Increases in collagen type IV and laminin in galactose-induced retinal capillary basement membrane thickening--prevention by an aldose reductase inhibitor.
Biochemical alterations in the composition of retinal capillary basement membrane components were investigated in galactosemic rats, an animal model that develops basement membrane lesions comparable to those of diabetic retinopathy. Normotensive Wistar-Kyoto rats fed a 30% galactose diet for 9 months developed significant thickening of retinal capillary basement membranes by comparison with animals fed a control test diet (P less than 0.001), or animals on a diet containing 30% galactose and 250 mg kg-1 of the aldose reductase inhibitor sorbinil (P less than 0.001). A quantitative electron microscopic immunogold technique applied on ultrathin sections of the retinas of these animals showed that the labeling densities of collagen type IV and laminin per unit cross-sectional area (which is presumably proportional to the concentrations of these molecules) were significantly increased in the retinal capillary basement membranes of galactose-fed rats, compared with animals on the control test diet. Increases in these two components of basement membranes were prevented by addition of sorbinil to the diet. However, there was no significant change in the labeling density of heparan sulfate proteoglycan (HSPG) core protein in the basement membranes of galactose-fed rats in comparison to animals on either the control diet or galactose-sorbinil diet. Two types of striated fibrillar materials were frequently found in areas of focal thickening of basement membranes of galactose fed rats only. Thinner fibrils reacted strongly with collagen type III antibody, whereas thicker fibrils reacted weakly with collagen type I antibody. Our results indicate that there is an increase in labeling densities of collagen type IV and laminin in thickened basement membranes of retinal capillaries of galactosemic rats along with the expression of interstitial collagens like collagen type III and an abnormal collagen that weakly cross-reacts with antibody to collagen type I, and these effects of galactosemia on the basement membranes are preventable by an aldose reductase inhibitor.


Rhodium-catalyzed enantioselective hydrogenation of beta-phthalimide acrylates to synthesis of beta2-amino acids.
[Structure: see text] The enantioselective hydrogenation of beta-phthalimide acrylates provides the corresponding chiral beta2-amino acids in excellent enantiomeric excess catalyzed by Rh-monophosphorus.


Interobserver agreement of EUS elastography in the evaluation of solid pancreatic lesions.
Previous reports assessing the reproducibility of endoscopic ultrasound elastography (EUS-E) in evaluation of solid pancreatic lesions (SPL) involved only experienced endosonographers. We aimed to assess the interobserver agreement (IOA) of EUS-E in the evaluation of SPL by endoscopists with different levels of experience in EUS and EUS-E. A cross-sectional observational multicenter study was designed and included 11 endoscopists who were divided into four groups: Group A (long experience in EUS and EUS-E); Group B (short experience in EUS and EUS-E); Group C (long experience in EUS and no experience in EUS-E); and Group D (no experience in EUS or EUS-E). The observers independently classified the patterns of 60 video sequences of EUS-E, after a 20-min training session. For each group, we calculated IOA (kappa statistic, k) of EUS-E and the diagnostic accuracy of EUS-E for pancreatic malignancy, by comparing the pattern of EUS-E indicative of malignancy (heterogeneous or homogenous blue) with the final diagnosis. The overall IOA was moderate (k = 0.42; 95% confidence interval (CI) 0.33-0.52). The IOA of Group A (k = 0.80; 95% CI 0.65-1.00) was significantly higher than that of Groups B (k = 0.54; 95%CI 0.40-0.71), C (k = 0.54; 95%CI 0.39-0.68), and D (k = 0.28; 95%CI 0.14-0.40). IOA of Groups B and C was not significantly different, but it was significantly higher than that of Group D. The diagnostic accuracy of Group A (area under the curve under summary receiver operating characteristic (AUROC) = 0.83; 95%CI 0.75-0.90) was not significantly different from that of Group B (AUROC = 0.77; 95%CI 0.71-0.83), but it was significantly higher than that of Groups C (AUROC = 0.74; 95%CI 0.67-0.81) and D (AUROC = 0.74; 95%CI 0.67-0.81). No significant difference was seen between Groups B, C, and D for diagnostic accuracy. EUS-E is reproducible in the evaluation of SPL, even between endoscopists with no or limited experience in EUS and/or EUS-E. Reproducibility and diagnostic accuracy increase with experience in EUS and EUS-E.


Exercise benefits the cardiac, autonomic and inflammatory responses to organophosphate toxicity.
The organophosphate, diisopropyl fluorophosphate (DFP), may impair cardiovascular, autonomic and immune function while exercise training is thougt to be restorative. Experiments determined effects of wheel exercise in C57B1 male mice, testing cardiovascular and autonomic function and characterization of the immunological profile. Sedentary (S) and exercise (ET) groups were treated with corticosterone (CORT) followed by injection of DFP. This model was associated with systolic and diastolic dysfunction in the S group, measured using echocardiography (ECHO). Chronic exercise ameliorated the cardiac deficit. Autonomic balance, accessed by heart rate variability (HRV), showed increased sympathetic and decreased parasympathetic modulation in S group. Autonomic balance in ET mice was not affected by DFP. Our DFP model resulted in mild neuroinflammation seen by increased IL5, IL12 and MIP2 in brain and plasma IL6 and IL1a. DFP had a negative impact on cardiac/autonomic function and inflammatory markers, effects reduced by exercise. Data suggest a beneficial effect of exercise training on the cardiovascular and autonomic responses to DFP/CORT.


Ecology of Antricola ticks in a bat cave in north-eastern Brazil.
Argasid ticks are a diverse group of acarines that parasitize numerous vertebrate hosts. Along with birds, bats serve as hosts for several argasid ticks, which are commonly found in bat caves. Argasid ticks have regained attention from tick taxonomists in recent decades, with a number of new species described in various zoogeographical regions. Nonetheless, studies on their ecology are still scarce. We conducted a 1-year longitudinal study to assess the presence of argasid ticks in a bat cave in the drylands of north-eastern Brazil and evaluate their possible response to abiotic factors. From July 2014 to June 2015, 490 ticks were collected (272 nymphs, 169 males and 49 females) in a cave chamber hosting a large colony of Pteronotus spp. bats, being relatively more frequent from July to December 2014. Adults were identified as Antricola guglielmonei, whereas nymphs were assigned to the genus Antricola. Almost all ticks (98%) were collected on the cave walls. Only 2% were on the ceiling and, surprisingly, no specimens were found on the floor and/or guano. Adults were usually clustered in the crevices and little mobile, whereas nymphs were dispersed and more active, moving over the walls or ceiling of the cave. Although present in most of the studied period, there was a significantly negative correlation between tick abundance and relatively humidity, and A. guglielmonei was more frequent during the dry season. Moreover, there was no evident correlation between the abundance of ticks and bats. Further long-term studies will be able to verify whether this pattern is repeated over time, and even whether other variables can influence the population dynamics of A. guglielmonei.


Efficacy and safety of computed tomography-guided percutaneous balloon compression for trigeminal neuralgia secondary to vertebrobasilar dolichoectasia.
Percutaneous balloon compression (PBC) of Gasserian ganglion has been popularly used to treat trigeminal neuralgia (TN), one of the most painful syndromes in human experience. Vertebrobasilar dolichoectasia (VBD) is a rare cause of TN and remains challenging to treat. To our knowledge, no study has reported the therapeutic outcome of PBC for VBD-related TN (VBD-TN). In this retrospective study, we collected and analyzed the medical records of all patients undergoing PBC procedure for VBD-TN under the guidance of CT plus three-dimensional reconstruction at the Pain Management Center of Beijing Tiantan Hospital from January 2017 to December 2022. All 23 patients (15 men and 8 women) had a substantial pain relief as modified Barrow Neurological Institute (BNI) I-IIIb immediately after procedure. The follow-up duration ranged from 2 to 63 months, and at the last follow-up visit, only 3 patients (13%) relapsed (BNI IV-V). The cumulative recurrence-free survival was 95%, 87%, and 74% within 1, 3, and 5 years, respectively. Patients' reported satisfactory rate was 100% as Likert scale 4-5 throughout the whole follow-up period, with no severe complications occurring. Our data revealed promising efficacy and safety of PBC procedure for treatment of VBD-TN, thus suggesting a valuable option for pain control in these rare cases of TN. However, there has been no supporting evidence that PBC treatment is a preferred option to other treatments.


Grouping of artificial objects in pigeons: an inquiry into the cognitive architecture of an avian mind.
How does a pigeon see the world? Although pigeons are known to be adept at learning large numbers of figures, colors, and natural images, various experiments show that their visual cognitive specialization is more geared towards seeing colors and textures instead of shapes. They also excel in the analysis of local features instead of shapes that can only be differentiated by their outline. We therefore embarked into a detailed analysis of the relative weight of colors versus shapes in an object grouping task. At the same time we used a design that gave us information on the question of the relative importance of the S+ and S- in cognitive tests. Our strategy was to use the classic matching to sample task in which pigeons have to associate a sample with another stimulus (S+), which belongs to the same arbitrary group while at the same time avoiding choosing another stimulus (S-), which is part of another arbitrary group. Our results clearly reveal that color is, relative to shape, the primary cue that pigeons use to guide their decisions. Although they are in principle able to use shape information, they utilize shape as the last cognitive resort. Our data further reveal that pigeons guide their decisions in a matching to sample task primarily by focusing on the S+, although they also utilize information from the S-, albeit to a smaller extent. They are flexibly able to use cognitive match- or nonmatch-strategies depending on the presence or absence of color- or shape-cues.


Simulation of low-pass hearing loss in a Finnish speech discrimination test.
Three different degrees of clinical hearing loss of low-pass type were stimulated by a filter apparatus. The equipment to simulate a given hearing loss is described. The speech discrimination curves corresponding to the normal hearing and to the three degrees of hearing loss were measured in normal hearing adults using Finnish PB-words. The stimulation of a light hearing loss of low-pass type yielded a two-staged discrimination curve. The discrimination curves of a moderate and a severe hearing loss crossed at a very high output level. The cause of this phenomenon is discussed on the ground of the exceptional vowel/consonant relation and intensity/frequency distribution in the Finnish language.


