing open-heart surgery was available. The treatment group received dipyridamole, 0.5 mg. per kilogram of body weight, in the beginning of cardiopulmonary bypass into the heart-lung machine and thereafter 10 mg. intravenously three times daily for 2 days. From the third day dipyridamole was administered by mouth, 75 mg. three times a day, until the patient was discharged from hospital. We found that dipyridamole had the effect of maintaining the thrombocyte count during cardiopulmonary bypass and the first and second postoperative days. Thereafter no significant difference was seen between the dipyridamole and control groups. The use of dipyridamole did not increase the postoperative hemorrhagic tendency. There were no significant differences in per- and postoperative blood loss and in bleeding and activated partial thromboplastin times between the groups.


Ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy patients with TMEM43 gene mutations.
Catheter ablation of VT in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging, frequently requiring multiple or epicardial ablation procedures; TMEM43 gene mutations typically cause aggressive disease. We sought to compare VT ablation outcomes for ARVC patients with and without TMEM43 mutations. Patients with prior ablation for ARVC-related VT were reviewed. Demographic, procedural, and follow-up data were reviewed retrospectively. Patients with confirmed TMEM43 gene mutations were compared to those with other known mutations or who had no known mutations. Thirteen patients (10 male, mean age 49 ± 14 years) underwent 29 ablation procedures (median 2 procedures/patient, range 1-6) with a median of 4 targeted VTs/patient (range 1-9). They were followed for a mean duration of 7.3 ± 4.2 years. Gene mutations included TMEM43 (n = 5), PKP2 (n = 2), DSG2 (n = 2), unidentifiable (n = 4). TMEM patients showed more biventricular involvement compared to non-TMEM patients (80% vs. 12.5%, P = 0.032), more inducible VTs during their ablation procedures (mean VTs/patient: 5.8 ± 3 vs. 2.6 ± 1, P = 0.021). Acute and long-term procedural outcomes did not show a significant difference between the two groups, however TMEM patients had worse composite endpoint of death or transplantation (60% vs. 0, P = 0.035; log-rank P = 0.013). TMEM43 mutation patients were more likely to have biventricular arrhythmogenic substrate and more inducible VTs at EP study. Despite comparable acute VT ablation outcomes, long-term prognosis is unfavorable.


Synthesis and antidepressant evaluation of three para-benzoquinone mono-oximes and their oxy derivatives.
A series of three para-benzoquinone mono-oximes and four oxy-derivatives were prepared and tested for their antidepressant properties. The (4E) oxime of 2-isopropyl-5-methyl-para-benzoquinone (4) and the corresponding 2-diethylamino-ethyl derivative (10) present antidepressant activities and were slightly more potent than the reference standard.


Epoxides as products of lipid autoxidation in rat lungs.
The nature and content of lipid epoxides in rat lung were examined in air-breathing control rats and those exposed to nitrogen dioxide. Exposure to 6.5 ppm NO2 for 24 hr resulted in significantly greater epoxide content in a number of lipid classes. It is proposed that lipid autoxidation in lung tissues may contribute to the levels of epoxide-containing lipids. Furthermore, the processes involved in epoxide formation may be predicted from autoxidation studies utilizing a system of unsaturated fatty acid monolayers on silica gel which serves as a model for biomembranes. The findings indicate that exposure to oxidizing gases can lead to an accumulation of lipid epoxides in both lung parenchymal tissue and on the alveolar surface.


