The prostacyclin synthesis stimulating plasma factor is unchanged during acute angina pectoris.
Earlier studies have demonstrated that the levels of prostacyclin synthesis stimulating plasma factor are changed during various clinical situations thus leading to disturbances in hemostatic balance. Therefore, we studied the plasma factor in 20 patients undergoing acute anginal attacks in order to see whether there is any influence or a timedependent change after the event. The patients were subdivided into males or females as well as into those with or without maturity onset diabetes and who were smokers or no-smokers. As in-vitro test systems the rat abdominal aorta, human coronary artery and cultured endothelial and smooth muscle cells obtained from minipigs were used. Our findings demonstrate that incubating the different tissue samples in plasma leads to a significant increase of prostacyclin formation or of its stable breakdown 6-oxo-PGF1 respectively, in comparison to buffer control incubation. However, in none of the groups was a change observed during an anginal attack or in rate 60 and 120 minutes thereafter. These findings suggest that the prostacyclin synthesis stimulating plasma factor is not involved in hemostatic dysregulation, which has been observed to occur during and immediately after a coronary anginal attack.


Diclofenac readily penetrates the cerebrospinal fluid in children.
Diclofenac, a nonselective nonsteroidal anti-inflammatory drug,, exerts analgesic action both in the peripheral tissues and in the central nervous system by inhibiting cyclooxygenase enzymes COX-1/2, but central nervous system penetration of diclofenac has not been evaluated in humans. Diclofenac penetrates the cerebrospinal fluid rapidly, and after a single intravenous dose of 1 mg kg(-1), sufficient concentrations to inhibit COX-1/2 are sustained for up to 4 h. The primary aim was to study the cerebrospinal fluid (CSF) penetration of intravenous diclofenac in children. The secondary aim was to evaluate the plasma diclofenac concentration at the onset of wound pain after inguinal surgery in children. A total of 31 children (24 boys) aged 3 months to 12 years received a single intravenous injection of diclofenac 1 mg kg(-1). Paired CSF and blood samples were obtained 5 min to 22 h (median 69 min) later. In children having inguinal surgery a second blood sample was obtained at the time that the children felt wound pain for the first time after surgery. Diclofenac concentrations in CSF, plasma and protein free plasma were measured by gas chromatography with mass spectrometric detection. In the 28 CSF samples obtained at 5 min to 3 h 43 min after injection, diclofenac concentrations ranged between 0.5 and 4.7 microg l(-1). At 5.5 h the CSF concentration was 0.1 microg l(-1), and no diclofenac was detected in the two CSF samples obtained at 22 h. The median of plasma diclofenac concentration at the time when pain returned after inguinal surgery was 104 microg l(-1) (range 70-272 microg l(-1)). No serious or unexpected adverse effects were reported. Diclofenac penetrates the CSF rapidly, and a sufficient concentration to inhibit cyclooxygenase enzymes is sustained for up to 4 h.


Inverting enantioselectivity of Burkholderia cepacia KWI-56 lipase by combinatorial mutation and high-throughput screening using single-molecule PCR and in vitro expression.
The enantioselectivity of lipase from Burkhorderia cepacia KWI-56 has been inverted using a novel in vitro technique for construction and screening of a protein library by single-molecule DNA amplification by PCR followed by in vitro coupled transcription/translation system termed single-molecule-PCR-linked in vitro expression (SIMPLEX). Four amino acid residues (L17, F119, L167, and L266) in the hydrophobic substrate-binding pocket of the lipase were selected for mutation based on a structural model of a substrate-enzyme complex, and a combinatorial mutation library was constructed by SIMPLEX and screened for (R) and (S)-configurations of p-nitrophenyl 3-phenylbutyrate. Some combinations of amino acid substitutions in the four positions of the lipase were found as effective for changing the enantiopreference from the (S)-form substrate to the (R)-form. Two variants were expressed in the original host cells and purified to homogeneity, showing completely reversed enantioselectivity for the (R)-form of ethyl 3-phenylbutyrate (selectivity factor E(R)=38 or 33), whereas the wild-type lipase was (S)-selective (selectivity factor E(S)=33). Thus the semi-rational and semi-random combinatorial design of a mutant library followed by a high-throughput screening based on their enzymatic activity should be a powerful tool to engineer the enantioselectivity of enzymes.


Discovery of holoenzyme-disrupting chemicals as substrate-selective CK2 inhibitors.
CK2 is a constitutively active protein kinase overexpressed in numerous malignancies. Interaction between CK2α and CK2β subunits is essential for substrate selectivity. The CK2α/CK2β interface has been previously targeted by peptides to achieve functional effects; however, no small molecules modulators were identified due to pocket flexibility and open shape. Here we generated numerous plausible conformations of the interface using the fumigation modeling protocol, and virtually screened a compound library to discover compound 1 that suppressed CK2α/CK2β interaction in vitro and inhibited CK2 in a substrate-selective manner. Orthogonal SPR, crystallography, and NMR experiments demonstrated that 4 and 6, improved analogs of 1, bind to CK2α as predicted. Both inhibitors alter CK2 activity in cells through inhibition of CK2 holoenzyme formation. Treatment with 6 suppressed MDA-MB231 triple negative breast cancer cell growth and induced apoptosis. Altogether, our findings exemplify an innovative computational-experimental approach and identify novel non-peptidic inhibitors of CK2 subunit interface disclosing substrate-selective functional effects.