Ciona robusta macrophage migration inhibitory factor (Mif1 and Mif2) genes are differentially regulated in the lipopolysaccharide-challenged pharynx.
The effects of lipopolysaccharide (LPS) on Mif (macrophage migration inhibitory factor) gene expression in the pharynx (haemapoetic tissue) of Ciona robusta were investigated using quantitative reverse-transcription PCR (qRT-PCR) and in situ hybridisation (ISH). To verify the induction of an inflammatory response in the pharynx, a qRT-PCR analysis was performed to evaluate the change in the expression of proinflammatory marker genes such as Mbl, Ptx-like, Tnf-α and Nf-kb, which were shown to be upregulated 1 h post LPS challenge. The change in the expression of the two Mif paralogs in the pharynx was assessed before and after stimulation, and qRT-PCR and ISH results showed that, although Mif2 and Mif2 were expressed in clusters of haemocytes in pharynx vessels, only Mif1 expression increased after LPS stimulation. This indicates that the Mif genes are differently regulated and respond to different ambient inputs that need further analysis.


Multidrug-resistant Escherichia coli from free-living pigeons (Columba livia): Insights into antibiotic environmental contamination and detection of resistance genes.
Bacterial resistance is a public and one health problem. Free-living birds can be reservoirs of multidrug-resistant bacteria and resistance genes. This study aimed to characterize the antimicrobial resistance of Escherichia coli isolated from free-living urban pigeons (Columba livia) in South Brazil. Ninety-two animals were sampled, and one isolate was obtained from each one. The isolates were characterized, and the antimicrobial resistance profile and beta-lactam and colistin resistance genes were investigated. The isolates were classified as phylogroups B1 (35%), B2 (33%), A (16%) and D (16%), and 14% of the strains had the eae virulence gene. All isolates were resistant to at least one antimicrobial, and 63% of them were multidrug-resistant. Geographical location where the pigeons were captured and presence of the eae gene were associated with multidrug resistance. blaVIM and mcr-1 genes were detected in one and two isolates, respectively. This is the first report of these genes in E. coli of pigeons. The blaVIM -positive isolate was classified as Shiga toxin-producing E. coli, and the isolates with mcr-1 were classified as Enterohaemorrhagic E. coli and Enteropathogenic E. coli, which raise additional concerns related to public health since these are zoonotic pathotypes. The results reveal that pigeons carry multidrug-resistant pathogenic E. coli, which may interest public health. Nonetheless, further studies on whether these animals are sources of contamination for humans must be performed to understand their role in spreading antimicrobial resistance.


Ureteral stenosis after kidney transplantation: true incidence and long-term followup after surgical correction.
Between March 1965 and December 31, 1982, 421 kidney transplantations were performed in our department. The over-all incidence of ureteral stenosis was 5.5 per cent. However, when the number of patients at risk at various times after transplantation was considered the probability for ureteral stenosis to develop was 4.6 per cent at 1 year, 7.7 per cent at 2 years and 9.7 per cent at 5 years. Preoperative and postoperative complications were frequent. The wound infection rate was 21.9 per cent and 2 of the 24 patients died of septic shock. Graft survival rate after definitive surgical correction of ureteral stenosis was 71 per cent at 1 and 2 years, and 65 per cent at 3 years. Late results justify the efforts to re-establish correct urinary drainage of the graft.


Correlation of in vitro and in vivo models for the oral absorption of peptide drugs.
The aim of this study was to evaluate two in vitro models, Caco-2 monolayer and rat intestinal mucosa, regarding their linear correlation with in vivo bioavailability data of therapeutic peptide drugs after oral administration in rat and human. Furthermore the impact of molecular mass (Mm) of the according peptides on their permeability was evaluated. Transport experiments with commercially available water soluble peptide drugs were conducted using Caco-2 cell monolayer grown on transwell filter membranes and with freshly excised rat intestinal mucosa mounted in Using type chambers. Apparent permeability coefficients (P (app)) were calculated and compared with in vivo data derived from the literature. It was shown that, besides a few exceptions, the Mm of peptides linearly correlates with permeability across rat intestinal mucosa (R (2) = 0.86; y = -196.22x + 1354.24), with rat oral bioavailability (R (2) = 0.64; y = -401.90x + 1268.86) as well as with human oral bioavailability (R (2) = 0.91; y = -359.43x + 1103.83). Furthermore it was shown that P (app) values of investigated hydrophilic peptides across Caco-2 monolayer displayed lower permeability than across rat intestinal mucosa. A correlation between P (app) values across rat intestinal mucosa and in vivo oral bioavailability in human (R (2) = 0.98; y = 2.11x + 0.34) attests the rat in vitro model to be a very useful prediction model for human oral bioavailability of hydrophilic peptide drugs. Presented correlations encourage the use of the rat in vitro model for the prediction of human oral bioavailabilities of hydrophilic peptide drugs.


Early recurrence of hyperthyroidism in patients with Graves' disease treated by subtotal thyroidectomy.
Prerequisites for surgical treatment of Graves' disease are that it can be done safely and that it is associated with a low incidence of recurrent hyperthyroidism. Early recurrence is especially undesirable. We studied 728 patients with Graves' disease treated by subtotal thyroidectomy using multivariate analysis in order to determine the factors related to early recurrence. The following factors were analyzed: age, sex, duration of medical treatment, weight of resected thyroid tissue, thyroid remnant size, preoperative level of thyroid-stimulating hormone (TSH) binding inhibitory immunoglobulin (TBII), and antimicrosomal hemagglutination antibody (MCHA). "Early recurrence" was defined as TSH suppression observed within the first year after surgery and continuing for at least 6 months. A total of 106 patients (14.6%) had early recurrence. Statistical analyses were performed by the chi-square test for univariate analysis and a logistic model for multivariate analysis. Significant factors were thyroid remnant size, MCHA, and TBII. These results indicated that TBII and MCHA are related to early recurrence of hyperthyroidism, and smaller remnant size is recommended for patients with a high MCHA titer or a high TBII level (or both) in order to avoid early recurrence.


Preparation of magnetic nitrogen-doped porous carbon by incomplete combustion with solvothermal synthesis for magnetic solid-phase extraction of benzoylurea insecticides from environmental water.
In this work, magnetic nitrogen-doped porous carbon (Fe3O4@N-PC) was prepared via incomplete combustion coupled with solvothermal synthesis for extraction of four benzoylureas (BUs) insecticides. Among them, nitrogen-doped porous carbon was produced through incomplete combustion of filter paper loaded with mixture formed by Zn(NO3)2·6H2O and polyethyleneimine solution, and magnetic nanoparticles were further introduced by solvothermal method. Compared with magnetic porous carbon (Fe3O4@PC), the surface hydrophilicity of Fe3O4@N-PC was improved by virtue of the doping of nitrogen atoms, and the dispersion of Fe3O4 was more uniform, which greatly exposed the adsorption site. The characterization of Fe3O4@N-PC were carried out by TEM, XRD, elemental analysis, XPS, BET and magnetic hysteresis curve. Besides, Fe3O4@N-PC was successfully used as magnetic solid-phase extraction (MSPE) adsorbent, which showed excellent enrichment factors and extraction recoveries toward polar BUs insecticides due to the polar surface and introduction of Lewis-basic nitrogen. The optimum amount of Fe3O4@N-PC adsorbent, extraction time, pH value, desorption solvent, desorption time and PEI concentration for BUs insecticides extraction were determined to be 3 mg, 10 min, 8, acetone/acetic acid (19:1, V/V), 6 min and 60 g L-1, respectively. Under this experimental condition, the enrichment factors ranged from 182 to 192 with good intra- and inter-day relative standard deviations (RSDs). The calibration lines were linear over the concentration in the range of 1-800 μg L-1, the limit of detection (LOD) and limit of quantification (LOQ) were 0.3 μg L-1 as well as 1 μg L-1, respectively. The recoveries for spiked sample ranged from 90.7 to 107.3% in spiked Yellow River water with the RSDs less than 7.0%. The results showed that the established MSPE strategy based on Fe3O4@N-PC could be used for the detection of trace BUs in complex samples.


Protective and autoimmune epitopes of streptococcal M proteins.
Several rheumatogenic serotypes of streptococcal M protein have been shown to contain both protective and cardiac tissue crossreactive epitopes. By synthesizing peptides copying different regions of M protein polypeptides, we were able to localize the protective and heart crossreactive epitopes. Some epitopes are only opsonic, some are only crossreactive, whereas others are both opsonic and tissue crossreactive. Multivalency of vaccines can be obtained by synthesizing protective peptides of one M serotype in tandem with protective peptides of other M serotypes. Such hybrid peptides evoke protective immune responses against the related streptococci without evoking tissue crossreactive immunity.


G-418, an elongation inhibitor of 80 S ribosomes.
The mode of action of the aminoglycoside G-418 was studied in wheat-germ, cell-free translation systems programmed with rat-liver polyadenylated RNA. Incorporation of amino acids into protein was effectively inhibited by G-418 in the microM concentration range. The inhibition pattern obtained was not uniform. The synthesis of polypeptides with higher molecular weights was more inhibited than that of smaller polypeptides. An identical inhibition pattern within a similar range of concentrations was obtained with cycloheximide, a known elongation inhibitor. Translation activity was abolished when the wheat-germ 80 S ribosomes were removed and could be partially reconstructed upon addition of the ribosomes. Incubation with G-418 prior to isolation yielded ribosomes defective in their reconstruction ability. The inhibition pattern was not uniform and exhibited again the same relationship between the size of a polypeptide and the extent of inhibition of its synthesis. Therefore, we suggest that in wheat-germ, cell-free translation systems G-418 affects the 80 S ribosomes and inhibits the elongation cycle.


Management of Hypersensitivity Reactions to Taxanes.
Taxanes are an important class of antineoplastic agents used in the treatment of a wide variety of cancers. However, paclitaxel and docetaxel, which are the most commonly used taxanes, elicit immediate hypersensitivity reactions (HSRs) in 5% to 10% of patients. Almost all patients that experience these reactions can be safely re-exposed to taxanes either through desensitization or challenge. This article describes the clinical presentation, diagnosis, and management of HSRs to taxanes and discusses the different options for their safe readministration.