4D printed multipurpose smart implants for breast cancer management.
Breast-conserving surgery (BCS) is the primary strategy for treating early-stage breast cancer; however, the incidence of local recurrence and breast tissue loss negatively impacts patients and survivors. Furthermore, radiotherapy and/or systemic therapies are frequently advised to avoid recidivism and increase the patient's chance of survival, resulting in longer duration of treatments, and unpleasant systemic side effects. Given the poor prognosis and the heterogeneity between individuals and tumors, a patient-centered approach is fundamental. Herein we developed a multipurpose 4D printed implant made of a blend of carboxymethyl cellulose sodium salt (CMC) and cellulose nanocrystals (CNC), loaded with doxorubicin (DOX). To predict printability performance, full rheological characterization was carried out. The smart device was programmed to change size, under swelling, to better fit in the tissue cavity, resulting in a great potential for personalization, thus improving the aesthetic outcomes. The influence of the formulation and printing parameters on the morpho transformation was investigated through the swelling test, confirming the possibility to program the 4D shape. The manufactured implants were characterized by a variety of methods, including in vitro release studies. Lastly, the anticancer activity was conducted in vitro, on MDA-MB-231 cells. Implants promoted an anticancer effect of -58% viability after 72 h incubation, even when tested 4 weeks after the printing process. Overall, the morpho transformation and the in vitro studies have shown that the implant could represent a potential strategy for breast cancer following resection, to fill the void in the breast resulting from the surgery and provide an anticancer effect to avoid recurrence.


An outbreak of tuberculosis in a middle school in Henan, China: Epidemiology and risk factors.
In 2013, a tuberculosis (TB) outbreak occurred in a middle school in Henan province of China. An outbreak survey was carried out in the school. This study was undertaken to investigate the detection rate of TB cases and those with strong Mantoux positive (SMP), defined as tuberculin skin test (TST) indurations of 15mm or larger and/or blisters, necrosis or lymphangitis, and to identify their risk factors. The TST, chest x-ray/radiography, and TB-suspicious symptoms interview were used to screen for TB cases. Their diagnosis was made by sputum smear microscopy, liquid culture, computed tomography (CT), and diagnostic therapy if necessary. We retrospectively analyzed the outbreak survey data of 4082 students and 278 staff in the school. Logistic regression models were used to identify the risk factors associated with SMP and TB disease. Approximately 3.55% of students and 16.55% of staff were SMP. SMP rate in students was significantly lower than that in staff (p<0.001). 55 TB cases in students and none in staff were identified in the school from February to November, 2013, with a detection rate of 1.35% for students. SMP and TB case detection rates were 20.29% and 41.77%, respectively, in the index class, both significantly higher than that in the other classes (3.26% and 0.55%, respectively; both p<0.001). In the index class, TB case detection rate over the study period in students with SMP was not significantly higher than that with TST indurations of <15mm (38.18% vs 21.43%, p = 0.24), but it was significantly higher in the other classes (7.81% vs 0.18%, p<0.001). Risk factors independently associated with SMP and TB cases shared the following with the index case: same dormitory-floor (adjusted odds ratio (AOR) 5.36, 95% CI 3.02-9.48, p<0.001 for SMP; AOR 2.67; 95% CI 1.03-6.96, p = 0.044 for TB cases), same classroom (AOR 4.01; 95% CI 1.95-8.26, p<0.001 for SMP; AOR 165.08; 95% CI 66.88-407.47, p<0.001 for TB cases), same teaching-floor in different classroom (AOR 5.41; 95% CI 3.02-9.71, p<0.001 for SMP; AOR 11.24; 95% CI 3.71-34.03, p<0.001 for TB cases) and same teaching-building on different floor (AOR 1.81; 95% CI 1.16-2.85, p = 0.009 for SMP; AOR 3.30; 95% CI 1.16-9.42, p = 0.025 for TB cases). The closer the contact was with the index case, the larger the AORs for SMP and TB cases were. Same dormitory-floor, same classroom, same teaching-floor and same teaching-building with the index case were all risk factors for both TB infection and disease for students in the outbreak, and the closer the contact was with the index case, the higher the risk was observed. Attention should also be paid to students with TST indurations <15mm, as well as to those with that ≥15mm for the index class in dealing with the outbreak.


