Hypoxia induces p53 accumulation in the S-phase and accumulation of hypophosphorylated retinoblastoma protein in all cell cycle phases of human melanoma cells.
Hypoxia has been shown to induce accumulation of p53 and of hypophosphorylated retinoblastoma protein (pRb) in tumour cells. In this study, the cell cycle dependence of p53 accumulation and pRb hypophosphorylation in four human melanoma cell lines that are wild type for p53 was investigated using two-parameter flow cytometry measurements of p53 or pRb protein content and DNA content. The hypoxia-induced increase in p53 protein was higher in S-phase than in G1 and G2 phases in all cell lines. The accumulation of p53 in S-phase during hypoxia was not related to hypoxia-induced apoptosis or substantial cell cycle specific cell inactivation during the first 24 h of reoxygenation. pRb was hypophosphorylated in all cell cycle phases by hypoxia treatment. The results did not support a direct link between p53 and pRb during hypoxia because p53 was induced in a cell cycle-specific manner, whereas no cell cycle-dependent differences in pRb hypophosphorylation were detected. Only a fraction of the cell populations (0.60+/-0.10) showed hypophosphorylated pRb. Thus, pRb is probably not the only mediator of the hypoxia-induced cell cycle block seen in all cells and all cell cycle phases. Moreover, the cell cycle-dependent induction of p53 by hypoxia suggests that the primary function of p53 accumulation during hypoxia is other than to arrest the cells.


West Nile Virus Neuroinvasive Disease Accelerating Probable Dementia With Lewy Bodies.
We describe a case of dementia with Lewy bodies immediately following encephalitis due to West Nile virus (WNV). The patient had rapid eye movement-sleep behavior disorder and constipation before the onset of encephalitis, which suggests that he would have ultimately developed dementia with Lewy bodies even without WNV infection. Our case illustrates the interactions between α-synuclein and WNV, as observed in mouse models, wherein synuclein expression augments after WNV infection and protects neurons against the virus.


Neighborhood deprivation and depressive symptoms in Chinese adolescents: Mediated by parenting styles and moderated by relative family status.
Previous research has shown that neighborhood and family have a crucial impact on adolescent mental health. However, limited research has been conducted on the intersection between neighborhood and family and the mechanisms behind its influence. This study investigates the direct and indirect associations between neighborhood deprivation and adolescent depressive symptoms through parental responsiveness and demandingness. The heterogeneity of neighborhood effects, varying across different relative family statuses, is also discussed. Using a sample (n = 6775) from the two waves of the China Education Panel Survey, this study used moderated mediation analysis to analyze simultaneously the mediation roles of parental responsiveness and demandingness and the moderating effect of relative family status. Neighborhood deprivation (W1) was positively associated with adolescent depressive symptoms (W2). Parental responsiveness (W2) rather than demandingness (W2) partially mediated the relationship between neighborhood deprivation and adolescent depression. Additionally, relative family status moderated the direct relationship between neighborhood deprivation and depression and the indirect relationship through parental responsiveness. First, Neighborhood deprivation in this study was self-reported. Second, relative family status was a single-item measure. Third, only family and neighborhood environments were discussed in this study. Finally, long-term changes in the mental health of adolescents in poor neighborhoods could not be captured in this study. The results highlight that neighborhood deprivation and relative family status can influence adolescent mental health individually and intersectively. This study also contributes to a more nuanced understanding of parenting styles in the Chinese context.


Lifetime obesity in patients with eating disorders: increasing prevalence, clinical and personality correlates.
The aims of our study were to examine the lifetime prevalence of obesity rate in eating disorders (ED) subtypes and to examine whether there have been temporal changes among the last 10 years and to explore clinical differences between ED with and without lifetime obesity. Participants were 1383 ED female patients (DSM-IV criteria) consecutively admitted, between 2001 and 2010, to Bellvitge University Hospital. They were assessed by means of the Eating Disorders Inventory-2, the Symptom Checklist-90-Revised, the Bulimic Investigatory Test Edinburgh and the Temperament and Character Inventory-Revised. The prevalence of lifetime obesity in ED cases was 28.8% (ranging from 5% in anorexia nervosa to 87% in binge-eating disorders). Over the last 10 years, there has been a threefold increase in lifetime obesity in ED patients (p < .001). People with an ED and obesity had higher levels of childhood and family obesity (p < .001), a later age of onset and longer ED duration; and had higher levels of eating, general and personality symptomatology. Over the last 10 years, the prevalence of obesity associated with disorders characterized by the presence of binge episodes, namely bulimic disorders, is increasing, and this is linked with greater clinical severity and a poorer prognosis.


Recovery from early cortical damage in rats. II. Effects of experience on anatomy and behavior following frontal lesions at 1 or 5 days of age.
Perinatal cortical damage is often associated with significant overall shrinkage of the remaining cortex and severe behavioral impairments. Environmental experience was manipulated in order to determine if the anatomical and behavioral effects of neonatal frontal decortication might be attenuated by rearing in a complex environment. Rats received frontal decortication on the day of birth or 5 days later and were subsequently raised, along with littermate controls, in a complex environment or in standard laboratory cages. In adulthood, the animals were tested on a battery of behavioral tests which showed that enrichment markedly attenuated the effects of the early lesions, especially for the 5-day operates, even on tests such as tongue extension that would not be expected to benefit from specific practice in the complex environment. Analysis of the remaining cortex revealed that all groups raised in the complex environment developed thicker cortex, the increase being most dramatic in the rats given lesions at 5 days of age.


Corrigendum: DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia.
[This corrects the article DOI: 10.3389/fgene.2018.00646.].