Bacterial microcolonies exist within the sphenoid bone in chronic rhinosinusitis and healthy controls.
Some patients with chronic rhinosinusitis (CRS) exhibit thickening of the sinus bones that has been termed osteitis. The histopathology and microbiology of these changes have not been fully described. The aim of this study was to look for the presence of bacteria and immune cells within samples of bone from patients with and without CRS and correlate these findings to radiological findings. Bone on the anterior face of the sphenoid was examined radiologically and histologically in 8 patients with CRS with nasal polyposis, 8 patients with CRS without polyposis, and 6 control patients with pituitary adenomas and normal sinuses. Bone thickness and density were measured by computed tomography (CT) scanning. Bone samples were collected intraoperatively and 20 tissue sections were analyzed for each patient. Bacteria were identified by Giemsa and Gram stains. Immune cells were identified by conventional histology and immunohistochemistry. Small colonies of bacteria were identified within the bone in 3 of 16 CRS patients and 2 of 6 control subjects (p = 0.6). Isolated immune cells were identified within the bone in 3 of 16 CRS patients and 2 of 6 control subjects (p = 0.6) but both bacteria and immune cells occurred together in only 1 case. The presence of bacteria or immune cells within bone samples did not correlate with either bone thickness or bone density. This study describes the presence of bacteria and immune cells within a minority of CRS patients and normal controls. The bacterial microcolonies identified do not appear to be the cause of the bone changes seen in many CRS patients.


Leptin enhances ovulation and attenuates the effects produced by food restriction.
The aims of this study were to investigate the effects of chronic feed deprivation on the ovulatory process, and to assess whether leptin administration is able to alter these effects. Prepuberal rats subjected to food restriction and primed with gonadotrophins were used. Body and ovarian weights were significantly decreased in proportion to the severity of the food restriction. Only the most severe feed deprivation was able to inhibit the ovulation rate. Either buffer or leptin was daily administrated to prepuberal rats fed either ad libitum or with a severe food restriction. Serum progesterone, ovulation rate and ovarian prostaglandin E2 were reduced in rats subjected to food restriction and stimulated by daily administration of leptin in rats fed ad libitum. Negative effects produced by a severe food restriction were partially reversed by chronic administration of leptin. The ovarian endothelium nitric oxide synthase expression was strongly inhibited in rats with food restriction and once again, leptin administration reversed this effect. In summary, the ovulatory process was significantly inhibited in response to a severe decrease in food intake, at least in part, to the direct or indirect impairment of some ovarian factors production as prostaglandins and nitric oxide. Chronic treatment with leptin enhanced the ovulatory process in comparison with control animals, and partially prevented these negative effects produced by a severe malnutrition.


A keratin of fetal skin is reexpressed in human keratinocytes transformed by SV40 virus or treated with the tumor promoter TPA.
SV40-transformation as well as treatment with tumor promoters produce alterations in morphology, differentiation and keratinization of human keratinocytes. Two cell lines of SV40-transformed keratinocytes and primary cultures of keratinocytes treated with the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) were found to contain an additional protein of 52.5 kD molecular weight (MW). This protein was identified by its reactivity with the monoclonal antibody TROMA-I as being keratin no. 8, a keratin normally present only in simple epithelia. Since this keratin is present in fetal epidermis but disappears gradually when fetal skin becomes multilayered after week 13 of development (Moll et al., Differentiation 23 (1982) 170. [23]), it suggests that SV40 virus and TPA are able to induce in human keratinocytes the reexpression of fetal characters.


Determination of biological activities of nanoparticles containing silver and copper in water disinfection with/without ultrasound technique.
The final and most crucial step in obtaining clean water is disinfection. More innovative methods of water disinfection have recently been sought. Water disinfection is a promising application for nanoparticles as disinfectants. As a contribution to the literature, biofilm and metal-containing nanoparticles as antiadhesion inhibitors were used in conjunction with ultrasound in this study. The microbroth dilution test was used to reveal the microbiological antibacterial activities of different concentrations of AgNO3 and CuCl2 containing nanoparticles against the Escherichia coli ATCC 25,922 strain, which is an indicator bacterium in water systems. Antibiofilm activities were then investigated using biofilm attachment and biofilm inhibition tests. The inhibitory effect of nanoparticle ultrasonic waves on biofilm contamination was determined using a novel approach. Human keratinocyte cells (HaCaT cell line) were used in cell culture studies after water disinfection, and their cytotoxic effects were demonstrated using the MTT assay. The findings suggest that the nanoparticles utilized might be a viable choice for water disinfection applications. Furthermore, employing ultrasound at low doses with nanoparticles resulted in greater results. One feasible option is to employ nanoparticles to cleanse water without producing cytotoxicity.


Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases.
Recent progress in our understanding of the regulation of epithelial tissue stem cells has allowed us to exploit their abilities and instruct them to self-organize into tissue-mimicking structures, so-called organoids. Organoids preserve the molecular, structural and functional characteristics of their tissues of origin, thus providing an attractive opportunity to study the biology of human tissues in health and disease. In parallel to deriving organoids from yet-uncultured epithelial tissues, the field is devoting a growing amount of effort to model human diseases using organoids. This Review describes multidisciplinary approaches for creating organoid models of human genetic, neoplastic, immunological and infectious diseases, and details how they have contributed to our understanding of disease biology. We further highlight the potential role as well as limitations of organoids in clinical practice and showcase the latest achievements and approaches for tuning the organoid culture system to position organoids in biologically defined settings and to grant organoids with better representation of human tissues.


Combined SSRI-RIMA treatment in refractory depression. Safety data and efficacy.
Eighteen patients with refractory depression (dysthymia with superimposed major depression) were treated with a combination of fluvoxamine and moclobemide for 6 weeks and compared with 18 patients treated with fluvoxamine only. Both groups had improved only slightly after 8 weeks of TCA treatment and 6 weeks of SSRI treatment. Two main observations can be made concerning safety and efficacy. Firstly, side effects in the SSRI-RIMA group were minimal. Secondly, the SSRI-RIMA combination treatment significantly improved depression in refractory depressed patients, with a decrease in depression of about 40%. The SSRI monotherapy group also significantly improved, though only by about 20%, indicating that positive effects of SSRI treatment may still develop even after 12 weeks of treatment. In conclusion, the study gives further support to the hypothesis that SSRI-RIMA combinations may be safe and well tolerated. This treatment may also offer some therapeutic advantages in at least some patients who have not responded to conventional pharmacological treatment.


Dendritic spine formation in response to progesterone synthesized de novo in the developing Purkinje cell in rats.
The cerebellar Purkinje cell (PC) is a typical site for neurosteroid formation. We have demonstrated that this neuron possesses intranuclear receptor for progesterone and actively synthesizes progesterone de novo from cholesterol only during rat neonatal life, when the formation of the cerebellar cortex occurs dramatically. In this study, we therefore analyzed the effect of progesterone on dendritic spine formation of the PC. In vitro studies using cerebellar slice cultures from newborn rats showed that progesterone increases the density of PC dendritic spines in a dose-dependent manner. This effect was blocked by the progesterone receptor antagonist, RU486. Furthermore, trilostane, a specific inhibitor of progesterone synthesis, inhibited the increase of spine density. These results suggest that progesterone can promote dendritic spine formation, and endogenous progesterone synthesized de novo in the developing PC may induce such an effect.


Role of lipoxygenase in the mechanism of acrosome reaction in mammalian spermatozoa.
The acrosome reaction (AR) in bull spermatozoa was induced by the Ca2(+)-ionophore A23187, by dilauroylphosphatidylcholine or by arachidonic acid in the presence of Ca2+ in the incubation medium. The occurrence of AR was determined by following the release of acrosin from the cells. Nordihydroguaiaretic acid (NDGA), an inhibitor of both lipoxygenase and prostaglandin-synthetase, caused 35%, 43% and 69% inhibition of AR at concentrations of 1, 10 or 100 microM, respectively. Eicosatetraynoic acid (ETYA), an analogue of arachidonic acid, caused 17%, 61% and 77% inhibition of AR at concentrations of 20, 40 or 80 micrograms/ml, respectively. When AR was induced by arachidonic acid, ETYA, causes 36% and 58% inhibition at concentrations of 2 or 20 micrograms/ml, respectively. Under identical conditions, 100 microM indomethacin, a specific inhibitor of prostaglandin-synthetase, showed no inhibition but rather 35% stimulation at acrosin release rate. The fact that AR is inhibited by NDGA and not by indomethacin indicates that the lipoxygenase, rather than prostaglandin-synthetase, is involved in the mechanism of AR. Since the inhibition by NDGA is seen in the presence of the Ca-ionophore, we suggest that lipoxygenase activity is not involved in enhancing calcium transport into the cell, but rather at other steps in AR mechanism. A thin-layer chromatography revealed the presence of 15-HETE, the classical product of 15-lipoxygenase activity, which was identified by HPLC. Under AR conditions, there is an elevation of lipoxygenase products and the addition of NDGA caused a reduction in their levels. The inhibition of acrosin release by NDGA can be eliminated by adding 15-HETE or 15-HPETE to the incubation medium. In conclusion, we suggest here for the first time, a physiological role for 15-lipoxygenase in the mechanism of AR in mammalian spermatozoa.


Repositioning "old" drugs for new causes: identifying new inhibitors of prostate cancer cell migration and invasion.
The majority of prostate cancer (PCa) deaths occur due to the metastatic spread of tumor cells to distant organs. Currently, there is a lack of effective therapies once tumor cells have spread outside the prostate. It is therefore imperative to rapidly develop therapeutics to inhibit the metastatic spread of tumor cells. Gain of cell motility and invasive properties is the first step of metastasis and by inhibiting motility one can potentially inhibit metastasis. Using the drug repositioning strategy, we developed a cell-based multi-parameter primary screening assay to identify drugs that inhibit the migratory and invasive properties of metastatic PC-3 PCa cells. Following the completion of the primary screening assay, 33 drugs were identified from an FDA approved drug library that either inhibited migration or were cytotoxic to the PC-3 cells. Based on the data obtained from the subsequent validation studies, mitoxantrone hydrochloride, simvastatin, fluvastatin and vandetanib were identified as strong candidates that can inhibit both the migration and invasion of PC-3 cells without significantly affecting cell viability. By employing the drug repositioning strategy instead of a de novo drug discovery and development strategy, the identified drug candidates have the potential to be rapidly translated into the clinic for the management of men with aggressive forms of PCa.


Isolation of alligator gar (Lepisosteus spatula) glucagon, oxyntomodulin, and glucagon-like peptide: amino acid sequences of oxyntomodulin and glucagon-like peptide.
Oxyntomodulin, glucagon, and a glucagon-like peptide (GLP) have been isolated from the endocrine pancreas of the alligator gar (Lepisosteus spatula), a ganoid fish. The three peptides were isolated by gel filtration and HPLC and were identified by size, composition, and glucagon-like immunoreactivity. The amino acid sequences of the oxyntomodulin and GLP were determined. The oxyntomodulin contains 36 amino acid residues and its sequence is H S Q G T F T N D Y S K Y L D T R R A Q D F V Q W L M S T K R S G G I T. The composition of the glucagon is identical to the N-terminal 29 residues of the gar oxyntomodulin. The single form of GLP found contains 34 amino acid residues in the following sequence: H A D G T Y T S D V S S Y L Q D Q A A K K F V T W L K Q G Q D R R E. These findings suggest that all three peptides are derived from a common precursor.


