Development and clinical usefulness of a new neuroendoscope system for CT-guided stereotactic brain surgery.
Since computed tomography (CT)-guided stereotactic surgery is essentially blind surgery, it always involves the risk of injuring viable brain tissue and vessels, and it is difficult to obtain a sufficient amount of biopsy specimen from cystic or necrotic lesions. Moreover, the direct observation of the lesion would provide extremely valuable information. The authors have therefore developed a new subminiature rigid endoscope and an ultrasonic aspirator for use in stereotactic surgery, as well as a new micromanipulative system to attach the equipment to the stereotactic frame so that they can be accurately inserted into the optimum position from any direction. The new neuroendoscope includes a graded refractive index glass rod only 1.0 mm in diameter (Selfoc, Nippon Sheet Glass Co., Osaka), which provides a focal depth from 1 mm to infinity, as well as an extremely bright and wide visual field with an angle of 70 degrees. Furthermore, because the outer probe and endoscopic sheath share the outer rigid metal tube 4.5 mm in outer diameter, a large internal channel of 2.1 mm in diameter allows the introduction of various microinstruments such as an ultrasonic aspirator probe, laser probe, and biopsy forceps. When a miniaturized video camera is attached, the surgical procedures can be controlled using the video monitor and photographed. The new probe for the ultrasonic aspirator has been developed in various types suitable for fragmentation and aspiration of hematomas and brain tumors, so under endoscopic control even the harder coagulants and tumors can be removed.(ABSTRACT TRUNCATED AT 250 WORDS)


SAMHD1 restricts the deoxyguanosine triphosphate pool contributing to telomere stability in telomerase-positive cells.
SAMHD1 (Sterile alpha motif and histidine/aspartic acid domain-containing protein 1) is a dNTP triphosphohydrolase crucial in the maintenance of balanced cellular dNTP pools, which support genome integrity. In SAMHD1 deficient fibroblasts isolated from Aicardi-Goutières Syndrome (AGS) patients, all four DNA precursors are increased and markedly imbalanced with the largest effect on dGTP, a key player in the modulation of telomerase processivity. Here, we present data showing that SAMHD1, by restricting the dGTP pool, contributes to telomere maintenance in hTERT-immortalized human fibroblasts from AGS patients as well as in telomerase positive cancer cell lines. Only in cells expressing telomerase, the lack of SAMHD1 causes excessive lengthening of telomeres and telomere fragility, whereas primary fibroblasts lacking both SAMHD1 and telomerase enter normally into senescence. Telomere lengthening observed in SAMHD1 deficient but telomerase proficient cells is a gradual process, in accordance with the intrinsic property of telomerase of adding only a few tens of nucleotides for each cycle. Therefore, only a prolonged exposure to high dGTP content causes telomere over-elongation. hTERT-immortalized AGS fibroblasts display also high fragility of chromosome ends, a marker of telomere replication stress. These results not only demonstrate the functional importance of dGTP cellular level but also reveal the critical role played by SAMHD1 in restraining telomerase processivity and safeguarding telomere stability.


[Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia].
The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5T MR unit. The former showed low intensity on opposed-phase T1-weighted images, while the latter showed high intensity on both fast STIR and opposed-phase T1-weighted images. MR spectroscopy quantitatively confirmed that the water: fat ratio was increased and the transverse relaxation time of water was changed in hyperplastic bone marrow, compared with normal bone marrow. In summary, MR imaging is able to detect hematopoietic regions among a wide range of bone marrow of aplastic anemia, while MR spectroscopy allowed us to quantitatively analyze the cell population of hyperplastic hematopoietic marrow in aplastic anemia.


Bits and q-bits as versatility measures.
Using Shannon information theory is a common strategy to measure any kind of variability in a signal or phenomenon. Some methods were developed to adapt information entropy measures to bird song data trying to emphasize its versatility aspect. This classical approach, using the concept of bit, produces interesting results. Now, the original idea developed in this paper is to use the quantum information theory and the quantum bit (q-bit) concept in order to provide a more complete vision of the experimental results.


Occurrence of cervical spine injuries during the rugby scrum.
A retrospective study of cervical spine injuries that occurred during the rugby scrum in the United States was undertaken. In the U.S., from 1970 to 1996, 36 (58%) of the 62 documented injured players injured their cervical spines during the scrum. Thirty-five men (97%) and one woman (3%) were injured. Twenty-three of the injuries (64%) occurred when the opposing packs came together (engagement), and 13 (36%) occurred when the scrum collapsed. Twenty-eight (78%) hookers, seven (19%) props, and one (3%) second-row player were injured. Twenty (56%) hookers and three (8%) props were hurt during engagement. Eight hookers (22%), four props (11%), and one second-row player (3%) were injured when the scrum collapsed. Significantly more injuries occurred during engagement than during collapse, and hookers were injured significantly more than props. We conclude that in the rugby scrum in the U.S., the hooker suffers most of the cervical spine injuries (78% in this study) and this position is by far the most vulnerable. This study should be used to develop rugby law (rule) changes and educate players, coaches, and referees in United States rugby.


Chemokine receptor CXCR4 activates the RhoA/ROCK2 pathway in spinal neurons that induces bone cancer pain.
Chemokine receptor CXCR4 has been found to be associated with spinal neuron and glial cell activation during bone cancer pain. However, the underlying mechanism remains unknown. Furthermore, the RhoA/ROCK2 pathway serves as a downstream pathway activated by CXCR4 during bone cancer pain. We first validated the increase in the expressions of CXCR4, p-RhoA, and p-ROCK2 in the spinal dorsal horn of a well-characterized tumor cell implantation-induced cancer pain rat model and how these expressions contributed to the pain behavior in tumor cell implantation rats. We hypothesized that spinal blockade of the CXCR4-RhoA/ROCK2 pathway is a potential analgesic therapy for cancer pain management. Adult female Sprague-Dawley rats (body weight of 180-220 g) and six- to seven-week old female Sprague-Dawley rats (body weight of 80-90 g) were taken. Ascitic cancer cells were extracted from the rats (body weight of 80-90 g) with intraperitoneally implanted Walker 256 mammary gland carcinoma cells. Walker 256 rat mammary gland carcinoma cells were then injected (tumor cell implantation) into the intramedullary space of the tibia to establish a rat model of bone cancer pain. We found increased expressions of CXCR4, p-RhoA, and p-ROCK2 in the neurons in the spinal cord. p-RhoA and p-ROCK2 were co-expressed in the neurons and promoted by overexpressed CXCR4. Intrathecal delivery of CXCR4 inhibitor Plerixafor (AMD3100) or ROCK2 inhibitor Fasudil abrogated tumor cell implantation-induced pain hypersensitivity and tumor cell implantation-induced increase in p-RhoA and p-ROCK2 expressions. Intrathecal injection of stromal-derived factor-1, the principal ligand for CXCR4, accelerated p-RhoA expression in naive rats, which was prevented by postadministration of CXCR4 inhibitor Plerixafor (AMD3100) or ROCK2 inhibitor Fasudil. Collectively, the spinal RhoA/ROCK2 pathway could be a critical downstream target for CXCR4-mediated neuronal sensitization and pain hypersensitivity in bone cancer pain, and it may serve as a potent therapeutic target for pain treatment.


Slowed gastric evacuation accounts for the reduction of food intake by anorectic drugs.
The effect of mazindol given orally on gastric emptying of a radiolabelled solid meal was examined in 10 obese females. The patients underwent the measurement of gastric emptying twice: 2 mg mazindol was compared with placebo according to a double-blind study protocol. Mazindol significantly delayed gastric emptying (P less than 0.02 for both the gastric half emptying time, t1/2, and emptying index, Ix). The inhibition of the late phase of gastric emptying by mazindol was reflected by a significant (P less than 0.05) decrease of the shape parameter S of the power-exponential fitted gastric emptying curves, as well as by the comparison of the amount of food retained within the stomach (P less than 0.05 at 80 min and P less than 0.02 at 90 min). Potential mechanisms and the meaning of the findings are discussed.


Intrarenal artery injection of capsaicin activates spontaneous activity of renal afferent nerve fibers.
The effects of intrarenal artery injection of capsaicin on multi- and single-unit spontaneous discharges of renal afferent nerve fibers were investigated in anesthetized rabbits. The results obtained are as follows: (1) intrarenal artery injection of capsaicin (20, 40, and 60 nmol/kg) increased the renal afferent nerve activity (ARNA) in a dose-dependent manner with unchanged arterial pressure; (2) pretreatment with ruthenium red (40 mmol/kg), a capsaicin receptor antagonist, completely abolished the effect of capsaicin; and (3) pretreatment with a nitric oxide synthase inhibitor L-NAME (N(6)-nitro-L-arginine methylester, 0.1 mmol/kg), significantly enhanced the ARNA response to capsaicin. The results suggest that intrarenal artery injection of capsaicin can activate ARNA via capsaicin receptors in anesthetized rabbits and that nitric oxide may be involved in regulating the activity of renal sensory nerve fibers as an inhibitory neurotransmitter.


Relationship between N-acetyl-beta-D-glucosaminidase activity and cell count, lactose, chloride, or lactoferrin in cow milk.
Activity of N-acetyl-beta-D-glucosaminidase was measured in foremilk samples collected from cows. A total of 64 samples were collected from these cows, some of which were affected by mastitis. They were examined for N-acetyl-beta-D-glucosaminidase activity, cell count in whole milk, and milk chloride, lactose, and lactoferrin. The correlation coefficient was .72 between activity and cell count, -.80 between activity and lactose, and .88 between activity and chloride. Therefore, the correlations between N-acetyl-beta-D-glucosaminidase activity and milk components, chloride and lactose, were larger than that between N-acetyl-beta-D-glucosaminidase activity and cell count. The correlation coefficient was high (.91) between N-acetyl-beta-D-glucosaminidase and lactoferrin. The N-acetyl-beta-D-glucosaminidase activity in cow's milk has potential for diagnosis of mastitis.


