Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters.
A series of four water-soluble salicylaldehyde thiosemicarbazones with a positively charged trimethylammonium moiety ([H2LR]Cl, R = H, Me, Et, Ph) and four copper(II) complexes [Cu(HLR)Cl]Cl (1-4) were synthesised with the aim to study (i) their antiproliferative activity in cancer cells and, (ii) for the first time for thiosemicarbazones, the interaction with membrane transport proteins, specifically organic cation transporters OCT1-3. The compounds were comprehensively characterised by analytical, spectroscopic and X-ray diffraction methods. The highest cytotoxic effect was observed in the neuroblastoma cell line SH-5YSY after 24 h exposure and follows the rank order: 3 > 2 > 4 > cisplatin > 1 >>[H2LR]Cl. The copper(II) complexes showed marked interaction with OCT1-3, comparable to that of well-known OCT inhibitors (decynium 22, prazosin and corticosterone) in the cell-based radiotracer uptake assays. The work paves the way for the development of more potent and selective anticancer drugs and/or OCT inhibitors.


Retention of primary bile salts by dry beans (Phaseolus vulgaris L.) during in vitro digestion: Role of bean components and effect of food processing.
The positive effect of common beans on reducing blood cholesterol levels has been linked to their ability to sequester bile salts (BS) and prevent their recycling. We have examined the preferences of major bean components (soluble/insoluble fiber, starch and proteins) to retain BS, and the role played by the bean matrix. Additionally, the kinetics of BS-release were evaluated in bean flours generated by a combination of hydrothermal or high-hydrostatic pressure (HHP), and mechanical treatments. An in vitro digestion model combined with dialysis was used to evaluate separately the retention of primary individual BS. Soluble fiber retained a significant proportion of BS mainly due to an increased digesta viscosity; however, the protein fraction exhibited the greatest BS retention without affecting viscosity. The thermal properties of proteins and starch were more significantly affected in presence of tauro-chenodeoxycholate, which correlated to the affinity of both fractions to retain more hydrophobic BS during digestion. Glyco-chenodeoxycholate and tauro-cholate were the most and least effectively retained BS by bean flours, respectively. Neither of the processing treatments had an impact on the binding preferences of bean flours to the primary BS; however, the largest BS retention was caused by HHP at 600 MPa. Bean materials preferentially delayed the release of chenodeoxycholate BS, which is probably related to BS micelle formation. These findings demonstrate that a combination of viscosity, molecular and compositional factors is triggering the BS-retention capacity of beans, and indicate the importance of evaluating contribution of individual bean components and as whole system.


Comparison of photorefractive keratectomy, astigmatic PRK, laser in situ keratomileusis, and astigmatic LASIK in the treatment of myopia.
To determine factors affecting refractive and visual outcomes in patients treated with astigmatic and spherical photorefractive keratectomy (A-PRK and PRK) and laser in situ keratomileusis (A-LASIK and LASIK). University referral refractive surgery clinic. Refractive and visual acuity results in 619 eyes of 388 consecutive patients having refractive surgery over a 2-year period by a single surgeon were retrospectively analyzed. Patients were divided into mild-to-moderate myopia (spherical equivalent [SE] less than -6.12 diopters [D]) and high myopia (SE -6.12 D or higher). Multivariate and logistic regression analyses were performed. Refractive results in flap-based and PRK-based procedures were comparable in mild-to-moderate myopia patients but were significantly better in high-myopia patients having flap-based procedures. Refractive stability was greater in flap-based procedures than in PRK-based procedures. Elliptical ablations yielded a marked reduction in the astigmatic cylinder in patients having A-LASIK and A-PRK, while spherical PRK induced small amounts of with-the-rule astigmatism. Complications were uncommon in both groups, consisting primarily of epithelial ingrowth in flap-based procedures and haze in PRK-based procedures. Multivariate regression identified the preoperative SE as a significant determinant of PRK outcomes (with higher success for lower myopia) and intraocular pressure as a minor determinant of outcomes in PRK-based and flap-based procedures. Logistic regression suggested that only the preoperative SE was a significant factor in predicting the likelihood of poor outcomes in PRK patients. Refractive outcomes were almost identical in patients having elliptical or spherical ablations with flap-based or PRK-based procedures. In eyes with mild-to-moderate myopia, there was little difference in refractive or visual outcomes between flap-based and PRK-based procedures; in eyes with high myopia, flap-based procedures offered more predictable refractive outcomes and better visual outcomes.


Abscisic acid and pyrabactin improve vitamin C contents in raspberries.
Abscisic acid (ABA) is a plant growth regulator with roles in senescence, fruit ripening and environmental stress responses. ABA and pyrabactin (a non-photosensitive ABA agonist) effects on red raspberry (Rubus idaeus L.) fruit development (including ripening) were studied, with a focus on vitamin and antioxidant composition. Application of ABA and/or pyrabactin just after fruit set did not affect the temporal pattern of fruit development and ripening; neither provitamin A (carotenoids) nor vitamin E contents were modified. In contrast, ABA and pyrabactin altered the vitamin C redox state at early stages of fruit development and more than doubled vitamin C contents at the end of fruit ripening. These were partially explained by changes in ascorbate oxidation and recycling. Therefore, ABA and pyrabactin applications may be used to increase vitamin C content of ripe fruits, increasing fruit quality and value. However, treatments containing pyrabactin-combined with ABA or alone-diminished protein content, thus partially limiting its potential applicability.


Linkage disequilibrium mapping of complex disease: fantasy or reality?
In the past year, data about the level and nature of linkage disequilibrium between alleles of tightly linked SNPs have started to become available. Furthermore, increasing evidence of allelic heterogeneity at the loci predisposing to complex disease has been observed, which has lead to initial attempts to develop methods of linkage disequilibrium detection allowing for this difficulty. It has also become more obvious that we will need to think carefully about the types of populations we need to analyze in an attempt to identify these elusive genes, and it is becoming clear that we need to carefully re-evaluate the prognosis of the current paradigm with regard to its robustness to the types of problems that are likely to exist.


Alcoholics Anonymous and nursing. Lessons in holism and spiritual care.
Alcoholic Anonymous (AA) is a worldwide, million-member organization that has assisted countless alcoholics to achieve sobriety through a spiritual program of recovery from alcoholism. Based on spiritual principles known as the "Twelve Steps" and "Twelve Traditions," AA has provided a model for other recovery programs such as Narcotics Anonymous (NA), Gamblers Anonymous (GA), and Sex and Love Addicts Anonymous (SLAA). Recovery in AA appears to involve a process of self-transcendence. In recent years, nursing scholars have increasingly explored the concepts of self-transcendence and spirituality as they apply to nursing theory and practice. This article explores the roots and spiritual dimensions of 12-step recovery programs. It further explores the ways in which theoretical and clinical knowledge about the delivery of spiritual care interventions may be gained from an understanding of AA's spiritual approach to recovery.


Thromboxane B2: a cardiodepressant of isolated rat hearts and inhibitor of sarcolemma Na+ - K+ stimulated ATPase activity.
The actions of thromboxane B2 on various parameters of cardiac performance were studied using the isolated perfused rat heart model. In concentrations from 100 pg/ml to 1 microgram/ml TXB2 significantly reduced the total generated myocardial contractile force. These changes were usually associated with an increase in the coronary perfusion pressure indicating an elevated coronary vascular resitance. Significant coronary pressure alterations were seen with TXB2 concentrations between 1 ng/ml and 1 microgram/ml. No significant changes were seen in either the resting tension or heart rate after TXB2 administration. However TXB2 (10 pg/ml to 10 ng/ml,, significantly reduced the amplitude of the electrical activity as observed in R wave changes of the surface electrocardiogram recording. In another series of experiments the action of TXB2 on rat heart sarcolemmal ATPase activity was studied. TXB2 significantly reduced the activity of the MG++ dependent - Na+ - K+ stimulated ATPase (Na+ - K+ ATPase) in these membrane preparations in concentrations from 10 ng/ml to 1 microgram/ml. Kinetic studies demonstrated that TXB2 reduced Vmax and increased the concentration required of ATP, Na+ and K+ for half-maximal enzyme activity. TXB2 did not inhibit either Ca++ or ouabain-induced depression of Na+ - K+ ATPase activity. The activity of either Mg++ or Ca++ - stimulated ATPase was not affected by TXB2. These results suggest possible important actions of TXB2 on rat heart activity which may be related to Na+ - K+ ATPase inhibition.


Secondary interactions, an unexpected problem emerged between hydroxyl containing analytes and fused silica capillaries in anion-exchange micro-liquid chromatography.
Relevant secondary interactions (hydrogen-bond type), additional to the main anion-exchange mechanism, were found when a method for As, Se and Cr speciation was developed based on microLC-inductively coupled plasma mass spectrometry (ICP-MS) coupling. In order to get the claimed analytical performance characteristics of the microbore columns, microLC systems are equipped with very narrow bore fused silica capillaries. When a mobile phase of NH(4)NO(3) at pH 8.7 was used, a notable tailing was observed for As(III), As(V), MMA and Se(IV), species containing hydroxyl groups in its chemical structure at this pH value. However, additional interactions appeared neither when the fused silica capillaries of the capillary LC system were substituted for polyetheretherketone (PEEK) nor operating at pH below 8.5. A mechanism to explain the additional interaction observed is proposed and tested in this work. It seems that high pH values produce a partial hydrolysis of the siloxane groups of the fused silica capillaries. Under these conditions, degradation products of silica, containing ionized silanol groups, reach the column and interact with the anion-exchange resin. Then, ionized silanol groups, retained on the column, can interact with the hydroxyl moiety of the aforementioned analytes leading to severe peak tailing and broadening. Different strategies were evaluated to solve the problem. The addition of a salt containing hydroxyl groups in the mobile phase such as hydrogen phosphate, the diminution of the pH and the use of PEEK capillaries in the microHPLC system demonstrated to be suitable. Finally, two alternative microHPLC-ICP-MS separations, based on a gradient elution of NH(4)NO(3) at pH 8.0 and NH(4)NO(3)/NH(4)H(2)PO(4) at pH 8.7, were optimized and compared. Results showed better peak shapes for some species when hydrogen phosphate was added to the mobile phase.