Atypical brainstem encephalitis: magnetic resonance imaging and oculographic features.
A 50-year-old woman had primary position upbeating nystagmus, abnormalities of the lower cranial nerves, mild cerebellar signs, and CSF lymphocytosis. CT and MRI showed enlargement of the pons. Eye movement recordings revealed impaired pursuit and optokinetic nystagmus, and visual-vestibular interactions were absent. The patient improved spontaneously.


Inactivation of rat pineal hydroxyindole-O-methyltransferase by disulfide-containing compounds.
Rat pineal hydroxyindole-O-methyltransferase activity in crude homogenates is reduced by treatment with disulfides. Cystamine (IC50 = 128 microM) and selenocystamine (IC50 = 13 microM) are the most potent compounds tested. Reduced cystamine (cysteamine) and diaminohexane are inactive. N,N'-Diacetylcystamine, penicillamine disulfide, and glutathione disulfide are less potent or inactive; but several peptides (oxytocin, vasopressin, and arginine vasotocin) are active. Inactivation by cystamine is time- and temperature-dependent and is accelerated at higher pH. Disulfide treatment of intact pinealocytes also inactivates the enzyme. Addition of dithiothreitol during the enzyme assay completely reactivates inactivated enzyme formed by disulfide treatment of homogenates or intact cells. Rat hydroxyindole-O-methyltransferase is also inactivated in the absence of added disulfides and dissolved O2. This spontaneous inactivation is time-, temperature-, and pH-dependent and can be completely prevented, but not reversed, by dithiothreitol. In contrast to the inhibitory effects of cystamine on the rat enzyme, cystamine does not alter bovine hydroxyindole-O-methyltransferase and increases ovine hydroxyindole-O-methyltransferase activity. The bovine and ovine enzymes do not become inactive in the absence of added disulfides. Together these observations indicate that rat pineal hydroxyindole-O-methyltransferase can be inactivated by a protein thiol:disulfide exchange mechanism. This mechanism may contribute to the physiological regulation of this enzyme in the rat pineal gland but does not appear to be a common feature of pineal hydroxyindole-O-methyltransferase regulation in all species.


Assessment of application-rate dependent effects of a long-term fire retardant chemical (Fire Trol 934) on Typha domingensis germination.
Although long-term fire retardants (LTR) gain increasingly acceptance as effective tools for wildfire management, recent studies indicate their potential harmfulness in the environment, especially in aquatic ecosystems. This study comprises a first laboratory impact assessment of LTR action in temporal Mediterranean wetlands, using seed germination of Typha domingensis as indicator of impact. Our aim was to identify application rates upon which seed germination could be significantly affected. We tested for low (1 l m(-2)) and high (3 l m(-2)) application rates of Fire Trol 934 which are recommended by the manufacturers as a function of fuel characteristics. In addition, we simulated the impact of a higher application rate of 5 l m(-2) because inhomogeneous dispersal of the LTR during fire control and prevention operations can result in locally elevated applications. Results of a microcosm experiment indicate that application rates of 1 or 3 l m(-2) can impact Typha germination rates in the short-term via indirect LTR-mediated effects on water quality, which suppressed necessary cues for germination. However, a subsequent experiment with Petri dishes, using seeds isolated from the LTR treated sediments did not show significantly different germination rates between the control and the treatments with application rates of 1 or 3 l m(-2). This suggests that retardant pre-application germination success could be recovered in nature once the retardant is eliminated. By contrast, seeds almost completely failed to germinate in the microcosm experiment and the subsequent Petri dish essay when an application rate of 5 l m(-2) was used. This suggests a critical level upon which Typha seed germination may be perpetually limited. Research should be extended to other plant species to provide fire managers with guidelines for environmentally safe use of LTR in the Mediterranean region.


Between and within subject variation of the first phase insulin response to intravenous glucose.
Eight normal subjects underwent two intravenous glucose tolerance tests to determine the between and within subject variation of the first phase insulin response. Variability was represented by the coefficient of variation. The between subject variation for the incremental 0-10 min insulin area was 58%, and the within subject variation was 22% (median value), range 3-55%. The variation of the first phase response expressed in four different ways was compared. The total and incremental (above fasting levels) 0-10 min areas provided less variable results (variation 52 and 58%) than the 1 + 3 min insulin levels (variation 72%) or mean of the incremental 3-5 min insulin levels (variation 66%). The ratio of the incremental 0-10 min insulin to glucose areas was as variable (variation 53%) as the insulin responses alone. The variability of insulin responses to intravenous glucose severely limits their value as early predictors of B-cell failure.


A highly selective and sensitive salamo-salen-salamo hybrid fluorometic chemosensor for identification of Zn2+ and the continuous recognition of phosphate anions.
A salamo-salen-salamo hybrid fluorescent chemical sensor (H4L) was synthesized and characterized. It exhibits high selectivity and sensitivity to Zn2+ in physiological pH range. Meanwhile, its zinc(II) complex (L-Zn2+) continuously responses phosphate anions in DMF/H2O (v/v, 9:1) solution. Moreover, the identification processes are explored using characterization methods such as UV-absorption spectra, IR spectra and ESI-MS spectrum. In addition, the coordination mechanism of H2PO4- and Zn2+ were successfully exploited to make the chemical sensor reproducible. In short, the sensors H4L and L-Zn2+ will be promising detection devices for Zn2+ and phosphate anions.


Exploring the link between adverse childhood experiences and mental and physical health conditions in pregnant Palestine refugee women in Jordan.
Adverse childhood experiences (ACEs) are linked to negative pregnancy outcomes. However, little is known about the prevalence of ACEs and their relationship to mental and health outcomes among pregnant Palestine refugee women. This was a cross-sectional study. Data were collected from 772 pregnant Palestine refugee women with a median (interquartile range) age of 27 (23, 32) years, attending five antenatal clinics in Jordan between February and June 2021. The modified 33-item ACE International Questionnaire was used to assess eight domains of ACEs: (1) marriage and family, (2) relationship with parents, (3) neglect, (4) household dysfunction/domestic violence, (5) abuse, (6) peer violence, (7) community violence, and (8) collective violence. Multivariate logistic regression was used to examine the association between ACEs and mental and health outcomes. The ethical approval was obtained from United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) Research Review Board in May 2020. Eighty-eight percent of women experienced at least one type of ACE, and 26% of women experienced ≥4 types of ACEs. Compared with women with 0-3 types of ACE exposure, those with ≥4 types of ACEs had 1.58 (95% confidence interval [CI] 1.10-2.28) times higher prevalence of obesity before pregnancy, 3.28 (95% CI 1.79-6.03) times higher prevalence of depression during pregnancy, and 2.01 (95% CI 1.39-2.91) times higher prevalence of ever been smoking cigarettes or hookah. Exposure to ACEs is prevalent among pregnant Palestine refugee women. Exposure to multiple types of ACEs was associated with obesity, mental health conditions, and smoking.


Evaluation of a youth agency's supervision practices: A mixed-method approach.
This research presents the findings from an evaluation and organizational development initiative that was requested by a Canadian youth agency working in a large urban setting. A team of four researchers affiliated with the Center for Research on Educational and Community Services (CRECS) at the University of Ottawa conducted the evaluation. The purpose of the evaluation was to identify the supervision needs and challenges of coordinators and front line staff, assess the efficiency of the current supervision practices, and evaluate the supervisors' and supervisees' satisfaction with these current practices. A literature review was performed to help provide a clear definition of 'supervision' and the different professional roles it encompasses. Additionally, research evidence pertaining both to what contributes to supervision efficacy and supervisor competency was reviewed to distill the most robust findings in the existing literature. The lines of evidence consisted of a document and file review, an online employee survey, group discussions (i.e. focus groups), and interviews with key informants. The results of the evaluation helped the research team formulate recommendations to the agency for the development of enhanced supervision practices across its various service areas.


Human anti-self antibodies with high specificity from phage display libraries.
Recently we demonstrated that human antibody fragments with binding activities against foreign antigens can be isolated from repertoires of rearranged V-genes derived from the mRNA of peripheral blood lymphocytes (PBLs) from unimmunized humans. The heavy and light chain V-genes were shuffled at random and cloned for display as single-chain Fv (scFv) fragments on the surface of filamentous phage, and the fragments selected by binding of the phage to antigen. Here we show that from the same phage library we can make scFv fragments encoded by both unmutated and mutated V-genes, with high specificities of binding to human self-antigens. Several of the affinity purified scFv fragments were shown to be a mixture of monomers and dimers in solution by FPLC gel filtration and the binding kinetics of the dimers were determined using surface plasmon resonance (k(on) = 10(5)-10(6) M-1s-1, k(off) = 10(-2)s-1 and Ka = 10(7) M-1). The kinetics of association are typical of known Ab-protein interactions, but the kinetics of dissociation are relatively fast. For therapeutic application, the binding affinities of such antibodies could be improved in vitro by mutation and selection for slower dissociation kinetics.


Blood-lead levels in patients with chronic liver diseases.
Blood-lead concentrations (Pb-B) were measured in 318 adult inpatients with chronic liver diseases. The Pb-B was highest (387 +/- 96 micrograms/l) in 102 patients with alcoholic liver disease without cirrhosis. The Pb-B was still high, but significantly lower in 60 patients with compensated alcoholic cirrhosis (342 +/- 100 micrograms/l) and in 72 patients with decompensated alcoholic cirrhosis (312 +/- 97 micrograms/l). This difference was in part due to a significant decrease of the hematocrit which fell from 44.4 +/- 4.9% to 42.4 +/- 27.2% and to 39.2 +/- 7.4% respectively. In patients with viral or cryptogenic liver diseases the Pb-B was 211 +/- 69 micrograms/l in 11 patients with chronic persistent hepatitis, 219 +/- 72 micrograms/l in 19 with chronic active hepatitis, 206 +/- 94 micrograms/l in 28 with compensated cirrhosis, and 226 +/- 98 micrograms/l in 26 with decompensated cirrhosis, without any significant difference. The Pb-B of the male patients showed no correlation to age, with the exception of 25 male patients with chronic persistent and active hepatitis (r = 0.626, P less than 0.001).