Pretreatment body mass index as a prognostic predictor in patients with oral squamous cell carcinoma.
To evaluate whether low body mass index (BMI) is a potential adverse prognostic factor in patients with oral squamous cell carcinoma (OSCC). This cross-sectional study included 320 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The pretreatment BMI was measured as a common indicator of the pretreatment nutritional status to calculate the overall survival in Kaplan-Meier method. The adverse histopathological features of margin status, depth of invasion (DOI), lymphovascular invasion (LVSI), perineural invasion (PNI), and extranodal extension (ENE) were analyzed using the Cox regression model. Low BMI (underweight), DOI > 5 mm, and ENE were identified as detrimental prognostic factors. On multivariate Cox regression analysis, the low BMI group (odds ratio [OR] = 1.683; 95% confidence interval [95% CI] 1.116-2.539; P = 0.022), DOI > 5 mm (OR = 2.399; 95% CI 1.459-3.943; P = 0.001), and ENE (OR = 2.467; 95% CI 1.540-3.951; P = 0.000) yielded reduced survival rate. The lower BMI had an important and significant effect on the survival of patients with oral cancer and their surgical outcomes. In addition to the adverse histopathological features, a DOI > 5 mm and positive ENE were also identified as the most important prognostic factors. Underweight patients with low BMI, DOI of > 5 mm, and positive ENE should receive more intensive nutritional supplementation and postoperative adjuvant therapy.


Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine.
Although the recent SARS coronavirus (SARS-CoV) that appeared in 2002 has now been contained, the possibility of re-emergence of SARS-CoV remains. Due to the threat of re-emergence, the overall fatality rate of approximately 10%, and the rapid dispersion of the virus via international travel, viable vaccine candidates providing protection from SARS are clearly needed. We developed an attenuated VSV recombinant (VSV-S) expressing the SARS coronavirus (SARS-CoV) spike (S) protein. In cells infected with this recombinant, S protein was synthesized, glycosylated at approximately 17 Asn residues, and transported via the Golgi to the cell surface. Mice vaccinated with VSV-S developed SARS-neutralizing antibody and were able to control a challenge with SARS-CoV performed at 1 month or 4 months after a single vaccination. We also demonstrated, by passive antibody transfer, that the antibody response induced by the vaccine was sufficient for controlling SARS-CoV infection. A VSV-vectored SARS vaccine could have significant advantages over other SARS vaccine candidates described to date.


Sleeping beauty transposon-mediated nonviral gene therapy.
Safe and effective delivery of genetic material to mammalian tissues would significantly expand the therapeutic possibilities for a large number of medical conditions. Unfortunately, the promise of gene therapy has been hampered by technical challenges, the induction of immune responses, and inadequate expression over time. Despite these setbacks, progress continues to be made and the anticipated benefits may come to fruition for certain disorders. In terms of delivery, nonviral vector systems are particularly attractive as they are simple to produce, can be stored for long periods of time, and induce no specific immune responses. A significant drawback to nonviral systems has been the lack of persistent expression, as plasmids are lost or degraded when delivered to living tissues. The recent application of integrating transposons to nonviral gene delivery has significantly helped to overcome this obstacle, because it allows for genomic integration and long-term expression. Recent advances in transposon-based vector systems hold promise as new technologies that may unlock the potential of gene therapy; however, technical and safety issues still need refinement.


Transcript analysis of glp-1 and lin-12, homologous genes required for cell interactions during development of C. elegans.
The glp-1 and lin-12 genes mediate several cell interactions during C. elegans development. We have identified the glp-1 gene in a region about 20 kb from lin-12. In collaboration with Yochem and Greenwald (1989; see accompanying paper), we show that a sequence identified by its similarity to lin-12 is in fact glp-1. We find a single 4.4 kb glp-1 transcript and a distinct 4.6 kb lin-12 transcript. Expression of the glp-1 transcript during development differs from that of lin-12. As expected from genetic analyses, glp-1 RNA is primarily in the germline while lin-12 RNA is primarily in the soma. Unexpectedly, we find that glp-1 RNA is also expressed in larval somatic tissues and that lin-12 RNA is abundant in early embryos. We suggest that glp-1 and lin-12 may play broader roles in development than previously thought.