Implication of Peripheral Neuropathy on Unplanned Readmissions in Patients Hospitalized for Complicated Diabetic Foot Disease.
Introduction. Unplanned readmissions are common following discharge in patients after hospitalization for diabetic foot disease (DFD) complications. The aim of this study was to identify factors associated with readmissions in these high-risk patients, treated in a multidisciplinary setting and the implication of measures that could effectively reduce readmission rates. Methods. Patients presenting with DFDs admitted between 2015 and 2017 were studied retrospectively in a single-centre patient database. The demographics and clinical comorbidities were analyzed and comparison was made between 2 groups: patients readmitted within 30 days of discharge and those who did not require readmission. Multivariate analysis was performed to identify risk factors associated with readmissions. Results. In total, 340 patients were included. The unplanned readmission rate was 10.9%. More than half of readmissions (71%) were related to wound deterioration and infection. In the readmission group, the patients had lower body mass index, higher rate of osteomyelitis, lower rate of debridement, and evidence of peripheral vascular disease below the knee in the index admissions but these were not significant. In the multivariate analysis, peripheral neuropathy was the only significant risk associated with unplanned readmissions (odds ratio: 2.78, 95% confidence interval: 1.23-6.29, P = .014). Conclusion. This study demonstrates a significant association between peripheral neuropathy and unplanned readmissions. The implications of this nonmodifiable risk factor in reducing readmissions include all levels of patient care delivery such as adequate preparation for discharge and transition back into the community. Recognition and education in successful long-term offloading of insensate diabetic feet may help reduce rates of unplanned readmission.


Spontaneous assembly of a polymeric helicate of sodium with LVO(2) units forming the strand: photoinduced transformation into a mixed-valence product.
The anionic cis-dioxovanadium(V) complex species LVO(2)(-) of a tridentate ONS ligand (H(2)L) can bind sodium ion in a bis-monodentate fashion like a bridging carboxylate group. The product [LVO(2)Na(H(2)O)(2)](infinity) (1) is a water soluble polymeric compound in which the complementary units are held together by the simultaneous use of hydrogen bonding and Coulombic interactions. Crystallographic characterization reveals that 1 is a single stranded helicate with LVO(2)(-) units forming the strand which surrounds the labile sodium ions that occupy the positions on the axis. In solution of protic solvents, viz. water and methanol, 1 is quite stable as indicated by electrical conductivity and (1)H NMR measurements. In aprotic solvents, viz. CH(3)CN, DMF, or DMSO, however, the extended hydrogen bonded network in 1 breaks apart and the helical structure collapses when irradiated with visible light. The product is a mixed-oxidation vanadium(IV/V) species obtained by photoinduced reduction as confirmed by EPR, time dependent (1)H NMR, and electronic spectroscopy. Compound 1 is a rare example of a nonnatural helix where hydrogen bonding interactions play a crucial role in stabilizing the single stranded polymeric structure such as that frequently observed in the biological world.


Nutrient affinity, half-saturation constants and the cost of toxin production in dinoflagellates.
The two parameters of the Michaelis-Menten model, the maximum uptake rate and the half-saturation constant, are not stochastically independent, and the half-saturation constant is not a measure of nutrient affinity, as commonly assumed. Failure to realise their interdependence and mechanistic interpretation may lead to the emergence of false trade-offs.


Marriage Patterns and Childbearing: Results From a Quantitative Study in North of Iran.
Social changes have rapidly removed arranged marriages and it seems the change in marriage pattern has played a role in childbearing. On the other hand, there is a great reduction in population in many countries which requires a comprehensive policy to manage the considerable drop in population. To achieve this goal, initially, the factors affecting fertility must be precisely identified. This study aims to examine the role of marriage patterns in childbearing. In this cross-sectional quantitative study, 880 married women 15-49 years old, living in the north of Iran were studied using a cluster sampling strategy. The results showed that there are no significant differences in reproductive behaviors of three patterns of marriage in Bobol city of Iran. It seems there is a convergence in childbearing due to the different patterns of marriage and Policymakers should pay attention to other determinants of reproductive behaviors in demographic planning.


Effects of rapamycin on DC-SIGN expression and biological functions in DC.
Rapamycin, a macrolide antibiotic, has potent immunosuppressive properties as an antirejection therapy in organ transplantation. Studies show that dendritic cells (DC) are important targets for rapamycin, which can inhibit DC maturation and DC-induced allogeneic T cell proliferation. In this study, we investigated the effects of rapamycin on the expressions of DC-SIGN and transcription factor PU.1 and the function of DC. Treatment with rapamycin significantly reduced the expression of DC-SIGN in a dose-dependent manner associated with suppression of PU.1 gene expression and the ability of DC to migrate and stimulate T cell proliferation. The expression of DC-SIGN was significantly suppressed using PU.1 siRNA. Intriguingly, rapamycin treatment largely decreased the expressions of PU.1 and DC-SIGN in THP-1 cells. In addition, treatment with rapamycin down-regulated the promoter activity of DC-SIGN. In conclusion, rapamycin inhibits DC-SIGN expression and suppresses the ability of DC to migrate and stimulate T cell proliferation through the PU.1 gene transcription pathway.


Effect of dexamethasone therapy on the neonatal ductus arteriosus.
Patent ductus arteriosus (PDA) is believed to be a contributing factor in the etiopathogenesis of bronchopulmonary dysplasia (BPD). We studied the effects of early dexamethasone therapy on persistent ductal patency and the role of PDA in the etiopathogenesis of BPD during the course of a randomized double-blind trial of dexamethasone to prevent BPD. Infants, who weighed between 700 and 999 g, had severe RDS, and had been given surfactant, were randomized to receive a 12-day course of dexamethasone (n = 13) or placebo (n = 17) starting within the first 12 hours of postnatal life. The diagnosis of PDA was made clinically and was confirmed by cardiac ultrasound. The incidence of clinically significant ductus in infants who weighed less than 1000 g was 23% in the dexamethasone-treated group, as compared with 59% in infants who were given placebo. This difference was marginally significant, p = 0.05, odds ratio 0.21, 95% confidence interval 0.04-1.05. None of the infants in the dexamethasone group had recurrence of PDA after indomethacin therapy as compared with three infants in the placebo group. Dexamethasone significantly reduced the number of days infants required ventilator and supplemental oxygen as compared with infants who received placebo. Dexamethasone, as compared with placebo, also reduced the incidence of BPD, p = 0.025, odds ratio 0.08, 95% confidence interval 0.01-0.58. Dexamethasone may reduce the incidence of PDA in premature infants who weigh less than 1000 g at birth and thereby reduce the incidence of BPD.


Biomechanical evaluation of a new augmentation method for enhanced screw fixation in osteoporotic proximal femoral fractures.
A biomechanical investigation on eight pairs of human cadaver proximal femurs was performed to evaluate the impact of a new augmentation method on the internal fixation of osteoporotic proximal femur fractures. The study focused on enhancing implant purchase to reduce the incidence of implant cut-out in osteoporotic bone. In a left-right comparison, a conventional hip screw fixation (control) was compared to the new cement augmentation method. After bone bed preparation through high pressure irrigation to remove fat, blood, and bone debris, the bones were augmented with low viscosity polymethylmethacrylate (PMMA) cement. Step-wise fatigue testing was performed by cyclically loading the femoral heads in a physiological manner, beginning at 1,500 N and increasing 500 N every 5,000 cycles to 4,000 N, and continuously monitoring head displacement. Failure was defined as >5.0 mm head displacement. The head displacement at 2,000 N was significantly smaller (p=0.018) for the augmented group as compared to the conventionally treated bones (0.09+/-0.01 mm vs. 0.90+/-0.32 mm; mean+/-SEM). The displacement rate at the second load step was significantly higher (p=0.018) for the conventionally treated bones as compared to the augmented ones. All of the nonaugmented specimens failed during testing, where 50% of the augmented specimens did not fail. The promising results of these experiments suggest that this new standardized irrigation/augmentation method enhances the implant anchorage and offers a potential solution to the problem of implant cut-out in osteoporotic metaphyseal bone.


Intra- and inter-rater reliability of lower leg waterplethysmography, bioelectrical impedance and muscle twitch force for the use in standing work evaluation.
Prolonged standing is associated with multiple risk factors for musculoskeletal and venous disorders. In Germany over 50% of the working population spend most of their working time in a standing position. Basic understanding of prolonged standing physiology is lacking. We therefore plan to investigate the influence of 5 h standing (including breaks) on lower limb oedema measured by waterplethysmography (WP) and bioelectrical impedance (BI) and fatigue in the triceps surae muscle using muscle twitch force (MTF). In order to interpret our results, test-retest and inter-rater reliability of these measurement methods was evaluated first. 20 subjects (9 female) were included to test each method three times (M1, M2, M3) in 30 min periods with two raters (R1, R2) on separate days. Intraclass correlation coefficient (ICC; 2,1), standard error of measurement (SEM) and smallest real difference (SRD) were calculated for both raters. The SEM and SRD calculated for WP were 27 and 75 ml, respectively, for R1 and 23 and 64 ml, respectively, for R2 with an ICC of 0.98 (p < 0.0001). Statistically significant mean differences between M1 and M2 (R1 = 23 ml, p = 0.004; R2 = 19 ml, p = 0.027) but not significant mean differences between M2 and M3 (R1 = -6 ml, p = 0.45; R2 = 4 ml, p = 0.27) were calculated for both raters. BI data revealed SEM and SRD values of 3.8 and 10.5 Ω, respectively, for R1 and 3.4 and 9.4 Ω, respectively, for R2 with an ICC of 0.24 (p = 0.001). The differences between M1 and M2 (R1 = 3.9 Ω, p = 0.0001; R2 = 2.4 Ω, p = 0.049) and between M2 and M3 (R1 = 2.3 Ω, p = 0.012; R2 = 2.0 Ω, p = 0.008) were found to be statistically significant for both raters. SEM and SRD for MTF were 0.19 and 0.53 N, respectively, for R1 and 0.23 and 0.64 N, respectively, for R2 with an ICC of 0.71 (p < 0.0001). Mean differences between M1 and M2 were statistically significant for rater 1 but not for rater 2 (R1 = 0.13 N, p = 0.022; R2 = 0.12 N, p = 0.082) and the same was found for the difference between M2 and M3 for both raters (R1 = 0.04 N, p = 0.37; R2 = 0.08 N, p = 0.12). All three measurement methods showed good reliability and should be suitable for detecting effects of standing work on oedema development and fatigue as seen in previous results of long term standing experiments. Inter-rater reliability is found to be satisfactory as well, demonstrated by the small differences in SEM values of R1 and R2. Statistically significant differences shown for all three measurement methods could be due to lacking standardisation of leg placement and thus an actual lower leg volume change between measurements, indicating possibilities for further improvement of SEM values.