High-performance lubricant additives based on modified graphene oxide by ionic liquids.
Graphene oxide (GO) is a layered material bearing a variety of oxygen-containing functional groups on its basal planes and edges, which allow it as a substrate to conduct a variety of chemical transformations. Here modified graphene oxide (MGO) was prepared using alkyl imidazolium ionic liquids (ILs) (1-butyl-3-methylimidazolium tetrafluoroborate (LB104), 1-butyl-3-methyl imidazolium hexafluorophosphate (LP104) and 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl) amide (LF106)) via epoxide ring-opening reaction, cation-π stacking or van der Waals interactions, with LB104 modified graphene (MG) exfoliated from graphite rod by a moderate electrochemical method as a comparison. The stability and tribological properties of MGO and MG as multialkylated cyclopentanes (MACs) additives were investigated in detail. The results show that GO is converted into graphene through the chemical modification using ILs, and MGO with good dispersion and stability in MACs significantly improves the tribological performance (friction and wear were reduced about 27% and 74% with pure MACs as a comparison, respectively). The excellent tribological properties are attributed to the formation of an ILs-containing graphene-rich tribofilm on the sliding surfaces, which as the third body can prevent the sliding surfaces from straight asperity contact and improve friction reducing and anti-wear behaviors.


The generality of the attentional boost effect for famous, unfamiliar, and inverted faces.
Familiarity and face inversion not only affect face recognition and memory but also influence attention. Face processing is less attention-demanding for familiar than for unfamiliar faces and for upright than for inverted faces. The automaticity raises the question of how face processing interacts with an increase in attention. Using a dual-task paradigm, we tested the interaction between attention and face familiarity and orientation. Participants encoded a series of faces to memory while simultaneously monitoring a stream of colored squares, pressing the space bar for target-colored squares and making no response to distractor-colored squares. Replicating previous findings of the attentional boost effect (ABE), we found that faces encoded with target squares were better remembered than faces encoded with distractor squares. If the automatic nature of familiar (or upright) face processing makes attention unnecessary, then the attentional boost should be attenuated for familiar relative to unfamiliar faces and for upright relative to inverted faces. Data from three experiments showed, however, that the ABE was the same for all types of faces. These results suggest that target detection did not simply elevate attention in an early encoding phase. Rather, selecting targets and rejecting distractors in the color task may have led to yoked temporal selection of target-concurrent faces for entry into memory.


Imaging findings of biliary hamartomas (von Meyenburg complexes).
To evaluate the imaging findings of biliary hamartomas (von Meyenburg complexes, vMCs) and discuss their differential diagnosis from other related diseases, imaging findings of biliary hamartomas on ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and hepatobiliary scintigraphy were prospectively analyzed in six patients. On ultrasound images, five of the six cases showed multiple small hyper- and hypoechoic lesions with comet-tail echoes, especially when magnified using the zoom function. In all six cases, multiple tiny hypodense lesions less than 10 mm in diameter were scattered throughout the liver with no enhancement on CT. These tiny lesions were demonstrated to be hyper- and hypointense on T2- and TI-weighted images, respectively, in three patients who underwent MRI examinations. MRCP was performed in two patients, and it clearly showed multiple tiny round and irregular-shaped hyperintense lesions. MRCP and hepatobiliary scintigraphy showed normal appearances of intra- and extrahepatic bile ducts in two and one patients, respectively. Imaging modalities are useful in the diagnosis and differential diagnosis of vMCs. A correct diagnosis might be obtained when typical imaging findings present even without histological confirmation.


Membrane-bound complement regulatory proteins inhibit complement activation by an immunotherapeutic mAb in a syngeneic rat colorectal cancer model.
MAb-mediated immunotherapy offers a potential tool for destroying metastasizing colorectal tumor cells. Promising results have been obtained by using xenograft models. However, overexpression of membrane-bound complement regulatory proteins (mCRP) impedes complement-mediated destruction of tumor cells in vitro. mCRP operate in a species selective manner. Therefore a syngeneic animal model is needed to investigate the contribution of mCRP in mAb-mediated immunotherapy. Here we present a syngeneic rat colorectal carcinoma model, which fulfills the conditions necessary to investigate the effect of mCRP expression on mAb-mediated immunotherapy of metastases of solid tumors.CC531 rat colorectal cancer cells were injected subcapsularly into the liver of syngeneic WAG/Rij rats. Four mAb (MG1(IgG2a), MG2(IgG2a), MG3(IgG3) and MG4(2a)(IgG2a)) directed against CC531 cells, were tested for their complement activating abilities in vitro and tumor homing capacities in vivo. Only MG4(2a) was found to activate complement in vitro and home to the tumor cells in vivo. This mAb induced C3-deposition and C-mediated lysis of CC531 cells in vitro when the effects of the C-inhibitors Crry/p65 and CD59 were neutralized. This implies an important role for these mCRP in restricting the effector functions of tumor-associated mAb on these cells. Although C activation could be induced by MG4(2a) in situ on tumor tissue sections, no deposition of C3 could be found on the tumor cells positive for MG4(2a) in vivo. This suggests that complement activation in vivo was inhibited by mCRP. The results indicate the suitability of this syngeneic animal model for studying the effects of mAb immunotherapy. However, the effect of mCRP on tumor cells need to be overcome, e.g. by the use of mAb against tumor antigens and mCRP.


mRNA-Based Reprogramming Under Xeno-Free and Feeder-Free Conditions.
Reprogramming somatic cells into induced pluripotent stem cells (iPSC) has provided a gateway for many novel discoveries in the field of tissue engineering, regenerative medicine and cell therapy. The need for an efficient, less laborious and fast reprogramming protocol under xeno-free, feeder-free and chemically defined conditions has never been greater. Here we describe a novel approach to reprogramming using the StemRNA 3rd Gen Reprogramming Kit (ReproCELL) which encompasses non-modified microRNAs (NM-miRNA), non-modified E3, K3, B18R RNAs (EKB NM-RNA) and non-modified mRNAs for six crucial transcription factors (OSKMNL NM-RNA).


True rupture of the caesarean section scar (a 15 year review, 1972-1987).
In a 15 year period (1972-1987) a total of 2434 parturients with one or more previous Caesarean sections were delivered at University College Hospital, Galway. There were 1084 (44.5%) patients booked for elective repeat Caesarean delivery, because they had two or more prior sections (maximum number = 10) or a recurrent indication for section other than the prior section. Trial of labour was undertaken in 1350 (55.5%) patients, and 81.26% achieved a vaginal delivery. Regional analgesia was employed in 25.5% and oxytocin in 31.9%. There were 6 (0.44%) or 1:225, true scar ruptures, resulting in 1 stillbirth and 2 neonatal deaths with no maternal death. There were 4 (0.37%), or 1:271, uterine ruptures in patients booked for elective repeat section: a classical scar rupture before labour, with a fresh stillbirth; placenta praevia percreta with bladder involvement in two patients (both resulting in maternal death), and a patient with placenta praevia accreta.


What is the effect of active ingredients in dentifrice on inhibiting the regrowth of overnight plaque? A systematic review.
The aim of this systematic review was to establish the adjuvant clinical effect of brushing with a dentifrice containing purported active ingredients as compared to a regular sodium fluoride dentifrice with respect to the inhibition of overnight dental plaque regrowth from studies with human participants. MEDLINE-PubMed, EMBASE and Cochrane CENTRAL were searched, up to June 2019. The inclusion criteria were controlled clinical trials with participants aged ≥ 18 years in good general health. Studies were included that evaluated the effect of toothbrushing with a dentifrice on the inhibition of overnight dental plaque regrowth when an active ingredient was added to the dentifrice as compared to a common sodium fluoride product. Data were extracted from the eligible studies, the risk of bias was assessed, and a meta-analysis was performed where feasible. Independent screening of 213 unique papers resulted in 10 eligible publications that provided 14 comparisons. Stannous fluoride and triclosan dentifrices were found as the active ingredients. The descriptive analysis indicated that all, but two comparisons demonstrated an additional effect on the active-ingredient dentifrice. The meta-analysis supported and strengthened these findings. It showed that when plaque was scored digitally, a DiffM was -3.15(95% CI [-4.61:-1.69], P < .001, prediction interval [-5.07;-1.24]). When plaque was scored clinically, the difference of means (DiffM) was -0.33(95% CI [-0.49:-0.16], P < .001, prediction interval [-0.87; 0.21]). The results of this review demonstrate moderate-quality evidence that brushing with an active-ingredient dentifrice with stannous fluoride or triclosan does provide an added clinically relevant effect concerning plaque inhibition capabilities that surpass the effect of a regular sodium fluoride dentifrice.


Endopolygalacturonase from Rhizoctonia fragariae. Purification and characterization of two isoenzymes.
An electrophoretically homogeneous preparation of endo-polygalacturonase (poly(1,4-alpha-D-galacturonide)glycanohydrolase, EC 22.214.171.124) from culture filtrates of Rhizoctonia fragariae, a pathogenic agent in strawberry plants, was resolved into two isoenzymes when subjected to isoelectrofocusing in a narrow pH range. The isoelectric points of the two isoenzymes were 6.76 +/- 0.03 and 7.08 +/- 0.05. The two polygalacturonases exhibited similar substrate specificity, pH optimum and pattern of degradation of sodium polypectate. The two enzymes consisted of a single polypeptide chain which had an apparent molecular weight of 36 000 as determined by gel filtration on Sephadex G-100.


The Association Between Hospital Occupancy and Mortality Among Medicare Patients.
Hospital crowding is a major challenge facing US health care systems, but few studies have evaluated the association between inpatient occupancy and patient mortality. The objective of this study was to determine how increasing hospital occupancy is associated with the likelihood of inpatient and 30-day out-of-hospital mortality using a novel measure of inpatient occupancy. The researchers conducted a retrospective, observational study using secondary data from the California Office of Statewide Health Planning and Development, including nonfederal, acute care facilities from 1998 to 2012. Using measures of relative hospital occupancy, the researchers ran logistic regressions to assess the relationship between increasing hospital occupancy and inpatient mortality and 30-day out-of-hospital mortality among Medicare patients age 65 years and older with myocardial infarction, heart failure, or pneumonia. Higher admission day occupancy (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.94-0.99) and higher discharge day occupancy (OR = 0.62, 95% CI: 0.60-0.64) were associated with decreased inpatient mortality. Thirty-day out-of-hospital mortality increased with higher discharge day occupancy (OR=1.28, 95% CI: 1.24-1.32) but was unrelated to admission day occupancy. This study found a counterintuitive relationship between admission and discharge day occupancy and inpatient mortality. Higher discharge day occupancy appears to displace deaths into the outpatient setting. Understanding why higher inpatient occupancy is associated with lower overall mortality merits investigation to inform best practices for inpatient care in busy hospitals.