Site-specific patterns of early response to nivolumab plus ipilimumab therapy in advanced renal cell carcinoma patients compared with tyrosine-kinase inhibitors.
This study aimed to identify patterns of early response to nivolumab and ipilimumab combination therapy (Nivo+Ipi) in primary and metastatic sites of advanced renal cell carcinoma (RCC). RCC patients treated with Nivo+Ipi or tyrosine-kinase inhibitors (TKIs) as first-line therapy were included. To exclude selection bias due to patient characteristics, baseline clinical data was adjusted by inverse probability of treatment weighting (IPTW). Overall response rate (ORR) and lesional response rates (LRR) in primary and metastatic sites were determined by measuring tumor diameters on serial CT images according to Response Evaluation Criteria in Solid Tumors, version 1.1. 33 patients were treated with Nivo+Ipi and 39 with TKIs as first-line therapy. After IPTW-adjusted analysis, ORR during the first 24 weeks of treatment was significantly higher in Nivo+Ipi group than in TKIs group (45.5% versus 21.7%, p < 0.01). LRR of the primary tumor tended to be higher in Nivo+Ipi group than in TKI group (14.8% versus 4.4%, p = 0.06). Mean LRR of all metastatic sites was not significantly different between the two groups, but tumor shrinkage rate of lung metastasis was significantly higher in Nivo+Ipi group than in TKIs group (68.5% versus -12.7%, p < 0.01). Univariate and multivariate analyses identified lung metastasis as the independent factor associated with prolonged progression-free survival and with higher ORR. Our study found that lung metastasis of advanced RCC exhibited early response to Nivo+Ipi therapy. Further studies are warranted to verify whether site-specific early response predicts overall survival benefit in advanced RCC patients treated with Nivo+Ipi.


Open sky Müller muscle-conjunctival resection in phenylephrine test-negative blepharoptosis patients.
To assess the efficacy of Müller muscle-conjunctival resection in patients in whom the phenylephrine test was negative. A non-randomized, prospective clinical trial was conducted on 20 eyelids of 15 consecutive patients with blepharoptosis who showed no change in the upper eyelid margin-reflex distance (MRD1) following instillation of topical phenylephrine. The technique used was open sky Müller muscle-conjunctival resection. The mean MRD1 increased by 3.3 mm. No patient required augmentation of the procedure, and all patients had excellent appearance of their skin crease and eyelid contour. No complications arose from the procedure, including no incidence of dry eye symptoms or signs. Müller muscle-conjunctival resection may offer a safe and effective means of treating blepharoptosis despite a negative phenylephrine test.


An evaluation of the effectiveness of a baby walker safety standard to prevent stair-fall injuries.
During the early 1990s the number of baby walker injuries treated in U.S. hospital emergency departments averaged almost 25,000 annually; about 80% resulted from falls down stairs. After initiating a regulatory proceeding in 1994, the U.S. Consumer Product Safety Commission staff worked with industry to develop requirements to address the stair-fall hazard. This study evaluates the effectiveness of the stair-fall requirements, which became effective in 1997 as part of a revised voluntary standard. Annual baby walker emergency department injury rates were constructed for the 1981-2002 study period. A multivariate negative binomial regression model was used to estimate the effectiveness of the stair-fall requirements in reducing the injury rate. The stair-fall requirements reduced the emergency department injury rate by an estimated 63% (95% CI, 52% to 71%). Given the substantial reduction in walker injuries, and the high level of industry conformance with the stair-fall requirements, the Commission terminated its regulatory proceeding in May, 2002. The success of the baby walker project highlights the ability of government and industry to work together cooperatively to develop effective safety improvements for consumer products.