[Protective effect of enalaprilat injection against early postburn organ damage in rats].
To investigate the dose-effect relationship of enalaprilat (ENA) injection on the organ damage following early burn injury in rats. A total of 54 SD rats were subjected to 30% total body surface area III scald injury, and were randomly divided into simple scald group (B group, with conventional fluid transfusion after scald), ENA treated group (E1, E2, E3 group, with intraperitoneal enalaprilat injection of 1, 2, 4 mg/kg after scald respectively). Other 6 rats were taken as normal control. Aortic systolic pressure (AOSP), aortic diastolic blood pressure (AODP), mean arterial pressure (MAP), angiotensin 1, blood urea nitrogen (Bun), creatinine (Cr), creatinine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST) of the simple scald group, E1 group, E2 group and E3 group were investigated at 6 h and 12 h post burn. Ang II, Bun, Cr, CK, ALT, AST levels in ENA treated group after 6 h and 12 hours were significantly lower than those of simple scald group (all P < 0.05). AOSP, AODP, MAP in ENA treated group after 6 and 12 hours were significantly higher than those of simple scald group (all P < 0.05). Low-dose enalaprilat, injection (1 mg/kg) could alleviate organ damage in post-burned rats, but has little effect on AOSP and AODP.


Estrogens, lipoproteins, and cardiovascular risk factors: an update following the randomized placebo-controlled trials of hormone-replacement therapy.
The effects of hormone-replacement therapy on cardiovascular risk factors are examined. In an attempt to explain the results of recent randomized controlled trials in which no benefit of hormone-replacement therapy for postmenopausal women has been observed, Changes in lipoproteins in response to hormone-replacement therapy have now been analysed for both primary and secondary prevention studies. In none of the large randomized controlled trials was there any effect of hormone-induced changes in low-density lipoprotein, high-density lipoprotein, or triglyceride on clinical outcome. Further detailed studies of lipoprotein metabolism have not revealed any adverse effect of hormone-replacement therapy. Recent analysis of the Heart Estrogen/Progestin-Replacement Study data suggests hormone-replacement therapy reduces the risk of developing diabetes. The effect of hormone-replacement therapy on inflammatory markers and on flow-mediated dilatation is largely beneficial, although the effect on flow-mediated dilatation is modulated according to endothelial function, which is adversely affected by known risk factors, including age and presence of atherosclerosis. In this respect the work on polymorphisms of estrogen receptor-alpha may in due course help to define those women who would benefit most from use of estrogen. Crucially, oral but not transdermal hormone-replacement therapy increases activated protein C resistance independently of the presence of factor V Leiden. This effect increases the risk of venous thromboembolic events, which is reflected in the results of a hospital case control study of thromboembolism. Despite the outcome of the hormone-replacement therapy trials, recent work has confirmed the putative antiatherogenic effects of hormone-replacement therapy on lipoprotein metabolism. Metabolic differences of route of administration of estrogen, particularly on haemostatic variables, may explain this clinical paradox, which continues to be an important research area.


An Overview of Diabetic Cardiomyopathy.
Diabetic cardiomyopathy (DCM) is a myocardial disorder that is characterised by structural and functional abnormalities of the heart muscle in the absence of hypertension, valvular heart disease, congenital heart defects, or coronary artery disease (CAD). After witnessing a particular form of cardiomyopathy in diabetic individuals, Rubler et al. came up with the moniker diabetic cardiomyopathy in 1972. Four stages of DCM are documented, and the American College of Cardiology/American Heart Association Stage and New York Heart Association Class for HF have some overlap. Diabetes is linked to several distinct forms of heart failure. Around 40% of people with heart failure with preserved ejection fraction (HFpEF) have diabetes, which is thought to be closely associated with the pathophysiology of HFpEF. Diabetes and HF are uniquely associated in a bidirectional manner. When compared to the general population without diabetes, those with diabetes have a risk of heart failure that is up to four times higher. A biomarker is a trait that is reliably measured and assessed as a predictor of healthy biological activities, pathological processes, or pharmacologic responses to a clinical treatment. Several biomarker values have been discovered to be greater in patients with diabetes than in control subjects among those who have recently developed heart failure. Myocardial fibrosis and hypertrophy are the primary characteristics of DCM, and structural alterations in the diabetic myocardium are often examined by non-invasive, reliable, and reproducible procedures. An invasive method called endomyocardial biopsy (EMB) is most often used to diagnose many cardiac illnesses.


CR-Unet: A Composite Network for Ovary and Follicle Segmentation in Ultrasound Images.
Transvaginal ultrasound (TVUS) is widely used in infertility treatment. The size and shape of the ovary and follicles must be measured manually for assessing their physiological status by sonographers. However, this process is extremely time-consuming and operator-dependent. In this study, we propose a novel composite network, namely CR-Unet, to simultaneously segment the ovary and follicles in TVUS. The CR-Unet incorporates the spatial recurrent neural network (RNN) into a plain U-Net. It can effectively learn multi-scale and long-range spatial contexts to combat the challenges of this task, such as the poor image quality, low contrast, boundary ambiguity, and complex anatomy shapes. We further adopt deep supervision strategy to make model training more effective and efficient. In addition, self-supervision is employed to iteratively refine the segmentation results. Experiments on 3204 TVUS images from 219 patients demonstrate the proposed method achieved the best segmentation performance compared to other state-of-the-art methods for both the ovary and follicles, with a Dice Similarity Coefficient (DSC) of 0.912 and 0.858, respectively.


Unique Genotypic Differences Discovered among Indigenous Bangladeshi Rice Landraces.
Bangladesh is a reservoir of diverse rice germplasm and is home to many landraces with unique, important traits. Molecular characterization of these landraces is of value for their identification, preservation, and potential use in breeding programs. Thirty-eight rice landraces from different regions of Bangladesh including some high yielding BRRI varieties were analyzed by 34 polymorphic microsatellite markers yielding a total of 258 reproducible alleles. The analysis could locate 34 unique identifiers for 21 genotypes, making the latter potentially amenable to identity verification. An identity map for these genotypes was constructed with all the 12 chromosomes of the rice genome. Polymorphism information content (PIC) scores of the 34 SSR markers were 0.098 to 0.89 where on average 7.5 alleles were observed. A dendogram constructed using UPGMA clustered the varieties into two major groups and five subgroups. In some cases, the clustering matched with properties like aromaticity, stickiness, salt tolerance, and photoperiod insensitivity. The results will help breeders to work towards the proper utilization of these landraces for parental selection and linkage map construction for discovery of useful alleles.


Surface plasmon resonance as a high throughput method to evaluate specific and non-specific binding of nanotherapeutics.
Surface plasmon resonance (SPR) is a powerful analytical technique used to quantitatively examine the interactions between various biomolecules, such as proteins and nucleic acids. The technique has been particularly useful in screening and evaluating binding affinity of novel small molecule and biomolecule-derived therapeutics for various diseases and applications including lupus medications, thrombin inhibitors, HIV protease inhibitors, DNA gyrase inhibitors and many others. Recently, there has been increasing interest in nanotherapeutics (nanoRx), due to their unique properties and potential for controlled release of encapsulated drugs and structure-specific targeting to diseased tissues. NanoRx offer the potential to solve many drug delivery challenges by enabling, specific interactions between molecules on the surface of the nanoparticle and molecules in the diseased tissue, while minimizing off-target interactions toward non-diseased tissues. These properties are largely dependent upon careful control and balance of nanoRx interactions and binding properties with tissues in vivo. Given the great promise of nanoRx with regard to engineering specific molecular interactions, SPR can rapidly quantify small aliquots of nanoRx formulations for desired and undesired molecular interactions. Moving forward, we believe that utilization of SPR in the screening and design of nanoRx has the potential to greatly improve the development of targeted nanoRx formulations and eventually lead to improved therapeutic efficacy. In this review, we discuss (1) the fundamental principles of SPR and basic quantitative analysis of SPR data, (2) previous applications of SPR in the study of non-particulate therapeutics and nanoRx, and (3) future opportunities for the use of SPR in the evaluation of nanoRx.


Regulation of alpha 1-acid glycoprotein externalization and intracellular accumulation in glucocorticoid-induced rat hepatoma cells.
alpha 1-Acid glycoprotein (alpha 1-AGP) is a glucocorticoid inducible gene product that is synthesized and secreted by certain rat hepatoma tissue culture (HTC) cell lines such as M1.54. Exposure to monensin, a Na+-K+ ionophore, causes a significant redistribution of alpha 1-AGP into two distinct fractions; immunoprecipitation of [35S]methionine-labeled proteins revealed that a 27% decrease in secretion accounts for a sixfold increase in accumulation of a stable intracellular species. The new intracellular alpha 1-AGP is more heterogeneous than normal while the extra-cellular form is 6000 Da smaller than normal. These effects are due to selective alterations in carbohydrate maturation; endo-beta-N-acetylglucosaminidase H (endo H) digestion demonstrated that both alpha 1-AGP species contain variable numbers of endo H-resistant oligosaccharide side chains ranging between zero and five. Ricin affinity chromatography revealed that the attachment of galactose residues is strikingly correlated with alpha 1-AGP externalization while neuraminidase digestions demonstrated that sialic acid attachment appears unessential for its secretion. Taken together, our results suggest that in the presence of monensin the cellular transport of intracellular destined and externalized alpha 1-AGP proceeds in common through the early segments of the Golgi and at a point prior to or at the compartment containing galactosyl transferase, alpha 1-AGP becomes committed for secretion.


Inhibition of hepatic drug metabolism by (+)-cyanidanol-3 (Catergen) in chronic alcoholic liver disease.
There are some controversies regarding the effect of (+)-cyanidanol-3 on hepatic drug metabolism. In the present study the effect of (+)-cyanidanol-3 was investigated on the microsomal and mitochondrial enzyme functions (hydroxylation, glucuronide production, D-glucaric acid excretion and acetylation) in alcoholic liver disease. Eight patients with biopsy-proven chronic alcoholic hepatitis were investigated before and after a 10-day, as well as after a further 30-day, treatment with (+)-cyanidanol-3 (Catergen), 3000 mg/day orally. Besides biochemical liver function tests (serum bilirubin levels, GOT, GGT), antipyrine metabolic clearance rate, mentholglucuronide production, urinary D-glucaric acid excretion and sulphadimidine kinetics were determined. Biochemical liver function tests improved markedly after the first period of treatment, at the same time antipyrine metabolic clearance rate decreased. Menthol-glucuronide production and D-glucaric acid excretion decreased significantly only after the second two course of Catergen administration. Sulphadimidine kinetics was not remarkably changed. Our findings suggest that (+)-cyanidanol-3 inhibits the hepatic microsomal drug metabolizing enzyme function in chronic alcoholic hepatitis.