Digital PCR for Minimal Residual Disease Quantitation Using Immunoglobulin/T-Cell Receptor Gene Rearrangements in Acute Lymphoblastic Leukemia: A Proposed Analytic Algorithm.
In minimal residual disease (MRD), where there are exceedingly low target copy numbers, digital PCR (dPCR) can improve MRD quantitation. However, standards for dPCR MRD interpretation in acute lymphoblastic leukemia are lacking. Here, for immunoglobulin/T-cell receptor-based MRD, we propose an objective, statistics-based analytic algorithm. In 161 postinduction samples from 79 children with acute lymphoblastic leukemia, MRD was performed by dPCR and real-time quantitative PCR (qPCR) using the same markers and primer-probe sets. The dPCR raw data were analyzed by using an automated algorithm. dPCR and qPCR results were highly concordant (P < 0.0001): 98% (50 of 51) of qPCR positive were positive by dPCR, whereas 95% (61 of 64) of qPCR negative results were also negative by dPCR. For MRD quantitation, both qPCR and dPCR were tightly correlated (R2 = 0.94). Using more DNA (1 μg × 7 versus 630 ng × 3), dPCR improved sensitivity of MRD quantitation by one log10 (median MRD positive cutoff 1.6 × 10-5). With dPCR, 83% (29 of 35) of positive-not-quantifiable results by qPCR could be assigned positive/negative MRD status. Seven replicates of tested samples and negative controls were optimal. Compared with qPCR, dPCR could improve MRD sensitivity by one log10. We proposed an automatable, statistics-based algorithm that minimized interoperator variance for dPCR MRD.


MJD and OTU deubiquitinating enzymes in Schistosoma mansoni.
The ubiquitination and deubiquitination of proteins can alter diverse cellular processes, such as proteolysis, trafficking, subcellular localisation, DNA repair, apoptosis and signal transduction. Deubiquitinating enzymes (DUBs) are responsible for removing ubiquitin from their target proteins. Previous reports have shown the presence of two subfamilies of DUBs in Schistosoma mansoni: Ub carboxyl-terminal hydrolase (UCH) and Ub-specific protease (USP). In this study, we analysed the ovarian tumour (OTU) and Machado-Joseph disease protein domain (MJD) proteases found in the Schistosoma mansoni genome database. An in silico analysis identified two different MJD subfamily members, SmAtaxin-3 and SmJosephin, and five distinct OTU proteases, SmOTU1, SmOTU3, SmOTU5a, SmOTU6b and SmOtubain. The phylogenetic analysis showed the evolutionary conservation of these proteins. Furthermore, the 3D structures confirmed the similarity of these proteins with human proteins. In addition, we performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and observed distinct expression profiles for all of the investigated transcripts between the cercariae, schistosomula and adult worm stages. Taken together, our data suggest that MJD and OTU subfamily members contribute to regulating the activity of the Ub-proteasome system during the life cycle of this parasite.


Effect of tympanic cavity evacuation and flushing on microbial isolates during total ear canal ablation with lateral bulla osteotomy in dogs.
To evaluate differences in bacterial numbers, identity, and susceptibility in samples obtained from the tympanic cavity on entry (preflush) and after evacuation and lavage (postflush) and assess perioperative and empiric antimicrobial selection in dogs that underwent total ear canal ablation (TECA) with lateral bulla osteotomy (LBO) or reoperation LBO. Prospective clinical study. 34 dogs. TECA with LBO or reoperation LBO was performed on 47 ears. Pre- and postflush aerobic and anaerobic samples were obtained from the tympanic cavity. Isolates and antimicrobial susceptibility patterns were compared. Different isolates (31/44 [70%] ears) and susceptibility patterns of isolate pairs (6/44 [14%] ears) were detected in pre- and postflush samples from 84% of ears. Evacuation and lavage of the tympanic cavity decreased the number of bacterial isolates by 33%. In 26% of ears, bacteria were isolated from post-flush samples but not preflush samples. Only 26% of isolates tested were susceptible to cefazolin. At least 1 isolate from 53% of dogs that received empirically chosen antimicrobials postoperatively was resistant to the selected drugs. Anaerobic bacteria were recovered from 6 ears. Accurate microbiologic assessment of the tympanic cavity should be the basis for selection of antimicrobials in dogs undergoing TECA with LBO. Bacteria remain in the tympanic cavity after evacuation and lavage. Cefazolin was a poor choice for dogs that underwent TECA with LBO, as judged on the basis of culture and susceptibility testing results.


Assessing the agreement between the partners at care transitions measure and the care transitions measure for elderly patients with chronic diseases.
Elderly patients with chronic diseases are very vulnerable during the transition from hospital to home and have a high need for transitional care. The quality of transitional care is closely related to patient health outcomes. Using appropriate scales to evaluate the quality of transitional care is important for efforts aimed at improving it. The study aimed to analyze the consistency between the Chinese version of the Partners at Care Transitions Measure (PACT-M) and the Care Transition Measure (CTM) in assessing the quality of transition care in elderly patients with chronic diseases. This is a cross-sectional study, we used a convenience sampling method to investigate patients with chronic diseases aged ≧ 65 years who were about to be discharged from the three affiliated hospitals of Zhengzhou University in Henan Province, from August 2021 to May 2022. The sample consisted of 196 elderly patients with chronic diseases. Data were collected using a demographic survey, PACT-M, and CTM. We used EpiData 3.1 software for systematic logical error checking, SPSS 21.0 to analyze the data, and the Bland-Altman analysis to analyze the consistency of the two scales. The mean total scores for PACT-M and CTM were 65.52 ± 6.23 and 52.07 ± 7.26, respectively. The 95% confidence interval (CI) for the mean difference and ratios were (-31.52, 4.61) and (0.85, 1.72), with 3.57% and 5.10% of the points outside the 95% CI limits, separately. The difference analysis of Bland-Altman showed a good consistency of the two scales, while the rate analysis did not meet the a priori definition of good consistency, but it is very close to 5%. Therefore, the consistency of the two scales in assessing the quality of transitional care for elderly patients with chronic diseases needs to be further validated.


A di-palladium urea complex as a molecular receptor for anions.
A new di-nuclear palladium complex containing thiol-urea ligands has been prepared, structurally characterized and its interaction with anionic species studied in solution.


Spirocyclic acylphloroglucinol derivatives from Hypericum beanii.
Four new acylphloroglucinols with an unusual 6/6/5 spirocyclic skeleton, hyperbeanols A-D (1-4), were isolated from the methanol extract of Hypericum beanii along with 16 known compounds. Their structures were established on the basis of spectroscopic and X-ray diffraction analysis. Hyperbeanols A-C were three stereoisomers different only at the relative configuration of C-4 and C-13, which were distinguished by the nuclear Overhauser effect spectroscopy (NOESY) spectroscopic data in combination with the single X-ray analysis of hyperbeanol A (1). The cytotoxic activity of hyperbeanols A-D against the cancer cell lines SK-BR-3, HL-60, SMMC-7721, PANC-1, MCF-7, and K562 was also evaluated.


Interaction of calcium, magnesium, and gastrin on gastric acid secretion.
A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 (SHG) in doses of 50, 200, and 500 ng/kg/hr was performed in 8 healthy volunteers. The study was repeated on separate days during i.v. infusion of magnesium sulphate (0.4 meq Mg2+/kg/hr), of calcium gluconate (0.1 meq Ca2+/kg/hr) and of magnesium sulphate plus calcium gluconate. Magnesium infusion resulted in an increase in the dose of SHG required for one-half maximal secretion (D50), whereas infusion of calcium decreased D50. The difference in D50 of SHG when administered in combination with magnesium and with calcium was significant. Combined infusion of SHG, magnesium, and calcium resulted in the same D50 of SHG as found when SHG was infused alone. The calculated maximal acid response was almost identical in the four experiments except for a minor but nonsignificant decrease during calcium infusion. The results indicate an interaction of calcium, magnesium, and gastrin on parietal cell function and extend the observations of others in intact humans as well as in isolated gastric mucosa.


Management of Cerebrospinal Fluid Rhinorrhea in the Sphenoid Sinus Lateral Recess Through an Endoscopic Endonasal Transpterygoid Approach With Obliteration of the Lateral Recess.
Cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess is a rare occurrence and poses unique challenges due to limited surgical access for surgical repair. To report our experience of surgical repair of cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess through an endoscopic endonasal transpterygoid approach with obliteration of the lateral recess. To evaluate the efficiency of this surgical procedure. A retrospective study. Twelve cases with cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess were reviewed. Assisted by image-guided navigation, cerebrospinal fluid rhinorrhea was repaired through an endoscopic endonasal transpterygoid approach, with obliteration of the lateral recess. Complications and recurrence were recorded. Medical photographs were used. This surgical approach provided a relatively spacious corridor to dissect the sphenoid sinus lateral recess and do postoperative surveillance. The repair area completely healed in 3 months after surgery. Cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess was successfully repaired on the first attempt in all cases (100%). No main complications or recurrence was observed during a mean follow-up time of 40.3 months. The endoscopic endonasal transpterygoid approach gives appropriate access for the treatment of spontaneous cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess. Multilayer reconstruction of a skull base defect with obliteration of the lateral recess is a reliable and simple method.


Standardization of 152Eu and 88Y.
The activities of 152Eu and 88Y have been measured by the digital coincidence counting (DCC) technique and compared with those of the conventional coincidence counting technique. In the DCC, the pulse amplitudes from both beta and gamma channels are digitized in commercial ADCs and the pulse input times are simultaneously determined by 10 MHz oscillation clock installed in the coincidence module. The activity of the measured source is determined from the information of pulse height and input time for each pulse by off-line analysis. The activity of 152Eu was determined from extrapolations of efficiency functions obtained at 3gamma gates and the result showed a good agreement with that of the conventional method with 0.2% of uncertainty. The activity of 88Y was also determined by the DCC technique, and the reliability of the result was proved through Asia Pacific Metrology Program (APMP) inter-comparison of 88Y.