Radiolabeling of methylphosphonate and phosphorothioate oligonucleotides and evaluation of their transport in everted rat jejunum sacs.
The therapeutic use of antisense oligonucleotides will likely involve their administration over protracted periods of time. The oral route of drug dosing offers many advantages over other possible routes when chronic drug administration is necessary. However, little is known about the potential for oligonucleotide uptake from the gastrointestinal tract. This issue is addressed in the current work. We have developed a simple procedure for radiolabeling oligonucleotides by reductive alkylation with 14C-formaldehyde. We have utilized this approach, as well as 5' addition of fluorophores, to prepare labeled methylphosphonate and phosphorothioate oligonucleotides for use in intestinal transport studies. An everted rat gut sac model was employed to compare the transport of oligonucleotides to that of model compounds whose permeation properties are better understood. We demonstrate that both methylphosphonate and phosphorothioate oligonucleotides are passively transported across the intestinal epithelium, probably by a paracellular route. The rates of transport for both types of oligonucleotides were similar, and were significantly greater than that of the very high MW polymer blue dextran, but were lower than the transport rate of valproic acid, a low MW compound known to have high oral availability. A significant degree of permeation of oligonucleotides across the gastrointestinal epithelium does occur, but it is still unclear whether this is sufficient to permit effective oral administration of oligonucleotides as drugs.


Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.
Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases.


InGaN/GaN nanowires as a new platform for photoelectrochemical sensors - detection of NADH.
InGaN/GaN nanowire heterostructures are presented as nanophotonic probes for the light-triggered photoelectrochemical detection of NADH. We demonstrate that photogenerated electron-hole pairs give rise to a stable anodic photocurrent whose potential- and pH-dependences exhibit broad applicability. In addition, the simultaneous measurement of the photoluminescence provides an additional tool for the analysis and evaluation of light-triggered reaction processes at the nanostructured interface. InGaN/GaN nanowire ensembles can be excited over a wide wavelength range, which avoids interferences of the photoelectrochemical response by absorption properties of the compounds to be analyzed by adjusting the excitation wavelength. The photocurrent of the nanostructures shows an NADH-dependent magnitude. The anodic current increases with rising analyte concentration in a range from 5µM to 10mM, at a comparatively low potential of 0mV vs. Ag/AgCl. Here, the InGaN/GaN nanowires reach high sensitivities of up to 91µAmM-1cm-2 (in the linear range) and provide a good reusability for repetitive NADH detection. These results demonstrate the potential of InGaN/GaN nanowire heterostructures for the defined conversion of this analyte paving the way for the realization of light-switchable sensors for the analyte or biosensors by combination with NADH producing enzymes.


Immunoadsorption with regenerating systems in neurological disorders --A single center experience.
In recent years, immunoadsorption is increasingly recognized as an alternative treatment approach replacing therapeutic plasma exchange in a variety of neurological disorders. While most experience is based on the application of single-use tryptophan adsorbers, less data exists on the application of more efficient regenerating adsorber columns. We here report the systematic use of a regenerating adsorber system in various neurological indications such as multiple sclerosis, encephalitis, myasthenia gravis and chronic inflammatory demyelinating polyneuropathy, providing the expected treatment success in regard to reduction of immunoglobulins and antibody clearance, together with a low rate of adverse events. As it has been shown for single-use columns before, immunoadsorption with regenerating adsorbers can be successfully applied in disorders without known specific antibodies such as multiple sclerosis. Regenerating systems offer the perspective to provide a more efficacious long term treatment perspective for such patients.


Deciphering the Polygenic Basis of Racial Disparities in Prostate Cancer By an Integrative Analysis of Genomic and Transcriptomic Data.
Prostate cancer prevalence in African Americans (AA) is over 1.5 times the prevalence in European Americans (EA). Among over a hundred index risk SNPs for prostate cancer, only a few can be verified using the available AAs' data. Their relevance to the prevalence inequality and other racial disparities has not been fully determined. We investigated this issue by an integrative analysis of five public datasets. We categorized the datasets into two classes. The training class consisted of the datasets generated by three genome-wide association studies. The test class contained the prostate adenocarcinoma data of The Cancer Genome Atlas and the data of African and European super-populations in the 1000-Genome project. The polygenic risk scores (PRS) of test samples for cancer occurrence were calculated according to the effects of genetic variants estimated from the training samples. We obtained the following findings. Africans' PRSs are higher than Europeans' scores (P < 1 × 10-6). AA patients' PRSs are higher than EA patients' scores (P < 3×10-9). The patients with tumors presenting fusion or abnormal expression in ERG and other E26 transformation-specific (ETS) family genes have lower PRSs than the patients without such aberrations (P < 7×10-5). Five tumor progression-related genes have the expression levels being significantly correlated with PRS (FDR < 0.01). Additional simulation analysis shows that the high prostate cancer prevalence in African populations makes it challenging to identify individual risk variants using African men's data. These results implicate that the index risk SNP-based PRS is compatible with the observed racial disparity in prostate cancer prevalence and ETS abnormal cancers may be less heritable compared with other subtypes. This study reveals the relevance of index risk SNP markers with racial disparities in prostate cancer. The findings also indicate that PRS can be used in prostate cancer subtype prediction.


Imaging features of retroperitoneal and pelvic schwannomas.
To describe the imaging features of retroperitoneal and pelvic schwannomas. The presenting cross-sectional imaging for 18 sequential patients with retroperitoneal or pelvic schwannomas was reviewed retrospectively. Note was made of tumour diameter, position, homogeneity, margin, shape, calcification and invasion into adjacent structures. Where MRI had been performed, T1 and T2 signal intensity relative to skeletal muscle, and the degree and pattern of enhancement with gadolinium, were also assessed. Imaging from 13 patients was available for review. The mean tumour diameter was 8.7 cm (range 4 to 15 cm); 9 schwannomas were located in the pelvis and 4 in the retroperitoneum; 12 cases showed smooth, regular margins and 1 case irregular, invasive margins. The tumours were homogeneous in 5 cases and heterogeneous with cystic change in 8; in 2 cases there was smooth expansion of a sacral nerve root exit foramen, and in 1 there was bony destruction of the sacrum and extension of tumour into the spinal canal. In 5 cases MRI was performed; on T1-weighted images all tumours were isointense; on T2-weighted images 4 tumours were hyperintense and 1 was isointense to skeletal muscle. In all cases the diagnosis was confirmed by core biopsy. Retroperitoneal and pelvic schwannomas typically form large, well-circumscribed masses in the retroperitoneum or presacral area, and frequently undergo cystic degeneration. They can occasionally cause bony changes in the spine, but otherwise do not invade or obstruct adjacent structures. Although they are rare, it is important for the radiologist to recognize the typical appearance of schwannomas because they can be mistaken for malignant tumours.


Cleft palate and accessory metacarpal of index finger syndrome: possible familial occurrence.
A case of cleft palate and accessory metacarpal of index finger syndrome is described and related to the presence of Pierre Robin syndrome in a stillborn sibling. The significance of this relationship is discussed.


Preoperative and intraoperative predictors of deep venous thrombosis in adult patients undergoing craniotomy for brain tumors: A Chinese single-center, retrospective study.
Brain tumor resection by craniotomy is associated with a high risk of deep vein thrombosis (DVT). This study evaluated the incidence and preoperative and intraoperative risk factors for DVT within 30 days of surgery. The analysis included: 1) basic clinical variables (patient age, sex, body mass index [BMI], tumor location, and tumor histology); 2) blood test results before operation, such as leukocytes, platelets, and coagulation parameters; and 3) surgical factors (total amount of blood lost, anesthesia mode, and surgery duration). Of the 1670 patients, 206 (12.34%) had DVT and nine (0.54%) had both DVT and pulmonary embolism (PE) after surgery. Preoperative and intraoperative factors independently associated with DVT/PE were: older age 46-55 years (odds ratio [OR]: 2.87; 95% confidence interval [CI]: 1.83-4.50; P < 0.001), age 56-65 years (OR: 5.24; 95% CI: 3.27-8.40; P < 0.001), age > 65 years (OR: 6.00; 95% CI: 3.45-10.45; P < 0.001), BMI (OR: 1.03; 95% CI: 1.00-1.05; P = 0.029), activated partial thromboplastin time [APTT] (OR: 0.91; 95% CI: 0.86-0.95; P = 0.000), D-dimer (OR: 1.69; 95% CI: 1.23-2.34; P = 0.001), high-grade glioma (OR: 2.09; 95% CI: 1.28-3.40; P = 0.003), glio-neuronal (OR: 3.30; 95% CI: 1.28-8.47; P = 0.013), craniopharyngioma (OR: 2.16; 95% CI: 1.13-4.10; P = 0.019), and surgery duration (OR: 1.82; 95% CI: 1.27-2.60; P = 0.001). Older age, BMI, preoperative APTT, D-dimer, tumor histology, and surgery duration independently increased the risk of developing postoperative DVT/PE. These findings provide prognostic information that will guide therapies aimed at minimizing the development of DVT/PE during hospitalization.


Bifunctional gene cluster lnqBCDEF mediates bacteriocin production and immunity with differential genetic requirements.
A comprehensive gene disruption of lacticin Q biosynthetic cluster lnqQBCDEF was carried out. The results demonstrated the necessity of the complete set of lnqQBCDEF for lacticin Q production, whereas immunity was flexible, with LnqEF (ABC transporter) being essential for and LnqBCD partially contributing to immunity.


A convenient and rapid method for genetic transformation of E. coli with plasmids.
A convenient and rapid method for the genetic transformation of Escherichia coli with plasmids is proposed. By mixing the recipient cells and plasmid DNA and spreading them directly on selective medium plates containing Ca2+, the so-called 'plate transformation' could achieve almost the same transformation efficiency as the classical transformation method with calcium. The whole protocol takes only about 2 min, its simplicity compared favorably, not only to the usual protocol, but also to all other documented modifications.


Neonatal herpes: incidence, prevention, and consequences.
The incidence, prevention (by cesarean section), and severe consequences (particularly mortality) of neonatal herpes were appraised. The incidence rate of neonatal herpes should be around one in every 15,000 deliveries with a range of one in 7,500 to 30,000 deliveries. Cesarean section for pregnancies exposed to herpes simplex virus fails to prevent newborns from acquiring neonatal herpes. The mortality rate of herpes patients could be around 25% if a better reporting and diagnostic system were available.