The role of limb movements in maintaining upright stance: the "change-in-support" strategy.
Change-in-support strategies, involving stepping or grasping movements of the limbs, are prevalent reactions to instability and appear to play a more important functional role in maintaining upright stance than has generally been appreciated. Contrary to traditional views, change-in-support reactions are not just strategies of last resort, but are often initiated well before the center of mass is near the stability limits of the base of support. Furthermore, it appears that subjects, when given the option, will select these reactions in preference to the fixed-support "hip strategy" that has been purported to be of functional importance. The rapid speed of compensatory change-in-support reactions distinguishes them from "volitional" arm and leg movements. In addition, compensatory stepping reactions often lack the anticipatory control elements that are invariably present in non-compensatory stepping, such as gait initiation. Even when present, these anticipatory adjustments appear to have little functional value during rapid compensatory movements. Lateral destabilization complicates the control of compensatory stepping, a finding that may be particularly relevant to the problem of falls and hip fractures in elderly people. Older adults appear to have problems in controlling lateral stability when stepping to recover balance, even when responding to anteroposterior perturbation. Increased understanding and awareness of change-in-support reactions should lead to development of new diagnostic and therapeutic approaches for detecting and treating specific causes of imbalance and falling in elderly people and in patients with balance impairments.


Nitrite in meat products determined by fluorescence quenching of p-aminobenzoate ion.
A direct fluorometric method is presented for determining nitrites in meat products by means of quenching. The extracted sodium nitrite is consumed in a diazotization reaction with a measured excess of the fluorescent reagent p-aminobenzoic acid (PABA) in boiling water and at pH less than or equal to 1.4. The amount of decrease in fluorescence (quenching) of PABA, in alkaline medium (pH 11.0) with excitation at 265 nm and fluorescence at 339 nm, is directly related to the amount of nitrite present. The slope for that standard curve is 1% decrease in relative fluorescence intensity per 2.76 ppm NaNO2. Results obtained for a series of 20 meat samples analyzed by this fluorometric method are in good agreement with results obtained by a colorimetric method with an average difference of +/- 6.1 ppm NaNO2.


Immunological recognition of three polynucleotide structures associating adenylic and uridylic acids.
The reactions of antibodies directed against the two double-stranded synthetic polyribonucleotide complexes poly(A).poly(U) or poly(I). poly(C) with three polynucleotide structures associating equimolar amounts of adenylic and uridylic acids were studied by immunodiffusion, quantitative precipitation and readioimmunoassay. The three sequence isomers of the same base composition but different nucleotide distribution were: the double helical complex poly(A).poly(U) containing two homopolymeric strands; the copolynucleotide poly(A-U) composed of a strictly repeating riboadenylic acid and ribouridylic acid sequence in both strands; and the copolymer poly(A,U) where the two strands contain both residues but in a random distribution. The three antigens reacted with anti-poly(A).poly(U) and antipoly(I).poly(C) antisera but not to the same extent. The random copolymer poly(A,U) reacted poorly with sera of both specificity. In contrast the reactivity of the alternating copolnucleotide poly(A-U) was widely different according to the specificity of the sera used. Whereas it was recognized by the anti-poly(A).poly(U) antibodies almost to the same extent than the homologous complex, its activity was much lower with anti-poly(I).poly(C) antisera. In addition, the relative efficiency of poly(A-U) was approximately 50 times lower than that of poly(A).poly(U) when tested with anti-poly(I).poly(C) antibody, thereby indicating recognition of different antigenic determinants in both duplexes. Antibodies directed against defined conformational determinants are therefore able to distinguish between three polynucleotide structures of the same base composition but different sequence.


Coating individual single-walled carbon nanotubes with nylon 6,10 through emulsion polymerization.
Solvent microenvironments are formed around individual single-walled carbon nanotubes (SWNTs) by mixing SWNT suspensions with water-immiscible organic solvents. These microenvironments are used to encapsulate the SWNTs with the monomer sebacoyl chloride. Hexamethylene diamine is then injected into the aqueous phase so the formation of nylon 6,10 is restricted to the interface between the microenvironment and water. This emulsion polymerization process results in uniform coatings of nylon 6,10 around individual SWNTs. The nylon-coated SWNTs remain dispersed in the aqueous phase and are highly luminescent at pH values ranging from 3 to 12. This emulsion polymerization method provides a general approach to coat nanotubes with various polymers.


Opportunistic infection of HIV-infected/AIDS patients in Indonesia: problems and challenge.
Infectious diseases are one of the biggest health-problem in the world, while HIV/AIDS itself ranks second in mortality. The latest situation shows a remarkable increase of HIV/AIDS cases in Indonesia. About 90.000 to 130.000 people in Indonesia are predicted of being infected with HIV nowadays. HIV may progress to AIDS as patient's immune status decreases. As well to the condition, opportunistic infections will occur and eventually it may lead to death. An efficient and effective approach in early detection and proper management of opportunistic infections, followed with sufficient anti retroviral administration, may reduce mortality. Other approaches in managing HIV/AIDS and opportunistic infections are needed to support a complete and holistic management for patients with HIV. Full participation from family, medical experts, government and public is strictly a must to overcome this problem.


Bioconcentration and Metabolism of Emodin in Zebrafish Eleutheroembryos.
Emodin is a major active anthraquinone of various herbal laxatives, which can exert many pharmacological effects. However, chronic use of anthranoid laxatives, even at low dosages, may cause melanosis coli (MC). It has been suggested that the accumulation of anthraquinones is a risk factor in the MC process. To investigate the accumulation of emodin, we conducted a bioconcentration study of emodin in zebrafish eleutheroembryos. Based on the economic cooperation and development (OECD) 305 test, zebrafish eleutheroembryos were exposed to emodin at a constant concentration for 48 h, before the test media were replaced by the blank medium for 24 h of depuration. To eliminate the effect of metabolism of emodin for assessment of the bioconcentration factor (BCF), we also conducted a modified test for which zebrafish eleutheroembryos were exposed to the non-renewed test media, whose emodin concentration decreased with time. At different exposure time points, zebrafish eleutheroembryos and exposure media were sampled for analysis of emodin concentration using HPLC-MS/MS. The results showed rapid accumulation of emodin in zebrafish eleutheroembryos to reach a steady-state concentration within 24 h. Meanwhile, emodin was actively metabolized by zebrafish eleutheroembryos to result in 29.5-40.7% of its elimination. In the groups with high or low concentrations of emodin, the standardized BCF (sBCF) values in the standard test were 24.0 and 20.0, while those in the modified test were 50.4 and 52.0. These results showed that emodin could accumulate in zebrafish eleutheroembryos when used for 48 h and beyond, suggesting that the accumulation of anthraquinones may be a risk factor in the MC process. Accordingly, emodin should be unsuitable for long-term use due to its accumulation.


Cortisol in burnout and vital exhaustion: an overview.
In this overview, we summarize findings on hypothalamus-pituitary-adrenal (HPA) axis functioning in burned out and (vitally) exhausted though otherwise healthy subjects as well as clinically diagnosed patients. The main focus will be on basal diurnal free cortisol regulation and cortisol responses to acute psychological stress. First, we describe normal HPA axis regulation as well as dysfunction which manifests in hyper- or hypoactivity. We also briefly illustrate three established methods to assess HPA axis activity, reactivity, and feedback functioning, namely the cortisol awakening rise (CAR), Trier Social Stress Test (TSST), and low-dose Dexamethasone Suppression Test (DST). Then, an up-to-date summary of empirical findings on the relationship between burnout, respectively vital exhaustion, and cortisol is provided including field as well as laboratory studies. Finally, we briefly discuss possible methodologically confounders and speculate on underlying mechanisms explaining, at least in part, how burnout and vital exhaustion might relate to disease vulnerability.


One-pot mass preparation of MoS2/C aerogels for high-performance supercapacitors and lithium-ion batteries.
In this paper, we report the successful design and synthesis of a hierarchically porous MoS2/C composite aerogel by simple one-pot mass preparation. The synthesis involves the in situ formation of MoS2 nanosheets on agarose molecular chains, the gelation of MoS2-deposited agarose monomers to generate a composite hydrogel, and in situ transformation of the composite hydrogel into a MoS2/C composite aerogel through carbonization. This composite aerogel can be used as a high-performance electrode material for supercapacitors and lithium-ion batteries. When tested as a supercapacitor electrode, it achieves a high specific capacitance of 712.6 F g-1 at 1 A g-1 and 97.3% capacity retention after 13 000 cycles at 6 A g-1. In addition, as a lithium-ion battery electrode, it exhibits a superior rate capability (653.2 mA h g-1 at 0.1 A g-1 and 334.5 mA h g-1 at 5.0 A g-1) and an ultrahigh capacity retention of nearly 100% after 1000 cycles at 1 A g-1. These performances may be ascribed to the unique structure of the MoS2/C composite aerogel, such as hierarchical pores, (002) plane-expanded MoS2 and interconnected carbon networks embedded uniformly with MoS2 nanosheets. This work may provide a general and simple approach for mass preparation of composite aerogel materials and pave the way for promising materials applied in both supercapacitors and lithium-ion batteries.


Methoxsalen as an in vitro phenotyping tool in comparison with 1-aminobenzotriazole.
The objective is to evaluate methoxsalen as an in vitro phenotyping tool in comparison to ABT as a nonspecific inactivator of P450 mediated metabolism. The reversible inhibition of methoxsalen and ABT against the P450, FMO, AO, MAO-A and -B, enzymes were evaluated using standard marker probe reactions. The time-dependent inhibition of P450 enzymes was evaluated in human liver microsomes. CES1 activities were determined by monitoring the depletion of known substrate, the clopidogrel. The metabolism of P450 substrates in the presence and absence of methoxsalen or ABT was evaluated in human liver microsomes. Methoxsalen is a direct inhibitor and inhibited the activities (>90%) of all enzymes at a concentration of 300 µM except for CYP2C9. Methoxsalen is also a potent time-dependent inhibitor of all P450 enzymes except for CYP2C19 (moderate) at a concentration of 300 µM. Methoxsalen inhibited the metabolism of P450 substrates in the pre-incubation mode. ABT is a potent TDI of several P450 except for CYP2C19 (47%) and CYP2C9 (27%). The results indicate that methoxsalen is a potent pan P450 inhibitor than ABT and can be a better tool in distinguishing P450 mediated metabolism form non-P450 metabolism in human liver microsomes.