Focal physiologic fluorodeoxyglucose activity in the gastrointestinal tract is located within the colonic lumen.
Physiologic activity of 18F-fluorodeoxyglucose (FDG) in the intestinal tract occurs frequently in patients undergoing PET/computed tomography (CT) imaging, appearing most often in the colon. The purpose of this study is to determine the localization of the FDG within the colon. We hypothesize that intestinal FDG activity is intraluminal. In a prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, patients with physiologic colonic FDG activity on PET/CT scans were enrolled to undergo repeat imaging 2 h after stimulation of colonic motility with a high-fat meal. We identified 13 patients who had focal FDG activity in their colon during a routine clinical PET/CT scan. After administration of a high-fat meal, 10 patients (77%) demonstrated antegrade movement of FDG along the colon, consistent with luminal clearance. Our results suggest that normal physiologic FDG activity within the large intestine, seen on PET/CT scans, is intraluminal.


Regrowth of Legionella pneumophila in a heat-disinfected plumbing system.
We examined the factors involved in the occurrence of Legionellaceae in a hospital water system and the recontamination by Legionella pneumophila after a thermal disinfection procedure was studied. Three months after the heat treatment (70 degrees C), the regrowth of the two prevalent Legionella strains (L. pneumophila serogroup 1 [Oxford-like] and L. pneumophila serogroup 2) reached the original level of cell numbers. Genomic analysis (pulsed-field gel electrophoresis) revealed the strains to be survivors of the decontamination. Temperature tolerance experiments showed that the serogroup 1 strain exhibited a higher tolerance to 60 degrees C than the serogroup 2 strain, which could account for the order of reappearance of the strains after the heat treatment. Potential host amoebae, including Acanthamoeba spp. and Vahlkampfia spp., which are known to play a critical role in the amplification process of Legionella, were isolated from the plumbing system. In-vitro studies demonstrated both Legionella strains for a similar rate of multiplication in A. castellanii. In competitive coinfections, however, the serogroup 1 strain achieved a higher rate of multiplication if compared with the serogroup 2 strain.


circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression.
In recent years, circular RNAs (circRNAs) have been shown to have critical regulatory roles in the resistance to anti-cancer drugs. However, the contributions of circRNAs to sorafenib resistance in hepatocellular carcinoma (HCC) remain largely unknown. The present study aims to explore the involvement of circFN1 in sorafenib resistance and how circFN1 is associated with the miR-1205/E2F1 pathway, which have been demonstrated to mediate this resistance in HCC cells. We investigated the expression of circRNAs in five paired sorafenib-sensitive HepG2 cells and sorafenib-resistant (SR)-HepG2 cells by microarray analysis. The quantitative real-time PCR analysis was used to investigate the expression pattern of circFN1 in HCC patient tissues and cell lines. Then, the effects of circFN1 on sorafenib resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. In this study, circFN1 was observed to be upregulated in HCC patient tissues and cell lines. Overexpression of circFN1 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. Our in vivo and in vitro data indicated that inhibition of circFN1 enhances the sorafenib sensitivity of HCC cells. Mechanistically, we found that circFN1 could promote the expression of E2F1 by sponging miR-1205. In summary, our study demonstrated that circFN1 contributes to sorafenib resistance by regulating the miR-1205/E2F1 signaling pathway. These results indicate that circFN1 may represent a potentially valuable target for overcoming sorafenib resistance for HCC.


Surgical treatment using an allograft dermal matrix for nasal septal perforation.
Numerous methods have been utilized to repair nasal septal perforation with varying degrees of success; however, no consensus has been reached on nasoseptal perforation repair. Here, the authors describe a surgical method based on human dermal allograft (Surederm, Hans Biomed Corp. Korea) for the repair of nasal septal perforations. Eleven patients with a nasal septal perforation were included in this study. The causes of these septal perforations included previous nasal surgery, trauma, foreign body (button battery), and idiopathy. There were several sites of perforation: 9 in the central area, 1 in the posterior-central area, and 1 in the anterior area. An interpositional graft incorporating Surederm was positioned between bilateral mucoperichondrial flaps using an intranasal approach. A silastic sheet was then left in the nasal septum bilaterally until complete healing had occurred through new nasal mucosa, which took a mean duration of 6 weeks. Outcomes in ten of the eleven patients were successful, with complete septal perforation closure. The remaining perforation, which was caused by a button battery, closed incompletely; however, its initial size of 2 cm was reduced to 5 mm. The described technique has a high success rate and can be performed under local anesthesia without external scarring. In the absence of donor site morbidity, this technique can also be utilized to repair posterior or multiple septal perforations without difficulty.


[Levosimendan for septic shock with takotsubo cardiomyopathy].
As a stress-induced disease, takotsubo cardiomyopathy can also occur in septic syndromes; however, the hemodynamic management is fundamentally different from the treatment approaches for classical septic cardiomyopathy, as beta mimetics can increase the heart failure symptoms in takotsubo cardiomyopathy. This article reports the case of an 82-year-old female patient who presented with acute abdomen due to adhesion ileus and takotsubo cardiomyopathy, developed severe septic shock with peritonitis and could be successfully hemodynamically stabilized with levosimendan.


The interaction of calmodulin with human erythrocyte spectrin. Inhibition of protein 4.1-stimulated actin binding.
The functional significance of calmodulin binding to human erythrocyte spectrin has been investigated under native conditions. Both native calmodulin and calmodulin derivatized with the photoactivable cross-linker methyl 4-azidobenzimidate (azidocalmodulin) have been used. When azidocalmodulin is photolyzed in the presence of erythrocyte ghosts, ghost extracts, or purified protein, it cross-links predominately to the beta subunit of erythrocyte spectrin. This cross-linking is calcium-dependent, requires photolysis, and is inhibited by 100 microM trifluoperazine or unlabeled calmodulin. Calmodulin labeled spectrin exhibits a specific and non-calcium-dependent inhibition of its ability to bind actin, even in the presence of protein 4.1. Its ability to self-associate or to bind spectrin-depleted membrane vesicles is unperturbed. Native calmodulin also inhibits protein 4.1-stimulated spectrin-actin binding, but unlike that of covalently bound calmodulin, inhibition by the uncross-linked calmodulin requires calcium. The degree of inhibition of spectrin-actin-4.1 binding induced by native calmodulin is significant since 109 microM calmodulin inhibits over 63% of the spectrin-actin binding induced by 4.5 microM protein 4.1. These results demonstrate a specific effect of calmodulin on erythroid spectrin function and suggest that calmodulin may influence the binding of protein 4.1 and actin to spectrin within the cytoskeleton.