Chemometric modeling and two-dimensional fluorescence analysis of bioprocess with a new strain of Klebsiella pneumoniae to convert residual glycerol into 1,3-propanediol.
The goal of this study was to show that the metabolism of Klebsiella pneumoniae under different aeration strategies could be monitored and predicted by the application of chemometric models and fluorescence spectroscopy. Multi-wavelength fluorescence was applied to the on-line monitoring of process parameters for K. pneumoniae cultivations. Differences observed in spectra collected under aerobiosis and anaerobiosis can be explained by the different metabolic states of the cells. To predict process variables such as biomass, glycerol, and 1,3-propanediol (1,3-PD), chemometric models were developed on the basis of the acquired fluorescence spectra, which were measured continuously. Although glycerol and 1,3-PD are not fluorescent compounds, the results showed that this technique could be successfully applied to the on-line monitoring of variables in order to understand the process and thus improve 1,3-PD production. The root mean square errors of predictions were 0.78 units, 10 g/L, and 2.6 g/L for optical density, glycerol, and 1,3-PD, respectively.


Possible involvement of protein kinase C in the attenuation of the morphine-induced Straub tail reaction in diabetic mice.
To investigate the role of protein kinase C in the attenuation of the morphine-induced Straub tail reaction in diabetic mice, we examined the effects of protein kinase C activator or inhibitor on the i.c.v. morphine-induced Straub tail reaction in mice. This reaction was less in diabetic mice than in normal mice. Intracerebroventricular pretreatment with phorbol 12,13-dibutyrate (50 pmol), a potent protein kinase C activator, attenuated the morphine-induced Straub tail reaction in normal mice, but not in diabetic mice. I.c.v. pretreatment with calphostin C (10 pmol), a selective protein kinase C inhibitor, enhanced the reaction in diabetic mice, but not in normal mice. The dose-response curve for the morphine-induced Straub tail reaction in normal mice, but not in diabetic mice, was shifted to the right by i.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol). Furthermore, i.c.v. pretreatment with calphostin C (3 pmol) shifted the dose-response curve to the left in diabetic mice, but not in normal mice. These results indicate that activation of protein kinase C reduces the morphine-induced Straub tail reaction in normal mice. Also, the attenuation of the morphine-induced Straub tail reaction in diabetic mice may be due in part to increased protein kinase C activity.


Eligibility for elective surgery in patients recovering from mild COVID-19: A propensity-matched analysis.
To study the timing of surgery after a recent Omicron variant infection, to provide a reference for policymakers, clinicians, and patients. This single-center propensity-matched analysis was designed and reported according to the EQUATOR-STROBE guidelines. Patients recovering from COVID-19 infection were divided into three groups based on the period from disappearance of respiratory symptoms to surgery: ≤7 days, 8-14 days, and >14 days groups. Outcome measures included postoperative respiratory complications, vascular thrombosis, myocardial infarction, ischemic stroke, and mortality. Between August 1 and December 31, 2022, 9023 surgical procedures were performed, of which 7490 surgeries met the inclusion criteria. Propensity matching resulted in a final cohort of 227 patients recovered from COVID-19 and 2043 SARS-CoV-2 negative patients. Compared with the SARS-CoV-2 negative group, the incidence of postoperative respiratory complications was significantly higher (15.91% vs. 6.71%, p = 0.028) only in the ≤7 days group. There were no statistically significant differences in the other 30-day outcomes between the SARS-CoV-2 negative and the three COVID-19 recovery groups. Patients who have recovered from mild COVID-19 may be eligible for elective surgery at least 7 days after recovery, since they do not have an increased risk of postoperative complications or mortality within 30 days.


Histopathological analysis of skin reactions after coronavirus disease 2019 vaccination: Increment in number of infiltrated plasmacytoid dendritic cell.
Skin disorders are frequent adverse events after coronavirus disease 2019 (COVID-19) vaccination. However, the pathogenesis of these disorders is not fully understood. Here, we report a case series of cutaneous adverse events following COVID-19 vaccination, and the results of our investigation reveal the underlying mechanism. Case 1: a 47-year-old female developed a wheal, confined to the COVID-19 vaccination site, 2 days after her first injection. She was treated with topical steroids and oral antihistamines. Case 2: a 51-year-old female showed generalized petechial erythema accompanied by fever, genital bleeding, thrombocytopenia, liver dysfunction, and disseminated intravascular coagulation, 2 days after her second injection. She was diagnosed with vaccine-induced macrophage activation syndrome and treated with anti-inflammatory therapy. Immunohistological analysis of the skin eruption, in both these cases, showed infiltration of CD123+ BDCA2+ plasmacytoid dendritic cells (p-DC). Despite the distinctive clinical features in these two cases, this finding suggests that p-DC might be involved in different cutaneous adverse events after COVID-19 vaccination.