A retrospective survey of dengue virus infection in fatal cases from an epidemic in Brazil.
Dengue virus can infect many cell types from the vascular, muscular and hematological systems causing diverse clinical and pathological signs. The purpose of the present study was to investigate by different diagnostic methods dengue virus in human tissue specimens obtained from fatal cases (n=29) during a large-scale dengue fever epidemic in 2002 in the State of Rio de Janeiro, Brazil. The combination of four procedures provided diagnostic confirmation of DENV-3 infection in 26 (89.6%) out of the 29 suspected fatal cases. Dengue virus (DENV) was isolated from 2/74 (2.7%) tissue samples, inoculated into C6/36 cells and identified as DENV-3, nested RT-PCR accusing 22/72 (30.5%) samples as DENV-3. Real-time RT-PCR yielded the highest positivity rate, detecting viral RNA in 45/77 (58.4%) clinical specimens, including the liver (n=18), lung (n=8), spleen (n=8), brain (n=6), kidney (n=3), bone marrow (n=1) and heart (n=1). Immunohistochemical tests recognized the DENV antigen in 26/59 (44%) specimens. Given the accuracy and effectiveness of real-time RT-PCR in this investigation, this approach may play an important role for rapid diagnosis of dengue infections.


A dual H-type tracheoesophageal fistula; why not being repaired simultaneously? A case report and review of literature.
H-type Tracheoesophageal Fistula (TEF) is a particular type of congenital esophageal anomalies, in which patients present with non-specific symptoms that can result in delayed diagnosis. Here, we report two pediatric cases with a rarer variant called "dual H-type TEFˮ. We present two cases of H-type TEF. The first was a 45-day-old boy with feeding problem and cyanosis while feeding, and the second was a three-month-old girl with cough and choking after feeding from the first day of birth. In both cases, two separate TEFs were detected during diagnostic evaluation by flexible bronchoscopy. Both were repaired simultaneously through a cervical incision. The first patient deteriorated 13 days after the surgery, disturbancing in acid-base balance and expired unfortunately. Hence, it is necessary to consider the possibility of double TEF in any newly diagnosed H-type TEF.


Predicting Professional Quality of Life and Life Satisfaction in Spanish Nurses: A Cross-Sectional Study.
Background: Dealing with suffering, grief, and death on a daily basis, together with the particular working conditions, may produce high levels of burnout in nurses, and hinder their well-being. The purpose of this research is to study the effect of self-care and self-compassion on nurses' professional quality of life and well-being. Methods: The research had a cross-sectional design, used correlational methodology and a structural equation model was hypothesized. Along the study, 210 nurses from the Healthcare Public System of the Balearic Islands, participated. The study took place from June to September 2018. Results: The hypothesized model showed an overall adequate fit. Practice environment predicted both self-care and self-compassion, whereas nursing stress did not. Self-care and self-compassion predicted nurses' professional quality of life, whereas the practice environment and nursing stress were not predictors. Finally, professional quality of life showed a positive relationship with life satisfaction. Conclusions: The study presents a comprehensive structural equation model in which self-care and self-compassion are the best predictors of nurses' professional quality of life. A direct relation of professional quality of life and nurses' well-being has also been found, while controlling for the effects of nurses' practice environment and stress.


Inhibition of carboxypeptidase U (TAFIa) activity improves rt-PA induced thrombolysis in a dog model of coronary artery thrombosis.
The objective of this study was to test the hypothesis if thrombolysis induced by recombinant tissue-type plasminogen activator, (rt-PA) could be facilitated by inhibiting carboxypeptidase U (CPU, active Thrombin Activatable Fibrinolysis Inhibitor, TAFIa) activity. The efficacy of rt-PA alone, or in combination with the carboxypeptidase inhibitor MERGETPA, was compared in a dog model of coronary artery thrombosis. Twenty dogs were randomised in two groups, one received rt-PA, 1 mg kg(-1), as intravenous infusion over 20 min starting 30 min after thrombus formation, and the other group received rt-PA, 1 mg kg(-1), as group one with the addition of MERGEPTA 5 mg kg(-1) starting 25 min prior to coronary artery occlusion and followed by infusion of 5 mg kg(-1) h(-1) until the end of experiment. Efficacy was assessed by determination of time to lysis, duration of patency and blood flow during patency. Both groups had similar baseline characteristics with respect to haemodynamic parameters, i.e., heart rate, blood pressure and coronary artery blood flow. Coadministration of rt-PA and MERGETPA resulted in significant decrease in time to lysis (15+/-1.5 min vs. 20+/-1.7 min, p=0.03), increased patency time (87+/-16 min vs. 46+/-12 min, p=0.047) and increased coronary blood flow during patency (1131 mL h(-1) vs. 405 mL h(-1), p=0.015), compared to rt-PA alone. These results indicate that an inhibitor of CPU activity may have a beneficial effect in patients undergoing thrombolytic therapy by attaining shorter time to reperfusion and improved coronary patency.


