Ig/EBP (C/EBP gamma) is a transdominant negative inhibitor of C/EBP family transcriptional activators.
Analysis of cDNA and genomic clones shows that the murine Ig/EBP (C/EBP gamma) gene encodes a small protein with a predicted molecular weight of 16.4 kDa which contains C/EBP family basic and leucine zipper domains but lacks the transcriptional activation domains present in C/EBP (C/EBP alpha) and NF-IL6 (C/EBP beta). In transfection assays Ig/EBP is neither an activator nor a repressor of transcription; however, Ig/EBP inhibits the transcriptional ability of NF-IL6 (C/EBP beta) and C/EBP (C/EBP alpha), acting as a transdominant negative regulator. Thus Ig/EBP resembles LIP, another negative regulator of the C/EBP family, in both structure and transcriptional activity. Of the three known C/EBP family inhibitors, Ig/EBP, LIP and CHOP-10, only Ig/EBP is ubiquitously expressed. Therefore, Ig/EBP may act as a general buffer for C/EBP activators in many cell types.


Conjunctival eosinophil infiltration evoked by histamine and immediate hypersensitivity. Modification by H1- and H2-receptor blockade.
The present histological studies have demonstrated that histamine causes dose-dependent eosinophil infiltration into the conjunctiva. A highly directional movement toward the conjunctival epithelium was observed, and the presence of large numbers of degranulating eosinophils appeared to result in epithelial cell damage and goblet cell discharge. Blockade of H2-receptors by systemic cimetidine pretreatment significantly inhibited the eosinophil infiltration elicited by an intermediate histamine dose, whereas the H1-receptor blockade produced by systemic pyrilamine pretreatment markedly reduced the response to all histamine doses. The pyrilamine-insensitive residual eosinophil infiltrate was not affected by administering a cimetidine-pyrilamine combination. In animals presensitized to ovalbumin, antigen challenge evoked extensive and directional emigration of eosinophils toward the conjunctival epithelium with resultant exfoliation and depletion of goblet cell populations. In conjunctival immediate hypersensitivity, neither cimetidine nor pyrilamine alone produced an inhibitory effect, but a cimetidine-pyrilamine combination caused a significant reduction in the number of infiltrating eosinophils and prevented epithelial damage and goblet cell depletion. These results suggest that histamine may participate in the recruitment of eosinophils during immediate hypersensitivity reactions. The differential effect of pyrilamine on the eosinophil infiltration evoked by histamine or immediate hypersensitivity may, perhaps, reflect the importance of increased microvascular permeability in facilitating eosinophil emigration.


The role of regulatory T cells in preeclampsia.
Preeclampsia is a multisystem disorder of unknown cause that is unique to human pregnancy affecting about 7-10% of pregnant women. CD4+CD25(bright) regulatory T (Treg) cells have been identified as a principle regulator of tolerance during pregnancy. The aim of this study was to demonstrate the change of peripheral CD4+CD25(bright) regulatory T lymphocytes in normal pregnancy and preeclampsia, and to explore its role in the pathogenesis of preeclampsia. We determined CD4+CD25(bright) Treg cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3+) cells at the peripheral blood using real time PCR. 30 preeclamptic cases (group 1), 10 normal pregnancy subjects (group 2) and 10 non-pregnant healthy controls (group 3) were included. There was a highly significant decrease as regards Treg count and percentage in preeclamptic cases compared to normal pregnancy subjects (P < 0.001), decrease in preeclamptic cases compared to non-pregnant healthy controls (P < 0.001) and a significant increase in normal pregnancy subjects compared to non-pregnant healthy controls (P < 0.05). There was a statistically significant decrease as regards RQ of foxp3 gene expression in preeclamptic cases compared to normal pregnancy subjects (P < 0.001). There was no significant correlation between RQ and studied variables in preeclamptic cases (P > 0.05). These findings suggest that the number of Treg cells are decreased in preeclampsia, and this decrease may break the maternal tolerance to the fetus.


Memantine effects measured with the Relevant Outcome Scale for Alzheimer's disease in an open-label, single-arm, multicenter clinical study.
The Relevant Outcome Scale for Alzheimer's disease (ROSA) is a novel, valid, and reliable instrument for multidimensional assessment of Alzheimer's disease (AD) symptoms across all severity stages. The ROSA and four standard instruments -- the Alzheimer's disease Assessment Scale-cognitive (ADAS-cog), Severe Impairment Battery (SIB), Disability Assessment for Dementia (DAD), and the Neuropsychiatric Inventory (NPI) -- were used in an open-label, multicenter, single-arm clinical study to assess treatment-induced changes in cognitive, functional, and behavioral symptoms in patients with AD at different severity stages. A total of 451 patients were treated with memantine (initiated at 5 mg/day and up-titrated with 5 mg weekly to a final dose of 20 mg/day) for 12 weeks. The study endpoints comprised changes from baseline in the scores of the ROSA, ADAS-cog, SIB, DAD, and NPI as well as global changes on the Clinical Global Impression of Change (CGI-C). Analyses were performed for the overall population and by AD severity stage (early, middle, late). The ROSA scores increased significantly after a 12-week treatment in all study groups except for early stage. Mean changes in the ADAS-cog score indicated a trend towards worsening in early and middle stages. Non-significant changes were shown by the SIB, NPI, and DAD assessments at week 12. The CGI-C demonstrated 'minimal improvement' or 'no change' for most of the patients. Overall, memantine treatment was safe and well tolerated. The results demonstrated the ROSA feasibility in daily practice for assessment of memantine effects over time in patients with moderate and late AD.


Gynostemma pentaphyllum Attenuates the Progression of Nonalcoholic Fatty Liver Disease in Mice: A Biomedical Investigation Integrated with In Silico Assay.
Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in developed countries. Oxidative stress plays a critical role in the progression of NAFLD. Modern pharmacological study and clinical trials have demonstrated the remarkable antioxidant activity of Gynostemma pentaphyllum (GP) in chronic liver disease. One aim of this study was to explore the potential protective effects and mechanisms of action of GP extract on NAFLD. The in vivo results showed that GP extract could alleviate fatty degeneration and haptic fibrosis in NAFLD mice. For exploring the hepatoprotective mechanisms of GP, we used network pharmacology to predict the potential active components of GP and their intracellular targets in NAFLD. Based on the network pharmacology results, we further utilized biomedical assays to validate this in silico prediction. The results showed that Gypenoside XL could upregulate the protein level of PPARα in NAFLD; the transcription level of several PPARα downstream target genes such as acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-1 (CPT-1) also increased after Gypenoside XL treatment. The overexpression of ACO and CPT-1 may involve the hepatoprotective effects of GP and Gypenoside XL on NAFLD by regulating mitochondrial fatty acid β-oxidation.


Toxicity of an algal mucopolysaccharide for Escherichia coli and Neisseria meningitidis strains.
Several bacterial strains of clinical significance have been tested to assess the toxic effect of a lectin-like algal mucopolysaccharide from Fucus vesiculosus on their growth. The toxic effect of the mucopolysaccharide has been found to be exerted only on Escherichia coli and Neisseria meningitidis strains. The degree of toxicity, measured by the effect on the growth of the bacteria, is variable depending on the strains of E. coli tested, whereas with N. meningitidis the results obtained indicate homogeneity between the strains, without significative variations among different serotypes even in the same serogroup.


Adaptive responses of the embryo to maternal diet and consequences for post-implantation development.
Maternal periconceptional (PC) nutrition, coupled with maternal physiological condition, can impact on reproductive performance and potential across mammalian species. Oocyte quality and embryo development are affected adversely by either nutrient restriction or excess. Moreover, the quality of maternal PC nutrition can have lasting effects through fetal development and postnatally into adulthood. Chronic disease, notably cardiovascular and metabolic disease, and abnormal behaviour have been identified in adult offspring in small and large animal models of PC nutrient restriction. These long-term effects associate with compensatory responses that begin from the time of early embryo development. This review assesses the field of PC nutrition in vivo on short- and long-term developmental consequences in rodent and ruminant models and considers the implications for human health.


VO2 Nanoflakes as the Cathode Material of Hybrid Magnesium-Lithium-Ion Batteries with High Energy Density.
The hybrid magnesium-lithium-ion batteries (MLIBs) combining the dendrite-free deposition of the Mg anode and the fast Li intercalation cathode are better alternatives to Li-ion batteries (LIBs) in large-scale power storage systems. In this article, we reported hybrid MLIBs assembled with the VO2 cathode, dendrite-free Mg anode, and the Mg-Li dual-salt electrolyte. Satisfactorily, the VO2 cathode delivered a stable plateau at about 1.75 V, and a high specific discharge capacity of 244.4 mA h g-1. To the best of our knowledge, the VO2 cathode displays the highest energy density of 427 Wh kg-1 among reported MLIBs in coin-type batteries. In addition, an excellent rate performance and a wide operating temperature window from 0 to 55 °C have been obtained. The combination of VO2 cathode, dual-salt electrolyte, and Mg anode would pave the way for the development of high energy density, safe, and low-cost batteries.


Physicians and care management: more acceptance than you think.
Physicians' acceptance of care management tools--practice guidelines, patient satisfaction surveys and practice profiling--is an important indication of whether these efforts to improve quality and control health costs will succeed. According to a new study by the Center for Studying Health System Change (HSC), a majority of physicians affected by these tools believe the overall effect of each on the quality and efficiency of care they provide has been positive. Physicians affected by related financial incentives are more likely to view care management techniques positively if they are risk adjusted to reflect the greater need for services by people with health problems.