Cancer incidence and mortality attributable to alcohol consumption.
Alcohol consumption is a major cause of disease and death. In a previous study, we reported that in 2002, 3.6% of all cases of cancer and a similar proportion of cancer deaths were attributable to the consumption of alcohol. We aimed to update these figures to 2012 using global estimates of cancer cases and cancer deaths, data on the prevalence of drinkers from the World Health Organization (WHO) global survey on alcohol and health, and relative risks for alcohol-related neoplasms from a recent meta-analysis. Over the 10-year period considered, the total number of alcohol-attributable cancer cases increased to approximately 770,000 worldwide (5.5% of the total number of cancer cases)-540,000 men (7.2%) and 230,000 women (3.5%). Corresponding figures for cancer deaths attributable to alcohol consumption increased to approximately 480,000 (5.8% of the total number of cancer deaths) in both sexes combined-360,000 (7.8%) men and 120,000 (3.3%) women. These proportions were particularly high in the WHO Western Pacific region, the WHO European region and the WHO South-East Asia region. A high burden of cancer mortality and morbidity is attributable to alcohol, and public health measures should be adopted in order to limit excessive alcohol consumption.


Is radical cystectomy indicated in patients with regional lymphatic metastases?
The records of 21 patients who had radical cystectomies for the treatment of locally advanced bladder cancer and were found to have regional lymphatic metastases have been reviewed. Ten of these patients had only one lymph node involved (N1), and 11 patients had metastases in more than one lymph node (N2-3). Four patients with N1 disease and 1 patient with N2-3 disease survived tumor-free greater than forty months postoperatively. Radical cystectomy can produce long-term disease-free survival in some patients with limited pelvic metastases.


Systematic bibliometric and visualized analysis of research hotspots and trends on the application of artificial intelligence in diabetic retinopathy.
Artificial intelligence (AI), which has been used to diagnose diabetic retinopathy (DR), may impact future medical and ophthalmic practices. Therefore, this study explored AI's general applications and research frontiers in the detection and gradation of DR. Citation data were obtained from the Web of Science Core Collection database (WoSCC) to assess the application of AI in diagnosing DR in the literature published from January 1, 2012, to June 30, 2022. These data were processed by CiteSpace 6.1.R3 software. Overall, 858 publications from 77 countries and regions were examined, with the United States considered the leading country in this domain. The largest cluster labeled "automated detection" was employed in the generating stage from 2007 to 2014. The burst keywords from 2020 to 2022 were artificial intelligence and transfer learning. Initial research focused on the study of intelligent algorithms used to localize or recognize lesions on fundus images to assist in diagnosing DR. Presently, the focus of research has changed from upgrading the accuracy and efficiency of DR lesion detection and classification to research on DR diagnostic systems. However, further studies on DR and computer engineering are required.


Identification of a new DNA polymerase activity in human KB cells.
We have isolated and partially characterized a new DNA polymerase activity from the purified nuclear fraction of cultured human KB cells. The physical and chemical properties of this enzyme which we have designated DNA polymerase N3 define it as a unique entity that can be distinguished from the several classes of eukaryotic D-DNA and R-DNA polymerase activity that have been recognized to date.


Diagnostic contribution of routine cerebro-spinal fluid analysis during myelography.
The laboratory summary sheets and patient charts concerning 500 consecutive myelograms were reviewed to see whether a routine cerebro-spinal fluid analysis at the time of a neuroradiological procedure made any significant diagnostic contribution. A relatively high frequency of abnormal findings was noted but in no case was significant clinical information obtained. Routine cerebrospinal fluid analysis during myelography does not on the basis of this study seem appropriate.


Effect of temperature on selenium removal from wastewater by UASB reactors.
The effect of temperature on selenium (Se) removal by upflow anaerobic sludge blanket (UASB) reactors treating selenate and nitrate containing wastewater was investigated by comparing the performance of a thermophilic (55 °C) versus a mesophilic (30 °C) UASB reactor. When only selenate (50 μM) was fed to the UASB reactors (pH 7.3; hydraulic retention time 8 h) with excess electron donor (lactate at 1.38 mM corresponding to an organic loading rate of 0.5 g COD L(-1) d(-1)), the thermophilic UASB reactor achieved a higher total Se removal efficiency (94.4 ± 2.4%) than the mesophilic UASB reactor (82.0 ± 3.8%). When 5000 μM nitrate was further added to the influent, total Se removal was again better under thermophilic (70.1 ± 6.6%) when compared to mesophilic (43.6 ± 8.8%) conditions. The higher total effluent Se concentration in the mesophilic UASB reactor was due to the higher concentrations of biogenic elemental Se nanoparticles (BioSeNPs). The shape of the BioSeNPs observed in both UASB reactors was different: nanospheres and nanorods, respectively, in the mesophilic and thermophilic UASB reactors. Microbial community analysis showed the presence of selenate respirers as well as denitrifying microorganisms.