Effect of sodium selenite and methyl methanesulfonate or N-hydroxy-2-acetylaminofluorene co-exposure on sister-chromatid exchange production in human whole blood cultures.
Sodium selenite (Na2SeO3) was tested for its sister-chromatid exchange (SCE)-inducing ability in human whole blood cultures and for the effect of its co-exposure with methyl methanesulfonate (MMS) or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) on SCE frequency. Long exposure times (77 h and 96 h) to 3.95 X 10(-6) M Na2SeO3 resulted in cell death as measured by mitotic indices, but mitotic figures were present after exposure to higher concentrations for a shorter time (19 h). High Na2SeO3 concentrations (7.90 X 10(-6) and 1.19 X 10(-5) M) resulted in a three-fold increase in the SCE frequency above background level (6--7 SCEs/cell). Exposure of lymphocytes to 1 X 10(-4) M MMS for the last 19 h of culture yielded an average SCE frequency of 30.17 +/- 0.75 while a similar exposure to 2.7 X 10(-5) M N-OH-AAF resulted in 13.61 +/- 0.43 SCEs/cell. Simultaneous addition of the high Na2SeO3 concentrations and MMS or N-OH-AAF to the cultures resulted in SCE frequencies that were 25--30% and 11--17%, respectively, below the sum of the SCE frequencies produced by the individual compounds.


Oral Bisphosphonates and Upper Gastrointestinal Cancer Risks in Asians with Osteoporosis: A Nested Case-Control Study Using National Retrospective Cohort Sample Data from Korea.
Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis. We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases. A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied. This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.


Flexible recoding of visual input for memory storage.
Working memory enables us to maintain relevant past information for future behavior. In this issue of Neuron, Kwak and Curtis (2022) demonstrate that early visual areas do not simply maintain but flexibly recode sensory percepts into mnemonic codes containing goal-relevant information.


Prediction of outcome following laminoplasty of cervical spondylotic myelopathy: Focus on the minimum clinically important difference.
The minimum clinically important difference (MCID) of the Japanese Orthopaedic Association (JOA) score has been reported to be around 2.5 points in cervical myelopathy. This study sought to define significant predictive factors on achieving the MCID following laminoplasty in a large series of patients with cervical spondylotic myelopathy (CSM). A total of 485 consecutive patients with CSM (295 males and 190 females; mean age: 67.0 years; age range: 42-91 years) who underwent laminoplasty were prospectively enrolled. The average postoperative follow-up period was 26.6 months (range: 12-66 months). We calculated the achieved JOA score. The relationships between outcomes and various clinical and imaging predictors including comorbidity and quantitative performance tests were examined. Logistic regression analysis was conducted to identify the predictors correlated with a JOA score of 2.5 points or more. Clinically meaningful gains were exhibited in 299 patients (61.6%) with a JOA score of ≥2.5 points, whereas 186 patients (38.4%) achieved a JOA score of <2.5 points. Univariate logistic regression analysis showed the predictive factors with a shorter duration of CSM symptoms, lower preoperative JOA scores, absence of hypertension, no use of anticoagulant/antiplatelet agents, and nonsmoking status. Multivariate logistic regression analysis determined that the duration of CSM symptoms (odds ratio: 0.771, 95% confidence interval: 0.705-0.844; p < 0.01) was the only significant predictive factor for achieving JOA scores of ≥2.5 points. An important predictor of MCID achievement following laminoplasty was shorter duration of CSM symptoms.