Localization of fibrinolytic activity in ovulation of the rat follicle as determined by the fibrin slide method.
The localization and changes of fibrinolytic activity during the process of ovulation were investigated by the fibrin slide method. In regular estrous cycle rats, fibrinolytic activity first appeared in the external area of the follicle wall (stigma) at 12 hr before ovulation. No activity was noted in the follicular cavity at this time. A peak of activity was seen at 2 hr before ovulation. After ovulation, the activity decreased markedly. The activity was completely inhibited on fibrin slides to which 10(-2) M trans-aminomethyl-cyclohexane carboxylic acid had been added. No activity was observed on plasminogen-free fibrin slides. These results suggest that fibrinolytic activity is one of the important factors involved in the rupture of the mature follicle wall, and that the fibrinolytic activity is due to plasminogen activator activity.


Association of renal failure with thyroid dysfunction: a retrospective cohort study.
Chronic renal failure is often associated with multiple organ co-morbidities, including thyroid dysfunction. This has been associated with poorer prognosis, particularly in patients with end-stage renal disease. This study aimed to examine the relationship between renal failure and thyroid dysfunction in an outpatient setting at the King Abdulaziz University Hospital, Saudi Arabia, from January 2011 to June 2012. Demographic and biochemical data were extracted from medical records. Differences in the levels of thyroid hormones and lipids between the four renal function groups were analyzed using the chi-square test for categorical variables and Kruskal- Wallis test for binomial variables. A total of 486 patients were included in the study population, of whom approximately half were female, and the median (range) age was 61 (17-90) years. According to creatinine measurements, renal function was normal in 48 participants, 290 had mild renal failure, 122 had moderate renal failure and 26 had severe renal failure. No significant relationships were observed between renal failure and cardiac or pulmonary dysfunction. Free triiodothyronine (FT3) levels were significantly reduced (P = 0.005) and both free thyroxin (FT4; P = 0.034) and parathyroid hormone (PTH; P = 0.028) significantly increased with increasing severity of renal failure. Patients with moderate to severe renal failure displayed reduced hemoglobin levels and were significantly more likely to be anemic (P <0.001). Highly significant increases in alkaline phosphatase (P <0.001), uric acid (P <0.001) and low-density lipoprotein-cholesterol (P = 0.014) levels were also observed with increasing renal dysfunction. To conclude, it was observed that renal dysfunction is associated with notable changes to other organ systems, including the thyroid. Further studies may investigate the association of multiple organ co-morbidities with prognosis in patients with chronic renal failure.


Post-Caesarean section niche-related impaired fertility: hypothetical mechanisms.
Caesarean section can result in an indentation of the myometrium at the site of the Caesarean scar, called a niche. Niches can cause symptoms of abnormal uterine blood loss, dysmenorrhoea, chronic pelvic pain and dyspareunia and are possibly related to subfertility. Various other explanations for the cause of subfertility after Caesarean section have been proposed in the literature, such as uterine pathology, intra-abdominal adhesions and women's reproductive choices. Not all niches cause symptoms and the relation with subfertility and a niche in the uterine scar still needs further study since direct evidence is lacking so far. Based on the limited available evidence, and in combination with observations made during sonographic hysteroscopic evaluations and laparoscopic niche repair, we propose and discuss three hypothetical mechanisms: (i) the environment for sperm penetration and implantation may be detrimental; (ii) there could be a physical barrier to embryo transfer and implantation; and (iii) psychogenic factors may reduce the likelihood of pregnancy. Several innovative surgical treatments have been developed and are being implemented for niche-related problems. Promising results are reported, but more evidence is needed before further implementation in daily practice. The additional value of niche resections should be compared to expectant management or fertility therapies, such as ART, in randomized controlled trials. Therefore, our suggested hypotheses should, for the time being, not be used for justification of any specific procedures outside clinical trials.


Communities of arbuscular mycorrhizal fungi in arable soils are not necessarily low in diversity.
Communities of arbuscular mycorrhizal fungi (AMF) in five agricultural field sites of different management intensities were studied. Variable regions of the ribosomal RNA genes were used to detect and identify AMF directly within colonized roots. Roots from a continuous maize monoculture showed low AMF diversity, in agreement with previous reports on molecular diversity of AMF in agricultural soils. In contrast, a substantially higher diversity of AMF was found throughout the long term 'DOK' field experiment, where organic and conventional agricultural practices have been compared side by side since 1978. In this experiment, a 7-year crop rotation is performed under lower levels of inorganic fertilizer input and chemical pest control. These results are in good agreement with analyses of the spore community previously conducted in these field sites. In a third site, an organically managed leek field with soil of very high phosphate content reflecting the highly intensive conventional field history and intensive tillage, we detected a low-diversity community comparable to the maize monoculture. In addition to fungi from Glomus group A, which have previously been reported to dominate arable soils, we regularly found members of the genera Scutellospora, Paraglomus and Acaulospora. The genus Acaulospora was shown to occur more frequently early in the growing season, suggesting that the life history strategy of AMF may influence the active community at a given time. These data show that the diversity of AMF is not always low in arable soils. Furthermore, low-input agriculture involving crop rotation may provide better conditions to preserve AMF diversity, by preventing the selection for the few AMF taxa tolerating high nutrient levels.


Epigenetic targeting of cancer stem cells by polyphenols (cancer stem cells targeting).
Epigenetic alterations are one of the main factors that disrupt the expression of genes and consequently, they have an important role in the carcinogenicity and the progression of different cancers. Cancer stem cells (CSCs) are accountable for the recurrence, metastasis, and therapeutic failure of cancer. The noticeable and specific pathways in CSCs can be organized by epigenetic mechanisms such as DNA methylation, chromatin remodeling, regulatory RNAs, among others. Since epigenetics modifications can be changed and reversed, it is a possible tool for cancer control and treatment. Epigenetic therapies against CSCs are emerging as a very new strategy with a good future expectation to treat cancer patients. Phenolic compounds are a vast group of substances with anticarcinogenic functions, antiinflammatory, and antioxidative activities. It seems these characteristics are related to neutralizing CSCs development, their microenvironment, and metabolism through epigenetic mechanisms. In the current work, the types of epigenetic changes known in these cells are introduced. In addition, some studies about the use of polyphenols acting through a variety of epigenetic mechanisms to counteract these cells will be reviewed. The reported results seem to indicate that the use of these phenolic compounds may be useful for CSCs defeat.


HBV-related cutaneous periarteritis nodosa in a patient 16 years after renal transplantation: efficacy of lamivudine.
Cutaneous periarteritis nodosa (PAN) is a clinical feature characterized by chronic, benign course; its pathogenesis is unknown. In patients submitted to renal transplantation cutaneous PAN is a rare complication. We report a case of cutaneous PAN associated with the reappearance of hepatitis B antigen 16 years after kidney transplantation. A 44-year-old man underwent successful renal transplantation in June 1980. In December 1996 he presented multiple painful erythematous subcutaneous nodules on both legs. Skin lesion biopsy showed the presence of cutaneous PAN. Six months later laboratory data demonstrated the presence of HbsAg. HBeAg, HBcAb and detectable HBV-DNA serum by polymerase-chain-reaction (PCR) assay. Anti-HBs and anti-HBe proved negative. In July 1998 the laboratory tests showed an important increase of HBV-DNA (5.1 billion by Branched DNA), and so lamivudine (100 mg/day) was introduced. HBV-DNA became undetectable by PCR after 3 months of therapy. Seven months later a new skin biopsy was performed. The typical signs of PAN were no longer evident. As HBV infecion was demonstrated six months after the clinical appearance of the PAN, in a patient who was believed to be immune to the virus, it is possible that, in the early stages, the hepatitis B antigen title was methodologically indeterminable, but sufficient to form circulating immune complexes responsible for vasculitis primer. Lamivudine therapy resulted efficacious in favouring the regression of cutaneous PAN, but its long-term efficacy requires further evaluation as regards potential selection of drug resistant hepatitis B virus (HBV) mutants during treatment.


Diagnostic Accuracy of Point-of-Care Gastric Ultrasound.
Pulmonary aspiration of gastric contents is associated with significant perioperative morbidity and mortality. Previous studies have investigated the validity, reliability, and possible clinical impact of gastric ultrasound for the assessment of gastric content at the bedside. In the present study, we examined the accuracy (evaluated as sensitivity, specificity, and likelihood ratios) of point-of-care gastric ultrasound to detect a "full stomach" in a simulated scenario of clinical equipoise. After a minimum fasting period of 8 hours, 40 healthy volunteers were randomized in a 1:1 ratio to either remain fasted or ingest a standardized quantity of clear fluid or solid. Each subject was randomized twice on 2 independent study sessions at least 24 hours apart. A gastric ultrasound examination was performed by a blinded sonographer following a standardized scanning protocol. Using a combination of qualitative and quantitative findings, the result was summarized in a dichotomous manner as positive (any solid or >1.5 mL/kg of clear fluid) or negative (no solid and ≤1.5 mL/kg of clear fluid) for full stomach. Data from 80 study sessions were analyzed. In this simulated clinical scenario with a pretest probability of 50%, point-of-care gastric ultrasound had a sensitivity of 1.0 (95% confidence interval [CI], 0.925-1.0), a specificity of 0.975 (95% CI, 0.95-1.0), a positive likelihood ratio of 40.0 (95% CI, 10.33-∞), a negative likelihood ratio of 0 (95% CI, 0-0.072), a positive predictive value of 0.976 (95% CI, 0.878-1.0), and a negative predictive value of 1.0 (95% CI, 0.92-1.0). Our results suggest that bedside gastric ultrasound is highly sensitive and specific to detect or rule out a full stomach in clinical scenarios in which the presence of gastric content is uncertain.