Family study of congenital hydrocephalus.
This study concerned 74 patients with uncomplicated congenital hydrocephalus who were born in Northern Ireland between 1974 and 1977. Three of their 159 sibs (1.89 per cent) were also themselves hydrocephalic, which represents a recurrence risk of 26 times the population incidence. There was a smaller but significant increase of congenital hydrocephalus among first-cousins; three of 846 (0.35 per cent) first-cousins were affected, five times the population frequency. The occurrence of neural-tube defects among sibs and cousins was similar to that for the general population. For the purpose of genetic counselling, this study indicates that once X-linked inheritance has been excluded in uncomplicated congenital hydrocephalus, the over-all empirical risk of recurrence is approximately one in 50; or one in 40 after an affected male and one in 80 after a female index patient.


Indigenous evolution of Plasmodium falciparum pyrimethamine resistance multiple times in Africa.
Resistance to pyrimethamine in Plasmodium falciparum is conferred by mutations in the gene encoding dihydrofolate reductase (DHFR). It is known that DHFR double mutants have evolved independently in multiple geographic areas, whereas the triple mutant prevalent in Africa appears to have originated in south-east Asia. In this study, we investigated whether other triple mutants may have evolved independently in Africa. We determined the DHFR genotypes and haplotypes of five microsatellite loci flanking the DHFR locus between 4.49 kb upstream and 1.48 kb downstream of 159 isolates collected from three African countries (Republic of Congo, Ghana and Kenya). The CIRNI type of DHFR triple mutant (with mutations underlined at amino acid positions 51, 59 and 108) was predominant in the Republic of Congo (82%) and Ghana (81%) and was the second most prevalent in Kenya (27%), where the CICNI type of DHFR double mutant was dominant. Three distinct microsatellite haplotypes were identified in the DHFR triple mutant. One haplotype was identical to that originating in south-east Asia. The other two haplotypes occurred in Ghana and Kenya, which were unique, previously undescribed and identical to those of the two DHFR double mutants found in the same locations. This study presents strong evidence for the unique, multiple independent evolution of pyrimethamine resistance in Africa. Indigenous evolution of the triple mutant from the double mutant appears to have occurred in a step-wise manner in Kenya and Ghana or in nearby countries in east and west Africa.


Evaluation of epratuzumab as a biologic therapy in systemic lupus erythematosus.
B cells play a key role in the pathogenesis of systemic lupus erythematosus. Some of the current biologic therapies target B cells or B-cell activating factors. Epratuzumab is a humanized monoclonal antibody, which targets CD22 on B cells. This review focuses on the safety and efficacy of epratuzumab in systemic lupus erythematosus based on the information from various published clinical trials and presentations at international meetings. Epratuzumab acts as a B-cell modulator through inhibition of B-cell receptor signaling. It has been shown to be efficacious in open-label and Phase I and Phase II randomized controlled trials. The drug has steroid-sparing properties and treatment is associated with significant improvements in Health Related Quality of Life and its safety profile is comparable to placebo.


Diabetes mellitus and the heart.
Diabetes mellitus is a risk factor for the development of coronary artery disease and chronic heart failure. When carefully screened for, diabetes or prediabetic disorders, are present in the majority of patients with clinically manifest ischaemic heart disease, and confer a major adverse impact upon morbidity and mortality. Important therapeutic modifications are required in the management of coronary artery disease and chronic heart failure associated with diabetes, and vice versa. However, despite optimal management, aided by recent landmark trials solely recruiting patients with diabetes, outcomes for patients with diabetes and heart disease remain poor. This review outlines the epidemiology, pathogenesis and management of diabetic heart disease, along with highlighting the many gaps in the evidence-base and suggesting future research priorities.


Importance of the Debye screening length on nanowire field effect transistor sensors.
Nanowire field effect transistors (NW-FETs) can serve as ultrasensitive detectors for label-free reagents. The NW-FET sensing mechanism assumes a controlled modification in the local channel electric field created by the binding of charged molecules to the nanowire surface. Careful control of the solution Debye length is critical for unambiguous selective detection of macromolecules. Here we show the appropriate conditions under which the selective binding of macromolecules is accurately sensed with NW-FET sensors.


Occipital epilepsy: spatial categorization and surgical management.
Occipital resections for epilepsy are rare. Reasons for this are the relative infrequency of occipital epilepsy, difficulty in localizing epilepsy originating in the occipital lobe, imprecisely defined seizure outcome in patients treated with focal occipital resections in the MR imaging era, and concerns about producing visual deficits. The impact of lesion location on vision and seizure biology, the management decision-making process, and the outcomes following resection need elaboration. The authors studied 21 consecutive patients who underwent focal occipital resections for epilepsy at Cleveland Clinic Epilepsy Center over a 13-year period during which MR imaging was used. Demographics, imaging, and data relating to the epilepsy and its surgical management were collected. The collateral sulcus, the border between the medial surface and the lateral convexity, and the inferior temporal sulcus were used to subdivide the occipital lobe into medial, lateral, and basal zones. Lesions that did not involve most or all of the occipital lobe (sublobar) were spatially categorized into these zones. Visual function, semiology, and scalp electroencephalography were evaluated in relation to these spatial categories. Preresection and postresection visual function and seizure frequency were evaluated and compared. Lastly, an exhaustive review and discussion of the published literature on occipital resections for epilepsy was carried out. Five lesions were lobar and 16 were sublobar. Patients with medial or lobar lesions had a much greater likelihood of preoperative visual field defects. Those with basal or lateral lesions had a greater likelihood of having a visual aura preceding some or all of their seizures and a trend (not significant) toward having a concordant lateralized onset by scalp electroencephalography. Invasive recordings were used in 8 cases. All patients had lesions (malformations of cortical development, tumors, or gliosis) that were completely resected, as evaluated on postoperative MR imaging. At last follow-up, 17 patients (81%) were seizure free or had only occasional auras (Wieser Class 1 or 2). The remaining 4 patients (19%) had a worthwhile improvement in seizure control (Class 3 or 4). Of the patients for whom both pre- and postoperative visual testing data were available, 50% suffered no new visual deficits, and 17% each developed a new quadrantanopia or a hemianopia. Lesional occipital lobe epilepsy can be successfully managed with resection to obtain excellent seizure-free rates. Individually tailored resections (in lateral occipital lesions, for example) may help preserve intact vision in a subset of cases (38% in this series). Invasive recordings may further guide surgical decision-making as delineated by an algorithm generated by the authors. The authors' results suggest that the spatial location of the lesion correlates both with the semiology of the seizure and with the presence of visual deficit.


Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats.
This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.


[Concurrent appearance of stomach polyposis and hepatocellular carcinoma].
An 18 year old woman had been known to have juvenile polyposis since five years with multiple hyperplastic polyps of the stomach and several polyps of the colon. Death occurred from hepatic coma with hepatocellular carcinoma. A lymphangiosis carcinomatosa was observed in some stomach polyps with a circumscribed infiltration into the stroma and into the adjacent glands. Such an unusual combination of diseases readily causes diagnostic confusion.


Current trends in thoracic surgery.
Thoracic surgery has evolved drastically in recent years. Although thoracic surgeons mainly deal with tumorous lesion in the lungs, mediastinum, and pleura, they also perform lung transplantation surgery in patients with end-stage lung disease. Herein, we introduce various major current topics in thoracic surgery. Minimally invasive surgical procedures include robot-assisted thoracic surgery and uniportal video-assisted thoracic surgery. Novel techniques for sublobar resection include virtual-assisted lung mapping, image-guided video-assisted thoracic surgery, and segmentectomy using indocyanine green. Three-dimensional (3D) computed tomography (CT) simulation consists of surgeon-friendly 3D-CT image analysis systems and new-generation, dynamic 3D-CT imaging systems. Updates in cadaveric lung transplantation include use of marginal donors, including donation after circulatory death, and ex vivo lung perfusion for such donors. Topics in living donor lobar lung transplantation include size matching, donor issues, and new surgical techniques. During routine clinical practice, thoracic surgeons encounter various pivotal topics related to thoracic surgery, which are described in this report.


Visual working memory for shape and 3D-orientation: a PET study.
In order to determine the neural substrate of working memory for shape and 3D-orientation, regional cerebral blood flow (rCBF) changes were estimated using positron emission tomography (PET). Subjects were scanned during the performance of two delayed-matching-to-sample tasks using flat polydedrical objects of different shapes and 3D-orientations presented in a virtual environment. The shape matching task was associated with activation in the occipito-temporal junction, occipito-parietal cortex and mesial frontal pole of the right hemisphere. During the orientation matching task, rCBF increased in the mesial occipito-temporal cortex, superior temporal gyrus and middle frontal gyrus of the left hemisphere. The right supramarginal gyrus was also activated. These results suggest that both visual pathways are engaged in the processing of objects presented in different orientations. The dorsal stream is involved mainly in working memory of 3D-orientation, while the ventral stream is involved especially in shape working memory.


Impact of eIF4E phosphorylation at Ser209 via MNK2a on tumour recurrence after curative surgery in localized clear cell renal cell carcinoma.
Background: We investigated the roles of eIF4E phosphorylation (Ser209) in tumour recurrence after curative nephrectomy for localized clear cell renal cell carcinoma (ccRCC). Methods: Expression of eIF4E, p eIF4E and MNKs (MAPK interacting kinases), was evaluated in surgical specimens obtained from consecutive non metastatic ccRCC patients (n = 290) by immunohistochemistry (IHC), immunoblotting, and qRT PCR at the protein and mRNA levels. In human RCC cell lines, the effects of eIF4E phosphorylation were examined using immunoblotting, proliferation, migration and invasion assays with pharmacological inhibitors (CGP57380 or ETP45835) and specific small interfering (si) RNAs against MNK1/2(a/b). Results: In postoperative follow-up (median, 7.9 y), 40 patients experienced metastatic recurrence. In multivariate Cox analyses, higher IHC expression of p eIF4E in ccRCC significantly predicted a longer recurrence-free interval. eIF4E is phosphorylated mainly by MNK2a in tumour specimens and cell lines. In 786-O and A-498 cell lines, pharmacological inhibition of MNKs decreased p-eIF4E and increased vimentin and N cadherin but did not influence proliferation. Similarly, MNK2 or MNK2a inhibition with siRNA reduced p-eIF4E and enhanced vimentin translation, cell migration and invasion in the cell lines. Conclusions: MNK2a-induced eIF4E phosphorylation may suppress metastatic recurrence of ccRCC, partially due to vimentin downregulation at the translational level, consequently leading to inhibition of epithelial-mesenchymal transition.