Hip osteoarthritis and the active patient: will I run again?
The popularity of running as a recreational sport for health gains has steadily increased. Runners may acquire several types of injuries including hip osteoarthritis (OA). Running is possible with mild forms of OA if proper joint mechanics, neuromuscular control, and technique are present. Recent literature will be discussed that builds upon previously published articles regarding forces encountered at the hip joint during running. This article will outline the biomechanics and necessary muscle forces during running, and theories regarding strengthening and neuromuscular control. Perspectives on treatment, based on known evidence and our clinical reasoning are presented.


Reproductive and developmental outcomes, and influence on maternal and offspring tissue mineral concentrations, of (-)-epicatechin, (+)-catechin, and rutin ingestion prior to, and during pregnancy and lactation in C57BL/6J mice.
Maternal nutrition can have a significant effect on developmental processes during pregnancy and lactation. While certain flavonoids have been postulated to be beneficial for health, little is known about the effects of ingestion during pregnancy and lactation on the mother and progeny. We report on the effects of maternal consumption of high levels of certain flavonoids on reproductive and developmental outcomes in a mouse model. C57BL/6J female mice were fed a control diet (CT), the CT diet supplemented with 1% or 2% of a mix of epicatechin and catechin (EC1, EC2), or rutin (RU1, RU2) prior to, during pregnancy, and lactation. A subset of dams was killed on gestation day (GD) 18.5 to evaluate fetal outcomes and the remainder was allowed to deliver to evaluate offspring. Maternal food intake, body and tissue weight did not differ among groups. The number of resorptions, implantations, litter size, postnatal survival, body weight, and skeletal development were also similar. Alterations in maternal and offspring liver mineral concentrations were observed. The current results indicate that consumption of high amounts of epicatechin, catechin, and rutin during gestation and lactation is not associated with any marked developmental effects, although changes in liver mineral concentrations were noted.


Evaluation of a single intravitreal injection of 5-fluorouracil in vitrectomy cases.
To evaluate the efficacy and toxicity of 5-fluorouracil (5-FU) after pars plana vitrectomy, 51 eyes were followed in a prospective and randomized clinical trial in which, upon completion of surgery, 26 eyes received 10 mg intravitreal 5-FU and 25 control eyes did not receive 5-FU. The only possible sign of 5-FU toxicity was prolonged corneal epithelial edema. Visual acuities of 20/200 or better were obtained in 67% of the 5-FU group and 56% of the control group. Successful macular reattachment was obtained in 60% of the 5-FU group and 77% of the control group. None of the eyes in either group developed substantial intraocular proliferation or membranes. The findings indicate that a single 10-mg intravitreal injection of 5-FU is well tolerated without permanent toxic damage.


[The in vitro effect of antiseptics on epithelial cells of human cornea and conjunctiva].
Effective and safe antiseptic eye preparations are necessary for prevention and treatment of infectious and inflammatory eye diseases. in vitro evaluation of the effect of antiseptic eye drops on corneal and conjunctival epithelial cells. Antiseptic eye drops «Bactavit», «Vitabact» and «Ocomistin» were the object of the study. Immortalized human corneal epithelial cell lines (HCE) and human conjunctiva (Chang Conjunctiva, Clone 1-5c-4) were used as the test systems. The viability of the cells was assessed by their metabolic activity and morphology using the MTT test and phase-contrast microscopy. Antiseptic eye drops belonging to different groups of chemical compounds induced cytotoxic effects on the cells of corneal epithelium (HCE) and human conjunctiva (Chang Conjunctiva, Clone 1-5c-4) of varying degrees, leading to morphological and functional changes in those cells. The study confirms the possibility of using cultured cells for the in vitro comparative assessment of the cytotoxic effect of antiseptic ophthalmic agents.


Genomic analyses of KEL alleles in alloimmunized thalassemia patients from Iran.
Serological methods are unreliable for red blood cells (RBCs) antigen typing in multi-transfused thalassemia patients due to the presence of donor RBCs in the recipient's circulation and interfering antibodies. Kell blood group system is important in transfusion medicine and Kell antibodies have shown as the most prevalent antibodies in thalassemia patients. We intended to determine the genotype of Kell antigens among Iranian alloimmunized thalassemia patients using molecular methods and compare the results with serological phenotyping. Two hundred thalassemia patients participated in this study. Blood group phenotype was performed by the serological method, while the genotype was determined for KEL*01, KEL*02, KEL*03, and KEL*04 alleles using PCR-Sequence Specific Primer (PCR-SSP) method. The genotypes of patients with incompatibility between phenotype and genotype were re-evaluated by Restriction Fragment Length Polymorphism-PCR (RFLP-PCR) and confirmed by DNA sequencing in all cases. Ten patients were found with discrepancies between genotype and phenotype; however, there was a complete agreement between the results of SSP-PCR, RFLP-PCR, and DNA sequencing. Six discrepancies were found in the KEL*01/KEL*02 allele when serologically phenotyped as K-k+. One patient with K-k- and three patients with Kpa-Kpb + phenotype were identified as KEL*01/KEL*02 and KEL*03/KEL*04, respectively. It can be concluded that molecular genotyping is more reliable compared with the serological method, especially in the patients who have received multiple transfusions. Therefore, using a combination of these techniques can lead to a better matched transfusion in these patients.