Chronic hallucinatory psychosis. A case report.
Chronic hallucinatory psychosis is a clinical picture described by Ballet in 1912. Together with paraphrenia and paranoia, it forms a part of the chronic delusions that describes the French nosology separately from schizophrenia. It is characterized by the presence of mental automatism, chronic hallucinations and secondary delusions. This is a fairly uncommon clinical picture in our setting and is often confused with other pictures. We report a case of a 52-year-old woman and we discuss various clinical and diagnostic issues related to the disturbance.


Categorical templates are more useful when features are consistent: Evidence from eye movements during search for societally important vehicles.
Unlike in laboratory visual search tasks-wherein participants are typically presented with a pictorial representation of the item they are asked to seek out-in real-world searches, the observer rarely has veridical knowledge of the visual features that define their target. During categorical search, observers look for any instance of a categorically defined target (e.g., helping a family member look for their mobile phone). In these circumstances, people may not have information about noncritical features (e.g., the phone's color), and must instead create a broad mental representation using the features that define (or are typical of) the category of objects they are seeking out (e.g., modern phones are typically rectangular and thin). In the current investigation (Experiment 1), using a categorical visual search task, we add to the body of evidence suggesting that categorical templates are effective enough to conduct efficient visual searches. When color information was available (Experiment 1a), attentional guidance, attention restriction, and object identification were enhanced when participants looked for categories with consistent features (e.g., ambulances) relative to categories with more variable features (e.g., sedans). When color information was removed (Experiment 1b), attention benefits disappeared, but object recognition was still better for feature-consistent target categories. In Experiment 2, we empirically validated the relative homogeneity of our societally important vehicle stimuli. Taken together, our results are in line with a category-consistent view of categorical target templates (Yu, Maxfield, & Zelinsky in, Psychological Science, 2016. doi: 10.1177/0956797616640237 ), and suggest that when features of a category are consistent and predictable, searchers can create mental representations that allow for the efficient guidance and restriction of attention as well as swift object identification.


Risk of Mania After Methylphenidate in Patients With Bipolar Disorder.
Bipolar disorder and attention-deficit/hyperactivity disorder are common comorbidities. Attention-deficit/hyperactivity disorder is commonly treated with stimulants (eg, methylphenidate), which, however, have been suggested to cause treatment-emergent mania in patients with bipolar disorder. Here, we assessed the risk of mania, depressive episodes, and psychiatric admissions after initiation of methylphenidate treatment in patients with bipolar disorder. Using Danish health registries, we identified all individuals registered with a diagnosis of bipolar disorder from January 1, 2000, to January 1, 2018, who were treated with methylphenidate. We applied a 1-year mirror-image model to compare the occurrence of mania, depression, and psychiatric admissions in the period leading up to and after methylphenidate treatment initiation. We furthermore assessed the trend in these outcomes from 4 years before to 1 year after initiation of methylphenidate treatment. A total of 1043 patients with bipolar disorder initiated treatment with methylphenidate. The number of manic episodes decreased by 48% after methylphenidate treatment initiation (P = 0.01), both among patients using mood stabilizers (-50%) and among patients not using mood stabilizers (-45%). The number of manic episodes, however, peaked approximately 6 months before methylphenidate. The results were similar for the secondary outcomes. Initiation of methylphenidate treatment was not associated with an increased risk of mania in patients with bipolar disorder. A decrease in mania, depressive episodes, and psychiatric admissions was observed after methylphenidate. However, these decreases seemed to be driven by regression to the mean after clinical deterioration preceding methylphenidate treatment, rather than by the methylphenidate treatment itself.


Atypical causes of hand pain.
The history and physical examination allow early identification of the cause of hand pain in most patients. In some cases, however, the etiology of the pain is not obvious and a diagnostic problem arises. The less common causes of hand pain include atypical mycobacterial infection, occult fractures, bone fragments, incomplete carpal coalitions, carpal ligament injuries and several uncommon forms of tendinitis.


Novel mutation of aspartoacylase gene in a Turkish patient with Canavan disease.
Canavan disease is a neurodegenerative disease with autosomal recessive inheritance. Although this disease is prevalant among Ashkenazi Jewish population, several cases have been reported from all over the world. Canavan disease is caused by a genetic mutation in aspartoacylase gene. We have identified a novel mutation, a homozygous C432+1G>A mutation, in a 10-month-old boy who has a typical Canavan phenotype (without macrocephaly) accompanied by typical brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and diffusion magnetic resonance findings. The patient's mother was found to be heterozygous for this mutation. We believe that future studies of aspartoacylase gene in various ethnic groups could lead to a better understanding of Canavan's pathophysiology and gene therapy.


Oncogenic features of the bone morphogenic protein 7 (BMP7) in pheochromocytoma.
BMP7 is a growth factor playing pro- or anti-oncogenic roles in cancer in a cell type-dependent manner. We previously reported that the BMP7 gene is overexpressed in pheochromocytomas (PCCs) developing in MENX-affected rats and human patients. Here, analyzing a large cohort of PCC patients, we found that 72% of cases showed elevated levels of the BMP7 protein. To elucidate the role of BMP7 in PCC, we modulated its levels in PCC cell lines (overexpression in PC12, knockdown in MPC and MTT cells) and conducted functional assays. Active BMP signaling promoted cell proliferation, migration, and invasion, and sustained survival of MENX rat primary PCC cells. In PCC, BMP7 signals through the PI3K/AKT/mTOR pathway and causes integrin β1 up-regulation. Silencing integrin β1 in PC12 cells suppressed BMP7-mediated oncogenic features. Treatment of MTT cells with DMH1, a novel BMP antagonist, suppressed proliferation and migration. To verify the clinical applicability of our findings, we evaluated a dual PI3K/mTOR inhibitor (NVP-BEZ235) in MENX-affected rats in vivo. PCCs treated with NVP-BEZ235 had decreased proliferation and integrin β1 levels, and higher apoptosis. Altogether, BMP7 activates pro-oncogenic pathways in PCC. Downstream effectors of BMP7-mediated signaling may represent novel targets for treating progressive/inoperable PCC, still orphan of effective therapy.


MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies.
Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.


Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment.
Ganoderic acid Me (GA-Me) is a natural bioactive compound derived from Ganoderma lucidum. Our present results suggested that GA-Me inhibited proliferation, induced DNA fragmentation and significantly activated caspase-9 and caspase-3 in HCT116 cells. As shown in our previous studies, GA-Me targets several genes to prevent cancer, including colorectal cancer (CRC). Thus, we hypothesized that GA-Me might be a multitarget ligand against cancer. However, its exact mechanism in CRC remains unclear. Here, whole-transcriptome sequencing was employed to assess the long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) profiles of GA-Me-treated HCT116 cells. In total, 1572 differentially expressed (DE) lncRNAs, 123 DEcircRNAs, 87 DEmiRNAs, and 1508 DEmRNAs were identified. DCBLD2 and RAPGEF5 were validated as two core mRNAs in the DElncRNA, DEcircRNA, and DEmiRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the biological functions and potential mechanisms of TCONS-00008997, XR-925056.2, circRNA-07908, hsa-miR-100-3p, hsa-miR-1257, hsa-miR-3182, NAV3, ADAM20, and STARD4, which were altered after GA-Me treatment. The regulatory relationships of the XR-925056.2-hsa-miR-3182-NAV3/ADAM20/STARD4, circRNA-07908|Chr22:38986298-39025349-hsa-miR-3182-NAV3/ADAM20, ENST00000414039/ENST00000419190-novel874_mature-MMP9 and circRNA-00314|Chr1:35470863-35479212/circRNA-05460|Chr17:72592203-72649268-novel874_mature-MMP9 immune-regulatory networks involved both noncoding RNAs (ncRNAs) and mRNAs. Molecular docking studies showed that Zn2+ and the His201, His205, His211, Glu202, and Ala165 residues of MMP2 contributed to its high affinity for GA-Me. Zn2+ and the Glu402 and Gly186 residues of MMP9 are important for its interaction with GA-Me. Our results suggested and confirmed that GA-Me is a potential multitarget lead compound for CRC treatment with unique polypharmacological advantages.


Age and risk for depression among the elderly: a meta-analysis of the published literature.
The goal of this study was to determine the relationship between age and risk for depression among the old and the oldest old. Method MEDLINE, EMBASE, and the Cochrane Library database were used to identify potential studies. The studies were divided into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study), or incident cases (for longitudinal study) of depression in each age group were extracted and entered into Review Manager 4.2 software. Qualitative meta-analyses of cross-sectional studies and of longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. The qualitative meta-analyses showed that, compared with younger participants (above vs. below 65 years, above vs. below 70 years, above vs. below 75 years, and above vs. below 80 years), older age groups had a significantly higher risk for depression. (All of the ORs and RRs were significant.) Compared with participants aged 55-89, those aged above 90 years had no higher risk for depression. (Neither the OR nor the RR was significant.) Despite the methodological limitations of this meta-analysis, older age appears to be an important risk factor for depression in the general elderly population (aged below 80 years), but not in the oldest population (aged above 85 years).


[Solitary chondromas and osteochondromas of the spine provoking myeloradicular compression. Apropos of 6 cases treated surgically].
3 spinal chondromas and 3 spinal osteochondromas are described and the relevant literature is reviewed. These oncotypes may remain symptomless or may present as a hard paravertebral swelling or with pain or, more rarely, with a slowly-developing neurological syndrome. Chondromas may appear et any age whereas osteochondromas are more likely to occur during the age of skeletal growth. Both have a predilection for males. Standard Xrays may be diagnostic in osteochondromas but do not always visualise chondromas, which may simulate malignant osteolytic lesions or giant cell tumors and their variants. Computed tomography is indispensable for defining the size of the lesion and its relationships with surrounding structures, for planning surgical treatment, and for following-up its evolution. For both oncotypes treatment is surgical. Recurrence is very rare even after subtotal removal. Malignant degeneration is likewise rare. Operative mortality is nil and neurological recovery is the rule.