Deoxyarbutin displays antitumour activity against melanoma in vitro and in vivo through a p38-mediated mitochondria associated apoptotic pathway.
Deoxyarbutin (DeoxyArbutin, dA), a natural compound widely used in skin lighting, displayed selectively cytotoxicity in vitro. In the study, we found that dA significantly inhibited viability/proliferation of B16F10 melanoma cells, induced tumour cell arrest and apoptosis. Furthermore, dA triggered its pro-apoptosis through damaging the mitochondrial function (membrane potential loss, ATP depletion and ROS overload generation etc.) and activating caspase-9, PARP, caspase-3 and the phosphorylation of p38. Treatment with p38 agonist confirmed the involvement of p38 pathway triggered by dA in B16F10 cells. The in vivo finding also revealed that administration of dA significantly decreased the tumour volume and tumour metastasis in B16F10 xenograft model by inhibiting tumour proliferation and inducing tumour apoptosis. Importantly, the results indicated that dA was specific against tumour cell lines and had no observed systemic toxicity in vivo. Taken together, our study demonstrated that dA could combate tumour in vitro and in vivo by inhibiting the proliferation and metastasis of tumour via a p38-mediated mitochondria associated apoptotic pathway.


Teacher ratings of children's problem and competence behaviors: normative and parametric characteristics.
Teacher-rated adjustment differences among young elementary school children from (a) a recent sample and a 1974 cohort, and (b) urban/suburban, male/female, and grade-level subgroups were examined. A problem behavior checklist (Classroom Adjustment Rating Scale) and a school competence measure (Health Resources Inventory) for 974 children from 5 urban and 5 suburban schools were completed by 101 first- to fourth-grade teachers. Children from the more current cohort were rated as significantly more maladjusted than those from the earlier sample on 8 of 10 adjustment variables. In the recent sample, girls and suburban children evidenced a greater number of school competencies and fewer problem behaviors than boys and urban children, respectively. The implications of these findings for the future use of the teacher rating scales are discussed.


[Indicator of periodontal therapeutic needs (CPITN) in adults aged between 35-44 years from three population groups in Cracow province].
Parodontological therapeutic needs in 180 persons aged between 35-44 years among inhabitants of Cracow, Wieliczka and villages of Cracow province have been determined. Among women and men under examination the following needs have predominated: the necessity of dental deposits removal and curretage of pathological gingival pockets (75.56--77.78%). In 39 persons (21.68%) there was a need of complex treatment.


Induction and peak gene expression of insulin-like growth factor II follow that of myogenin during differentiation of BC3H-1 muscle cells.
Acting through hormonal and/or autocrine/paracrine mechanisms, the insulin-like growth factors (IGFs) stimulate the differentiation of muscle cells. Previous studies have suggested that one mechanism by which IGFs stimulate muscle cell differentiation is by increasing the expression of myogenin, a DNA binding protein that regulates the expression of muscle-specific genes. While exogenous IGF peptides increase myogenin mRNA, the role of endogenously produced IGF peptides in myogenin expression has not been established. In addition, the potential role of IGFs in regulating the expression of Id, a protein in myoblasts that can inhibit the action of myogenin-like peptides, is also unknown. In the present study, we have examined the kinetics of accumulation of myogenin and IGF-II mRNAs during differentiation of BC3H-1 mouse muscle cells and have explored the potential role of IGFs in regulating Id expression. During differentiation induced by serum withdrawal, induction of myogenin expression preceded that of IGF-II, the principal IGF peptide expressed by these cells. In addition, Id expression decreased within two hours in serum-free medium and was not affected by IGF treatment. Thus, these studies suggest that endogenously-produced IGF-II may stimulate muscle cell differentiation after both the decrease in Id and the induction of myogenin gene expression have occurred.


ABR in the diagnosis of vestibular schwannomas: a meta-analysis.
The aim of this study is to rigorously evaluate the role of auditory brainstem response (ABR) testing in the diagnosis of vestibular schwannomas (VS). Searches were conducted in multiple online databases, supplemented by hand searches. From the studies chosen for final inclusion, relevant data were extracted and meta-analysis of pooled data was performed. 623 studies were identified from which 43 met inclusion criteria for analysis (1978 to 2009) including 3314 patients. Pooled sensitivity for ABR detection of vestibular schwannomas was 93.4% (95% CI 92.6-94.3, P=0.0000). For tumors less than 1cm (8 studies, 176 patients) sensitivity was 85.8% (95% CI 80.6-90.1, P=0.0116). For tumors greater than 1cm (6 studies, 251 patients) pooled sensitivity was 95.6% (95% CI 93.1-98.2, P=0.0660). Sensitivity of ABR to detect extracanalicular tumors was higher than for intracanalicular tumors, though pooled data were not statistically valid. Pooled specificity (8 studies, 2432 patients) was 82.0% (95% CI 80.5-83.6, P=0.0000). Although MRI remains the gold standard, emerging trends towards more conservative management coupled with limited financial resources may prompt many clinicians to review the role of ABR testing in screening for retrocochlear pathology. In light of the high sensitivity and specificity of ABR testing for VS, we strongly urge its reconsideration as a useful diagnostic tool for patients with clinically suspected VS.


Non-invasive assessment of carotid PWV via accelerometric sensors: validation of a new device and comparison with established techniques.
Carotid pulse wave velocity (PWV) is considered as a surrogate marker for carotid stiffness and its assessment is increasingly being used in clinical practice. However, at the moment, its estimation needs specific equipment and a moderate level of technical expertise; moreover, it is based on a mathematical model. The aim of this study was to validate a new system for non-invasive and model-free carotid PWV assessment based on accelerometric sensors by comparison with currently used techniques. Accelerometric PWV (accPWV) values were obtained in 97 volunteers free of cardiovascular disease (age 24-85 years) and compared with standard ultrasound-based carotid stiffness parameters, such as carotid PWV (cPWV), relative distension (relD) and distensibility coefficient (DC). Moreover, the comparison between accPWV measurements and carotid-femoral PWV (cfPWV) was performed. Accelerometric PWV evaluations showed a significant correlation with cPWV measurements (R = 0.67), relD values (R = 0.66) and DC assessments (R = 0.64). These values were also significantly correlated with cfPWV evaluations (R = 0.46). In addition, the first attempt success rate was equal to 76.8 %. The accelerometric system allows a simple and quick local carotid stiffness evaluation and the values obtained with this system are significantly correlated with known carotid stiffness biomarkers. Therefore, the presented device could provide a concrete opportunity for an easy carotid stiffness evaluation even in clinical practice.