Measuring functional disability in children with developmental disorders in low-resource settings: validation of Developmental Disorders-Children Disability Assessment Schedule (DD-CDAS) in rural Pakistan.
Developmental disorders (DDs) in children are a priority condition and guidelines have been developed for their management within low-resource community settings. However, a key obstacle is lack of open access, reliable and valid tools that lay health workers can use to evaluate the impact of such programmes on child outcomes. We adapted and validated the World Health Organization's Disability Assessment Schedule for children (WHODAS-Child), a lay health worker-administered functioning-related tool, for children with DDs in Pakistan. Lay health workers administered a version of the WHODAS-Child to parents of children with DDs (N = 400) and without DDs (N = 400), aged 2-12 years, after it was adapted using qualitative study. Factor analysis, validity, reliability and sensitivity to change analyses were conducted to evaluate the psychometric properties of the adapted outcome measure. Among 800 children, 58% of children were male [mean (s.d.) age 6.68 (s.d. = 2.89)]. Confirmatory Factor Analysis showed a robust factor structure [χ2/df 2.86, RMSEA 0.068 (90% CI 0.064-0.073); Tucker-Lewis Index (TLI) 0.92; Comparative Fit Index (CFI) 0.93; Incremental Fit Index (IFI) 0.93]. The tool demonstrated high internal consistency (α 0.82-0.94), test-retest [Intra-class Correlation Coefficient (ICC) 0.71-0.98] and inter-data collector (ICC 0.97-0.99) reliabilities; good criterion (r -0.71), convergent (r -0.35 to 0.71) and discriminative [M (s.d.) 52.00 (s.d. = 21.97) v. 2.14 (s.d. = 4.00); 95% CI -52.05 to -47.67] validities; and adequate sensitivity to change over time (ES 0.19-0.23). The lay health worker administrated version of adapted WHODAS-Child is a reliable, valid and sensitive-to-change measure of functional disability in children aged 2-12 years with DDs in rural community settings of Pakistan.


Selective thyromimetics for atherosclerosis and dyslipidaemia: another old target making progress.
Whereas many new targets for drug discovery have been identified from new biology, such as that from the Human Genome Project, some targets have been known for decades but have not been exploited. One such target, selective thyromimetics, is reviewed from a historical perspective and in the light of recent developments. The history of thyromimetics in atherosclerosis and dyslipidaemia is reviewed as the background to the recent publication of the first human data on a new selective thyromimetic, KB-2115 (eprotirome). The published data provide proof of concept/mechanism, opening the way to larger studies in a wider range of subjects and in combination with statins.


Experimental data on the prevention of retrolental fibroplasia by D-penicillamine.
Superoxide dismutase activity of alveolar macrophages, lung, liver, retina and choroid has been studied in rats and rabbits exposed to oxygen at high concentration by itself and in combination with D-penicillamine. Prolonged hyperoxia caused an increase in superoxide dismutase activity while D-penicillamine was found to inhibit the inductive effect of oxygen. It is assumed that the antioxidative effect of D-penicillamine makes it unnecessary to augment the production of superoxide dismutase.


Protective effect of ginsenoside Rg1 on MPP+-induced apoptosis in SHSY5Y cells.
The neuroprotective mechanism of Rg1 was studied in this paper by means of its obvious anti-apoptotic effect on human SHSY5Y cells. SHSY5Y cells were treated with MPP+ (1-methyl-4-phenyl-pyridinium) for 72 hours to induce apoptosis. During the apoptosis, production of reactive oxygen species (ROS), activation of c-Jun N-terminal kinase (JNK) and activation of caspase-3 were observed. The results showed that the signal transduction pathway of MPP+-induced apoptosis might be ROS to JNK, then to caspase-3. MPP+-induced apoptosis in SHSY5Y cells was obviously inhibited in both NAC (N-acetylcysteine) pretreated groups and Rg1 pretreated groups. Meanwhile, compared to that of the controls, our results showed decreased level of ROS, less JNK activity and lower expression of cleaved caspase-3 in pretreated NAC groups and in Rg1 pretreated groups. The protection by Rg1 might be mediated by removing of ROS. The removal of ROS might inhibit the activity of JNK and the expression of cleaved caspase-3. These results suggest that ginsenoside Rg1 may take effect through its anti-apoptotic activity in neurodegenerative diseases.


Discontinuation of denosumab in men with prostate cancer.
In patients with non-metastatic prostate cancer, treated with radiation therapy and androgen deprivation therapy for 3 years and DMAB on average for 5 years, BMD was in the normal or osteopenic range. Discontinuation of DMAB led to a bone loss of 2-5%. In men with osteopenia, the bone loss was prevented by zoledronate. Patients with prostate cancer receiving androgen deprivation therapy (ADT) are treated with denosumab (DMAB) to prevent fractures and preserve bone mass. We wanted to investigate the change in BMD in men with non-metastatic prostate cancer discontinuing DMAB. We conducted a retrospective cohort study based on medical records from patients referred to the Department of Endocrinology from the Department of Urology, Aarhus University Hospital between June 1, 2018, and June 1, 2021. We retrieved information on biochemistry and DXA performed 0-6 months after the last DMAB injection and a second DXA performed approximately 12 months after the first. In case of a BMD T-score ≤ - 1 at the lumbar spine or total hip at the first DXA, the patients were treated with zoledronate. The primary endpoint was change in lumbar spine BMD. We included 50 patients with non-metastatic prostate cancer. The mean DMAB treatment duration was 5 ± 0.1 years. Among the patients treated with zoledronate (n = 9), BMD was maintained at the spine and femoral neck after a mean of 16 months. We found a significant decrease in BMD; - 4.9 ± 4.2%, - 1.9 ± 3.5%, and - 2.4 ± 3.6% at the spine, total hip, and femoral neck between the first and second DXA in the patients not treated with zoledronate (n = 24) (p ≤ 0.01 for all). One patient who did not receive ZOL sustained multiple fragility vertebral fractures after DMAB discontinuation. In men with non-metastatic prostate cancer, discontinuation of DMAB after stopping ADT led to an average bone loss of 2-5%. Zoledronate prevented bone loss in men with osteopenia.


Counting the cost: The potential impact of African Swine Fever on smallholders in Timor-Leste.
In September 2019, Timor-Leste, where pigs are kept by more than 70 percent of households, became the eleventh Asian country to report African Swine Fever (ASF). Drawing on our recent, as-yet unpublished research we show that while national pork consumption is low, pigs hold tremendous monetary value for smallholders within the economy of ceremonies. Given the sums of money paid for live pigs, the value of the national pig herd is around USD160 million - more than USD1000 per pig keeping household. Accordingly, pigs serve to buffer families against shocks and pressures, especially for health and education expenses. While not a zoonosis, the potential for ASF to lead to significant, negative impacts for smallholder farmers in Timor-Leste - some of the world's most vulnerable people - cannot be underestimated. We argue that Timor-Leste faces significant challenges in responding to ASF and there is a strong case for international support.


Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction.
We assess the availability of plasma biomarkers to monitor the brain damage and the therapeutic efficacy of edaravone. The study consisted of 51 patients with ischemic cerebral infarcts. They were divided into 2 groups: GI (n = 24) had cortical lesions, and GII (n = 27) had lesions in the basal ganglia or brain stem. Edaravone was administered to 27 randomly selected patients (GIa, n = 13; GIIa, n = 14) and its efficacy was studied by comparing their plasma OxLDL, S-100B, and MnSOD levels to those in patients without edaravone (GIb, n = 11, GIIb, n = 13). Three days after the start of edaravone, plasma OxLDL was significantly lower in GIa than GIb patients (0.177 +/- 0.024 ng/microg apoB vs 0.219 +/- 0.026, P < 0.05). In GIIa patients, pre- and posttreatment plasma OxLDL was not significantly different (0.156 +/- 0.013 vs 0.152 +/- 0.020). In GIa patients, S-100B and MnSOD were significantly lower than in GIb patients (P < 0.05). The neurological condition at the time of discharge had recovered in GIa but not GIb patients. Ours is the first evidence to confirm the efficacy of edaravone by plasma biomarkers. In patients with cortical infarcts, edaravone reduced oxidative damage, thereby limiting the degree of brain damage.


Bronchial reactivity to histamine is correlated with airway remodeling in adults with moderate to severe asthma.
Chronic eosinophilic inflammation may promote airway remodeling, including thickening of the reticular basement membrane (RBM), hypertrophy and hyperplasia of the airway smooth muscles (ASM), and an increase in the production of tenascin. The authors examined the correlation between airway remodeling and bronchial reactivity to histamine (Hist) and acetylcholine (ACh) in patients with moderate to severe asthma. In 30 adult patients with asthma, the authors assessed bronchial hyperresponsiveness (BHR) to various concentrations of ACh and Hist by measuring decreases in forced expiratory volume in one second (FEV₁) of >20% from the preprovocation state, and % recoveries of FEV₁ after inhalation of β-stimulant. After corticosteroid therapy, the authors evaluated the thickening of RBM and ASM and the production of tenascin in bronchial specimens. The % decrease in FEV₁ was correlated with the % recovery in FEV₁ after provocation by ACh or Hist. Hypertrophy of ASM was correlated with the % decrease in FEV₁ after provocation by Hist, but not by ACh. Thickening of ASM, up-regulation of tenascin in RBM, and duration of asthma were inversely correlated with the % recovery of FEV₁ after provocation by Hist, but not by ACh. In adult patients with moderate to severe asthma, a strong bronchial contraction provoked by Hist and a subsequent small recovery indicate airway remodeling.


Association of Complete Radiologic and Pathologic Response following Locoregional Therapy before Liver Transplantation with Long-Term Outcomes of Hepatocellular Carcinoma: A Retrospective Study.
To evaluate long-term outcomes of patients with hepatocellular carcinoma (HCC) who show a complete response (CR) vs non-CR on pretransplantation imaging studies or pathologic evaluation of liver explants after locoregional therapy (LRT) before liver transplantation. Patients listed for liver transplantation for HCC (March 1998 to December 2010) undergoing LRT with available multiphase MR/CT imaging before transplantation were included. Pathologic response was evaluated based on liver explant pathology. A total of 108 patients (17 women; 16%) met the inclusion criteria. Radiologic CR was achieved in 65 patients (60%) vs non-CR in 43 (40%), and pathologic CR was achieved in 36 patients (33%) vs non-CR in 72 (67%). Mean 5-year overall survival (OS) from the time of listing and recurrence-free survival (RFS) after liver transplantation were significantly better for patients with pathologic CR vs non-CR on explant pathology (OS, 83.3% vs 65.2% [28% difference; P = .046]; RFS, 80.6% vs 62.5% [29% difference; P = .045]). Mean 5-y OS and RFS were not significantly different between patients with radiologic CR or non-CR on pretransplantation imaging (OS, 75.4% vs 65.1% [P = .12]; RFS, 74% vs 62.8% [P = .17]). Achievement of a pathologic CR vs non-CR in response to LRT before liver transplantation for HCC is associated with improved OS from time of listing and improved RFS after liver transplantation. However, current imaging paradigms fall short of accurate delineation of response to LRT, resulting in poor correlation of outcomes between pathologic and radiologic CR.