Evaluation of medical students in radiology. Written testing using uncued multiple-choice questions.
Evaluation of uncued multiple-choice questions (UMCQ) was compared with traditional multiple-choice questions (MCQ) for assessing medical student performance during radiology electives. Methods for analyzing and improving the quality of UMCQ examinations are described. The authors compared the performance of radiology medical students on similarly constructed MCQ and UMCQ tests. For the UMCQ examination, the reliability (coefficient alpha), standard error of measurement, item difficulty index, and corrected item-to-total test coefficient (point biserial correlation) were analyzed. Students' level of performance was lower on UMCQs (mean percent correct score = 68.9 +/- 10.2 standard deviation [SD]) than on MCQs (mean percent correct score = 75.6 +/- 12.4 SD). Coefficient alpha for the UMCQ format was .7690 (standard error of measurement mean = 4.89%). Analysis of the item difficulty index and point biserial correlation for each test item provided information for improving the quality of the UMCQ examination. Because the UMCQ measures students' abilities to recall critical information without providing cues, this format can be used to overcome some of the limitations of conventional MCQs. With simple computerization, analysis of UMCQ testing instruments provides important feedback to both the examinees and the examiner.


Liposomal glycosphingolipids activate natural killer T cell-mediated immune responses through the endosomal pathway.
Natural killer T (NKT) cells recognize lipid antigens, such as glycosphingolipids (GSLs), via CD1d and contribute to host defense against various pathogens. Here, we demonstrate that GSLs isolated from Sphingomonas bacteria and inserted into liposomes (GSL-liposomes) enhance the activation of NKT cells and dendritic cells (DCs). GSL-liposomes remarkably enhanced the production of IFN-gamma from splenocytes in vitro and this enhancement depended on the content of the pH-sensitive lipid dioleoyl-phosphoethanolamine (DOPE) in the liposomes. GSL-liposomes containing DOPE were clearly broken in late endosomes and this may facilitate effective loading of GSLs onto CD1 molecules. Treatment with GSL-liposomes also activated NKT cells and DCs in vivo. Collectively, our results strongly suggest that GSL-liposomes can effectively induce NKT cell-mediated immune responses and may be useful as an immune adjuvant for inducing protective immunity.


Effectiveness of laparoscopic total and partial fundoplication on extraesophageal manifestations of gastroesophageal reflux disease: a randomized study.
The aim of the present study was to evaluate the clinical effect of partial and total fundoplication on extraesophageal symptoms in a selected cohort of patients with gastroesophageal reflux disease (GERD). Hundred patients with documented GERD were randomized to either undergo floppy Nissen (n = 50) or Toupet fundoplication (n = 50). Symptom scores of cough, asthma, hoarseness, and distortion of taste were prospectively evaluated using a standardized symptom questionnaire before surgery and at 3- and 12-month follow-up. Statistical significance was set at a P-value of 0.05. All evaluated symptoms exhibited substantial improvement after Nissen fundoplication at 3- and 12-month follow-up. Similar therapeutic results were documented for Toupet fundoplication, although statistical significance could not be reached for asthma at long-term follow-up. In conclusion, the application of laparoscopic fundoplication is justified for patients with documented GERD and atypical symptoms refractory to medical treatment. Toupet fundoplication may have a lesser effect on asthma.


Alcohol Drinking Among Kosovar Adolescents: An Examination of Gender-Specific Sociodemographic, Sport, and Familial Factors Associated With Harmful Drinking.
Adolescent alcohol consumption is a significant public-health problem, although there is a lack of studies investigating this issue in Kosovo. The aim of this investigation was to examine the prevalence of alcohol drinking, and the factors associated with harmful drinking (HD) in Kosovar 17-18 years old adolescents. The sample comprised 636 girls and 366 boys (17-18 years old) from Pristina, Kosovo. The independent variables included sociodemographic factors, variables examining familial-monitoring and conflict (familial-variables), and sport-factors. Alcohol-drinking (dependent variable) was measured by means of the alcohol use disorders identification test scale. 39% of the girls and 43% of the boys reported HD (odds ratio (OR) = 1.17; 95% confidence interval = 0.90-1.55). A higher likelihood of HD is found for those girls whose mothers have an advanced education (OR = 1.59), who reported a higher level of conflict with their parents (OR = 1.95), whose parents are frequently absent from home (OR = 1.93), and who reported lower religiosity (OR = 0.90). HD is more frequent among boys who have participated longer in sports (OR = 1.49), whose fathers have an advanced education (OR = 1.80), and who reported higher level of familial conflict (OR = 2.87). The prevalence of HD is high. Knowing the problems related to alcohol drinking in girls (violence, trafficking, etc.), public-health authorities should urgently develop a specific preventive programme (SPP) to combat the misuse of alcohol. In preparing SPP, special attention should be paid to the varying influences of the studied factors on HD in boys and girls.