Getting to the elephants: Gesture and preschoolers' comprehension of route direction information.
During early childhood, children find spatial tasks such as following novel route directions challenging. Spatial tasks place demands on multiple cognitive processes, including language comprehension and memory, at a time in development when resources are limited. As such, gestures accompanying route directions may aid comprehension and facilitate task performance by scaffolding cognitive processes, including language and memory processing. This study examined the effect of presenting gesture during encoding on spatial task performance during early childhood. Three- to five-year-olds were presented with verbal route directions through a zoo-themed spatial array and, depending on assigned condition (no gesture, beat gesture, or iconic/deictic gesture), accompanying gestures. Children presented with verbal route directions accompanied by a combination of iconic (pantomime) and deictic (pointing) gestures verbally recalled more than children presented with beat gestures (rhythmic hand movements) or no gestures accompanying the route directions. The presence of gesture accompanying route directions similarly influenced physical route navigation, such that children presented with gesture (beat, pantomime, and pointing) navigated the route more accurately than children presented with no gestures. Across all gesture conditions, location information (e.g., the penguin pond) was recalled more than movement information (e.g., go around) and descriptive information (e.g., bright red). These findings suggest that speakers' gestures accompanying spatial task information influence listeners' recall and task performance.


[Changes in blood pressure, proteinuria and renal hemodynamics in type I diabetes with manifestations of diabetic nephropathy after 2 months of captopril therapy].
In 15 type I diabetics with manifest diabetic nephropathy the authors investigated the antihypertensive and antiproteinuric effect of captopril and in seven patients of this group also its effect on renal haemodynamics. Captopril treatment or its combination with hitherto used antihypertensive treatment was associated after two months with a significant drop of the systolic and diastolic blood pressure from 150/95 (120/70-195/110) to 130/90 (110/65-180/115) mmHg, (p < 0.005 < 0.05). The median aortic pressure declined from 118.5 (92-140.8) to 106.5 (84-1334.8) mm Hg (p < 0.005). Nine of 11 patients (82%) could be changed to reduced antihypertensive therapy. The antiproteinuric effect was manifested in 11 patients (73%). Quantitative proteinuria dropped from 2.7 (0.83-8.65) to 1.85 (0.38-8.84) g/24 h., (p < 0.05) without a significant change of serum creatinine: 109 (70-342) vs. 135 (90-288) mumol/l, p = n.s.). The change of proteinuria, as compared with the baseline value, was -41 (-77 - +88)%, (p < 0.05) and did not correlate with the change of the median aortic pressure (correlation coefficient = -0.165, p = n.s.). In the group of seven patients the change of the median aortic pressure was -15% (-26.1 - +6.6), (p < 0.05). No statistically significant change of glomerular filtration was observed: 0.96 (0.32-1.38) vs. 0.96 (0.19-1.71) ml/s, p = n.s.); effective renal plasma flow: 6.32 (2.24-7.74) vs. 7.22 (1.68-10.55) ml/s, (p = n.s.); filtration fraction: 0.136 (0.123-0.220) vs. 0.130 (0.110-0.236), change 0.0 (-43.0 - +31.0)% (p = n.s.) and renal vascular resistance: 15429 (12907-54148) vs. 13243 (7099-77832)%, (p. = n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)


Opinion limits study for the multi-selection bounded confidence model.
In this work, we study the opinion limit states for a generalized bounded confidence agent-based opinion model. Agents can select multiple opinions in the network, and the confidence bound is considered on the distance between the average of the selected opinions and agent opinion itself. The number of selection agents for a certain agent, which is also called the selection number, means the agent opinion interaction degree. It is known that when the confidence bound is large sufficiently, opinions reach consensus almost surely. We mainly study the opinion consensus and the opinion polarization when the confidence bound is small sufficiently. Firstly, we provide and prove the upper and lower bounds for the opinion consensus probability of this bound confidence model. It shows that the opinion consensus probability almost always decreases as the confidence bound decreases. Secondly, the opinion consensus probability is larger than the one for the opinion evolution of the Deffuant-Weisbuch model. Finally, we demonstrate the ultimate probability distribution of one agent opinion and compare it with the gossip form and the general bounded confidence form, and demonstrate how the opinion polarization probabilities evolve as the selection number changes. Specially, different from other studies, we find that the opinion polarization would happen more easily if the opinion interaction degree is strengthened. In a sum, the multiple selection mechanism will increase the opinion consensus probability and the opinion polarization probability, respectively, comparing to the single selection mechanism.


Inhibition of endoplasmic reticulum stress reverses synaptic plasticity deficits in striatum of DYT1 dystonia mice.
Striatal plasticity alterations caused by endoplasmic reticulum (ER) stress is supposed to be critically involved in the mechanism of DYT1 dystonia. In the current study, we expanded this research field by investigating the critical role of ER stress underlying synaptic plasticity impairment imposed by mutant heterozygous Tor1a+/- in a DYT1 dystonia mouse model. Heterozygous Tor1a+/- mouse model for DYT1 dystonia was established. Wild-type (Tor1a+/+, N=10) and mutant (Tor1a+/-, N=10) mice from post-natal day P25 to P35 were randomly distributed to experimental and control groups. Patch-clamp and current-clamp recordings of SPNs were conducted with intracellular electrodes for electrophysiological analyses. Striatal changes of the direct and indirect pathways were investigated via immunofluorescence. Golgi-Cox staining was conducted to observe spine morphology of SPNs. To quantify postsynaptic signaling proteins in striatum, RNA-Seq, qRT-PCR and WB were performed in striatal tissues. Long-term depression (LTD) was failed to be induced, while long-term potentiation (LTP) was further strengthened in striatal spiny projection neurons (SPNs) from the Tor1a+/- DYT1 dystonia mice. Spine morphology analyses revealed a significant increase of both number of mushroom type spines and spine width in Tor1a+/- SPNs. In addition, increased AMPA receptor function and the reduction of NMDA/AMPA ratio in the postsynaptic of Tor1a+/- SPNs was observed, along with increased ER stress protein levels in striatum of Tor1a+/- DYT1 dystonia mice. Notably, ER stress inhibitors, tauroursodeoxycholic acid (TUDCA), could rescue LTD as well as AMPA currents. The current study illustrated the role of ER stress in mediating structural and functional plasticity alterations in Tor1a+/- SPNs. Inhibition of the ER stress by TUDCA is beneficial in reversing the deficits at the cellular and molecular levels. Remedy of dystonia associated neurological and motor functional impairment by ER stress inhibitors could be a recommendable therapeutic agent in clinical practice.


Twelve-month outcomes of a bioabsorbable implant for in-office treatment of dynamic nasal valve collapse.
To examine 12-month outcomes for in-office treatment of dynamic nasal valve collapse (NVC) with a bioabsorbable implant. Prospective, multicenter, nonrandomized study. One hundred sixty-six patients with severe-to-extreme class of Nasal Obstruction Symptom Evaluation (NOSE) scores were enrolled at 16 U.S. clinics (November 2016-July 2017). Patients were treated with a bioabsorbable implant (Latera, Spirox Inc., Redwood City, CA) to support the lateral wall, with or without concurrent inferior turbinate reduction (ITR), in an office setting. NOSE scores and Visual Analog Scale (VAS) were measured at baseline and 1, 3, 6, and 12 months postoperatively. The Lateral Wall Insufficiency (LWI) score was determined by independent physicians observing the lateral wall motion video. One hundred five patients were treated with implant alone, whereas 61 had implant + ITR. Thirty-one patients reported 41 adverse events, all of which resolved with no clinical sequelae. Patients showed significant reduction in NOSE scores throughout 12 months postoperatively (77.4 ± 13.4 baseline vs. 36.2 ± 22.7 at 1 month postoperatively, 33.0 ± 23.4 at 3 months, 32.1 ± 24.6 at 6 months, and 30.3 ± 24.3 at 12 months; P < 0.001). They also showed significant reduction in VAS scores postoperatively (69.7 ± 18.1 baseline vs. 31.3 ± 27.1 at 12 months postoperatively, P < 0.001). These results were similar in patients treated with implant alone and those treated with the implant + ITR. Consistent with patient-reported outcomes, postoperative LWI scores were demonstrably lower (1.42 ± 0.09 and 0.93 ± 0.08 pre- and postoperatively, P < 0.001). In-office treatment of dynamic NVC with a bioabsorbable implant improves clinical evidence of LWI at 6 months and improves nasal obstructive symptoms in a majority of patients up to 12 months. 2b Laryngoscope, 130:1132-1137, 2020.


Piezo-phototronic effect on electroluminescence properties of p-type GaN thin films.
We present that the electroluminescence (EL) properties of Mg-doped p-type GaN thin films can be tuned by the piezo-phototronic effect via adjusting the minority carrier injection efficiency at the metal-semiconductor (M-S) interface by strain induced polarization charges. The device is a metal-semiconductor-metal structure of indium tin oxide (ITO)-GaN-ITO. Under different straining conditions, the changing trend of the transport properties of GaN films can be divided into two types, corresponding to the different c-axis orientations of the films. An extreme value was observed for the integral EL intensity under certain applied strain due to the adjusted minority carrier injection efficiency by piezoelectric charges introduced at the M-S interface. The external quantum efficiency of the blue EL at 430 nm was changed by 5.84% under different straining conditions, which is 1 order of magnitude larger than the change of the green peak at 540 nm. The results indicate that the piezo-phototronic effect has a larger impact on the shallow acceptor states related EL process than on the one related to the deep acceptor states in p-type GaN films. This study has great significance on the practical applications of GaN in optoelectronic devices under a working environment where mechanical deformation is unavoidable such as for flexible/printable light emitting diodes.