Estimating chemical biotransformation rates from food web concentrations.
Biotransformation is widely recognized as the most important and most uncertain determinant of bioaccumulation. A step-wise method for estimating organism-specific biotransformation half-lives from field observations and using established food web modeling is developed. As a proof of concept, the method is applied to the case of nine polycyclic aromatic hydrocarbons (PAHs) in a well-studied food web in Bohai Bay, China. The estimated half-lives are in good agreement with the existing literature. The proposed biotransformation estimation method, through data mining, for sufficiently defined ecosystems, may greatly reduce the necessary animal testing involved in chemical assessments by providing useful guidance to experimentalists and regulators.


Effects of neural-derived estradiol on actin polymerization and synaptic plasticity-related proteins in prefrontal and hippocampal cells of mice.
Neural-derived 17β-estradiol (E2) plays an important role in the synaptic plasticity of the hippocampus and prefrontal cortex, but the mechanism is not well defined. This study was designed to explore the effect and mechanism of neural-derived E2 on synaptic plasticity of the hippocampus and prefrontal cortex. Primary cultured hippocampal and prefrontal cells in mice were randomly divided into the DMSO (D), aromatase (Rate-limiting enzymes for E2 synthesizes) inhibitor letrozole (L), and ERs antagonist (MPG) treated groups. After intervention for 48 h, the cell was collected, and then, the expressions of AMPA-receptor subunit GluR1 (GluR1), synaptophysin (SYN), p-21-Activated kinase (PAK) phosphorylation, Rho kinase (ROCK), p-Cofilin, F-actin, and G-actin proteins were detected. Letrozole or ER antagonists inhibited the expression of GluR1, F-actin/G-actin, p-PAK and p-Cofilin proteins in prefrontal cells significantly. And the expressions of GluR1 and F-actin/G-actin proteins were declined in hippocampal cells markedly after adding letrozole or ERs antagonists. In conclusion, neural-derived E2 and ERs regulated the synaptic plasticity, possibly due to promoting actin polymerization in prefrontal and hippocampal cells. The regional specificity in the effect of neural-derived E2 and ERs on the actin polymerization-related pathway may provide a theoretical basis for the functional differences between the hippocampus and prefrontal cortex.


Complete mitochondrial genome and phylogenetic analysis of black-fin stream jewel goby Stiphodon percnopterygionus (Gobiiformes: Gobiidae) from Taiwan.
The complete mitochondrial genome of the black-fin stream jewel goby Stiphodon percnopterygionus has been amplified and sequenced. The whole mitochondrial genome is 16,502 base pairs (bp) in total length and consisting of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1 control region (CR). The overall base composition is 28.1% for A, 17.1% for G, 28.7% for C and 26.0% for T with AT comprising 54.1%. A phylogenetic tree was constructed using mitochondrial protein-coding genes (PCGs) sequence data for 34 related taxa of the order Gobiiformes showed that S. percnopterygionus is closely related to S. tuivi. These findings will contribute for phylogenetic, phylogeography and further genetic studies in genus Stiphodon and related gobiid fishes.


Green synthesis of nanosilver as a sensor for detection of hydrogen peroxide in water.
Present "green" synthesis is an efficient, easy-going, fast, renewable, inexpensive, eco-friendly and non-toxic approach for nanosilver formation, which offers numerous benefits over physiochemical approaches. The X-ray diffraction (XRD) pattern suggests the formation and crystallinity of nanosilver. The average particle size of silver nanoparticles was 8.25±1.37 nm as confirmed by transmission electron microscopy (TEM). The UV-vis absorption spectrum shows a characteristic absorption peak of silver nanoparticles at 410 nm. FTIR confirms Azadirachtin as reducing and stabilizing agent for nanosilver formation. In addition, the nanosilver modified electrode (Ag/GC) exhibited an excellent electro-catalytic activity toward the reduction of hydrogen peroxide (H(2)O(2)). The produced nanosilver is stable and comparable in size. These silver nanoparticles show potential applications in the field of sensors, catalysis, fuel cells and nanodevices.


A double-blind comparison of escitalopram and paroxetine in the long-term treatment of generalized anxiety disorder.
This study compared the efficacy and tolerability of escitalopram, a newer SSRI, with paroxetine in the treatment of generalized anxiety disorder (GAD). Patients with DSM-IV-defined GAD were randomized to receive 24 weeks of double-blind flexible-dose treatment with either escitalopram (10-20 mg/day) or paroxetine (20-50 mg/day), followed by a 2-week, double-blind, down-titration period. Mean change from baseline to endpoint (LOCF) in Hamilton Anxiety Scale (HAMA) scores was the primary efficacy variable. Mean baseline HAMA scores for the escitalopram (N = 60) and paroxetine (N = 61) groups were 23.7 and 23.4, respectively. After 24 weeks of treatment, mean changes in HAMA scores were -15.3 and -13.3 for escitalopram and paroxetine, respectively (p = 0.13). Significantly fewer patients withdrew from escitalopram than paroxetine treatment due to adverse events (6.6% vs. 22.6%; p = 0.02). The frequency of treatment-emergent adverse events was higher with paroxetine vs. escitalopram: overall (88.7% vs. 77.0%), insomnia (25.8% vs. 14.8%), constipation (14.5% vs. 1.6%), ejaculation disorder (30.0% vs. 14.8%), anorgasmia (26.2% vs. 5.9%), and decreased libido (22.6% vs. 4.9%). Conversely, diarrhea and upper respiratory tract infection were reported more with escitalopram than paroxetine (21.3% vs. 8.1%, and 14.8% vs. 4.8%, respectively). These results support the use of escitalopram as a first-line treatment for GAD.


Comparative effectiveness of multivessel coronary bypass surgery and multivessel percutaneous coronary intervention: a cohort study.
Randomized trials of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) suggest that patient characteristics modify the effect of treatment on mortality. To assess whether clinical characteristics modify the comparative effectiveness of CABG versus PCI in an unselected, general patient population. Observational treatment comparison using propensity score matching and Cox proportional hazards models. United States, 1992 to 2008. Medicare beneficiaries aged 66 years or older. Multivessel CABG or multivessel PCI. The CABG-PCI hazard ratio (HR) for all-cause mortality, with prespecified treatment-by-covariate interaction tests, and the absolute difference in life-years of survival in clinical subgroups after CABG or PCI, both over 5 years of follow-up. Among 105 156 propensity score-matched patients, CABG was associated with lower mortality than PCI (HR, 0.92 [95% CI, 0.90 to 0.95]; P < 0.001). Association of CABG with lower mortality was significantly greater (interaction P ≤ 0.002 for each) among patients with diabetes (HR, 0.88), a history of tobacco use (HR, 0.82), heart failure (HR, 0.84), and peripheral arterial disease (HR, 0.85). The overall predicted difference in survival between CABG and PCI treatment over 5 years was 0.053 life-years (range, -0.017 to 0.579 life-years). Patients with diabetes, heart failure, peripheral arterial disease, or tobacco use had the largest predicted differences in survival after CABG, whereas those with none of these factors had slightly better survival after PCI. Treatments were chosen by patients and physicians rather than being randomly assigned. Multivessel CABG is associated with lower long-term mortality than multivessel PCI in the community setting. This association is substantially modified by patient characteristics, with improvement in survival concentrated among patients with diabetes, tobacco use, heart failure, or peripheral arterial disease. National Heart, Lung, and Blood Institute.


Density dependence of Anaphes sordidatus (Hymenoptera: Mymaridae) parasitism on eggs of Listronotus oregonensis (Coleoptera: Curculionidae).
Listronotus oregonensis (LeConte) (Coleoptera: Curculionidae) oviposits in carrot leaves and the larvae feed in carrot roots. Its eggs are parasitized by Anaphes sordidatus (Girault) (Hymenoptera: Mymaridae) throughout its oviposition period. This parasitoid is the major biotic mortality factor for L. oregonensis. Parasitism by A. sordidatus was studied for three years in sequentially sown plots of carrots, Daucus carota var. sativa. Over the scason, significantly fewer L. oregonensis eggs were oviposited in later sown carrots than in earlier sown carrots because oviposition started later in late sown plots of carrots. A positive temporal density-dependent relationship was observed each year between parasitism rates and host densities. This positive density dependence occurred in early and mid-summer for earlysown carrots where host density reached 1-2 host eggs per plant but disappeared in late summer when host density decreased while parasitism remained high. Latesown carrots had low host egg density (0.2 host egg per plant) and contributed little to the total number of eggs. In these late sown plots, parasitism increased rapidly to over 80% but no density dependence was observed. Spatially, few statistically significant regressions were found but all indicated a positive spatial density-dependence. Most non-significant regressions occurred because the range of egg density was too small between plots for a given date.


Emergency femoral hemodialysis catheter placement complicated by prevesical hematoma.
The femoral vein is the most popular location for temporary catheterization during emergency hemodialysis. Common complications are infection, thrombosis, arterial puncture, and groin hematoma. We report herein a patient with femoral vein perforation and prevesical hematoma.


Marginal Effects in Multivariate Probit Models.
Estimation of marginal or partial effects of covariates x on various conditional parameters or functionals is often a main target of applied microeconometric analysis. In the specific context of probit models, estimation of partial effects involving outcome probabilities will often be of interest. Such estimation is straightforward in univariate models, and results covering the case of quadrant probability marginal effects in bivariate probit models for jointly distributed outcomes y have previously been described in the literature. This paper's goals are to extend Greene's results to encompass the general M≥2 multivariate probit (MVP) context for arbitrary orthant probabilities and to extended these results to models that condition on subvectors of y and to multivariate ordered probit data structures. It is suggested that such partial effects are broadly useful in situations wherein multivariate outcomes are of concern.