Epstein-Barr virus as an agent of haematological disease.
Epstein-Barr virus (EBV) encodes genes that permit its persistence in human B lymphocytes and genes that ensure its replication in epithelial cells. Immune restraints on the virus are usually so effective that most EBV infections are limited to a minute fraction of B lymphocytes and of epithelial cells. As a result, most EBV infections are never symptomatic. Occasionally, the virus causes disease, often with the cooperation of the immune system or other less characterized cofactors. Infectious mononucleosis, a generally self-limited lymphoproliferative illness common in adolescents and young adults, is due to primary EBV infection and to the brisk cellular immune response it elicits. Lymphoproliferative disorders of EBV-infected B cells arise almost exclusively when cellular immunity is grossly compromised. EBV-positive Burkitt's lymphoma contain a translocated and deregulated c-myc oncogene and EBV-positive non-Hodgkin's lymphomas are characterized by the presence of Reed-Sternberg's and Hodgkin's cells, features that have not been directly linked to EBV. Many recent observations, however, including evidence that virus infection precedes malignant transformation and is often associated with a characteristic pattern of viral gene expression, provide continued interest in the relationship between the virus and these haematological malignancies.


Antineoplastic effects of butanolic residue of Pfaffia paniculata.
We have previously reported a reduction in the accumulation of ascitic fluid in Ehrlich tumor-bearing mice following treatment with the powdered roots of Pfaffia paniculata. The aim of this study was to investigate which extracts from these roots presented antineoplastic properties. Thus, the effects of the ethanolic extract, butanolic residue, or aqueous residue from Pfaffia paniculata on animal survival and tumor growth in mice bearing this tumor were studied. Butanolic residue-treated mice survived longer than untreated mice. This result points to an antineoplastic effect exerted by the butanolic fraction from the roots of P. paniculata on this tumor model.


Categorical perception effects for facial identity in robustly represented familiar and self-faces: the role of configural and featural information.
Categorical perception of robustly represented faces (self, friend) and unfamiliar faces is investigated, and the relative roles of configural and featural information are examined. Participants performed identification and discrimination tasks on morph series containing the self-face and a friend's face (self-Friend 1), two friends' faces (Friend 2-Friend 3), and two unfamiliar faces (Unfamiliar 1-Unfamiliar 2), presented in upright and inverted orientations. For upright faces, categorical perception effects were observed for both familiar morph series but not for the unfamiliar morph series, suggesting that robust representation is a requirement for categorical perception in facial identity. For inverted faces, categorical perception was observed for the self-Friend 1 morph series only. This suggests that categorical perception is tied to configural processing for familiar non-self-faces, but can be observed for self-faces during featural processing-consistent with evidence that self-face representations contain strong configural and featural components. Finally, categorical perception is not enhanced by the presence of the self-face relative to other familiar faces when upright, but shows a trend of being enhanced for self-faces when inverted, adding to the debate on the ways in which robustly represented faces can elicit categorical perception.


Hepatic gene expression in mouse models of non-alcoholic fatty liver disease after acute exercise.
Non-alcoholic fatty liver disease (NAFLD) patients benefit from physical exercise. This study aimed to investigate the effect of acute exercise on hepatic gene expression in different mouse models of NAFLD. C57BL/6J mice were fed with a control (CD) or a high fat (HFD) diet. AlbCrePtenflox/flox (Pten-KO) and Fxr-/- mice, two genetic models of NAFLD with insulin hypersensitivity and resistance, respectively, were fed with CD. After 4 weeks, mice were randomly assigned to exercise or sedentariness. Mice were killed 15 min or 3 h after the running/sedentary period. Genome-wide hepatic gene expression was evaluated with the Illumina Micro-array platform. Quantitative polymerase chain reaction confirmed changes in gene expression. Acute exercise transiently affected the expression of genes involved in the immune response in C57BL/6 mice fed with CD and this effect normalized in the recovery phase. Acute exercise affected genes involved in gluconeogenesis in the insulin resistant Fxr-/- model. Genes involved in lipid metabolism were affected in C57BL/6 mice fed with CD, but not in mouse models of NAFLD. Genes involved in DNA damage response pathways were deregulated only in C57BL/6 mice fed with CD and not in mouse models of NAFLD. The simultaneous analysis of different NAFLD models revealed that an acute exercise bout affects hepatic gene expression differentially according to animal models and that most of the differentially expressed genes are involved in glucose and fatty acid metabolism, immune regulation, and DNA damage response.