Epidermal basement membrane alpha 5(IV) expression in females with Alport syndrome and severity of renal disease.
X-linked Alport syndrome is a progressive nephritis caused by mutations of the COL4A5 gene. This gene encodes the collagen alpha 5(IV) chain, which is abnormally distributed in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). It has been reported a negative correlation between alpha 5(IV) chain distribution in EBM and the degree of proteinuria in heterozygous females with Alport syndrome. In the present study, we evaluated the distribution of the alpha 5(IV) chain in the EBM and the degree of proteinuria in 22 females with X-linked Alport syndrome. The distribution of the cutaneous alpha 5(IV) chain was measured by a confocal laser microscope using an anti-alpha 5(IV) monoclonal antibody. The expression ratio of alpha 5(IV) distribution was quantified dividing the extension of the positive signal and the maximal extension of the specimen. Urinary protein excretion was expressed as urinary protein over urinary creatinine ratio. Proteinuria was present in five of the 22 patients. In two patients with proteinuria, alpha 5(IV)chain was normally distributed; in the remaining three, the expression ratio of alpha 5(IV)chain was 35%, 47%, and 48%. Of the 17 patients without proteinuria, two displayed a complete absence of the alpha 5(IV) chain in EBM, five displayed a normal staining, and the remaining 10 had an expression ratio between 18% and 65%. Our data suggest that there is no correlation between the severity of the glomerular involvement (expressed by proteinuria) and the staining of the alpha 5 chain in the EBM in females with X-linked Alport syndrome.


Prevalence of Low Birth Weight, Premature Birth, and Stillbirth Among Pregnant Adolescents in Canada: A Systematic Review and Meta-analysis.
Although most studies show that adolescent pregnant women are at a higher risk for adverse birth outcomes, there has been limited research examining this relationship in Canada. This systematic review and meta-analysis investigated the prevalence of low birthweight (LBW), preterm birth (PTB), and stillbirth in Canadian adolescent women compared to adult women. Studies were included if they were primary research and included a sample of adolescent mothers (≤19 years) and adult mothers (≥20 years) who gave birth to singleton infants in Canada. Birth outcomes must have been measured consistently in at least 3 studies for inclusion. Comprehensive electronic literature searches were conducted from database inception until August 2020 in 5 databases. Random effects meta-analysis models were used to estimate pooled odds ratios (pOR) for LBW, PTB, and stillbirth between adolescent and adult pregnant women. Outcomes reported included PTB (8 studies), LBW (6 studies), and stillbirth (3 studies). Compared to adult mothers, adolescent mothers had a 56% increase in the prevalence of LBW (pOR 1.56, 95% confidence interval [CI] 1.24, 1.97), a 23% increase in PTB (pOR 1.23, 95% CI 1.06, 1.42), a 20% increase in stillbirth (pOR 1.20, 95% CI 1.05, 1.37). Heterogeneity, as assessed by I2, was high for LBW and PTB and was low for stillbirth. A subgroup analysis did not remove the high heterogeneity, and some studies did not adjust for confounding variables and were missing information on sociodemographic and behavioral factors. Future research is needed to investigate the mechanisms surrounding these differences by maternal age.


Occupational practices and the making of health news: a national survey of US Health and medical science journalists.
News media coverage of health topics can frame and heighten the salience of health-related issues, thus influencing the public's beliefs, attitudes, and behaviors. Through their routine coverage of scientific developments, news media are a critical intermediary in translating research for the public, patients, practitioners, and policymakers. Until now, little was known about how health and medical science reporters and editors initiate, prioritize, and develop news stories related to health and medicine. We surveyed 468 reporters and editors representing 463 local and national broadcast and print media outlets to characterize individual characteristics and occupational practices leading to the development of health and medical science news. Our survey revealed that 70% of respondents had bachelor's degrees; 8% were life sciences majors in college. Minorities are underrepresented in health journalism; 97% of respondents were non-Hispanic and 93% were White. Overall, initial ideas for stories come from a "news source" followed by press conferences or press releases. Regarding newsworthiness criteria, the "potential for public impact" and "new information or development" are the major criteria cited, followed by "ability to provide a human angle" and "ability to provide a local angle." Significant differences were seen between responses from reporters vs. editors and print vs. broadcast outlets.


[Ye shes dpal'byor and Gan lu si bu (The four Tantras of nectar)].
Yeshes Palbyor was born in Haiyan County, Qinghai Province in 1704. As a youngster he studied medicine, Buddhism and linguistics in Ta'er Monastery. At the age of 28, he returned to Gunglung Monastery in his home town until his death. He devoted his whole life to the study of clinical therapeutics and Mongolian medicine. Gan lu si bu was his representative work, in which he advanced the theory of Six Basic Syndromes and Chills and Fever.


[116 multiple primary cancers in the digestive system].
To study the clinical characteristics, diagnosis, strategy of treatment and prognosis of multiple primary cancers in the digestive system. All malignant lesions in the digestive system encountered in the past 10 years were analysed by a computer software. 116 cases of multiple cancers were observed with an incidence of 1.74%. Male to female ratio was 2.7:1. There were 62 synchronous carcinomas and 54 metachronous ones. In decreasing sequence, they were: colon > stomach > rectum > liver. The 1-, 3-and 5-year survival rates of the synchronous ones were 42.3%, 23.1% and 11.5%. Those of metachronous ones were 95.2%, 85.7% and 76.2%. High frequency of multiple primary cancers is found in the colon, especially over the right side. Metachronous carcinomas usually give better prognosis than the synchronous ones. The longer the interval between the development of the two primary lesions, the better the prognosis. Multiple cancers of the colon have satisfactory prognosis. The key to improve the treatment is to be vigilant against lesions in the digestive tract so as to arrive at a timely diagnosis and treatment. The strategy of combining radical treatment with immuno-supportive therapy is advocated.


Active transport of sugars by the intestine of snail (Cryptomphalus hortensis Müller).
Sugar transport by sacs of everted intestine of snail have been measured in vitro at 30 degrees C. D-galactose, D-glucose and 3-O-methylglucose were actively transported against a concentration gradient from the mucosal to the serosal compartment. The transport of these sugars was inhibited by 5 times 10(-8) to 10(-6) M phlorizin. L-arabinose was also accumulated in the serosal compartment against a concentration gradient; in this case, transport was not affected by phlorizin. The snail intestine did not show any ability for D-fructose active transport but there was a clear uptake of this sugar by the tissue. The O2 uptake of the snail intestine was not significantly affected by the presence of either sugars or phlorizin.


Successful reconstruction of the rat ureter by a syngeneic collagen tube with a cardiomyocyte sheet.
Ureteral injuries require surgical intervention as they lead to loss of renal function. The current reconstructive techniques for long ureteral defects are problematic. Consequently, this study aimed to reconstruct the ureter in a rat model using subcutaneously prepared autologous collagen tubes (Biotubes). The lower ureter of LEW/SsNSlc rats was ligated to dilate the ureter to make anastomosis easier, and reconstruction was performed six days later by anastomosing the dilated ureter and bladder with a Biotube that was prepared subcutaneously in syngeneic rats. Some rats underwent left nephrectomy and ureter reconstruction simultaneously as negative controls to evaluate the effects of urine flow on patency. The other rats were divided into three groups as follows: a group in which the ureter was reconstructed with the Biotube alone, a group in which cardiomyocyte sheets made from the neonatal hearts of syngeneic rats were wrapped around the Biotube, and a group in which an adipose-derived stem cell sheets made from the inguinal fat of adult syngeneic rats were wrapped. Contrast-enhanced computed tomography and pathological evaluations were performed two weeks after reconstruction. In the Biotube alone group, all tubes were occluded and hydronephrosis developed, whereas the urothelium regenerated beyond the anastomosis when the left kidney was not removed, suggesting that urothelial epithelial spread occurred with urinary flow. The patency of the ureteral lumen was obtained in some rats in the cardiomyocyte sheet covered group, whereas stricture or obstruction of the reconstructed ureter was observed in all rats in the other groups. Pathological evaluation revealed a layered urothelial structure in the cardiomyocyte sheet covered group, although only a small amount of cardiomyocyte sheets remained. Urinary flow may support the epithelial spread of the urothelium into the reconstructed ureter. Neonatal rat cardiomyocyte sheets supported the patency of the regenerated ureter with a layered urothelium.


Effects of an adapted physical activity program on the physical condition of elderly women: an analysis of efficiency.
Specific research tools and designs can assist in identifying the efficiency of physical activity in elderly women. To identify the effects of physical activity on the physical condition of older women. A one-year-long physical activity program (123 sessions) was implemented for women aged 60 years or older. Four physical assessments were conducted, in which weight, height, BMI, blood pressure, heart rate, absences, grip strength, flexibility, VO2max, and static and dynamic balance were assessed. The statistical analyses included a repeated measures analysis, both inferential (analysis of variance--ANOVA) and effect size (Cohen's d coefficient), as well as identification of the participants' efficiency (Data Envelopment Analysis--DEA). Despite the observation of differences that depended on the analysis used, the results were successful in the sense that they showed that physical activity adapted to older women can effectively change the decline in physical ability associated with aging, depending on the purpose of the study. The 60-65 yrs group was the most capable of converting physical activity into health benefits in both the short and long term. The >65 yrs group took less advantage of physical activity. Adherence to the program and actual time spent on each type of exercise are the factors that determine which population can benefit from physical activity programs. The DEA allows the assessment of the results related to time spent on physical activity in terms of health concerns. Article registered in Clinicaltrials.gov under number NCT01558401.


The Effect of Naphthazarin on the Growth, Electrogenicity, Oxidative Stress, and Microtubule Array in Z. mays Coleoptile Cells Treated With IAA.
Naphthazarin (5,8-dihydroxy-1,4-naphthoquinone, DHNQ) is a naturally occurring 1,4-naphthoquinone derivative. In this study, we focused on elucidating the toxic effect of this secondary metabolite on the growth of plant cells. The dose-response curves that were obtained for the effects of DHNQ on endogenous and IAA-induced growth in maize coleoptile segments differ in shape; in the first case, it is linear, while in the presence of auxin it is bell-shaped with the maximum at 1 μM. It was found that DHNQ at almost all concentrations studied, when added to the incubation medium inhibited endogenous growth (excluding naphthazarin at 0.001 μM) as well as growth in the presence of IAA. Simultaneous measurements of the growth and external medium pH of coleoptile segments indicated that DHNQ diminished or eliminated proton extrusion at all of the concentrations that were used. Interestingly, the oxidative stress in maize coleoptile cells, which was measured as hydrogen peroxide (H2O2) production, catalase activity, redox activity and malondialdehyde (MDA) content, increased at the lower concentrations of DHNQ (<1 μM), thus suggesting a specific character of its action. It was also found that naphthazarin at concentration higher than 0.1 μM caused the depolarization of the membrane potential (E m). An analysis of the organization and anisotropy of the cortical microtubules showed that naphthazarin at all of the concentrations that were studied changed the IAA-induced transverse microtubule reorientation to an oblique reorientation. Our results indicate that naphthazarin diminished the growth of maize coleoptile cells by a broad spectrum of its toxic effects, thereby suggesting that naphthazarin might be a hypothetical component of new bioherbicides and biopesticides.