[Patterns of structural and functional changes in the retina and choroid in acute posterior multifocal placoid pigment epitheliopathy].
The study analyzes the patterns of pathological changes in the retina and choroid in acute posterior multifocal placoid pigmented epitheliopathy (APMPPE). The results of the examination of two patients with bilateral APMPPE were analyzed retrospectively. The examination had included visometry, tonometry, static perimetry, autofluorescence, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The analysis revealed signs of the inflammatory nature of the choriocapillary vascular wall lesion with the development of their local obstruction and, consequently, local ischemia of the retinal pigment epithelium (RPE) and the outer layers of the retina in the acute period. At the same time, partial destruction of the ellipsoid zone, uneven hyperreflectivity of the RPE with local areas of its elevation and impaired connection with photoreceptors were revealed. The subsequent restoration of choriocapillaris perfusion was accompanied by significant restoration of the functional and structural state of the RPE over a larger area, as well as partial restoration of the ellipsoid zone of the retina. Two years after the onset of the disease, separate areas of defects of the RPE and the outer retina were observed, coinciding in localization with zones of severe circulatory deficiency at the level of choriocapillaris in the acute stage. According to the results of multimodal imaging, choriocapillaritis is the initial link in the pathogenesis of APMPPE. The change in RPE and the outer retina is secondary to the local ischemic zones due to choriocapillaris nonperfusion. The nature of RPE change over a larger area manifests as a functional structural disorder, with the potential for recovery in case of choriocapillaris reperfusion.


Structure-activity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI.
Several 5,10-dihydroindeno[1,2-b]indole derivatives incorporating methoxy, hydroxyl, and halogen (F, Cl, and Br) moieties on the indene fragment of the molecule were prepared and tested against five carbonic anhydrase (CA, EC 188.8.131.52) isoforms. The inhibitory potencies of these compounds against the human (h) isoforms hCA I, II, IV, VI and bovine (b) isoform bCA III were assessed. Most of them exhibited low micromolar inhibition of these enzymes. K(I) values of these compounds against hCA I and hCA II were in the range of 2.14-16.32 μM, and 0.34-2.52 μM, respectively. Isozyme hCA IV was inhibited with K(I)-s in the range of 0.435-5.726 μM, while hCA VI with K(I)-s of 1.92-12.84 μM bCA III was inhibited with K(I)-s in the range of 2.13-17.83 μM. The structurally related compounds, 1,2-dimethoxybenzene, catechol and indole were also tested in order to understand the structure activity relationship. In silico docking studies of some derivatives within the active site of hCA I and II were also carried out in order to rationalize the inhibitory properties of these compounds and understand their inhibition mechanism.


Polyploidization of Epstein-Barr virus (EBV)-carrying lymphoma lines decreases the inducibility of EBV-determined early antigen following P3HR-1 virus superinfection or iododeoxyuridine treatment.
Four tetraploid cell lines were derived from the Epstein-Barr virus (EBV)-carrying, nonproducer Burkitt lymphoma line Raji after colcemide treatment. EBV early antigen (EA) was induced by P3HR-1 virus superinfection and by iododeoxyuridine treatment. Inducibility was reduced in all tetraploid lines compared to the near-diploid counterpart. The average number of EBV genome equivalents per tetraploid cell was 60-70, compared to 50 in diploid cells. This contrasts with the EBV genome amplification previously observed in somatic cell hybrids.


Breznakia blatticola gen. nov. sp. nov. and Breznakia pachnodae sp. nov., two fermenting bacteria isolated from insect guts, and emended description of the family Erysipelotrichaceae.
Two novel, obligately anaerobic Firmicutes from the family Erysipelotrichaceae were isolated from the intestinal tracts of a cockroach (strain ErySL, Shelfordella lateralis) and a scarab beetle larva (strain Pei061, Pachnoda ephippiata). Phylogenetic analysis indicated that the strains belong to a monophyletic group of hitherto uncultured bacteria from insect guts that are only distantly related to any described species (<90% 16S rRNA gene sequence similarity). Ultrastructural analysis revealed a Gram-positive cell envelope and, in the case of strain ErySL, a wide electron-lucent space between the cytoplasmic membrane and cell wall. In older cultures, cells formed pleomorphic rods with a thicker peptidoglycan layer. Both strains were obligately anaerobic and fermented glucose to formate, ethanol, and acetate as major products, but strain Pei061 tolerated up to 1% oxygen in the headspace. The same type of metabolism was observed with Erysipelothrix inopinata, except that the latter grew, albeit poorly, even under air. However, previous claims of a microaerophilic or facultatively anaerobic metabolism in the genus Erysipelothrix could not be substantiated. Based on phenotypic and phylogenetic evidence, we propose to classify the isolates as members of a new genus, Breznakia blatticola gen. nov. sp. nov. and Breznakia pachnodae sp. nov., with strain ErySL(T) (=DSM 28867(T)=JCM 30190(T)) and strain Pei061(T) (=DSM 16784(T)=JCM 30191(T)) as type strains, and provide an emended description of the family Erysipelotrichaceae.


Interatrial electrical connections: the precise location and preferential conduction.
The atria are assumed to be connected electrically to each other at the level of the Bachmann's bundle, coronary sinus (CS) musculature, and interatrial septum, and these connections may have an important role in the interatrial conduction and perpetuation of various types of atrial tachyarrhythmias. However, the number, location, and preferential connections of the interatrial conduction related to the site of activation have not been examined yet. The endocardium of both atria and the CS were mapped during continuous pacing from the left superior and inferior pulmonary veins, right pulmonary veins, upper and lower right atrium, or right atrial septum at various paced cycle lengths in 14 canines. The electrograms were recorded by custom-made form-fitted electrodes mounted on a specially designed device that allowed the septal aspects of the electrode forms to be spatially fixed to each other accurately. Four distinct interatrial electrical connections were identified at the Bachmann's bundle, CS, and antero-superior and postero-inferior septa. Decremental conduction was not seen in any of the connections. Bachmann's bundle was the most preferential connection during pacing from any epicardial site. The transseptal connections were evident only during pacing from the interatrial septum. The preference among the four connections was determined by the site of stimulation and the propagation of the activation related to the myocardial architecture. These unique preferential connections may play a significant role in the interatrial conduction and perpetuation of atrial tachyarrhythmias.


Differential expression of E-cadherin and cytokeratin 19 and net proliferative rate of gingival keratinocytes in oral epithelium in periodontal health and disease.
The effects of periodontal disease on the oral gingival epithelium (OGE) have not been documented fully because they may not be as dramatic as those seen on the junctional epithelium. The aim of this study was to estimate the changes occurring in the OGE with respect to its proliferation and E-cadherin and cytokeratin 19 (K19) expression during pocket formation. Gingival samples were collected from 17 periodontally healthy subjects and 18 subjects with chronic periodontitis. K19 and E-cadherin levels were analyzed immunohistochemically. The net proliferative rate was calculated as the difference between the proliferative rate and the apoptotic rate as determined by immunohistochemical analysis of Ki-67 and p53, respectively. There was a significant increase in the net proliferative rate of the OGE during pocket formation (periodontitis group, 220.90+/-46.85; healthy group, 107.60+/-25.86; P<0.001). There was a significant reduction in E-cadherin expression (periodontitis group, 0.837+/-0.428; healthy group, 1.846+/-0.555) and a significant increase in K19 expression during pocket formation (periodontitis group, 1.45+/-0.686; healthy group, 0.533+/-0.410). OGE appears to undergo significant changes in proliferation and differentiation during pocket formation that do not seem to be restricted to proteolytic destruction by the invading microorganisms.


Psychometric Evaluation of the Nursing Outcome "Pain: Adverse Psychological Response" in Patients With Chronic Pain.
To culturally adapt into Spanish and validate the outcome "Pain: Adverse psychological response" (code 1306) in patients with chronic pain. A three-stage study was conducted: (a) translation and cultural adaptation, (b) content validation, and (c) clinical validation. The Spanish version of the outcome "Pain: Adverse psychological response" has high content validity ( 0.91). Fourteen indicators were organized into two factors. This version offers good reliability in both inter-observer agreement (kappa = 0.72) and internal consistency (alpha = 0.89). The Spanish adaptation of "Pain: Adverse psychological response" is a reliable and valid instrument for the measurement of emotional aspects of chronic pain. The Spanish adaptation of this outcome offers nurses a set of structured indicators to measure the adverse emotional impact of chronic pain.


Computer assisted orthopedic surgery; its influence on prosthesis size in total knee replacement.
Improvement of alignment and position of the components in TKAs using Computer Assisted Orthopaedic Surgery (CAOS) has been described. However, much less is known about the accuracy of CAOS in determining the size of the components. The purpose of this study was to evaluate the size of the femoral and tibial component using the CAOS system from Brainlab. The component sizes were compared to pre-operative templating and post-operative scoring the adequateness of size. Forty TKAs (NexGen) were evaluated: 20 using CAOS and 20 conventional. Statistical analysis of the templated and implanted size indicated a fair agreement for the femur (kappa 0.38) and the tibia (kappa 0.35). In the CAOS group significantly more oversizing occurred for the femoral component (p=0.020). No significant difference was found for the tibial component. We conclude there is a risk of oversizing the femoral component of the NexGen system when using CAOS.


[The preclinical care of polytraumatized patients].
In industrially developed countries, trauma is the major mortality factor for people younger than 40 years. The preclinical management of polytraumatized patients influences the prognosis of mortality and morbidity. In this period, a number of decisions have to be made under unfavourable conditions and with limited time. This situation represents a great challenge for the whole rescue team. Diagnostic overview, protection of the vital functions under the special situation of shock, immobilization of the spine and the treatment of the isolated injuries are part of the preclinical management efforts. Rescue of the polytraumatized patient, organization and announcement of transfer and the protection of the rescue team have to be taken into account.


The role of ascorbate peroxidase, guaiacol peroxidase, and polysaccharides in cassava (Manihot esculenta Crantz) roots under postharvest physiological deterioration.
This study aimed to investigate the role of ascorbate peroxidase (APX), guaiacol peroxidase (GPX), polysaccharides, and protein contents associated with the early events of postharvest physiological deterioration (PPD) in cassava roots. Increases in APX and GPX activity, as well as total protein contents occurred from 3 to 5 days of storage and were correlated with the delay of PPD. Cassava samples stained with Periodic Acid-Schiff (PAS) highlighted the presence of starch and cellulose. Degradation of starch granules during PPD was also detected. Slight metachromatic reaction with toluidine blue is indicative of increasing of acidic polysaccharides and may play an important role in PPD delay. Principal component analysis (PCA) classified samples according to their levels of enzymatic activity based on the decision tree model which showed GPX and total protein amounts to be correlated with PPD. The Oriental (ORI) cultivar was more susceptible to PPD.