Difference in Interoception between Long-Distance Runners and Sprinters: An Event-related Potential Study.
Interoception is a sense of the physiological state of one's body. Interoception that is generated by processing physiological information in the insular cortex plays an important role in achieving optimal performance in competitive sports. This study aimed to reveal the difference in interoceptive ability between long-distance runners and sprinters and its neural correlates by recording the stimulus-preceding negativity (SPN) that is generated from the insular cortex. Based on previous findings, we predicted that long-distance runners would show better interoceptive ability and larger SPNs compared with sprinters. We used a questionnaire and a heartbeat counting task to evaluate the interoceptive sensitivity and accuracy, respectively, of both long-distance runners and sprinters. We recorded SPNs during the execution of a time estimation task where participants estimate 3 s by pressing a button. Results of the questionnaire revealed that sprinters exhibited a higher interoceptive ability associated with attention control of their own bodies than did long-distance runners. Sprinters also showed a larger SPN over the left centroparietal regions compared with long-distance runners. In contrast to our prediction, sprinters exhibited a superior interoceptive ability and a greater activity of the insular cortex relative to long-distance runners. These results suggest that sprinters might be more susceptible to their internal bodily signals compared with long-distance runners, exhibiting greater activation of the anterior insula.


Receptor binding and analgesic properties of oxymorphazone.
The 14-hydroxydihydromorphinone hydrazones have been quite useful in studying aspects of opiate receptor binding and function. The most extensively studied, naloxazone, effectively and selectively inhibits high affinity (mu1) sites in vitro and morphine analgesia in vivo. We now report on the actions of oxymorphazone on receptor binding in vitro and on analgesia in vivo. Oxymorphazone effectively lowers 3H-opioid binding despite extensive washes with the same selectively for high affinity, or mu1, binding sites as naloxazone. Acutely, oxymorphazone was less potent in vivo than oxymorphone (ED50's of 0.8 and 0.4 mg/kg, respectively). Both quantal dose response curves were parallel. At higher doses (100 mg/kg), 83% of animals given oxymorphazone over 20 hr previously were analgesic whereas none of the oxymorphone animals were (p less than 0.001). Oxymorphazone also produced prolonged analgesia after icv administration. These results, in addition to other studies, suggest that oxymorphazone's actions cannot be adequately explained by pharmacokinetic differences from oxymorphone and supports the hypothesis that the drug works via prolonged receptor binding.


The anaphase promoting complex is required for memory function in mice.
Learning and memory processes critically involve the orchestrated regulation of de novo protein synthesis. On the other hand it has become clear that regulated protein degradation also plays a major role in neuronal plasticity and learning behavior. One of the key pathways mediating protein degradation is proteosomal protein destruction. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets proteins for proteosomal degradation by the 26S proteasome. While the APC/C is essential for cell cycle progression it is also expressed in postmitotic neurons where it has been implicated with axonal outgrowth and neuronal survival. In this study we addressed the role of APC/C in learning and memory function by generating mice that lack the essential subunit APC2 from excitatory neurons of the adult forebrain. Those animals are viable but exhibit a severe impairment in the ability to extinct fear memories, a process critical for the treatment of anxiety diseases such as phobia or post-traumatic stress disorder. Since deregulated protein degradation and APC/C activity has been implicated with neurodegeneration we also analyzed the effect of Apc2 deletion in a mouse model for Alzheimer's disease. In our experimental setting loss of APC2 form principle forebrain neurons did not affect the course of pathology in an Alzheimer's disease mouse model. In conclusion, our data provides genetic evidence that APC/C activity in the adult forebrain is required for cognitive function.


High fat feeding is associated with stimulation of the hypothalamic-pituitary-adrenal axis and reduced anxiety in the rat.
Previous studies have shown that diet-induced obesity is associated with insulin resistance and impaired feedback control of the hypothalamic-pituitary-adrenal (HPA) axis. The objective of this study was to test the hypothesis that hyper-secretion of glucocorticoid, evoked by feeding rats a high fat (HF) diet for 12 weeks, also influences behavioural and neural responses to the elevated plus-maze (EPM) test of anxiety. HF-fed animals exhibited anxiolytic-like behaviour in the EPM but were also hyperactive in this test. Covariant analysis established that the anxiolytic-like behaviour was not secondary to the increase in activity. The HF diet significantly increased basal levels of plasma corticosterone. The groups exposed to the EPM also displayed increased plasma corticosterone levels compared to the relevant control group, although the increment was smaller in the HF-fed animals. Glucocorticoid receptor (GR) immunoreactivity in the cytoplasmic fraction of parietal cortex and hypothalamus and the particulate fraction of the parietal cortex were increased by HF feeding. The behavioural changes evoked by HF feeding did not correlate significantly with changes in GR immunoreactivity in each treatment group or 5-HT turnover in the brain areas studied. It is concluded that anxiolytic properties evoked in the EPM by high fat feeding are unlikely to be related to the changes in HPA function seen in animals fed this diet.


How Strong Is the Evidence for Sodium Bicarbonate to Prevent Contrast-Induced Acute Kidney Injury After Coronary Angiography and Percutaneous Coronary Intervention?
Hydration with sodium bicarbonate is one of the strategies to prevent contrast-induced acute kidney injury (CI-AKI). The purpose of this study was to determine how strong is the evidence for sodium bicarbonate to prevent CI-AKI after coronary angiography (CAG) and/or percutaneous coronary intervention (PCI).We conducted PubMed, EMBASE, and CENTRAL databases to search for randomized controlled trials (RCTs) comparing the efficacy of sodium bicarbonate with sodium chloride to prevent CI-AKI after CAG and/or PCI. Relative risk (RR), standardized mean difference (SMD), or weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated. Heterogeneity, publication bias, and study quality were evaluated, sensitivity analyses, cumulative analyses, and subgroup analyses were performed. The risk of random errors was assessed by trial sequential analysis (TSA).Sixteen RCTs (3537 patients) met the eligibility criteria. Hydration with sodium bicarbonate showed significant beneficial effects in preventing CI-AKI (RR 0.67; 95% CI: 0.47-0.96, P = 0.029), decreasing the change in serum creatinine (SCr) (SMD -0.31 95% CI: -0.55 to -0.07, P = 0.011) and estimated glomerular filtration rate (eGFR) (SMD -0.17 95% CI: -0.30 to -0.04, P = 0.013). But no significant differences were observed in the requirement for dialysis (RR 1.11; 95% CI: 0.60-2.07, P = 0.729), mortality (RR 0.71; 95% CI: 0.41-1.21, P = 0.204) and reducing the length of hospital stay (LHS) (WMD -1.47; 95% CI: -4.14 to 1.20, P = 0.279). The result of TSA on incidence of CI-AKI showed the required information size (RIS = 6614) was not reached and cumulative z curve did not cross TSA boundary. The result of TSA on the requirement for dialysis and mortality demonstrated the required information sizes (RIS = 170,510 and 19,516, respectively) were not reached, and the cumulative z-curve did not cross any boundaries.The evidence that sodium bicarbonate reduces the incidence of CI-AKI is encouraging but more well-designed randomized controlled trails are required to allow definitive firm conclusion to be drawn.


NRF2 assessment in discarded liver allografts: A role in allograft function and salvage.
Antioxidant defence mechanisms, such as the nuclear factor-erythroid 2-related-factor-2 (NRF2) axis, are integral to oxidative stress responses and ischemic injury. Hepatic antioxidant capacity is contingent on parenchymal quality, and there is a need to develop new insights into key molecular mechanisms in marginal liver allografts that might provide therapeutic targets. This study examines the clinical relevance of NRF2 in donor livers and its response to normothermic machine perfusion (NMP). Discarded donor livers (n = 40) were stratified into a high NRF2 and low NRF2 group by quantifying NRF2 expression. High NRF2 livers had significantly lower transaminase levels, hepatic vascular inflammation and peri-portal CD3+ T cell infiltration. Human liver allografts (n = 8) were then exposed to 6-h of NMP and high NRF2 livers had significantly reduced liver enzyme alterations and improved lactate clearance. To investigate these findings further, we used a rat fatty-liver model, treating livers with an NRF2 agonist during NMP. Treated livers had increased NRF2 expression and reduced transaminase derangements following NMP compared to vehicle control. These results support the association of elevated NRF2 expression with improved liver function. Targeting this axis could have a rationale in future studies and NRF2 agonists may represent a supplemental treatment strategy for rescuing marginal donor livers.


Hexa-peri-benzocoronene with two extra K-regions in an ortho-configuration.
There are three possible isomers for hexa-peri-hexabenzocoronene (HBC) with two extra K-regions, but only two of them have been reported, namely with the meta- and para-configurations. Herein, we describe the synthesis of HBC 4 with two extra K-regions in the ortho-configuration, forming a longer zigzag edge compared with the other two isomers. The structure of 4 was validated by laser desorption/ionization time-of-flight mass analysis and nuclear magnetic resonance spectra, as well as Raman and infrared spectroscopies supported by density functional theory calculations. The optical properties of 4 were investigated by UV/vis absorption and ultrafast transient absorption spectroscopy. Together with the analysis of aromaticity, the influence of the zigzag edge on the π-conjugation pathway and HOMO-LUMO gaps of the three isomers were investigated.