Potential of thermoresponsive hydrogel as an alternative therapy for rat knee osteoarthritis.
Osteoarthritis is a degenerative condition that is highly prevalent and primarily affects the joints. The knee is the most commonly affected site, impacting the lives of over 300 million individuals worldwide. This study presents a potential solution to address the unmet need for a minimally invasive technique in the treatment of osteoarthritis: a biocompatible, injectable, and thermoresponsive hydrogel. In comparison to commercially available products such as lyophilized platelets, dextrose, and triamcinolone, the thermoresponsive hydrogel exhibits significantly superior performance in dynamic behaviors, including print area, stability, and step cycle, when tested on rats with knee osteoarthritis. However, it demonstrates similar treatment efficacy to these products in static behaviors, as observed through histopathological and immunohistochemical analysis. Therefore, the thermoresponsive hydrogel holds promise as an effective alternative therapy for osteoarthritis. Moreover, by blending the hydrogel with drugs, controlled and sustained release can be achieved, thereby facilitating the long-term management of osteoarthritis symptoms.


Feasibility, Acceptability, and Preliminary Outcomes of a Culturally Adapted Evidence-Based Treatment for Latino Youth With ADHD.
Objective: To advance our knowledge about the most effective way to treat Latino youth with ADHD, the current feasibility and pilot study compared a culturally adapted evidence-based treatment (CAT) for ADHD to standard evidence-based treatment (EBT). Method: Following a comprehensive ADHD assessment, 61 Latino families of school-aged children (mean age of 8 years) were randomly assigned to either CAT or standard EBT (i.e., parent management training). Results: CAT outperformed standard EBT when examining homework completion and mother-reported treatment satisfaction. Apart from two trends favoring CAT, CAT and EBT both resulted in significant improvements in parent- and teacher-reported ADHD symptoms and functional impairment, as well as mother- and father-reported parental functioning. Conclusion: CAT outperformed standard EBT when examining several engagement and acceptability outcomes. CAT and EBT were equally effective when examining traditional treatment outcomes, which is impressive considering the robustness of standard EBT, especially when delivered by culturally competent staff.


Spectral weights in level discrimination by preschool children: synthetic listening conditions.
On most auditory discrimination and detection tasks young children perform more poorly than adults. The current experiment applies a technique which potentially can reveal the extent to which the adult-child performance difference results from suboptimal attentional strategies or simply greater internal noise in the children. In this experiment preschool children and adults were asked to discriminate between complex tones comprised of three random-amplitude sinusoidal components. A trial-by-trial correlational analysis [R. A. Lutfi, J. Acoust. Soc. Am. 97, 1333-1334 (1995)] provided an estimate of the weight listeners placed on the level information from individual spectral components in making the discrimination. The patterns of weights were interpreted as measures of "attentional strategy." Both children and adults produced reliable patterns of weights. This is an especially important result since measuring a single weighting pattern requires large numbers of trials and hence multiple sessions with the children. While individual weighting patterns were reliable, weighting patterns differed both within and across groups. Moreover, neither the children nor the adults produced weighting patterns that would maximize percent correct in the task. A substantial proportion of the responses from both children and adults could be predicted from their weighting patterns even when performance was near chance. However, differences in overall performance between children and adults could not be accounted for by differences in their weighting functions.


ZEB1 promotes tumorigenesis and metastasis in hepatocellular carcinoma by regulating the expression of vimentin.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains poor. Epithelial‑to‑mesenchymal transition (EMT)‑induced markers have emerged as key regulators of tumor development and progression in HCC. The aim of the present study was to investigate the role of zinc finger E‑box‑binding homeobox 1 (ZEB1) in the tumorigenesis of HCC and to elucidate the mechanism underlying the correlation between ZEB1 and vimentin (VIM). The expression levels of ZEB1 and VIM were assessed by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction analysis in HCC tissues and cell lines. The biological significance of ZEB1 was examined by downregulating the expression of ZEB1 in Huh‑7 cells. A luciferase reporter assay was used to investigate the association between ZEB1 and VIM. The expression levels of ZEB1 and VIM were higher in tumor tissues compared with those in adjacent normal tissues, and they were significantly associated with a poor prognosis in patients with HCC, whereas ZEB1 silencing led to the attenuation of HCC cell proliferation, invasion and migration. Furthermore, it was observed that ZEB1 was able to bind to a certain site in the VIM promoter and regulate the transcriptional activity of VIM. Therefore, the present study demonstrated that ZEB1 is a potential biomarker of the tumorigenesis and progression of HCC, and it may regulate transcription of the VIM gene.


Filtration of chlorine and hydrogen chloride gas by engineered UiO-66-NH2 metal-organic framework.
Chlorine (Cl2) and hydrogen chloride (HCl) are heavily utilized industrial chemicals that present significant respiratory health risks. The metal-organic framework UiO-66-NH2 has shown an unprecedented ability in powder form to remove chlorine gas. Here, we engineered UiO-66-NH2 into 20×40 mesh granules and evaluated their ability to remove chlorine and hydrogen chloride gas challenges. The exposed materials were characterized with nitrogen isotherms, powder X-ray diffraction, and attenuated total reflectance - Fourier transform infrared spectroscopy. Breakthrough results revealed that UiO-66-NH2 sorption of chlorine and hydrogen chloride met or exceeded sorption of state-of-the-art metal-impregnated activated carbon materials on a mass and volume basis in engineered form.


Hemodynamic changes associated with intravenous infusion of the calcium antagonist verapamil in the treatment of severe gestational proteinuric hypertension.
The calcium antagonist verapamil was intravenously infused after plasma volume expansion with dextran-70 in nine patients with severe gestational proteinuric hypertension. The hemodynamic response of these patients was monitored using a flow-directed pulmonary artery catheter. Verapamil produced a statistically significant reduction in mean arterial pressure and systemic vascular resistance without adversely affecting the cardiac output. The decrease in blood pressure was smooth and controlled and was associated with an insignificant increase in heart rate. There were no adverse fetal effects as evidenced by cardiotocographic monitoring. The apparent efficacy of verapamil in this study justifies further investigation.


Hyper-CVAD versus dose-adjusted EPOCH as initial treatment for adults with acute lymphoblastic leukemia.
We recently performed a single-arm phase II trial of DA-EPOCH in adults with acute lymphoblastic leukemia (ALL). We sought to compare these results to those with standard Hyper-CVAD. We created a retrospective matched cohort of patients who received Hyper-CVAD (n = 69) at our center and otherwise met eligibility criteria for the DA-EPOCH trial (n = 53). Our outcomes support the use of Hyper-CVAD over DA-EPOCH in Ph- disease for both overall survival (OS; HR 0.18, p = .004) and event-free survival (EFS; HR 0.51, p = .06). In contrast, outcomes were similar in Ph+ disease (OS HR 0.97, p = .96; EFS HR 0.65, p = .21). Rates of morphologic remission and measurable residual-disease negativity were similar between the regimens. Hyper-CVAD was associated with significantly more febrile neutropenia (OR 1.9, p = .03) and a greater incidence of Grade 4 or 5 adverse events (20% vs. 6%). Average transfusions per cycle of both red blood cells (p < .001) and platelets (p < .001) were five-fold higher with Hyper-CVAD. Our findings support continued use of Hyper-CVAD for Ph- ALL but suggest that DA-EPOCH may be a reasonable alternative for Ph+ ALL. These data also highlight a potential role for DA-EPOCH in resource-limited settings or when more intense therapy is not feasible.


Validated stability-indicating TLC method for the determination of noscapine.
A sensitive, selective, precise and stability-indicating thin-layer chromatographic (TLC) method was developed and validated for the analysis of noscapine, both as a bulk drug and in its formulation. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform-methanol (10:0.5 v/v). Densitometric analysis of noscapine and its degradation products was carried out in the absorbance mode at 254 nm. This system was found to give compact symmetrical spots for noscapine (R(f) value 0.85 +/- 0.04). Noscapine was subjected to acid and alkali hydrolysis, oxidation and photo degradation. The drug undergoes photo degradation and also degrades under acidic and basic conditions. The prepared degradation products were identified and verified through infrared (IR) and mass spectral analyses. The degraded products were also well resolved from the pure drug with significantly different R(f) values and they were quantitatively determined. The method was validated for linearity, precision, robustness, limit of detection (LOD), limit of quantitation (LOQ), specificity and accuracy. Linearity was found to be in the 1.0-10.0 microg, 0.4-3.2 microg, 1.0-9.0 microg and 0.5-5.0 microg/band ranges for noscapine, cotarnine, meconine and opionic acid, respectively. The polynomial regression analysis for the calibration plots showed a good polynomial relationship with r(2) of 0.9998, 9989, 9996 and 0.9997 for noscapine and its three degradation products, cotarnine, meconine and opionic acid, respectively. Statistical analysis proves that the method is repeatable and specific for the estimation of noscapine. As this approach could effectively separate the drug from its degradation products it can be employed as a stability-indicating method in Quality Control laboratories.


Glucuronidation: driving factors and their impact on glucuronide disposition.
Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances. Although it is usually the secondary metabolic pathway for a compound preceded by phase I hydroxylation, glucuronidation alone could serve as the dominant metabolic pathway for many compounds, including some with high aqueous solubility. Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases (UGTs) into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters. Therefore, elimination of parent compound via glucuronidation in a metabolic active cell is controlled by two driving forces: the formation of glucuronides by UGT enzymes and the (polarized) excretion of these glucuronides by efflux transporters located on the cell surfaces in various drug disposition organs. Contrary to the common assumption that the glucuronides reaching the systemic circulation were destined for urinary excretion, recent evidences suggest that hepatocytes are capable of highly efficient biliary clearance of the gut-generated glucuronides. Furthermore, the biliary- and enteric-eliminated glucuronides participate into recycling schemes involving intestinal microbes, which often prolong their local and systemic exposure, albeit at low systemic concentrations. Taken together, these recent research advances indicate that although UGT determines the rate and extent of glucuronide generation, the efflux and uptake transporters determine the distribution of these glucuronides into blood and then to various organs for elimination. Recycling schemes impact the apparent plasma half-life of parent compounds and their glucuronides that reach intestinal lumen, in addition to prolonging their gut and colon exposure.