What factors facilitate interprofessional collaboration outcomes in interprofessional education? A multi-level perspective.
Interprofessional education (IPE) harnesses the power of teams to facilitate collaborative learning across disciplines. However, prior research has not paid sufficient attention to the role of team-level factors on IPE outcomes, posing a major theoretical and methodological limitation. In response to this, using social interdependence theory (SIT), this study aimed to delineate the independent contributions of both team-level and student-level interprofessional attitudes (teamwork, roles, and responsibilities; patient-centeredness; and community-centeredness) in predicting IPE collaboration outcomes (goal achievement, team effectiveness, and team performance) employing multi-level analysis. To test whether interprofessional attitudes at the team and student levels predict IPE collaboration outcomes, conducted multilevel modeling. We used the pretest and posttest data from 323 healthcare students in Hong Kong from Chinese medicine, medicine, nursing, pharmacy, and social work programmes enrolled in the IPE Cancer module. Among the interprofessional attitudes, "teamwork, roles, and responsibilities" was found to be the best predictor of IPE outcomes, both at the student and team levels. Students who recognized the benefits of shared learning had better goal achievement and team effectiveness. Furthermore, teams that emphasized shared learning also had better overall team performance. Students' attitudes towards teamwork, roles, and responsibilities in interprofessional collaborative practice, both at the student and team levels, are important to attaining positive student- and team-level outcomes. The study contributes to the expansion of existing knowledge in medical education, theoretically, by adopting SIT as a lens through which collaborative learning in healthcare teams can be understood, and methodologically, by applying multi-level approaches and delineating important student- and team-level predictors of IPE outcomes.


Accessing causal relations in semantic memory.
Most studies investigating semantic memory have focused on taxonomic or associative relations. Little is known about how other relations, such as causal relations, are represented and accessed. In three experiments, we presented participants with pairs of words one after another, describing events that referred to either a cause (e.g., spark) or an effect (e.g., fire). We manipulated the temporal order of word presentation and the question participants had to respond to. The results revealed that questions referring to the existence of a causal relation are answered faster when the first word refers to a cause and the second word refers to its effect than vice versa. However, no such asymmetry was observed with questions referring to the associative relation. People appear to distinguish the roles of cause and effect when queried specifically about a causal relation, but not when the same information is evaluated for the presence of an associative relation.


Highlighting metabolic indicators of olive oil during storage by the AComDim method.
Lipid oxidation during olive oil storage induces changes in the metabolite content of the oil, which can be measured using so-called quality indices. High values indicate poor quality oils that should be labeled accordingly or removed from the market. Based on quality indices measured over two years for two olive oils, the AComDim method was used to highlight the influence of five factors (olive oil type, oxygen, light, temperature and storage time) on oxidative stability during storage. To identify the significant factors, two full factorial experimental designs were built, each containing four of the five factors examined. The results showed that all five factors, as well as some two-factor interactions, were significant. Phenols and hydroperoxides were identified as being the most sensitive to these factors, and potential markers for the ageing of olive oil.


Evaluation and comparison of the effect of different surface preparations on bond strength of glass ionomer cement with nickel-chrome metal-ceramic alloy: a laboratory study.
Retention of fixed partial dentures is mostly dependent upon the bond between metal and cement as well as cement and tooth structure. However, most of the time clinical failure of bond has been observed at metal and cement interface. The treatment of metal surface, prior to luting, plays a crucial role in bonding cement with the metal. This study is conducted to evaluate and compare the effect of different surface preparations on the bond strength of resin-modified glass ionomer cement with nickel-chromium metal ceramic alloy. Fifty caries-free extracted molar teeth were made flat until the dentin of the occlusal surface was exposed. After fabrication of the wax patterns and subsequent castings, the castings were subjected to porcelain firing cycles. The nickel-chromium metal ceramic alloy discs were also divided into five groups and subjected to various surface treatments: (1) Unsandblasted (U), (2) sandblasted (S), (3) sandblasted and treated with 10% aqueous solution of KMnO4 (SK), (4) unsandblasted and roughened with diamond abrasive points (UD) and (5) unsandblasted and roughened with diamond abrasive points and treated with 10% aqueous solution of KMnO(4) (UDK). After surface treatments, the castings were cemented using Fuji PLUS encapsulated resin-modified glass ionomer cement. The obtained values of all the groups were subjected to statistical analysis for Tensile and Shear bond strength. Different surface treatments of the metal affects the bond strength values of resin-modified glass ionomer cement when used as luting agent.