Utilization of Human Samples for Assessment of Mitochondrial Bioenergetics: Gold Standards, Limitations, and Future Perspectives.
Mitochondrial bioenergetic function is a central component of cellular metabolism in health and disease. Mitochondrial oxidative phosphorylation is critical for maintaining energetic homeostasis, and impairment of mitochondrial function underlies the development and progression of metabolic diseases and aging. However, measurement of mitochondrial bioenergetic function can be challenging in human samples due to limitations in the size of the collected sample. Furthermore, the collection of samples from human cohorts is often spread over multiple days and locations, which makes immediate sample processing and bioenergetics analysis challenging. Therefore, sample selection and choice of tests should be carefully considered. Basic research, clinical trials, and mitochondrial disease diagnosis rely primarily on skeletal muscle samples. However, obtaining skeletal muscle biopsies requires an appropriate clinical setting and specialized personnel, making skeletal muscle a less suitable tissue for certain research studies. Circulating white blood cells and platelets offer a promising primary tissue alternative to biopsies for the study of mitochondrial bioenergetics. Recent advances in frozen respirometry protocols combined with the utilization of minimally invasive and non-invasive samples may provide promise for future mitochondrial research studies in humans. Here we review the human samples commonly used for the measurement of mitochondrial bioenergetics with a focus on the advantages and limitations of each sample.


Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.
Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested.


Eliminating common biases in modelling the electrical conductivity of carbon nanotube-polymer nanocomposites.
Modelling carbon nanotube-polymer nanocomposites to predict their electrical conductivity demands high computational power. Past research has led to the assumption that conductive networks follow a periodic pattern; however, the impact of the underlying biases had never been investigated. This work provides insights into evaluating such biases and eliminating them to improve simulation accuracy.


Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance.
Intraperitoneal injection of sterile zymosan produces an inflammatory response ultimately resulting in multiple-organ failure. The purpose of the present study was to characterize the hormonal and metabolic alterations produced as a result of this nonbacterial nonendotoxic inflammatory agent and to determine whether these changes were mediated by enhanced production of tumor necrosis factor (TNF). Rats were injected intraperitoneally with either zymosan or saline and studied 18 h later. Under basal conditions, zymosan-injected rats were euglycemic but showed a 43% increase in hepatic glucose production and peripheral glucose uptake. The enhanced glucose flux in zymosan-treated rats was associated with elevations in plasma insulin (45%), glucagon (5-fold), corticosterone (2-fold), epinephrine (34%), and norepinephrine (115%). In vivo studies using 2-deoxyglucose (2-DG) demonstrated that the zymosan-induced increase in whole body glucose disposal resulted from an enhanced uptake by skeletal muscle (68%), diaphragm (3.7-fold), liver (144%), spleen (52%), and fat (133%). Under euglycemic hyperinsulinemic conditions, zymosan-treated rats exhibited both hepatic and peripheral insulin resistance, with the latter resulting from a decreased insulin-mediated glucose uptake by skeletal muscle, heart and diaphragm. Arterial TNF levels were increased by 1 h and remained elevated throughout the experimental protocol. Pretreatment of rats with a neutralizing anti-TNF antibody before zymosan prevented the elevation in basal glucose flux and attenuated the insulin resistance. We conclude that the inflammatory state induced by zymosan enhances basal glucose turnover and impairs insulin action and that these changes appear to be largely due to the enhanced endogenous production of TNF.


Biostable Shape Memory Polymer Foams for Smart Biomaterial Applications.
Polyurethane foams provide a wide range of applications as a biomaterial system due to the ability to tune their physical, chemical, and biological properties to meet the requirements of the intended applications. Another key parameter that determines the usability of this biomaterial is its degradability under body conditions. Several current approaches focus on slowing the degradation rate for applications that require the implant to be present for a longer time frame (over 100 days). Here, biostable shape memory polymer (SMP) foams were synthesized with added ether-containing monomers to tune the degradation rates. The physical, thermal and shape memory properties of these foams were characterized along with their cytocompatibility and blood interactions. Degradation profiles were assessed in vitro in oxidative (3% H2O2; real-time) and hydrolytic media (0.1 M NaOH; accelerated) at 37 °C. The resulting foams had tunable degradation rates, with up 15% mass remaining after 108 days, and controlled erosion profiles. These easy-to-use, shape-filling SMP foams have the potential for various biomaterial applications where longer-term stability without the need for implant removal is desired.


[The capacity of bottle-nosed dolphins for generalization according to a relative sign].
In bottle-nosed dolphins by a new modification of previously suggested method, a conditioned reflex was elaborated and consolidated to a relative spatial sign--choice of always left object from two similar ones in conditions of a permanent change of place of this pair of stimuli against the background of one of the sides of an open-air cage. Specialization of the reflex was checked by presentation of a pair of stimuli under different changes of surroundings, including discordance of external orientors and also the way of stimuli presentation. Then the initial objects were substituted by others (12 pairs of stimuli) sharply differing from the initial ones by the form, size, material etc. Retention of adequate choice also at the change of the medium of stimuli presentation, testified to the ability of dolphins of abstraction and generalization by relative sign, i.e. at the choice from two objects of the type "to the right--to the left in general".


[Echocardiographic parameters in patients with Wolf-Parkinson-White syndrome before and during one year after radiofrequency catheter ablation of accessory atrioventricular junction].
We present in this paper results of assessment of morphofunctional state of myocardium in patients with the Wolf-Parkinson-White syndrome before and during one year after radiofrequency catheter ablation (RFA) of accessory atrioventricular junction (AAVJ) and comparison of them with analogous parameters of the group of healthy volunteers as well as in dependence on electrophysiological properties of AAVJ and its localization. One hundred sixty patients took part in the conducted study: main group comprised 160 patients (80.7%) with WPW syndrome (114 men [81.4%], 26 women [18.6%], mean age 39.5+/-15.3 years), comparison group comprised 20 practically healthy persons (15 men [75.0%], 5 women [25%], mean age 41.9+/-5.3 years). All main group patients were subjected to endocardial electrophysiological investigation and RFA of AAVJ. Transthoracic echocardiography (EchoCG) was carried out in patients of main group before and in 2, 6, and 12 months after operation of RFA of AAVJ, and once in control group. Analysis of parameters of central hemodynamics according to data of transthoracic EchoCG in patients with WPW syndrome before RFA of AAVJ demonstrated that before conduct of operative intervention no significant differences were revealed in the studied parameters compared with analogous characteristics of the clinical comparison group. During whole period of dynamic observation (2, 6, and 12 months after fulfilled RFA of AAVJ) in patients with WPW syndrome the studied parameters of central hemodynamics did not undergo substantial changes compared with initial characteristics. We failed to establish significant differences of EchoCG parameters in patients with WPW syndrome in dependence on electrophysiological properties of AAVJ (concealed, manifest) and on AAVJ localization (right, left, septal). According to EchoCG data in patients with WPW syndrome so called "minor" anomalies of development of connective tissue of the heart were diagnosed in 69 (49.3%) patients while in control group - in 2 (10%) patients.


The effect of social support on the health of Indigenous Australians in a metropolitan community.
The factors driving the disparity in health outcomes between Indigenous and non-Indigenous Australians continue to be poorly understood. Despite this, studies confirm that social connections are a very important part of Indigenous life, and it is likely these connections play an important role in influencing health outcomes among this population. Examining the support provided by social connections in relation to health behaviour may assist our understanding of health outcomes among Indigenous Australians. The current study is focused on exploring Indigenous participants' impressions of their social network and social support using Participatory Action Research methodology and qualitative methods. The objective was to identify the influence of social support on the health outcomes of Indigenous people within a Western Australian metropolitan community. Seventeen members of the community were interviewed during the study. The participants had extensive social networks that mainly comprised members of their kinship group. The consequences of this social network included: (1) the positive effects of social support from bonded relationships; (2) the negative effects of social support produced by over-obligation and unidirectional support involving bonded relationships; (3) limited or inadequate social support caused by withdrawal from bonded relationships; (4) lack of social support from bridging relationships; and (5) a strong desire for connection and a sense of belonging.


Bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases.
To efficiently deconstruct recalcitrant plant biomass to fermentable sugars in industrial processes, biocatalysts of higher performance and lower cost are required. The genetic diversity found in the metagenomes of natural microbial biomass decay communities may harbor such enzymes. Our goal was to discover and characterize new glycoside hydrolases (GHases) from microbial biomass decay communities, especially those from unknown or never previously cultivated microorganisms. From the metagenome sequences of an anaerobic microbial community actively decaying poplar biomass, we identified approximately 4,000 GHase homologs. Based on homology to GHase families/activities of interest and the quality of the sequences, candidates were selected for full-length cloning and subsequent expression. As an alternative strategy, a metagenome expression library was constructed and screened for GHase activities. These combined efforts resulted in the cloning of four novel GHases that could be successfully expressed in Escherichia coli. Further characterization showed that two enzymes showed significant activity on p-nitrophenyl-α-L-arabinofuranoside, one enzyme had significant activity against p-nitrophenyl-β-D-glucopyranoside, and one enzyme showed significant activity against p-nitrophenyl-β-D-xylopyranoside. Enzymes were also tested in the presence of ionic liquids. Metagenomics provides a good resource for mining novel biomass degrading enzymes and for screening of cellulolytic enzyme activities. The four GHases that were cloned may have potential application for deconstruction of biomass pretreated with ionic liquids, as they remain active in the presence of up to 20% ionic liquid (except for 1-ethyl-3-methylimidazolium diethyl phosphate). Alternatively, ionic liquids might be used to immobilize or stabilize these enzymes for minimal solvent processing of biomass.