Comparing solid phase extraction and direct injection for the analysis of ultra-trace levels of relevant explosives in lake water and tributaries using liquid chromatography-electrospray tandem mass spectrometry.
Off-line solid phase extraction and direct injection analysis were evaluated for the determination of traces of explosives such as TNT and its mono and diamino metabolites, HMX, RDX, nitroglycerin and PETN in lake water and tributaries applying liquid chromatography-electrospray tandem mass spectrometry. Improved chromatographic separation was achieved on a phenyl based stationary phase with baseline resolution of the mono- and diamino metabolites of TNT. Identification and quantification of the target compounds was performed by multiple reaction monitoring applying electrospray ionization in either the positive mode for the diaminometabolites of TNT or the negative mode for all other compounds. An extensive method validation was performed and limits of quantification were obtained for the explosives in preconcentrated lake water samples from 0.03 to 1 ng l(-1) and 0.1 to 5 ng l(-1) in river water. Direct injection analysis revealed comparable results to preconcentrated water samples for the most persistent explosives. Analysis of lake water samples collected at different depths showed the presence of HMX, RDX and PETN at concentrations from 0.1 to 0.4 ng l(-1). The analysis of main tributaries revealed concentrations from 0.1 to 0.9 ng l(-1) of the same compounds. They seem to be responsible for the contamination of the explosives in the lakes.


Incidence of serious injury and death during sport and recreation activities in Victoria, Australia.
Participation in sport and recreation is widely encouraged for general good health and the prevention of some non-communicable diseases. However, injury is a significant barrier to participation, and safety concerns are a factor in the decision to participate. An understanding of the sport/recreation activities associated with serious injury is useful for informing physical activity choices and for setting priorities for the targeting of injury prevention efforts. To describe the epidemiology of serious injuries sustained in sport/recreation activities by adults in Victoria, Australia. The Victorian State Trauma Registry and the National Coroner's Information Service were used to identify and describe sport/recreation related serious injuries, including deaths, occurring during the period July 2001 to June 2003. Age adjusted rates of serious injury and death were calculated using participation figures for each sport and general population data. There were 150 cases of serious injury and 48 deaths. The rates of serious injury and death were 1.8 and 0.6 per 100,000 participants per year respectively. Motor, power boat, and equestrian sports had the highest rates of serious injury. Most deaths were due to drowning. Although the risk of serious injury through sport/recreation participation is low, motor, power boat, and equestrian sports should be priorities for further research into injury prevention. Most sport/recreation related deaths are due to drowning, highlighting this area for prevention efforts.


Modification of Ti6Al4V surface by diazonium compounds.
Ti6Al4V alloy is the most commonly used in orthopedic industry as an endoprosthesis. Ti6Al4V exhibits good mechanical properties, except the abrasion resistance. Surface modification of Ti6Al4V in order to obtain organic layer, and then the attachment of the polymer, can allow for overcoming this problem. The aim of the work was the modification of Ti6Al4V surface by diazonium compounds: salt or cation generated in situ and examine the influence of the reducing agent - ascorbic acid, and the temperature of reaction on modification process. Moreover, the simulated body fluid was used for the assessment of the organic layer stability on Ti6Al4V surface. The evaluation of the modification was carried out using the following methods: Raman microspectroscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Higher temperature of modification by 4-hydroxymethylbenzenediazonium cation, provides the largest amount of organic layer on the Ti6Al4V alloy. In the case of the Ti6Al4V modified by Variamine Blue B salt, the amount of organic layer is not dependent on the reaction condition. Moreover, the ascorbic acid and the presence of TiO2 does not effect on the modification. The modified surface is completely coated with the organic layer which is stable in simulated body fluid.