Communicating Intelligence Research.
Despite intelligence research being among the most replicable bodies of empirical findings-a Rosetta stone across the social sciences-the communication of intelligence research with non-intelligence researchers and the public remains a challenge, especially given ongoing public controversies throughout the history of the field. Hunt argued that "we have a communication problem." This article is a call for intelligence researchers to consider communication at multiple levels-communication with other intelligence researchers, communication with non-intelligence researchers, and communication with the public, defined here as policymakers, practitioners, students, and general readers. It discusses ongoing tensions between academic freedom and social responsibility and provides suggestions for thinking about communication and effective research translation and implementation of intelligence research from the frameworks of science and policy research communication. It concludes with some recommendations for effective communication and stresses the importance of incentivizing more scholars to responsibly seek to educate and engage with multiple publics about the science of intelligence.


The effect of subliminal oedipal and competitive stimulation on dart throwing: another miss.
Silverman and his associates have reported that subliminal presentation of oedipally relevant competitive stimuli can modify dart-throwing performance in male subjects. This study replicated their paradigm, but also examined the effects on performance of nonoedipal competitive stimuli. Our results failed to support Silverman's. Both types of subliminally presented competitive stimuli failed to have any systematic effect on dart-throwing performance.


Spontaneous esophageal perforation presenting with right-sided pleural effusion.
Boerhaave's Syndrome (spontaneous esophageal perforation) is an uncommon clinical entity that frequently presents with an antecedent history of marked vomiting followed by chest or abdominal pain. Misdiagnosis is the most important contributing factor in the continuing high morbidity and mortality of this disease. We report an atypical presentation of Boerhaave's Syndrome in an elderly female who presented to the Emergency Department with dyspnea, right sided chest pain, right pleural effusion, and hypovolemic shock without an identifiable antecedent event. A chest radiograph revealed massive right hydropneumothorax. After placement of a chest tube, the patient was admitted to the intensive care unit. Only 36 hours after admission did the diagnosis of Boerhaave's Syndrome become evident. She underwent operative repair and, after a prolonged stay, was discharged in relatively good condition 3 months after her admission. The absence of vomiting prior to presentation and the right sided effusion are the distinguishing features of this particular case.


Microvascular Complications, Peripheral Artery Disease and Mortality in Patients with Type 2 Diabetes Mellitus, in Two Counties of Southern Lithuania over 13 Years: Analysis Using a Cohort Database of the National Health Insurance.
Background and Objectives: People living with diabetes mellitus are at risk of developing many serious and life-threatening complications. The present study aimed to determine the occurrence of microvascular complications, peripheral artery disease, and mortality in patients with type 2 diabetes mellitus (T2DM), in 2 Lithuanian counties. Materials and Methods: The data on residents aged ≥ 18 years, who were diagnosed for the first time in 2004 with uncomplicated T2DM, were obtained from the National Health Insurance Fund database. The occurrence of T2DM microvascular complications, peripheral artery disease, and mortality during the period from 2004 to 2016 were assessed by gender and age groups (<65 and ≥65 years). Results: During the 13 years, 46.9% of the patients developed T2DM complications. More men than women developed at least 1 T2DM complication (50.8% vs. 44.8%, p = 0.035). The mean time for developing any T2DM complication was 9.2 years. The probability of occurrence of any complication was 0.07 in the second year and increased to 0.59 in the thirteenth year of living with diabetes. Within the 13 years, 38.2% of the patients died. More men (43.1%) than women (35.5%) died during the analysis period (p = 0.036). Mortality was higher among older patients (60.7%) than among younger patients (22.2%) (p < 0.001). Conclusions: The results of this study provide a comprehensive picture of microvascular complications, peripheral artery disease, and mortality among patients with T2DM of two Lithuanian counties. Information about the occurrence of T2DM complications and mortality will assist further studies in estimating the burden of T2DM and in performing economic evaluations of T2DM prevention and treatment in Lithuania.


Immune surveillance mechanisms of the skin against the stealth infection strategy of Pseudomonas aeruginosa-review.
The present review aims to provide insight into the complex interactions between the host and Pseudomonas aeruginosa-an opportunistic microbial agent causing skin infections. Heat, humidity and skin pH are among the factors beneficial for the development of this Gram-negative agent. To cause infection, Pseudomonas aeruginosa should first overcome the primary mechanisms of defense including the cell elements and humoral factors of the skin, as well as non-specific responses-phagocytosis, inflammation, acute phase response. All they are analysed with emphasis on the fact that their detailed understanding would help revealing their potential and allow for their efficient control. The microorganism, being more alterable and more flexible than the host, uses stealth strategies and modes of life. The review goes over the arsenal of virulence factors, used by Pseudomonas aeruginosa to attack the host defense mechanisms. The bacterial pathogenic strategies for invasion, resulting in collapse of skin defense are analysed. Several novel therapeutic approached to Pseudomonas aeruginosa skin infections are briefly reviewed.


Child feeding practices in children with Down syndrome in relationship to ethnicity and BMI.
Children with Down syndrome (DS) exhibit higher overweight and obesity rates than their typically developing peers, although it is unknown whether parent feeding practices for children with DS are associated with child weight status or parental and demographic factors, especially in the Hispanic and Latino populations. A prospective study of 68 children with DS from 2 to 7 years of age, who received care at a single, large, pediatric academic hospital was conducted to evaluate parent child feeding practices. Parents completed the Child Feeding Questionnaire+ (CFQ+) assessing seven primary factors of feeding practices and comparisons to children without DS were conducted. Data for body mass index (BMI) and BMI-for-sex/age z score (BMIz scores) were collected in clinic at the time of CFQ+ completion for both parent and child. Parents of children with DS endorsed higher perceived responsibility but lower concern about child weight and restriction compared to previously reported feeding practices in typically developing children. Hispanic/Latino parents of children with DS reported higher perceived responsibility and monitoring than non-Hispanic/Latino parents of children with DS. Higher BMIz scores in children with DS correlated with greater perceived child weight (p = 0.001) and concern about child weight (p = 0.008). Differences in BMIz scores were observed when comparing sex/ethnicity groups as determined by one-way ANOVA (F(3,64) = 4.170, p = 0.009); with Hispanic/Latino boys with DS more likely to have obesity. Our results suggest a need for specific DS Guidelines to educate providers and parents of children with DS on recommended feeding practices prior to parental concern about their child's weight, especially in the Hispanic/Latino population.


Physicochemical prediction of a brain-blood distribution profile in polycyclic amines.
Recent investigation into the pharmacological character of the pentacyclo[22.214.171.124(2,6).0(3,10).0(5,9)]undecyl and related polycyclic amines has revealed interesting facts regarding their possible use as neuroprotective agents. At this stage however, a clear shortcoming in the quest for further development of this novel class of compounds is the lack of concrete data on their ability to cross the blood-brain barrier (BBB). Working towards the aim of predicting BBB permeability, a series of related N-substituted 8-amino-8,11-oxapentacyclo[184.108.40.206(2,6).0(3,10).0(5,9)]undecanes were synthesised. Compounds were characterised by both experimental and calculative methods, followed by biological assessment and statistical manipulation of the results obtained. In doing so, a simple biological model was established for the comparative evaluation of brain-blood distribution properties within the class. A highly sensitive ESI-MS.MS analytical procedure was developed for the detection of these compounds in biological tissues, indicating significant drug concentrations in the brain after intraperitoneal administration to C57Bl/6 mice. Stepwise multiple linear regression analysis of all data yielded two meaningful models (R(2)=0.9996 and R(2)=0.7749) depicting lipophilicity (log P(oct)), solvent accessible molecular volume (SV), molar refractivity (MR) and system energy as the prime determinants of the brain-blood profile for these amines. The inherently high lipophilicity potential within the series is attributed to strong hydrophobic influences dominating hydrogen bonding effects. A possible conformational and energy dependent preference at the site of permeation is also suggested. The proposed estimations allow for the expedient and reliable prediction of brain partitioning behaviour for related polycyclic amines, facilitating the early rejection of unsuitable candidates and enabling research to focus on neuroprotective activity.


Primary associates of mortality among dialysis patients: trends and reassessment of Kt/V and urea reduction ratio as outcome-based measures of dialysis dose.
Information from a large clinical database was used to construct time trends for the leading associates of mortality among dialysis patients. The changing strengths of association of those measures with mortal risk were also evaluated. Strength did not change in meaningful ways for serum albumin, creatinine, or anion gap concentrations. It declined for the urea reduction ratio (URR), however, as prevalent values of the URR increased. Irrational patterns of association between the URR and other measures suggested reevaluation of the urea kinetic method for prescribing and judging dialysis dose. Two premises on which the urea kinetic equations rest are not valid if the context for their use is clinical outcome instead of predicting blood urea nitrogen (BUN) concentration. Rigorous use of the Kt/V criterion for dialysis dose could lead to clinical judgment errors, particularly underdialysis for small or malnourished persons. Changes for prescribing dose and judging therapy are recommended.


Reproducible Peak Clusters on Differential Mouse Mortality Curves and Their Relation to the Gompertz Model.
It is shown that differentiation of mouse mortality curves (number of animals that died at a certain age plotted versus their lifespan) results in the appearance of eight clearly distinguished clusters of peaks corresponding to increased mortality rates. Smoothing of the original mortality curves and subsequent transformation of the differential mortality curves according to the Gompertz model makes the peaks and the corresponding clusters less pronounced and drives the logarithm of the force mortality curve toward a straight line. The positions of the clusters on the lifespan axis (expressed in days) were calculated as weighted means by dividing the sum of the products of multiplication of the peak heights and their position on the lifespan axis by the sum of the peak heights within a cluster. To prove that the peaks and their clusters are not random, we have demonstrated that the positions of the clusters on the lifespan axis do not depend on the extent of mortality curve smoothing or the group of mice analyzed.