Regulation of lipogenesis in adipocytes. Independent effects of thyroid hormones, cyclic AMP and insulin on the uptake of deoxy-D-glucose.
Thyroidectomy is known to enhance fat cell phosphodiesterase activity; as a result, the response to lipolytic hormones is markedly reduced. Thyroidectomy also stimulates overall lipogenesis and the uptake of glucose: the present experiments investigated whether there was a correlation between cyclic AMP and glucose uptake. The parameter measured was the transport and phosphorylation (uptake) of deoxy-D-glucose in the presence of two modifiers of the cyclic AMP pool: phosphodiesterase inhibitors and the analogue, dibutyryl cyclic AMP. The inhibition by methylxanthines and dibutyryl cyclic AMP of deoxy-D-glucose uptake observed, was the same in fat cells from normal and thyroidectomized rats: the latter nonetheless still maintained their enhanced glucose uptake. It was therefore concluded that thyroid hormones and cyclic AMP control this step by different, separate pathways. Insulin, well known for its lipogenic effect, enhanced deoxy-D-glucose uptake in fat cells from both normal and thyroidectomized rats to the same extent (about 40%). An additive effect of thyroidectomy and insulin on glucose uptake was thus demonstrated. These results imply that glucose uptake in the adipocyte is controlled by at least three factors: thyroid hormones, cyclic AMP and insulin, each of which can act independently. Maximum glucose uptake is achieved in the presence of a combination of low concentrations of cyclic AMP, of insulin, and in the absence of thyroid hormones.


Hemopoiesis-stimulating activity of immobilized oligonucleotides and hyaluronidase during cytostatic-induced myelosuppression.
The hemopoiesis-stimulating effect of combined treatment with immobilized oligonucleotides and hyaluronidase preparations was studied during cytostatic-induced myelosuppression caused by cyclophosphamide administration. Immobilized hyaluronidase was shown to increase the efficiency of correction of changes in the erythroid and granulocytic hemopoietic stems with immobilized oligonucleotides. This potentiation of the effect of immobilized oligonucleotides by immobilized hyaluronidase was related to an increase in functional activity of committed hemopoietic precursors.


Detection of a 65 kDa ras binding protein in rat and sheep brain cytosol using a chemical cross linking agent.
The ability of a ras protein to associate with proteins present in rat brain cytosol in vitro was investigated using chemical cross-linking agents and the 125I-labelled v-H-ras protein. Two iodinated protein complexes with apparent molecular weights of 40 and 85 kDa were observed when a mixture of rat brain cytosol and [125I] ras was treated with the cross-linking agent disuccinimidyl suberate and subjected to SDS-PAGE. Formation of the [125I] Formation of the[125I] 85 kDa complex was enhanced by a high concentration of EDTA while generation of the 40 kDa species was abolished by this treatment. Formation of the [125I] 85 kDa complex was inhibited by unlabelled ras protein, GTP, GTP gamma S, and GDP but not by ATP gamma S and GMP. Chromatography of the cross-linked brain cytosol[125I] ras mixture on DEAE cellulose partially resolved the [125I] 85 kDa complex from the [125I] ras protein. The [125I] 85 kDa complex (formed using ethyleneglycolbis (succinimidylsuccinate) as the cross-linking agent) could be immunoprecipitated using a rabbit anti-ras polyclonal antibody. Treatment of the immunoprecipitate with hydroxylamine to cleave the cross-link yielded [125]I-labelled ras. A substantial enrichment of the proportion of the [125I] 85 kDa complex in the cross-linked extract was achieved by preparative SDS-PAGE. It is concluded that the in vitro chemical cross-linking approach employed here has detected two ras binding proteins in rat brain cytosol: a 65 kDa heat-sensitive and a 20 kDa heat-stable protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in structure of ventral epidermis of Rana ridibunda during metamorphosis.
The organisation of the ventral epidermis organisation was followed throughout ontogenesis in Rana ridibunda. Epidermis of tadpoles with 2-3 limbs was organised into two layers: a stratum germinativum consisting of elongated columnar cells, and an outer stratum corneum consisting of two types of cuboid cells. Two types of cells can be distinguished; they are a light (clear) cell and a dark (dense) cell. In the 4-legged tadpoles the stratum corneum cells start to flatten and a replacement layer appeared underneath. A well-defined stratum germinativum is found and within it, epidermal glands. Moulting took place for the first time in tadpoles just before metamorphosis, and a well-organised stratum granulosum was formed still containing the two main types of epidermal glands. The flask cells appear in the juveniles for the first time, greatly increasing in numbers in the adult epidermis.


Increasing the power of clinical trials through judgment analysis.
A method for increasing the statistical power of clinical trials to detect clinically important differences is described. Inconsistency in physicians' overall judgments of treatment effectiveness adds "noise" to a trial that may mask either the superiority or the inferiority of particular treatments. The method described here uses "judgment analysis" to reduce errors in an individual's overall judgments of treatment effectiveness. The method can also be used to reduce error variance due to differences in judgment between physicians and may thus be particularly useful in multicenter trials. The method is illustrated with results from a recent trial.


Maternal serum alpha-fetoprotein values in type 1 and type 2 diabetic patients.
Maternal serum alpha-fetoprotein (MSAFP) values are reported to be lower in type 1 diabetic patients, and a correction factor is often applied. We sought to determine whether type 2 diabetic patients require the same MSAFP adjustments as type 1 diabetic patients. We performed a retrospective review of MSAFP levels from a university laboratory in type 1 and type 2 diabetic patients between July 2000 and August 2006, matched 1:2 with controls. Groups were compared using analysis of variance and Student t testing. Seventy-seven type 1 and 75 type 2 diabetic patients were compared with 304 controls. Type 1 and type 2 diabetic patients differed significantly from each other and controls before corrections. Diabetic patients were similar to each other, but significantly lower than controls, after weight corrections. These differences were eliminated by a 10% correction factor. Type 1 and type 2 diabetic patients require both weight and diabetes corrections to adjust MSAFP values to nondiabetic levels.


Multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney: CT and MRI findings and clinical characteristic.
The aim of this study was to clarify the radiologic and clinical characteristics of multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney. Fourteen patients with unique and characteristic multiple hemorrhagic subcapsular cortical cysts of the kidney, not categorized in any existing renal cystic diseases, were retrospectively reviewed. The clinical information including age, sex, symptom, family history of renal or renal cystic disease, and laboratory data were collected. CT and MRI findings including distribution, number and size of cysts, and CT attenuation and signal intensity on T1- and T2-weighted MRI of cysts were analyzed. All patients except one were young and none had a family history of renal or renal cystic disease. Common clinical symptoms were flank or abdominal pain and hematuria. In all cases, only the left kidney was involved at initial presentation. Cysts were small (median cyst size, 4-15 mm), numerous, and distributed mainly along the subcapsular cortex of the kidney. Cysts were hyper-attenuated on unenhanced CT, extremely hypointense on T2-weighted MRI, and mildly hyperintense on T1-weighted MRI. All patients except one had normal renal function. Imaging follow-up revealed stable or mildly progressive disease in seven patients. Two patients developed several hemorrhagic subcapsular cortical cysts in the right kidney at follow-up. Three of five patients with a renal pathology specimen showed concurrent IgA nephropathy. We have identified a unique renal cystic disease with multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney that has a characteristic manifestation both radiologically and clinically. • Multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney is a unique non-familial renal cystic disease with a characteristic manifestation both radiologically and clinically. • Most cases of multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney are stable or slowly progressive, and do not require invasive intervention.


Cognitive effects of valproate.
The effects of valproate on cognition are usually considered to be minimal, but few formal neuropsychological studies are available. We studied the psychomotor performances of 20 seizure-free epileptics during fixed valproate monotherapy and after its withdrawal. Our findings suggest some adverse effects of valproate which appear to be completely reversible after withdrawal.


N(6)-2'-O-dibutyryl cyclic AMP stimulates glycogenolysis and inhibits fatty acid synthesis in rat liver in vivo but has little effect on gluconeogenesis. In adipose tissue: it enhances lipogenesis and glycogenesis. These last effects can be explained by an increase of insulin release.


Pregnancy and Lactation: Risk or Protective Factors for Breast Cancer?
Pregnancy and lactation represent the most effective protective elements against breast cancer; counter-intuitively breast cancer incidence shows a small but noticeable increase up to 5 years after delivery. The cumulative effect is however favourable and women show a reduction in breast cancer risk which is proportional to the total duration of lactation and to the number of full-term pregnancies.


The weak immunosuppressant cyclosporine D as well as the immunologically inactive cyclosporine H are potent inhibitors in vivo of phorbol ester TPA-induced biological effects in mouse skin and of Ca2+/calmodulin dependent EF-2 phosphorylation in vitro.
Various biological effects induced by the tumor promoting phorbol ester TPA in mouse skin are comparably suppressed by the immunologically inactive cyclosporine H (CsH) and by the strongly immunosuppressive cyclosporine A (CsA). These effects inhibited include the development of edema, stimulation of alkaline phosphatase activity, DNA and protein synthesis, as well as tumor promotion. Furthermore, CsH, like CsA, inhibits the Ca2+/calmodulin-dependent phosphorylation of the elongation factor 2 (EF-2) in vitro and the TPA-induced increases in the amount of EF-2 in vivo. Similar observations were made using the weak immunosuppressant CsD. We conclude from these results that the ability of cyclosporines to act as immunosuppressants and their ability to inhibit TPA-effects are based on two different mechanisms of action. Inhibition of TPA-effects may involve suppression of calmodulin-dependent processes, such as augmentation and phosphorylation of EF-2.


Renal haemodynamic changes in response to moderate hyperglycaemia in type 1 (insulin-dependent) diabetes mellitus.
The prevailing blood-glucose level has been found to influence renal haemodynamics in type 1 (insulin-dependent) diabetes mellitus. In a group of 48 type 1 diabetic patients with normal serum creatinine (less than 120 mumol l-1) and without persistent proteinuria, no relationship was present between blood glucose, corrected to near normoglycaemia (6.8 [6.2 to 7.3] mmol l-1 (median [95% confidence interval]), and glomerular filtration rate (GFR), effective renal plasma flow (ERPF) determined with 125I-iothalamate and 131I-hippuran respectively. GFR tended to increase (2 [-1 to +4] ml min-1 1.73 m-2, 0.05 less than P less than 0.10) and ERPF did not change after a blood glucose rise of 7.9 (7.0 to 8.9) mmol l-1, achieved by an intravenous glucose load in 31 patients. The individual changes in GFR and ERPF were correlated (r = 0.60, P less than 0.005). The changes in GFR were inversely related to baseline blood glucose (r = -0.45, P less than 0.02), but not to baseline GFR. GFR increased (3.5 [0 to +12] ml min-1 1.73 m-2, P less than 0.01) if baseline blood glucose was less than or equal to 6.8 mmol l-1 (n = 16) but ERPF did not. Achievement of near normoglycaemia before measurement of kidney function in type 1 diabetes appears to reduce the influence of variation in glycaemia on renal haemodynamics and thus would improve comparison between and within individuals. Moderate hyperglycaemia can cause a small rise in the glomerular filtration rate.