Prolactin measurement during inferior petrosal sinus sampling improves the localization of pituitary adenomas in Cushing's disease.
Inferior petrosal sinus sampling (IPSS) distinguishes pituitary-dependent Cushing's disease (CD) from ectopic ACTH syndrome with a high degree of certainty, but has not been reliable in predicting the location of an adenoma within the pituitary gland. We investigated whether prolactin measurements during IPSS would improve pituitary tumour localization. Fifty-four patients with suspected ACTH-dependent Cushing's syndrome who underwent IPSS between 1997 and 2009 were studied retrospectively. Twenty-eight patients who had an identifiable tumour that stained for ACTH on histopathology are the subject of this study. Intersinus ACTH gradients before and after adjustment for prolactin were compared with surgical findings and pathology. Magnetic resonance imaging localized a pituitary adenoma in 17/28 (61%) patients. Using a maximum intersinus ACTH gradient of ≥1·4 before or after CRH stimulation, we could diagnose the tumour location correctly in 15/28 (54%) patients. By comparison, tumour lateralization by means of a dominant (≥1·4) prolactin-adjusted ACTH intersinus gradient was correct in 21/28 (75%) patients (P = 0·041). Tumour localization was correct in 23/28 (82%) patients when MRI and prolactin-adjusted ratio data were combined. Fourteen patients with proper bilateral IPS venous sampling (as determined by concurrent IPS to peripheral prolactin ratio ≥1·8) either had correct localization of the tumour (n = 12) or had a central lesion (n = 2). In none of these 14 patients was the dominant prolactin-adjusted ACTH ratio associated with a tumour on the opposite side of the gland. Prolactin measurement, during IPSS, improves our ability to correctly localize the pituitary adenoma site in CD.


Evaluating the tolerance and efficacy of laser-assisted delivery of tranexamic acid, niacinamide, and kojic acid for melasma: A single center, prospective, split-face trial.
Although many treatment options are available, the treatment of melasma remains challenging. To investigate the efficacy and safety of combined treatment for melasma with a quality (Q)-switched 1064-nm neodymium: yttrium-aluminum-garnet (Nd:YAG) laser and a topical mixture of tranexamic acid, niacinamide, and kojic acid. Twenty-five patients with melasma were enrolled. One side of the face was treated with low-fluence Q-switched 1064-nm Nd:YAG laser alone, while the other side was treated with a combination of laser treatment and a topical mixture of tranexamic acid, niacinamide, and kojic acid. Each treatment consisted of five sessions at 2-week intervals, and patients were followed up 4 weeks after the last treatment. Overall improvement was assessed using the hemi Melasma Area and Severity Index (MASI) score. A specialized imaging system (Markview®, PSIPLAUS Inc., Suwon, Korea) was used to record images of the patients' faces, and photographic assessment was performed by two independent evaluators at 2, 4, 6, 8, and 12 weeks using a five-point grading scale. Although both sides of the face showed clinical improvement, combination treatment demonstrated a greater improvement in the mean hemi MASI score compared to laser treatment alone. Improvement in melasma at 12 weeks, according to the evaluation of patient images by two independent evaluators, was greater with combination treatment. This study demonstrated that the combination of treatment with a low-fluence Q-switched 1064-nm Nd:YAG laser and a topical mixture of tranexamic acid, niacinamide, and kojic acid would be a good option for melasma treatment.


Multiplying insights from perturbation experiments: predicting new perturbation combinations.
Experimentally exploring the effect of all perturbation combinations is not feasible. In their recent study, Theis and colleagues (Lotfollahi et al, 2023) present an approach that uses deep generative models to predict the effects of new perturbations from high-throughput single perturbation experiments.


Depression, help-seeking perceptions, and perceived family functioning among Spanish-Dominant Hispanics and Non-Hispanic Whites.
Guided by Beck's (1967) cognitive theory of depression, we assessed whether perceived family functioning (PFF) mediated the relationship between depressive symptomatology and help-seeking inclinations. Study 1 included 130 Spanish-Dominant Hispanics and Study 2 included 124 Non-Hispanic Whites obtained using online crowd sourcing. Participants completed measures of depressive symptomatology, PFF, and several scales measuring aspects of help seeking inclinations and self-stigma. Study 2 also included an experiment. With an eye toward potential future interventions, we assessed the malleability of PFF. Specifically, participants were randomly assigned to recall positive or negative family experiences and then PFF was measures for a second time. Both studies found PFF mediates the relationship between depressive symptomatology and the help seeking scales. Among non-depressed people, the positive manipulation improved PFF; however, among participants with elevated depressive symptomatology, writing about a positive family experience worsened PFF. With the exception of the experiment, most of the data were cross-sectional. For the experiment, it is possible that different manipulations or primes could have different effects. Whether investigating responses from Spanish-Dominant Hispanics or Non-Hispanic Whites, PFF mediates the negative relationship between heightened depressive symptomatology and familial help-seeking beliefs, as well as self-stigma. However, even though the mediation analysis offers preliminary support that increasing PFF can potentially increase help-seeking behaviors of Hispanic and Non-Hispanic White people with depression, the results of the interaction analysis, specifically the negative impact of writing about positive family memories on people with elevated depression, illustrates the challenges of persuading people with depression.


A novel single-base mutation in CaBRI1 confers dwarf phenotype and brassinosteroid accumulation in pepper.
Dwarfing is the development trend of pepper breeding. It is of great practical and scientific value to generate new dwarf germplasms, and identify new genes or alleles conferring dwarf traits in pepper. In our previous study, a weakly BR-insensitive dwarf mutant, E29, was obtained by EMS mutagenesis of the pepper inbred line 6421. It can be used as a good parent material for breeding new dwarf varieties. Here, we found that this dwarf phenotype was controlled by a single recessive gene. Whole-genome resequencing, dCAPs analysis, and VIGs validation revealed that this mutation was caused by a nonsynonymous single-nucleotide mutation (C to T) in CaBRI1. An enzyme activity assay, transcriptome sequencing, and BL content determination further revealed that an amino-acid change (Pro1157Ser) in the serine/threonine protein kinase and catalytic (S_TKc) domain of CaBRI1 impaired its kinase activity and caused the transcript levels of two important genes (CaDWF4 and CaROT3) participating in BR biosynthesis to increase dramatically in the E29 mutant, accompanied by significantly increased accumulation of brassinolide (BL). Therefore, we concluded that the novel single-base mutation in CaBRI1 conferred the dwarf phenotype and resulted in brassinosteroid (BR) accumulation in pepper. This study provides a new allelic variant of the height-regulating gene CaBRI1 that has theoretical and practical values for the breeding of the plants suitable for the facility cultivation and mechanized harvesting of pepper varieties.


Pentoxifylline to treat radiation proctitis: a small and inconclusive randomised trial.
This prospective randomised controlled study of 40 patients could not show a statistically significant advantage with 6 months of pentoxifylline compared with standard measures for late radiation-induced rectal bleeding. However, a modest benefit cannot be excluded and larger randomised placebo-controlled trials with longer durations of pentoxifylline treatment may be justified.


Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island.
Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex. We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (β = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28). Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.


[BAK/KBV/AWMF curriculum "Quality assurance--medical quality management": concept of goal-oriented conversion to general practice applications].
Since 1996, the curriculum "Quality management for physicians" exists with a three-level training concept. Based on these contents, a purposeful course program has been developed by the ZQ, and through May 1998 four level I-, four level II- and four level III-courses have been performed in Hannover. Thus, 50 physicians are qualified for new professional roles as hospital quality managers. The evaluation of a standardized questionnaire shows that the concept is highly accepted--meanwhile also by other professionals in health care. As a new model of quality assurance/quality evaluation is now developed for German hospitals, the contents of the training program will be updated for actual needs.


Cardiac MRI e-prime predicts myocardial late gadolinium enhancement and diastolic dysfunction in hypertrophic cardiomyopathy.
Myocardial fibrosis leads to diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). To evaluate a manual method of measuring mitral annular relaxation velocity (termed cardiac MRI e') as a measure of diastolic dysfunction on routine cardiac MRI and its relationship with myocardial late-gadolinium enhancement (LGE) and feature tracking measures of diastolic dysfunction in patients with HCM. CMR e', feature tracking measures of diastolic function, left atrial, left ventricular (LV) parameters and LGE were retrospectively measured in 75 patients with HCM (mean age, 54.7 years ± 15.3, 54 men). Multivariate regression and partial Spearman correlations were performed. Cardiac MRI e' measures correlated with LGE (r = 0.49, P < 0.001) and multiple feature tracking measures of diastolic function, adjusted for patient demographics, left atrial and left ventricular parameters. Cardiac MRI e' measures were independently predictive of LGE ≥ 10% (mean total cardiac MRI e': LGE < 10% vs LGE ≥ 10% was 3.5 cm/s vs. 1.7 cm/s, P < 0.001). Superior CMR e' had an AUC of 0.79 [95%CI 0.66-0.92, P < 0.0001]) in predicting patients with LGE ≥ 10% and a cutoff of 1.7 cm/s resulted in a sensitivity and specificity of 81.0% and 78.0% respectively. Cardiac MRI e' is a manual measure of LV diastolic dysfunction acquired on routine cardiac MRI without specialized software and is an independent predictor of LGE ≥ 10% and diastolic dysfunction in HCM.


Template-Independent Poly(A)-Tail Decay and RNASEL as Potential Cellular Biomarkers for Prostate Cancer Development.
The post-transcriptional messenger RNA (mRNA) decay and turnover rate of the template-independent poly(A) tail, localized at the 3'-untranslated region (3'UTR) of mRNA, have been documented among subtle mechanisms of uncontrolled cancer tissue growth. The activity of Poly(A) deadenylase and the expression pattern of RNASEL have been examined. A total of 138 prostate tissue specimens from 46 PC patients (cancer specimens, corresponding adjacent surgically healthy tissues, and in their normal counterparts, at least 2 cm from carcinoma) were used. For the stratification prediction of healthy tissue transition into malignant phenotype, the enzyme activity of tumor-adjacent tissue was considered in relation to the presence of microfocal carcinoma. More than a four-times increase in specific enzyme activity (U/L g.prot) was registered in PC on account of both the dissociation of its inhibitor and genome reprogramming. The obtained ROC curve and Youden index showed that Poly(A) deadenylase identified PC with a sensitivity of 93.5% and a specificity of 94.6%. The RNASEL expression profile was raised significantly in PC, but the sensitivity was 40.5% and specificity was 86.9%. A significantly negative correlation between PC and control tissue counterparts with a higher expression pattern in lymphocyte-infiltrated samples were reported. In conclusion, significantly upregulated Poly(A) deadenylase activity may be a checkpoint for the transition of precancerous lesion to malignancy, while RNASEL may predict chronic inflammation.