Profiling dyslexia in bilingual adolescents.
This article addresses the issue of whether difficulties with reading and writing in a second language learner stem from developmental dyslexia or from issues associated with second language acquisition. In line with a phonological explanatory model of dyslexia, phonological processing and reading (decoding at both word and text levels) were tested, using data from 10 Spanish-Swedish speaking adolescents whose teachers had identified them as possibly having dyslectic difficulties, and a matched comparison group of 10 Spanish-Swedish speaking adolescents with no reading difficulties. Unlike previous studies, this analysis takes into account results from both languages and uses a matched bilingual comparison group as the norm. Based on these results, a bilingual dyslexia continuum is proposed as an analytical tool to be used for the assessment of developmental dyslexia from a bilingual perspective. The systematized continuum offers various degrees of difficulty -from high indications of dyslexia to no indications of dyslexia-and the positioning along this continuum by the target group participants of this study provides examples of both over- and under-identification of dyslexia. Overall, a greater number of participants in the target group were under-identified rather than over-identified by the schools. An important insight of this study is that the positioning of bilingual participants on the continuum would have been different if the analysis had taken only one of the two languages into account. Furthermore, possible effects from differences between Spanish and Swedish orthographies and syllable structure were observed, as, in general, the participants read more accurately in Spanish. The present data also suggest that decoding processing might vary more in second-language learners with dyslexia compared to monolingual individuals with dyslexia.


Uveitis-mediated immune cell invasion through the extracellular matrix of the lens capsule.
While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule as immune resolution is occurring at D26. 3D surface rendering image analytics of confocal z-stacks and scanning electron microscopy imaging of the lens surface show the degradation of the lens capsule as these lens-associated immune cells integrate with and invade the lens capsule, with a subset infiltrating both epithelial and fiber cell regions of lens tissue, abrogating its immune privilege. Those immune cells that remain on the surface often become entwined with a fibrillar net-like structure. Immune cell invasion of the lens capsule in uveitis has not been described previously and may play a role in induction of lens and other eye pathologies associated with autoimmunity.


Amantadine, apomorphine and zolpidem in the treatment of disorders of consciousness.
Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes of the patients' neurological status, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to improve our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition.


Learning to See Through Obstructions With Layered Decomposition.
We present a learning-based approach for removing unwanted obstructions, such as window reflections, fence occlusions, or adherent raindrops, from a short sequence of images captured by a moving camera. Our method leverages motion differences between the background and obstructing elements to recover both layers. Specifically, we alternate between estimating dense optical flow fields of the two layers and reconstructing each layer from the flow-warped images via a deep convolutional neural network. This learning-based layer reconstruction module facilitates accommodating potential errors in the flow estimation and brittle assumptions, such as brightness consistency. We show that the proposed approach learned from synthetically generated data performs well to real images. Experimental results on numerous challenging scenarios of reflection and fence removal demonstrate the effectiveness of the proposed method.


Calcium phosphate particle induction of metalloproteinase and mitogenesis: effect of particle sizes.
Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals [hydroxyapatite (HA), octacalcium phosphate, tricalcium phosphate] are common in osteoarthritis knee effusions, and are often associated with low-grade synovial proliferation and inflammation. Calcium-containing crystals including HA, are known to have a number of biologic effects on culture cells such induction of mitogenesis, stimulation of Prostaglandin E2 (PGE2) production via the phospholipase A2/cyclo-oxygenase pathway, activation of phospholipase C and inositol phospholipid hydrolysis, induction of metalloproteinase synthesis and induction of proto-oncogenes (c-fos and c-myc). While endocytosis of HA particles is prerequisite of the mitogenic effect of calcium-containing crystals in fibroblasts, it is not known whether endocytosis is required for crystal-induced metalloproteinase synthesis. In the present series of experiments, we examine the effect of three different sizes (106, 46, and 17 microns mean diameters) well-characterized spherical HA particles on the induction of mitogenesis and metalloproteinase synthesis on human fibroblasts. We showed that endocytosis is required for HA particles to induce synthesis of metalloproteinases.


Enhancing Image Characteristics of Retinal Images of Aggressive Posterior Retinopathy of Prematurity Using a Novel Software, (RetiView).
Purpose. To report pilot data from a novel image analysis software "RetiView," to highlight clinically relevant information in RetCam images of infants with aggressive posterior retinopathy of prematurity (APROP). Methods. Twenty-three imaging sessions of consecutive infants of Asian Indian origin with clinically diagnosed APROP underwent three protocols (Grey Enhanced (GE), Color Enhanced (CE), and "Vesselness Measure" (VNM)) of the software. The postprocessed images were compared to baseline data from the archived unprocessed images and clinical exam by the retinopathy of prematurity (ROP) specialist for anterior extent of the vessels, capillary nonperfusion zones (CNP), loops, hemorrhages, and flat neovascularization. Results. There was better visualization of tortuous loops in the GE protocol (56.5%); "bald" zones within the CNP zones (26.1%), hemorrhages (13%), and edge of the disease (34.8%) in the CE images; neovascularization on both GE and CE protocols (13% each); clinically relevant information in cases with poor pupillary dilatation (8.7%); anterior extent of vessels on the VNM protocol (13%) effecting a "reclassification" from zone 1 to zone 2 posterior. Conclusions. RetiView is a noninvasive and inexpensive method of customized image enhancement to detect clinically difficult characteristics in a subset of APROP images with a potential to influence treatment planning.


The Effect of Prenatal Treatments on Offspring Events in the Presence of Competing Events: An Application to a Randomized Trial of Fertility Therapies.
When studying the effect of a prenatal treatment on events in the offspring, failure to produce a live birth is a competing event for events in the offspring. A common approach to handle this competing event is reporting both the treatment-specific probabilities of live births and of the event of interest among live births. However, when the treatment affects the competing event, the latter probability cannot be interpreted as the causal effect among live births. Here we provide guidance for researchers interested in the effects of prenatal treatments on events in the offspring in the presence of the competing event "no live birth." We review the total effect of treatment on a composite event and the total effect of treatment on the event of interest. These causal effects are helpful for decision making but are agnostic about the pathways through which treatment affects the event of interest. Therefore, based on recent work, we also review three causal effects that explicitly consider the pathways through which treatment may affect the event of interest in the presence of competing events: the direct effect of treatment on the event of interest under an intervention to eliminate the competing event, the separable direct and indirect effects of treatment on the event of interest, and the effect of treatment in the principal stratum of those who would have had a live birth irrespective of treatment choice. As an illustrative example, we use a randomized trial of fertility treatments and risk of neonatal complications.


Brief Report: Phenotypic Differences and their Relationship to Paternal Age and Gender in Autism Spectrum Disorder.
Two modes of inheritance have been proposed in autism spectrum disorder, transmission though pre-existing variants and de novo mutations. Different modes may lead to different symptom expressions in affected individuals. De novo mutations become more likely with advancing paternal age suggesting that paternal age may predict phenotypic differences. To test this possibility we measured IQ, adaptive behavior, and autistic symptoms in 830 probands from simplex families. We conducted multiple linear regression analysis to estimate the predictive value of paternal age, maternal age, and gender on behavioral measures and IQ. We found a differential effect of parental age and sex on repetitive and restricted behaviors. Findings suggest effects of paternal age on phenotypic differences in simplex families with ASD.


Does early migraine treatment shorten time to headache peak and reduce its severity?
To explore whether early treatment would shorten the duration of headache from headache onset to its peak and reduce headache severity at peak. Prior clinical studies almost exclusively focused on headache relief after dosing. No data are available on whether early intervention affects the duration from headache onset to peak and headache severity at peak. Adult migraineurs were enrolled in this observational study from multi-site headache clinics. Patients recorded their migraine experiences via an electronic diary over 1 month. Patients reported the time and pain severity at onset, dosing, and peak. We used a linear mixed model to evaluate the impact of the timing of treatment and to adjust for covariates and correlation of observations within subjects. A total of 182 patients reported 970 migraine episodes, 620 of which were treated before headaches progressed to peak. Mean time from headache onset to peak varied from 1.9 hours to 8.9 hours for patients treated within 15 minutes of onset and those who waited for 4 or more hours, respectively. However, early intervention was not associated with reduced headache severity at peak. In multivariate analysis, early treatment, use of triptans, and mild migraine headache in the past 3 months were significantly associated with shorter time from onset to headache peak. A separate model indicated that the timing of medication was not associated with the duration between dosing and headache peak, but use of triptans shortened the time from dosing to headache peak. Early treatment and use of triptans may lead to shorter duration from migraine headache onset to its peak but did not alleviate headache severity at peak. This could result in decreased migraine burden by reducing total migraine headache duration.


Effect of Relative Humidity on Mechanical Degradation of Medium Mn Steels.
Medium Mn steels have been considered as the next-generation materials for use in the automotive industry due to their excellent strength and ductility balance. To reduce the total weight and improve the safety of vehicles, medium Mn steels look forward to a highly promising future. However, hydrogen-induced delayed cracking is a concern for the use of high strength steels. This work is focused on the service characteristics of two kinds of medium Mn steels under different relative humidity conditions (40%, 60%, 80% and 100%). Under normal relative humidity (about 40%) at 25 °C, the hydrogen concentration in steel is 0.4 ppm. When exposed to higher relative humidity, the hydrogen concentration in steel increases slowly and reaches a stable value, about 0.8 ppm. In slow strain rate tensile tests under different relative humidity conditions, the tensile strength changed, the hydrogen concentration increased and the elongation decreased as well, thereby increasing the hydrogen embrittlement sensitivity. In other words, the smaller the tensile rate applied, the greater the hydrogen embrittlement sensitivity. In constant load tests under different relative humidity conditions, the threshold value of the delayed cracking of M7B ('M' referring to Mn, '7' meaning the content of Mn, 'B' denoting batch annealing) steel maintains a steady value of 0.82 σb (tensile strength). The threshold value of the delayed cracking of M10B significantly changed along with relative humidity. When relative humidity increased from 60% to 80%, the threshold dropped sharply from 0.63 σb to 0.52 σb. We define 80% relative humidity as the 'threshold humidity' for M10B.