Screening of beta-thalassemia mutations by PCR and ASO analysis in an Italian population of mixed geographic origin.
We used the polymerase chain reaction (PCR) and allele-specific-oligonucleotide hybridization (ASO) or restriction enzyme analysis (RE) to investigate the molecular defect in 100 Italian subjects heterozygous for beta-thalassemia, members of 50 couples at risk for the disease: 93 out of the 100 alleles studied were identified after investigating 9 known mutations. The mutation was identified in both members of the couple in 43/50 cases; in the remaining 7 couples the defect was identified only in one subject. The PCR-ASO or-RE method is a suitable, though still complex, approach to prenatal diagnosis of beta-thalassemia in a population with heterogeneous molecular defects.


Evaluation of metabolic changes induced by polyphenols in the crayfish Astacus leptodactylus by metabolomics using Fourier transformed infrared spectroscopy.
In the present study, the effects of polyphenols on the chemical composition of the hepatopancreas of the Astacus leptodactylus, a highly sought farmed crayfish, have been investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The hepatopancreas spectrum was quite complex and contained several peaks arising from the contribution of different functional groups belonging to protein, lipids and carbohydrates. The PCA statistical analysis revealed that there were significant differences between crayfish fed a diet without polyphenols and crayfish fed a diet containing polyphenols. Such differences indicated an increase in lipids and proteins in the hepatopancreas of polyphenol-fed crayfish. In conclusion, the analysis of the infrared spectral profile of the hepatopancreas of Astacus leptodactylus, allowed us to elucidate the changes in different biomolecules in response to polyphenol treatment, and confirms the suitability of ATR-FTIR spectral data to analyze diet-induced metabolic effects. These considerations, coupled with the small amount of sample and no preparation needed, make ATR-FTIR a useful tool for routine analyses where the metabolic impact of substances is investigated, especially with a large number of samples.


Preparation of steel slag porous sound-absorbing material using coal powder as pore former.
The aim of the study was to prepare a porous sound-absorbing material using steel slag and fly ash as the main raw material, with coal powder and sodium silicate used as a pore former and binder respectively. The influence of the experimental conditions such as the ratio of fly ash, sintering temperature, sintering time, and porosity regulation on the performance of the porous sound-absorbing material was investigated. The results showed that the specimens prepared by this method had high sound absorption performance and good mechanical properties, and the noise reduction coefficient and compressive strength could reach 0.50 and 6.5MPa, respectively. The compressive strength increased when the dosage of fly ash and sintering temperature were raised. The noise reduction coefficient decreased with increasing ratio of fly ash and reducing pore former, and first increased and then decreased with the increase of sintering temperature and time. The optimum preparation conditions for the porous sound-absorbing material were a proportion of fly ash of 50% (wt.%), percentage of coal powder of 30% (wt.%), sintering temperature of 1130°C, and sintering time of 6.0hr, which were determined by analyzing the properties of the sound-absorbing material.


Analysis of hemoglobin oxygen equilibrium curves. Are unique solutions possible?
As a hemoglobin tetramer is oxygenated, it converts from a form with low ligand affinity to a high-affinity structure. This allosteric transition occurs in partially liganded molecules, typically after two or three ligands are bound. As a result of the co-operative nature of the process, the populations of the partially liganded forms are low. The relative proportions and precise properties of these intermediate substrates are therefore difficult to measure and are subject to controversy. The problem is compounded by compensating effects; for example, over-estimation of the oxygen affinity of triply liganded forms will result in under-estimation of the proportion of these species. Specifically, published values for the oxygen affinity of the triply liganded species vary for identical conditions by a factor of more than 6. In analyses based on the highest affinity values, the triply liganded species virtually disappears. However, this affinity is usually calculated from the last few per cent of the oxygenation curve, and this part of the curve is extremely sensitive to the normalization of the data. We conclude that unique solutions for the ligand affinity and substrate populations may be impossible to achieve, and that unusual mechanisms based on particular combinations of parameters, therefore, should be viewed with caution.


The effect of nintedanib on lung functions and survival in idiopathic pulmonary fibrosis: real-life analysis of the Czech EMPIRE registry.
The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry. Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated. During 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN). Our real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.


Comparative Analysis of RNA-Extraction Approaches and Associated Influences on RT-qPCR of the SARS-CoV-2 RNA in a University Residence Hall and Quarantine Location.
Wastewater-based epidemiology (WBE) provides an early warning and trend analysis approach for determining the presence of COVID-19 in a community and complements clinical testing in assessing the population level, even as viral loads fluctuate. Here, we evaluate combinations of two wastewater concentration methods (i.e., ultrafiltration and composite supernatant-solid), four pre-RNA extraction modifications, and three nucleic acid extraction kits using two different wastewater sampling locations. These consisted of a quarantine facility containing clinically confirmed COVID-19-positive inhabitants and a university residence hall. Of the combinations examined, composite supernatant-solid with pre-RNA extraction consisting of water concentration and RNA/DNA shield performed the best in terms of speed and sensitivity. Further, of the three nucleic acid extraction kits examined, the most variability was associated with the Qiagen kit. Focusing on the quarantine facility, viral concentrations measured in wastewater were generally significantly related to positive clinical cases, with the relationship dependent on method, modification, kit, target, and normalization, although results were variable-dependent on individual time points (Kendall's Tau-b (τ) = 0.17 to 0.6) or cumulatively (Kendall's Tau-b (τ) = -0.048 to 1). These observations can support laboratories establishing protocols to perform wastewater surveillance and monitoring efforts for COVID-19.


Partial median "I" sternotomy: minimally invasive alternate approach for aortic valve replacement.
Minimally invasive aortic valve replacement using the inversed L-like partial upper sternotomy has evolved during the last 10 years. It is performed with excellent results with regard to sternal stability and cosmesis. However, the lateral incision may result in sternal overriding, instability, or fracture. We present an alternate minimally invasive approach to aortic valve replacement. We performed a partial median "I" sternotomy in 30 consecutive patients: After a 6- to 8-cm skin incision, the sternum was incised from the jugulum downward to the corpus, ending at the level of the fourth or fifth intercostal space. No lateral incision of the sternum was performed. The access to the heart and aorta was excellent. During the postoperative course and during follow-up, clinical examination revealed sternal stability and normal wound healing in all patients. These results show that the partial median I sternotomy can be performed safely and provides excellent clinical and cosmetic results.