Spermatic vein ligation in varicocele: prognosis and associated male and female infertility factors.
The fertility outcome of 129 spermatic vein ligations with good postoperative anatomic results is analyzed. For each couple, specific attention was also directed to other infertility factors. The study analyzes four groups: group I, 55 patients with varicocele only; group II, 16 patients with varicocele and prostatovesiculitis; group III, 16 patients with varicocele and a severe degree of testicular failure; and group IV, 42 patients with a varicocele only and associated female infertility factors. In each group, the pregnancy rate within 6 to 24 months after the operation was recorded. The control subjects were 36 patients with varicocele only who had declined or postponed intervention for 6 months. The best results were obtained in group I. Sperm motility improved following ligation and was associated with a greater percentage of pregnancies within a shorter period: 51% and 62% within 6 and 12 months, respectively, as compared with the control group (14% within 6 months). The prostatic disease required additional treatment for a longer period, but results similar to those of group I were eventually obtained (50% pregnancy rate). With testicular failure or female infertility factors, the prognosis worsened (31% overall pregnancy rate).


Sexual and gender minority adverse childhood experiences (SGM-ACEs), perceived social support, and adult mental health.
Building on decades of research into the long-term developmental impacts of adverse childhood experiences (ACEs), researchers have called for expanding the ACEs framework to include experiences specific to minoritized identities. Recent empirical research has led to the development of a measure of sexual and gender minority adverse childhood experiences (SGM-ACEs). Within the SGM-specific ACEs framework, research on the long-term impact to adult mental health and the role of perceived social support are not well studied. The purpose of this paper was two-fold. First, examine whether SGM-ACEs adversely impact mental health in SGM adults. Second, examine the role of perceived social support in the association between SGM-ACEs and adult mental health. Data were collected using a multifaceted sampling strategy. In total, 1819 self-identified SGM Texans completed an online survey inquiring about ACEs, SGM-ACEs, mental health, and demographic characteristics. We estimated two competing structural equation models (SEM) examining the associations between SGM-ACEs and anxiety and depressive symptoms, and whether perceived social support may moderate or mediate his association. While both models demonstrated that SGM-ACEs were significantly associated with higher anxiety and depressive symptoms. However, we found more support for the mediation model such that SGM-ACEs had direct effects on anxiety and depressive symptoms, and an indirect effect on anxiety symptoms through family support. Our findings confirmed that exposure to SGM-ACE is associated with poorer adult mental health. Additionally, SGM-ACEs exposure undermines SGM individuals' perceptions of family support, which increases symptoms of anxiety.


da Vinci® single-site platform: anthropometrical, docking and suturing considerations for hysterectomy in the cadaver model.
The paper describes specific technical requirements, limitations, anthropometrical, docking and suturing considerations on the performance of robotic hysterectomy using the da Vinci® Single-Site Platform in the cadaver model A data set was collected for each procedure including port placement, docking sequence, robotic arms placement and angles, robotic instrumentation, optimal ergonomics, operative time, and cadaver anthropometrical measurements. Pearson correlation coefficients were calculated to determine whether age, BMI or docking approach were correlated with docking difficulty and likelihood of successful procedure completion. Analysis of the data was performed using SPSS v19.0.0. The planned surgical procedure was successfully completed with single-port robotics in 87.5% of cases. High BMI was correlated with difficulty docking the robot, correlation coefficient 0.98. Further work is needed in the development and advancement of single-site robotic platforms, articulated instrumentation, and optics.


Adverse events reported after first dose of SARS-CoV-2 vaccine in the Northern Region of Ghana.
The study examined the associated adverse events following SARS-CoV-2 vaccination among healthcare workers during the first dose of the vaccine in the Northern Region of Ghana. The study was a cross-sectional survey involving 463 healthcare workers. The data were collected using a structured questionnaire. The data were analysed descriptively, and binary logistics was performed using SPSS version 25. The mean age was 33.4 ± 9.7 years, the majority (43.6%) being ≤30 years and males (57.2%). The self-reported prevalence of SARS-CoV-2 vaccine adverse events was 75.5%. Common systemic adverse events comprised headache (47.5%), dizziness (18.4%) and local adverse events included generalized body pains (44.0%) and abscess around the injection sites (11.2%). The study found a high prevalence of self-reported SARS-CoV-2 vaccine adverse events involving both systemic and local adverse events. Our study gives useful information that can be used for public health-targeted interventions to boost public confidence in SARS-CoV-2 vaccines.


Increased activity of monoamine oxidase by epoxy resin hardeners.
In order to investigate the potency of amines to cause metabolic changes which are related to scleroderma, serum monoamine oxidase (MAO) activity to workers in an epoxy resin handling process was measured. Mean serum MAO activity of 15 workers exposed to amine was 33.5 +/- 6.4 units, whilst that of control workers was 28.9 +/- 7.8 (P less than 0.05). The finding was confirmed in an in vitro experiment. After 24 h treatment with amine, the MAO activity of cultured skin fibroblasts was elevated in a dose-response manner. These results suggested the potency of amine to produce an increase in MAO activity, and this phenomenon seems to be related to the cases of occupational scleroderma-like disorder which were observed in an epoxy resin polymerizing process.


A novel mutation of anti-Mullerian hormone gene in Persistent Mullerian Duct Syndrome presented with bilateral cryptorchidism: a case report.
We report a novel mutation in a case of Persistent Mullerian Duct Syndrome (PMDS). PMDS is characterized by the persistence of female reproductive organs derivatives in a 46,XY subject due to the failure of the Mullerian duct to regress in utero. To date, 53 different mutations of the anti-Mullerian hormone (AMH) gene, including the present one, have been identified. A 2-week-old male presented with bilateral cryptorchidism and normal male external genitalia. His karyotype was 46,XY. hCG stimulation test was normal. At age 1 year and 4 months, he underwent laparoscopic surgery which revealed a uterus and fallopian tubes. The anti-Mullerian hormone (AMH) level was undetectable (<0.01 ng/mL). Diagnosis of Persistent Mullerian Duct Syndrome, probably due to an AMH mutation, was made. A unique homozygous T to G base substitution was found at position 2219, near the middle of the exon 5, changing codon CTG to CGG in anti-Mullerian hormone (AMH) gene. This mutation causes leucine to be converted to arginine at position 426 belonging to a (L)RA(L)LLLKALQ highly conserved sequence in the AMH gene. Both parents are heterozygous for the mutation. Persistent Mullerian Duct Syndrome (PMDS) is a rare cause of bilateral cryptorchidism, when in doubt the existence of Mullerian derivatives should be explored by laparoscopy. Assay of serum AMH helps to distinguish between mutations of AMH and AMH receptor. If serum AMH is very low or undetectable, sequencing of the AMH gene usually confirms the presence of a mutation.


Neurologic disturbances in Paget disease of bone: response to calcitonin.
The neurologic manifestations of Paget disease and the therapeutic effect of calcitonin were studied in 49 patients. Twenty-four patients (49%) had neurologic disorders involving cranial nerves other than the auditory system, brainstem, spinal cord, or spinal roots and nerves. Eighteen of the 24 patients (75%) showed significant subjective or objective improvement after calcitonin treatment. The effect of calcitonin treatment on spinal cord compression was dramatic in three of six patients. The observations made of these patients support previous data suggesting that the neurologic signs and symptoms of Paget disease have their pathogenesis in both mechanical impingement and vascular distortion. The importance of early detection of neurologic signs and symptoms is emphasized, since prompt treatment with calcitonin may prevent severe complications.


Intracerebroventricular infusion of CRF increases extracellular concentrations of norepinephrine in the hippocampus and cortex as determined by in vivo voltammetry.
Previous studies have indicated that intracerebroventricular (i.c.v.) infusions of corticotropin-releasing factor (CRF) activate locus coeruleus (LC) noradrenergic neurons and increase the metabolism and extracellular concentrations of norepinephrine (NE) in several brain regions, suggesting increased release. To examine the temporal aspects and mechanism of the presumed release of NE, CRF was infused i.c.v. and the oxidation current was recorded using carbon fiber voltammetric electrodes placed in rat hippocampus or cortex. The CRF (1 microg, i.c.v.) caused a significant increase of oxidation current with a delay of approximately 5 min, and a peak at approximately 35 min. Similar responses were observed in the medial prefrontal cortex. The hippocampal response was markedly attenuated when CRF was infused into rats pretreated with DSP-4 to deplete NE, suggesting that the observed changes in current resulted from oxidation of NE. The increase of NE-like current did not occur when 25 microg alpha-helical CRF9-41 (ahCRF) was injected immediately before 1 microg CRF, suggesting that the response was mediated by cerebral CRF-receptors. Subcutaneous pretreatment with the ganglionic blocker, chlorisondamine, at a dose of 3 mg/kg had no effect on the voltammetric response to CRF, but a 6 mg/kg dose completely prevented the response. The beta-adrenoceptor antagonists, S-propranolol (5 mg/kg), nadolol (5 and 10 mg/kg), and timolol (5 mg/kg) attenuated the NE response to i.c.v. CRF to varying degrees. When chlorisondamine (3 microg) or nadolol (5 microg) were given i.c.v. before the CRF, the hippocampal responses were not blocked. These results suggest peripheral actions of ganglionic and beta-adrenergic blockers. We conclude that peripheral autonomic mechanisms, and probably both central and peripheral beta-adrenoceptors, contribute to the increased secretion of hippocampal NE in response to i.c.v. CRF.