The effects of task demands on bimanual skill acquisition.
Bimanual coordination is essential for everyday activities. It is thought that different degrees of demands may affect learning of new bimanual patterns. One demand is at the level of performance and involves breaking the tendency to produce mirror-symmetric movements. A second is at a perceptual level and involves controlling each hand to separate (i.e., split) goals. A third demand involves switching between different task contexts (e.g., a different uni- or bimanual task), instead of continuously practicing one task repeatedly. Here, we studied the effect of these task demands on motor planning (reaction time) and execution (error) while subjects learned a novel bimanual isometric pinch force task. In Experiment 1, subjects continuously practiced in one of the two extremes of the following bimanual conditions: (1) symmetric force demands and a perceptually unified target for each hand or (2) asymmetric force demands and perceptually split targets. Subjects performing in the asymmetric condition showed some interference between hands, but all subjects, regardless of group, could learn the isometric pinch force task similarly. In Experiment 2, subjects practiced these and two other conditions, but in a paradigm where practice was briefly interrupted by the performance of either a unimanual or a different bimanual condition. Reaction times were longer and errors were larger well after the interruption when the main movement to be learned required asymmetric forces. There was no effect when the main movement required symmetric forces. These findings demonstrate two main points. First, people can learn bimanual tasks with very different demands on the same timescale if they are not interrupted. Second, interruption during learning can negatively impact both planning and execution and this depends on the demands of the bimanual task to be learned. This information will be important for training patient populations, who may be more susceptible to increased task demands.


Pest categorisation of Oligonychus mangiferus.
The EFSA Panel on Plant Health performed a pest categorisation of the mango red spider mite, Oligonychus mangiferus (Rahman and Sapra, 1940) (Acari: Prostigmata: Tetranychidae), for the territory of the EU. This species is not included in the EU Commission Implementing Regulation 2019/2072. The polyphagous mite feeds on more than 50 host plants including tropical fruits such as mangoes and avocados and temperate fruits such as pears, peaches, pomegranates and grapes. It occurs in Africa, Asia, Oceania and South America. O. mangiferus is multivoltine and can develop throughout the year as long as temperatures are above 12°C. The species produces dense webs on the above-ground parts of their host plants, where all stages of development (egg, larva, nymph and adult) can be found. This species is considered a pest of mango, grapevine, lychee and pomegranate, mostly in areas with hotter climates than those occurring in the EU. Potential entry pathways for O. mangiferus include plants for planting with foliage, fruit and cut flowers. Plants for planting of a few hosts (i.e. Pinus, Prunus, Pyrus, Rosa, Vitis and Arecaceae) are banned from entering into the EU from countries where O. mangiferus is known to occur and can be considered as closed entry pathways. However, other plants for planting, as well as the fruit and the cut flowers pathways remain open. There are no EU records of interception. Should O. mangiferus enter the EU, the ample availability of hosts and the climatic conditions in the EU would most probably allow this species to successfully establish and spread, at least in southern MSs, where economic impact in different fruit production (e.g. pomegranate, mango and grape) is anticipated. O. mangiferus satisfies the criteria that are within the remit of EFSA to assess for this species to be regarded as a potential Union quarantine pest.


Sweep visual evoked potential testing as a predictor of recognition acuity in albinism.
To determine if sweep visual evoked potential (VEP) acuity is predictive of recognition acuity in children with albinism. A retrospective review was performed in children with albinism who underwent sweep VEP testing from 1992 to 2003. All patients had a complete ophthalmologic examination with either binocular or monocular sweep VEP testing and at least 5 years of follow-up. Positive predictability of sweep VEP acuity was defined as final recognition acuity within 1 Snellen line of initial sweep VEP acuity. Of the 13 patients included in the study, 11 had nystagmus, iris transillumination defects, and foveal hypoplasia at initial examination. The mean age at initial sweep VEP testing was 3.1 years (range, 0.1-10.0 years). Five of 13 patients had initial sweep VEP acuity that was predictive of final recognition acuity. Five additional patients had final recognition acuity, which surpassed initial sweep VEP acuity by 2 to 3 lines. Of these 10 patients, the mean duration for recognition acuity to reach VEP acuity was 5.4 years. There was no correlation between predictive VEP acuity and foveal pigmentation, refractive error, strabismus, nystagmus, or longer follow-up. Sweep VEP testing can be used as a predictive tool for recognition acuity in children with albinism. Predictability was found in a clinical spectrum of albinism.


Increased numbers of beta APP-immunoreactive neurones in the entorhinal cortex after head injury.
In a previous publication we hypothesized that Alzheimer's disease (AD) can be induced by the age-related increase in expression of beta-amyloid precursor protein (beta APP) in the medial temporal lobe. Head injury has also been identified as a risk factor for AD and as such, similarities should exist between the pathology found after head injury and the earliest stages of pathology in AD. In this study, we have quantified the number of beta APP-immunoreactive neurones in the medial temporal cortex (pre-alpha cells, layer II) of 13 head injured and 17 control patients. Significantly more beta APP immunoreactive neurones were observed in head injury cases (mean 18.4 per cluster) compared with controls (mean 13.4 per cluster, p < 0.05). These data provide a mechanism to explain how an environmental event such as head injury can generate the same molecular pathology (increased neuronal beta APP) as is found in the earliest stages of AD.


Evaluation of hypernasality in vowels using voice low tone to high tone ratio.
The voice low tone to high tone ratio (VLHR) is defined as the power ratio of low frequency to high frequency energy obtained by dividing the voice spectrum with a specific cutoff frequency. In a previous study, VLHR correlated significantly with nasalance and perceptual rating of hypernasality for a single vowel. The methodology was optimized in this study by investigating the correlations among other vowels. Voice signals of six sustained vowels vocalized by subjects with hypernasality were collected. Vowel nasalance was obtained with a nasometer, and hypernasality rating scores were provided by two speech-language pathologists. The VLHRs calculated using different cutoff frequencies were correlated with nasalance and hypernasality rating scores. Eight subjects with hypernasality caused by palatal fistula or velopharyngeal insufficiency. VLHR, nasalance, and hypernasality rating score. The correlation of VLHR with nasalance and hypernasality rating was most significant using a cutoff frequency of 600 Hz. The correlation of VLHR with nasalance was significant (r = .62, p < .01, Pearson's correlation), as was the correlation of VLHR with hypernasality score (Spearman's rank correlation coefficient = .62, p < .01). VLHR correlated significantly with nasalance and hypernasality in the six sustained vowels and may provide another quantitative index for the evaluation of hypernasality in sustained vowels.


Association of hyperchloremia and acute kidney injury in pediatric patients with moderate and severe traumatic brain injury.
Acute kidney injury (AKI) is an established complication of adult traumatic brain injury (TBI) and known risk factor for mortality. Evidence demonstrates an association between hyperchloremia and AKI in critically ill adults but studies in children are scarce. Given frequent use of hypertonic saline in the management of pediatric TBI, we believe the incidence of hyperchloremia will be high and hypothesize that it will be associated with development of AKI. Single-center retrospective cohort study was completed at an urban, level 1 pediatric trauma center. Children > 40 weeks corrected gestational age and < 21 years of age with moderate or severe TBI (presenting GCS < 13) admitted between January 2016 and December 2021 were included. Primary study outcome was presence of AKI (defined by pediatric Kidney Disease: Improving Global Outcomes criteria) within 7 days of hospitalization and compared between patients with and without hyperchloremia (serum chloride ≥ 110 mEq/L). Fifty-two children were included. Mean age was 5.75 (S.D. 5.4) years; 60% were male (31/52); and mean presenting GCS was 6 (S.D. 2.9). Thirty-seven patients (71%) developed hyperchloremia with a mean peak chloride of 125 (S.D. 12.0) mEq/L and mean difference between peak and presenting chloride of 16 (S.D. 12.7) mEq/L. Twenty-three patients (44%) developed AKI; of those with hyperchloremia, 62% (23/37) developed AKI, while among those without hyperchloremia, 0% (0/15) developed AKI (difference 62%, 95% CI 42-82%, p < 0.001). Attributable risk of hyperchloremia leading to AKI was 62.2 (95% CI 46.5-77.8, p = 0.0015). Hyperchloremia is common in the management of pediatric TBI and is associated with development of AKI. Risk appears to be associated with both the height of serum chloride and duration of hyperchloremia.


Porcine deltacoronavirus causes diarrhea in various ages of field-infected pigs in China.
Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes acute diarrhea in suckling piglets. In Henan province of China, three swine farms broke out diarrhea in different ages of pigs during June of 2017, March of 2018 and January of 2019, respectively. PCR method, Taqman real-time RT-PCR method, sequencing, histopathology and immunohistochemistry (IHC) were conducted with the collected samples, and the results showed that PDCoV was detected among the suckling piglets, commercial fattening pigs and sows with diarrhea. PDCoV-infected suckling piglets were characterized with thin and transparent intestinal walls from colon to caecum, spot hemorrhage at mesentery and intestinal bleeding. PDCoV RNA was detected in multiple organs and tissues by Taqman real-time RT-PCR, which had high copies in ileum, inguinal lymph node, rectum and spleen. PDCoV antigen was detected in the basal layer of jejunum and ileum by IHC. In this research, we found that PDCoV could infect various ages of farmed pigs with watery diarrhea and anorexia in different seasons in a year.