Mortality, survival and prevalence: traumatic spinal cord injury in Olmsted County, Minnesota, 1935-1981.
Mortality, prevalence, and survival from traumatic spinal cord injury were examined in Olmsted County, Minnesota, from 1935 through 1981. One hundred and fifty-four incident cases and 30 additional cases who were Olmsted County residents on at least one of four prevalence dates were identified. The average annual age-adjusted mortality for spinal cord injury, including deaths attributable to spinal cord injury occurring at any time after injury was 28.5 per million population. The rates in males were consistently greater than females, peaking to 61.0 in the period 1965-74. Thirty-eight percent of cases did not survive long enough to be hospitalized. Survival was 58% in the first week post-injury. However, for those who survived the first day and the first year, the 10-year survival was 77 and 87%, respectively. Early fatality in males was associated with single marital status (p = 0.0033) and concomitant head trauma (p = 0.0122), and in females with pedestrian or bicyclist status at injury (p less than 0.0001). Long-term survival was dependent on age (p less than 0.0001) and functional disability (p = 0.04). Point prevalence of spinal cord injured patients increased from 197 per million population in 1950 to 473 in 1980. This increase in prevalence was due at least in part to increasing incidence over time. An improvement in survival over the time period of the study could not be detected.


Retracted: Ant Colony Algorithm-Based Audit Supervision to Promote the Optimization of New Infrastructure Investment Environment.
[This retracts the article DOI: 10.1155/2022/7454982.].


Tracing the evolution of vertebrate fibrillar collagens from an ancestral alpha chain.
From considerations of gene structure, phylogenetic analysis, modular organisation of related proteins and fibril shapes, we suggest a model for the evolution of contemporary vertebrate fibrillar collagens from a common ancestral alpha chain.


Conversion of levulinic acid to 2-butanone by acetoacetate decarboxylase from Clostridium acetobutylicum.
In this study, a novel system for synthesis of 2-butanone from levulinic acid (γ-keto-acid) via an enzymatic reaction was developed. Acetoacetate decarboxylase (AADC; E.C. 18.104.22.168) from Clostridium acetobutylicum was selected as a biocatalyst for decarboxylation of levulinic acid. The purified recombinant AADC from Escherichia coli successfully converted levulinic acid to 2-butanone with a conversion yield of 8.4-90.3 % depending on the amount of AADC under optimum conditions (30 °C and pH 5.0) despite that acetoacetate, a β-keto-acid, is a natural substrate of AADC. In order to improve the catalytic efficiency, an AADC-mediator system was tested using methyl viologen, methylene blue, azure B, zinc ion, and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) as mediators. Among them, methyl viologen showed the best performance, increasing the conversion yield up to 6.7-fold in comparison to that without methyl viologen. The results in this study are significant in the development of a renewable method for the synthesis of 2-butanone from biomass-derived chemical, levulinic acid, through enzymatic decarboxylation.


Hormonal, cardiovascular, and subjective responses to acute stress in smokers.
There are complex relationships between stress and smoking; smoking may reduce the emotional discomfort of stress, yet nicotine activates stress systems and may alter responses to acute stress. It is important to understand how smoking affects physiological and psychological outcomes after stress and how these may interact to motivate smoking. This study aimed to examine the magnitude and time course of hormonal, cardiovascular, and psychological responses to acute psychosocial stress in smokers and non-smokers to investigate whether responses to acute stress are altered in smokers. Healthy male non-smokers (n = 20) and smokers (n = 15) participated in two experimental sessions involving a standardized public speaking stress procedure and a control non-stressful task. The outcome measures included self-reported mood, cardiovascular measures (heart rate and blood pressure), and plasma hormone levels (noradrenaline, cortisol, progesterone, and allopregnanolone). Smokers exhibited blunted increases in cortisol after the Trier Social Stress Test, and they reported greater and more prolonged subjective agitation than non-smokers. Stress-induced changes in progesterone were similar between smokers and non-smokers, although responses overall were smaller among smokers. Stress did not significantly alter levels of allopregnanolone, but smokers exhibited lower plasma concentrations of this neurosteroid. These findings suggest that smoking dampens hormonal responses to stress and prolongs subjective discomfort. Dysregulated stress responses may represent a breakdown in the body's ability to cope efficiently and effectively with stress and may contribute to smokers' susceptibility to acute stress, especially during abstinence.


Patients with lung cancer undergoing immune checkpoint inhibitors: A meta-analysis of dermatological toxicities.
Immune checkpoint inhibitors are affirming as standard care for advanced lung cancer treatment. Despite their proved efficacy, alone or in combination, they are capable to provoke several cutaneous immune-mediated adverse events. This systematic review aimed to determine the prevalence of cutaneous toxicity in patients with lung cancer undergoing immune checkpoint inhibitors alone, combined, or associated with chemotherapy and/or radiotherapy. The searches were performed in CINAHL, Cochrane CENTRAL, LILACS, LILIVO, PubMed, Scopus, and Web of Science. We included both clinical trials and observational studies that described cutaneous toxicities presented by patients during treatment with immunological checkpoint inhibitors. The final sample consisted of 24 studies in which 9127 patients were evaluated. In included studies, the drug under consideration were ipilimumab, pembrolizumab nivolumab, and atezolizumab, at different dosages. The most prevalent dermatological toxicities were alopecia (27%), pruritus, and rash (10%). Remarkably, the prevalent severity was graded 1-2 for both alopecia, pruritus and rash.


Rapid progression and future of environmental DNA research.
Environmental DNA based research is a new field within molecular ecology that is seeing an amazing increase in research activity. In our Communications Biology article, we studied the degradation of eDNA in variable systems. Presented here is a short overview of eDNA science and current research activities underway in North Wales.