Overexpression of transcription factor SlWRKY28 improved the tolerance of Populus davidiana × P. bolleana to alkaline salt stress.
WRKY transcription factors (TFs) have been suggested to play crucial roles in the response to biotic and abiotic stresses. This study is the first to report the alkaline salt regulation of the WRKY gene. In this study, we cloned a WRKY gene (SlWRKY28) from the Salix linearistipularis and then transferred to the Populus davidiana × P. bolleana for expression. Sequence analysis on the transcriptome of Salix linearistipular showed the significant up-regulation of WRKY gene expression in response to salt-alkali stress in seedlings. Our data showed that SlWRKY28 localized to the nucleus. Furthermore, the expression of the SlWRKY28 from female plants increased with saline-alkali stress according to the northern blot analysis results. The results of 3,3'-Diaminobenzidine (DAB) staining showed that hydrogen peroxide (H2O2) concentration was lower under stress, but ascorbate peroxidase (APX) enzyme activity was significantly higher in the overexpressed plants than that in non-transgenic (NT) plants. We found out the SlWRKY28 induced regulation of the enzyme gene in the reactive oxygen species (ROS) scavenging pathway is a potential mechanism for transgenic lines to improve their resistance to alkaline salt. This study shows theoretical and practical significance in determining SlWRKY28 transcription factors involved in the regulation of alkaline salt tolerance.


Treatment of myelodysplastic syndrome with a DNA methyltransferase inhibitor: lack of evidence for induction of chromosomal instability.
In several large phase II trials, low-dose treatment with the azanucleoside 5-aza-2'-deoxycytidine (decitabine, DAC) resulted in complete hematologic and cytogenetic responses in 23 and 31% of MDS patients, respectively. The question of induction of chromosomal instability by this demethylating agent was addressed by serial karyotypic analyses. 53/122 DAC-treated patients had all normal metaphases at time of treatment start. In 46/53 patients, sequential cytogenetic analyses were performed. 9/46 patients (20%) acquired clonal chromosomal abnormalities during follow-up (4/9 transient). 8/9 abnormalities were gains or losses of entire chromosomes. The rate and pattern of cytogenetic evolution are thus not higher than in historical MDS cohorts not receiving specific treatment.


FT-IR studies on interactions among components in hexanoyl chitosan-based polymer electrolytes.
Fourier transform infrared (FT-IR) spectroscopic studies have been undertaken to investigate the interactions among components in a system of hexanoyl chitosan-lithium trifluoromethanesulfonate (LiCF(3)SO(3))-diethyl carbonate (DEC)/ethylene carbonate (EC). LiCF(3)SO(3) interacts with the hexanoyl chitosan to form a hexanoyl chitosan-salt complex that results in the shifting of the N(COR)(2), CONHR and OCOR bands to lower wavenumbers. Interactions between EC and DEC with LiCF(3)SO(3) has been noted and discussed. Evidence of interaction between EC and DEC has been obtained experimentally. Studies on polymer-plasticizer spectra suggested that there is no interaction between the polymer host and plasticizers. Competition between plasticizer and polymer on associating with Li(+) ions was observed from the spectral data for gel polymer electrolytes. The obtained spectroscopic data has been correlated with the conductivity performance of hexanoyl chitosan-based polymer electrolytes.


Autometallographic detection of mercury in testicular tissue of an infertile man exposed to mercury vapor.
A 25-year-old male patient presented with unexplained infertility. Semen analysis showed azoospermia or severe oligoasthenoteratospermia with elevated serum FSH. The history revealed that he had been employed in a chemical factory for 5 years working with chloralkali-electrophoresis. Mercury concentrations in hair, blood, and urine samples were considerably above levels of unexposed controls. Bilateral testicular biopsies revealed marked interstitial lymphatic infiltration. About 33% of the tubules analyzed showed a Sertoli-cell-only (SCO) syndrome and tubular atrophy. Fewer than 4% of tubules showed qualitatively intact spermatogenesis. Autometallographic (AMG) analysis of the biopsy material yielded silver-enhanced mercury grains, primarily in the interstitial Leydig cells. Sections from a control patient not exposed to mercury were devoid of mercury grains.


Effects of sodium thiosulfate (Na2S2O3) during resuscitation from hemorrhagic shock in swine with preexisting atherosclerosis.
Controversial data are available on hydrogen sulfide (H2S) during hemorrhage and resuscitation, depending on timing, dosing, mode of application, and the H2S donor used. Sodium thiosulfate (Na2S2O3) is a recognized drug devoid of major side effects, which attenuated murine acute lung injury and cerebral ischemia/reperfusion injury. Therefore, we tested the hypothesis whether Na2S2O3 would mitigate organ dysfunction in porcine hemorrhage-and-resuscitation. We studied animals with pre-existing coronary artery disease because of the reduced coronary arterial expression of the H2S producing enzyme cystathionine-γ-lyase (CSE) in this prospective, randomized, controlled, blinded experimental study. 20 anesthetized and instrumented pigs underwent 3 h of hemorrhage (removal of 30 % of the blood volume and subsequent titration of mean arterial pressure to 40 mmHg). Resuscitation (72 h) comprised re-transfusion of shed blood, crystalloids, and continuous i.v. norepinephrine. Animals randomly received vehicle or Na2S2O3 (0.1 g·kg-1 h-1) for 24 h. Before, at the end of and every 24 h after shock, hemodynamics, metabolism, blood gases, lung, heart, kidney, and liver function and injury were evaluated together with cytokines and parameters of oxidative and nitrosative stress. Immediate post mortem lung, kidney, heart, and liver specimen were analyzed for marker proteins of inflammation and oxidative and nitrosative stress and mitochondrial respiratory activity in the heart, kidney, and liver. Immuno-histochemical analysis comprised lung extra-vascular albumin accumulation, nitrotyrosine formation, and CSE and glucocorticoid receptor (GCR) expression. Na2S2O3 significantly attenuated shock-induced impairment of lung mechanics and gas exchange (plateau and positive end-expiratory pressure at 72 h p = 0.0006/p = 0.0264; Horovitz index at 48 h p = 0.0261), which coincided with a higher tissue GCR expression (p = 0.0415). During resuscitation from hemorrhagic shock Na2S2O3 attenuated shock-induced acute lung injury in co-morbid swine, most likely due to a GCR expression related mechanism.


Power Transformers OLTC Condition Monitoring Based on Feature Extraction from Vibro-Acoustic Signals: Main Peaks and Euclidean Distance.
The detection of On-Load Tap-Changer (OLTC) faults at an early stage plays a significant role in the maintenance of power transformers, which is the most strategic component of the power network substations. Among the OLTC fault detection methods, vibro-acoustic signal analysis is known as a performant approach with the ability to detect many faults of different types. Extracting the characteristic features from the measured vibro-acoustic signal envelopes is a promising approach to precisely diagnose OLTC faults. The present research work is focused on developing a methodology to detect, locate, and track changes in on-line monitored vibro-acoustic signal envelopes based on the main peaks extraction and Euclidean distance analysis. OLTC monitoring systems have been installed on power transformers in services which allowed the recording of a rich dataset of vibro-acoustic signal envelopes in real time. The proposed approach was applied on six different datasets and a detailed analysis is reported. The results demonstrate the capability of the proposed approach in recognizing, following, and localizing the faults that cause changes in the vibro-acoustic signal envelopes over time.


Plasma levels of adiponectin and soluble thrombomodulin in hypothyroid patients with normal thyroid function following levothyroxine replacement therapy.
Hypothyroidism is associated with increased morbidity from cardiovascular disease, and adiponectin (ApN) is a newly-identified adipocytokine, which is expressed in human adipose cells and may have a protective effect against the development of coronary artery disease. The aim of the study was to evaluate the involvement of ApN secretion in hypothyroid patients with normal thyroid function following levothyroxine (L-T(4)) replacement therapy, and to associate plasma ApN levels with intima-media thickness (IMT) in the common carotid artery (CCA), an indicator of early atherosclerosis, and cardiovascular parameters including soluble thrombomodulin (sTM), a plasma endothelial injury marker. The CCA IMT and plasma levels of ApN and sTM were measured in 52 hypothyroid patients and in age-, sex- and body mass index (BMI)-matched normal control subjects. Thirty-six of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T(4) replacement therapy. Although the basal CCA IMT was significantly higher in hypothyroid patients [0.633 +/- 0.018 mm (mean +/- S.E.)] than in control subjects (0.552 +/- 0.022 mm, P < 0.005), both groups had similar baseline ApN and sTM levels [10.23 +/- 0.76 vs. 10.10 +/- 0.93 microg/ml: NS; and 2.58 +/- 0.14 vs. 2.68 +/- 0.20 ng/ml: NS, respectively]. Simple regression analysis revealed that plasma ApN was significantly correlated in a positive manner with age (r = 0.339, P = 0.015), HDL-cholesterol (r = 0.295, P = 0.048), and sTM (r = 0.490, P = 0.0005), but not with CCA IMT (r = 0.059, P = 0.742). In multivariate analysis, the plasma ApN level was significantly associated with that of sTM (r = 0.546, P = 0.0001) and with serum high-density lipoprotein (HDL)-cholesterol levels (r = 0.291, P = 0.029) in hypothyroid patients. During 1 year of L-T(4) replacement therapy, hypothyroid patients showed a significant decrease in CCA IMT, to 0.553 +/- 0.016 mm (P < 0.0001), a level comparable to normal controls, but no significant change in ApN (from 10.79 +/- 1.07 to 10.6 9+/- 1.14 microg/ml, NS) or sTM (from 2.59 +/- 0.15 to 2.74 +/- 0.18 ng/ml, NS). Hence, we provide evidence that ApN and sTM might not contribute to enhanced atherosclerosis, as reflected by increased CCA IMT in hypothyroid patients. However, this is the first report to demonstrate a positive and significant association of sTM with ApN. These data support the hypothesis that sTM is one of the determinant of ApN and thus suggest the presence of an sTM-associated regulatory mechanism for ApN secretion in hypothyroid patients.


Higher versus lower blood pressure targets after cardiac arrest: A meta-analysis of randomized controlled trials.
A few mostly underpowered randomized controlled trials (RCTs) have been used to study the impact of blood pressure (BP) targets in out-of-hospital cardiac arrest (OHCA) patients. We aimed to perform an updated meta-analysis to compare the outcomes between the higher BP target and the lower BP target groups following OHCA. A systematic search was conducted on PubMed, Embase and the Cochrane Library until December 2022. We pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) using RevMan 5.4. Our search yielded four RCTs with a total of 1114 patients. Regarding our primary outcome of all-cause mortality, there was no significant difference between higher versus lower BP target goals in post-OHCA patients (OR 1.12, 95% CI: 0.86 to 1.45). Furthermore, there were no significant differences between the two groups in good neurological outcome, the incidence of arrhythmia, need for renal replacement therapy, and the levels of neuron-specific enolase at 48 h. The length of ICU stay of patients treated with the higher BP target was significantly lower but by a small margin. These findings do not support the use of a higher BP target but are subject to confirmation by large-scale RCTs investigating homogenous BP goals.