Schistosoma mansoni Mass Drug Administration Regimens and Their Effect on Morbidity among Schoolchildren over a 5-Year Period-Kenya, 2010-2015.
Schistosomiasis control programs are designed to reduce morbidity by providing mass drug administration (MDA) of praziquantel to at-risk populations. We compared morbidity markers between two cohorts of Kenyan schoolchildren that initially had high prevalence of Schistosoma mansoni infections. One cohort (N = 416 at year 1) received four rounds of annual MDA in a community-wide treatment (CWT) strategy. The other cohort (N = 386 at year 1) received school-based treatment (SBT) every other year over the 4-year period. We measured infection with S. mansoni and soil-transmitted helminths (STH) as well as subtle morbidity markers at year 1, year 3, and year 5 and compared cohorts with mixed models after controlling for age and gender. At year 5, neither overall S. mansoni prevalence nor the prevalence of high infection-intensity S. mansoni infection was significantly reduced compared with baseline in either the CWT cohort (N = 277 remaining) or the SBT cohort (N = 235 remaining). Nevertheless, by year 5, children in both cohorts demonstrated significant decreases in wasting, ultrasound-detected organomegaly, and STH infection along with significantly improved pediatric quality-of-life scores compared with year 1. Stunting did not change over time, but children who were S. mansoni egg-positive at year 5 had significantly more stunting than children without schistosomiasis. The only significant difference between arms at year 5 was a lower prevalence of STH infections in the CWT group.


The features of sperm maturation in the epididymis of a marsupial, the brushtailed possum Trichosurus vulpecula.
Possum spermatozoa undergo a distinctive process of maturation in the epididymis, as shown by change in the properties of the sperm surface, by modification of their morphology and by their increasing capacity for progressive motility. Modification of the sperm surface over the head and tail is demonstrated by the different affinities of sperm from successive regions of the epididymis for FITC-conjugated wheat germ agglutinin and concanavalin A, and for cationic ferric oxide colloidal particles. Changes in sperm head morphology are caused by (1) a dramatic reshaping and consolidation of the acrosome in which excess plasma membrane overlying it is sloughed as a cluster of vesicles, (2) a reorientation of the nucleus almost parallel to the axis of the tail and (3) distal movement of the droplet from its initial envelopment of the nucleus to an eccentric position on the anterior segment of the midpiece. Spermatozoa released from the testis and caput epididymidis are essentially immotile or exhibit only lazy uncoordinated movements, whereas many from the corpus and most from the more distal regions of the epididymis display an energetic, progressive motility imparted by a rapid and stiff tail beat of narrow arc. This maturation of the capacity for motility is accompanied by an enhanced stability of the dense fibers and sheath, which became more resistant to the disruptive action of SDS and DTT, and by changes in the ultrastructure of the sperm tail. These include modification of the matrix of the mitochondria and also an unusual differentation of the midpiece into two distinct segments. The anterior segment is defined by profuse peri-mitochondrial stacks of membranes which developed as spermatozoa pass through the epididymis. These membranes, although prominent in mature spermatozoa fixed in situ, appear sparse and disorganised in spermatozoa fixed after 15 to 30 minutes of active motility in physiological medium, suggesting their possible utilisation in motile spermatozoa. The posterior segment is characterised by a thick peri-mitochondrial cytoplasmic sleeve, by spirally arranged parallel fibrous bands immediately beneath the plasma membrane and, subsequently, as spermatozoa pass into the lower corpus epididymidis, by rows of flask-shaped surface invaginations which develop between the spiral bands. Despite broad similarities in the features of sperm maturation in this marsupial and in eutherian mammals, there are distinct differencesin the structural organisation of their spermatozoa, particularly in the pserm head. Until more is known of the details of fertilisation in marsupials the significance of these differences will remain unclear.


Developmental mechanisms underlying pathology of arteries.
This review tries to provide a general, and very speculative, view of growth control mechanisms that may be common to the development of blood vessels and to pathological processes including cell proliferation. From a developmental point of view, vascular growth is most likely to include local autocrine or paracrine mechanisms that permit the two cells of the vessel wall to grow, organize into the characteristic tubular and layered structures of the vessel wall, and eventually achieve a return to quiescence. The "real" mechanisms controlling growth in vivo are difficult to ascertain from studies in culture. For example, a large list of angiogenesis molecules must be able to generate endothelial replication, but in culture many of these molecules are inhibitory for each endothelial replication. Similarly, in culture, we have a long list of smooth muscle mitogens, but none of these have as of yet been proven to control smooth muscle growth in vivo. Endothelial growth control has been attributed to the presence of membrane molecules able to inhibit endothelial replication and to the actions of soluble growth factors and their receptors. Unfortunately for the former hypothesis we still lack specific molecules with the properties of contact inhibition of replication. The data discussed here, however, suggest that modulation of expression or function of cell-cell adhesive molecules could be critical both to morphogenic changes and to mitogenesis by release of cells from cell-cell contact. Moreover, our data and data from other laboratories suggest that angiogenic factors, including the HBGFs and TGF-beta, may function in angiogenesis by altering cell-cell and cell-cell substrate interactions rather than via a primary effect on cell replication. This view of angiogenesis is consistent with the absence of a mitogenic effect of some angiogenic factors. Although endothelial cell replication is obviously necessary to angiogenesis, the lack of mitogenic effect of some factors suggests a need for a more general explanation of the actions of angiogenic factors. Endothelial injury may be interrelated with smooth muscle growth. The simplest possibility is that a failure of the endothelial cell barrier function, due either to denudation or an increase in adhesivity for leukocytes, would permit access of platelets or leukocytes to the vessel wall. These extrinsic cells, in turn, would stimulate smooth muscle cell replication by release of growth factors. The second possibility is that the endothelial cell may itself release growth factors into the vessel wall.(ABSTRACT TRUNCATED AT 400 WORDS)


Being more than a mother: A qualitative study of Asian immigrant mothers in Australia who have children with disabilities.
Studies on mothers of children with disabilities commonly report on their poor quality of life, high stress and mental health symptoms. However, the impact of caring for a child with disability on mother's everyday activities is less understood. The aim of this study is to explore the everyday activities of north-east and south-east Asian (NESEA) migrant mothers of children with disabilities, living in Australia. Informed by a grounded theory approach, this qualitative study used purposive snow-ball sampling to recruit NESEA mothers who had immigrated to Australia for at least two years and had at least one child with disabilities. Eleven mothers were interviewed. Grounded theory analysis was used to derive themes. The overarching theme is 'Transforming'. Five subthemes emerged: 1) Journeying into the unknown; 2) Being the carer; 3) Being an immigrant; 4) Pillars of support; and 5) Empowered for everyday activities. This study revealed the everyday activities and roles of NESEA immigrant mothers who have children with disabilities, their enablers and barriers in engaging in their valued activities and their positive transformation. Findings underpin the importance of facilitating mothers' participation in activities and roles that promote their well-being. Service providers and policy makers can create opportunities for immigrant mothers to participate in health promoting activities.


Degradation of oxytetracycline in aqueous solution by heat-activated peroxydisulfate and peroxymonosulfate oxidation.
Oxytetracycline (OTC) is a broad-spectrum antibiotic that resists biodegradation and poses a risk to the ecosystem. This study investigated the degradation of OTC by heat-activated peroxydisulfate (PDS) and peroxymonosulfate (PMS) processes. Response surface methodology (RSM) was used to evaluate the effect of process parameters, namely initial pH, oxidant concentration, temperature, and reaction time on the OTC removal efficiency. According to the results of the RSM models, all four independent variables were significant for both PDS and PMS processes. The optimum process parameters for the heat-activated PDS process were pH 8.9, PDS concentration 3.9 mM, temperature 72.9°C, and reaction time 26.5 min. For the heat-activated PMS process, optimum conditions were pH 9.0, PMS concentration 4.0 mM, temperature 75.0°C, and reaction time 20.0 min. The predicted OTC removal efficiencies for the PDS and PMS processes were 89.7% and 84.0%, respectively. As a result of the validation experiments conducted at optimum conditions, the obtained OTC removal efficiencies for the PDS and PMS processes were 87.6 ± 4.2 and 80.2± 4.6, respectively. PDS process has higher kinetic constants at all pH values than the PMS process. Both processes were effective in OTC removal from aqueous solution and RSM was efficient in process optimization.


Effects of postmortem interval on biomolecule integrity in the brain.
Postmortem brain research is invaluable to the study of neurologic and neuropsychiatric disorders, including Alzheimer disease, schizophrenia, and major depression. A major confounder in molecular studies using human brain tissue is postmortem interval (i.e. the amount of time between a subject's death and processing of tissue). We examined the integrity of biomolecules that were of interest to molecular studies of neurologic disorders, including RNA, microRNA, histone modifications, and proteins, at various postmortem intervals in an animal model to assess their robustness and suitability for experimentation. Sprague-Dawley rats were selected as model and subjected to 2 conditions: a variable postmortem interval at room temperature and a fixed time of 24 hours at 4°C, which simulates the period commonly spent in the morgue before brain collection. Eight time points were investigated. MicroRNA was impressively resistant to postmortem intervals; methylated histone modifications showed a threshold between 72 and 96 hours, mirroring results from histone proteins at 72 hours. RNA degradation was transcript-specific, with housekeeping genes being more robust than genes with lower expression. Our results suggest that molecules commonly investigated in genetic and epigenetic studies were highly stable through the postmortem intervals investigated. These results support the continued use of postmortem tissue for neuropsychiatric research.