Optical imaging of the spontaneous neuronal activities in the male rat major pelvic ganglion following denervation of the pelvic nerve.
Measurement of groups of neuronal activities following pelvic nerve transection to the major pelvic ganglion (MPG) of the rat was performed using voltage-sensitive dye (RH795) and an optical recording system. In control MPG, averaged neuron diameters were 32.0 +/- 0.6 x 22.6 +/- 0.4 microm. Application of KCl (10-50 mM) to the ganglia exhibited excitation which increased in a dose-dependent fashion. Fluctuating membrane potentials were not observed in control ganglion neurons. After the denervation of pelvic nerve chronically (2-6 weeks), the spontaneous neuronal activities were recorded in 91% of the experiments (n = 32). The activity was occurring somewhat periodically (2-15 s). Averaged neuron diameters were 41.3 +/- 1.3 x 24.7 +/- 0.9 microm in denervated MPG which is significantly larger than control. Since average neuron size increased 4 weeks after the denervation, the new excitatory activities could have influenced the change of the neuron size. The new activities might produce contraction of target organs in the pelvic viscera.


Glucagon like-peptide-1 receptor is covalently modified by endogenous mono-ADP-ribosyltransferase.
Our previous study revealed a mono-ADP-ribosyltransferase mediated in vitro mono-ADP-ribosylation of IC(3) peptide, a peptide with sequence corresponded to third intracellular loop of glucagon like-peptide-1 (GLP-1) receptor. Furthermore, Arg(348) was shown to be modified amino acid residue although its mutation did not eliminate mono-ADP-ribosylation completely. In order to further study the signaling mechanisms of GLP-1 receptor, we took on lease a possibility that an alternative site of enzymatic modification exist so mono-ADP-ribosylation of Cys(341) was hypothesized. The results confirmed both Arg(348) and Cys(341) as a site of mono-ADP-ribosylation where Arg(348) is modified predominantly. Sum of mono-ADP-ribosylation rate of both single IC(3) mutants coincided with IC(3) rate. What is in vivo role of Cys(341) mono-ADP-ribosylation is entirely speculative but our study represents an important step toward a complete understanding of signaling via GLP-1 receptor.


Treatment of electropolishing industrial wastewater and its impact on the immobilisation of Daphnia magna.
The amount of industrial pollution entering the environment and its impact on living organisms is an ongoing concern. At the same time, due to an increasing awareness, new methods of wastewater treatment are being explored that are not only effective but also environmentally acceptable. Meeting environmental standards for permitted concentrations is a necessity, but investigating the effects of wastewater on living organisms is also an important issue. In this paper, the influence of metal ions (Fe(III), Cr(III), Ni(II), Cu(II)) in industrial wastewater from electropolishing of stainless steel on Daphnia magna has been investigated. Daphnids have been exposed to wastewater both before and after treatment (Ca(OH)2 precipitation, sorption with peat). Immobilisation in a 48-h acute toxicity test and EC50 has been determined. In the case of studied industrial wastewater, the organic content (expressed as total organic carbon) of the effluent has a positive impact in terms of the survival of D. magna and increases the range of heavy metal concentrations tolerated by them. The application of a two-stage process with Ca(OH)2 neutralisation followed by sorption with peat allows for the removal of almost 100% of metal ions from the wastewater. The reduction obtained ensured a limited impact on D. magna and a decrease in immobilisation to less than 10%. Proper execution of the wastewater treatment process ensures a reduction of its negative impact on living organisms.


Excretion of methoxyphenamine and its metabolites in rat urine.
Metabolites of methoxyphenamine in urine obtained after oral administration of the drug to rats have been isolated by Sephadex LH-20 column chromatography and identified as the O-, N,O- and N-demethylated derivatives of methoxyphenamine by thin-layer chromatography, spectrometry, and comparisons with synthesized compounds. The unchanged drug and the metabolites excreted in urine have been extracted and determined by gas chromatography after treatment with trifluoroacetic anhydride.


Studies on the human spontaneous electromyelogram (EMyeloG). II. Patients with peripheral nerve, root and spinal cord disorders.
Using an intrathecal recording technique the spontaneous electromyelogram (EMyeloG) was recorded in 44 patients having peripheral nerve, spinal root and lower motor neurone disorders (17 cases), suprasegmental spinal cord disorders (18 cases) and diffuse involvement of the posterolateral funiculus or spinal ganglia (9 cases). In the first 17 cases, labelled as 'afferent group,' the spontaneous EMyeloG was significantly reduced, parallelling the paucity of afferent signals entering the spinal cord. However, the spontaneous EMyeloG was found to be normal in cases with the diffuse anterior horn cell involvement and motor polyneuropathy. In the second 18 cases labelled as 'efferent group,' the spontaneous EMyeloG was more prominent and the amplitude and frequency of the spontaneous cord potentials were significantly increased. Especially in patients with spastic paraparesis various peripheral afferent stimuli could produce more significant facilitation of the EMyeloG in the 'efferent group' than in normal subjects. In the third group labelled as 'mixed group' a different type of abnormal spontaneous action potentials was observed in addition to increase of the spontaneous EMyeloG. These potentials were positive or mainly positive and their duration was long, being 10-25 msec. It was concluded that the human spontaneous EMyeloG recorded from an intrathecal electrode probably originates from the interneurones of the posterior horns, facilitated by peripheral afferent inputs and inhibited by suprasegmental descending pathways, especially the pyramidal tract.


Functionalization of MWCNT and their application in properties development of green wood nanocomposite.
Starch based wood nanocomposites (WSNC) were prepared successfully from starch and soft wood with multi-walled carbon nanotube (MWCNT) as nano reinforcing agent through a completely green path. The most important part of this scheme was the use of water as the solvent. In this technique, starch was grafted with methylmethacrylate (MMA) and MWCNT was functionalised with hydroxyl groups (f-MWCNT). Dimethyloldihydroxyethyleneurea (DMDHEU) was used as a cross-linker to prepare the green material from methylmethacrylate grafted starch (MMA-g-starch), soft wood flour and functionalised MWCNT. The functionalization of MWCNT was confirmed by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and Raman analysis. Different properties of the WSNC were investigated by varying the concentration of f-MWCNT. The prepared nanocomposites exhibited outstanding thermal stability, mechanical properties and water resistance capacity compared to untreated wood composites. The flammability of the wood composites decreased up to 30% with just addition of 0.50phr f-MWCNT.


The characteristics of face configural effect in illiterates and literates.
Literacy acquisition can modulate the way we process visual words and language. However, little is known about its function in reshaping how we process non-linguistic materials, like faces. In this study, we explored this question by comparing the facial recognition skills of illiterate and literate adults in China. Our results showed that illiterates were less sensitive to changes in spatial configuration among key features in upright faces when stimuli were presented simultaneously. The differences in sensitivity of spatial configuration between the literates and illiterates were also observed in house processing. These results thus provide evidence that literacy acquisition during childhood could reshape configural processing.


A green versatile packaging based on alginate and anthocyanin via incorporating bacterial cellulose nanocrystal-stabilized camellia oil Pickering emulsions.
This study aims to develop a versatile intelligent packaging based on alginate (Alg) and anthocyanin (Ant) by incorporating bacterial cellulose nanocrystal-stabilized camellia oil Pickering emulsions. Firstly, bacterial cellulose nanocrystals (BCNs) matrix produced from kombucha was incorporated with camellia oil into via ultrasonic triggering, forming a stable and multifunctional camellia oil-bacterial cellulose nanocrystal Pickering nanoemulsions (CBPE). The microstructure and rheology results of the emulsion confirmed the stabilized preparation of CBPE. Subsequently, the CBPE was integrated into the three-dimensional network structure composed of alginate/anthocyanin. The composite film (Alg-Ant-CBPE) was designed through Ca2+ crosslinking, intermolecular hydrogen bonding and dehydration condensation. The fabricated color indicator films with different concentrations of CBPE (0.1 %-0.4 %), showed varying degree of improvement in hydrophobicity, UV shielding, mechanical strength, thermal stability, water vapor barrier properties and antioxidant capacities. When applied to yogurt, the Alg-Ant-CBPE4 exhibited more pronounced color changes compared to Alg-Ant, enabling visual detection of food freshness. In conclusion, the incorporation of Pickering nanoemulsion provides an effective and promising approach to enhance the performance of polysaccharide-based intelligent packaging.


Microneedle patches integrated with lateral flow cassettes for blood-free chronic kidney disease point-of-care testing during a pandemic.
Chronic kidney disease (CKD) is the most neglected chronic disease affecting over 750 million persons in the world. Currently, many patients with cancers or other chronic diseases (i.e., CKD) struggle to receive clinical treatment or examination due to hospitals cancelling or delaying in the COVID-19 pandemic, which may increase the risk of death. Cystatin C (Cys C) has been proposed as a potential glomerular filtration rate (GFR) marker for the early detection of acute kidney injury and CKD. However, most traditional methods for Cys C detection are immunoassays using serum as a sample and are tedious to perform and economically burdensome. To diagnose the disease in the early stage and carry out daily management during the current pandemic, we developed an integration of hydrogel microneedle patch (HMNP) and lateral flow cassette (LFC) to rapidly detect Cys C in skin interstitial fluid (ISF) in 25 min for blood-free CKD management anytime and anywhere by the naked eye that can reduce the impact of an individual's quality of life and life expectancy. Conceivably, this strategy presents a wide scope in the application of numerous other diseases if corresponding analytes are available in skin ISF.


Macular pigment densities derived from central and peripheral spectral sensitivity differences.
Estimates of the density spectrum of the macular pigment (Wyszecki G, Stiles WS. Color Science: Concepts and Methods. Quantitative Data and Formulas. 1st ed. New York: Wiley, 1967); (Vos JJ. Literature review of human macular absorption in the visible and its consequences for the cone receptor primaries. Institute for Perception. Soesterberg, The Netherlands, 1972) are partially based on the difference between central and peripheral spectral sensitivities, measured under conditions chosen to isolate a single cone class (Stiles WS. Madrid: Union Internationale de Physique Pure et Appliquée, 1953;1:65-103). Such derivations assume that the isolated spectral sensitivity is the same at both retinal locations, save for the intervening macular pigment. If this is true, then the type of cone class mediating detection should not influence the calculated difference spectrum. To test this assumption, we measured central and peripheral spectral sensitivities in a deuteranope, a protanope and a normal trichromat observer: (a) for short-wave sensitive (S-) cone detection; and (b) for long-wave sensitive (L-) cone detection (deuteranope), for middle-wave sensitive (M-) cone detection (protanope) or for both L- and M-cone detection (normal trichromat). The difference spectra determined for L- or M-cone detection deviate significantly from those measured for S-cone detection, at wavelengths below 450 nm. A theoretical analysis suggests that the discrepancies are owing, in part, to regional variation in the optical density of the cone pigments; and that such receptor variation cannot be ignored when deriving the standard density spectrum of the macular pigment.