Effects of cadmium on the expression of placental lactogens and Pit-1 genes in the rat placental trophoblast cells.
Cadmium is an endocrine disrupter (ED) with detrimental effects on mammalian reproduction. The placenta is a primary target for cadmium toxicity during pregnancy. Very little of this metal crosses the placenta to the fetus, and consequently it accumulates in high concentrations in the placenta. Cadmium affects on steroid synthesis and has estrogen- and androgen-like activities. In this study, we investigated the toxic effects of cadmium on placental trophoblast cells as well as the mRNA levels of placental lactogens (PLs), which are under the control of estrogen and play a pivotal role during pregnancy. Pregnant F344 Fisher rats were injected subcutaneously with 0, 0.2, and 2.0mg/kg BW/day of cadmium (CdCl(2)) dissolved in saline from days 11 to 19 of pregnancy and were sacrificed on day 20. The mRNA levels of the PL-Iv and -II genes and Pit-1alpha and beta isotype genes, the trans-acting factor of PLs, were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction, respectively. The frequency of the placental trophoblast cells was observed histochemically. Developmental data and apoptotic chromosomal DNA fragmentation of placental cells were also observed. The mRNA levels of PL-Iv and -II were reduced in a dose-dependent manner by cadmium. The mRNA levels of the Pit-1alpha and beta isotype genes were also reduced by cadmium. In the uterus-conjugated region of the placental junctional zone, the frequency rates of trophoblast cells were lower in the cadmium-treated groups than in the control group. High-dose cadmium exposure (2.0mg) induced not only the reduction of trophoblast cell frequency but also apoptotic chromosomal DNA fragmentation in the junctional zone of the placenta. Developmental metrics such as placental and fetal weights and a number of live fetuses, decreased, while a numbers of resorptions, dead fetuses, and post-implantation losses increased significantly (p<0.05) in the cadmium-treated groups compared to the control. These data suggested that cadmium inhibits the expression of PL genes and reduces the number of trophoblast cells in the rat placenta via an estrogen-like activity, leading to significant toxic effects on placental growth and physiological function in rats.


Atherogenic index of plasma and risk of cardiovascular disease among Cameroonian postmenopausal women.
The paucity of data regarding the relationship between atherogenic index of plasma (AIP) and risk of cardiovascular disease (CVD) in postmenopausal women living in sub-Saharan Africa prompted us to conduct this study which aimed at assessing the interplay between AIP and risk of CVD among Cameroonian postmenopausal women. This was a cross-sectional study conducted among 108 postmenopausal women in Yaoundé, Cameroon. Risk of CVD was calculated using the Framingham risk score, (FRS), and the AIP was derived as log (triglycerides/high-density lipoproteins cholesterol). Mean age of participants equaled 56.4 ± 6.9 years. AIP values ranged from -0.40 to 0.85 with a mean of 0.21 ± 0.27. There was a positive and significant correlation between AIP and body mass index (r = 0.234; p = 0.015), systolic blood pressure (r = 0.350; p < 0.001), diastolic blood pressure (r = 0.365; p < 0.001), fasting plasma glucose (r = 0.314; p = 0.001), uric acid (r = 0.374; p < 0.001), and total cholesterol (r = 0.374; p < 0.001), but not with age (r = -0.104; p = 0.284). The FRS varied between 1.2 % and >30 % with a mean of 13.4 ± 8.7 %. In univariable model, AIP significantly influenced the risk of CVD (β = 11.94; p < 0.001; R(2) = 0.136). But in the multivariable model, after adjusting for confounders, AIP did not impact the risk of CVD anymore (adjusted β = 1.98; p = 0.487; R(2) = 0.486). AIP may not be an independent factor impacting the risk of CVD among Cameroonian postmenopausal women. More studies are needed to better elucidate the interaction between AIP and risk of CVD in our setting.


The dedicated endoscopic operating room.
The establishment of neuroendoscopy has been one of the major achievements in neurosurgery in the last 2 decades. The use of the endoscope increases efficacy and safety in each procedure. The integration of endoscopy with other operating techniques or imaging technologies enhances the safety and reliability of the technique. The efficacy of the procedures, patient safety, and extent of resection have been increased by the integration of endoscopy with all of these sophisticated operative tools and imaging sources. Endoscopy has led to shortening of operative time and of the duration of hospital stay. A dedicated endoscopic operating room should provide workflow optimization, ergonomic solutions, and highest safety standards for the patient.


Treatment of idiopathic internal jugular vein thrombosis in a healthy woman with enoxaparin and rivaroxiban: Case report and literature narrative review.
Venous thrombosis is a medical condition that occurs when a blood clot forms in a vein. These clots usually develop in the lower leg, thigh, or pelvis but can also occur in the arm. It is essential to know about Venous thrombosis because it can happen to anybody and cause severe illness and disability. Fortunately, if the diagnosis is early, the outcomes will be excellent. However, idiopathic or spontaneous internal jugular vein thrombosis is a rare but potentially fatal condition. Method: here, we presented a rare case of Internal jugular vein thrombosis (IJVT) and reviewed the literature on cases of IJVT to describe clinical features, associated risk factors, possible complications, ways of investigations, and outcomes. Among 57 cases (56 in the literature plus our case), 25 patients out of 57 had a chief complaint of neck swelling, and only five complained of neck pain; on the other hand, four patients were asymptomatic. Thirty-five patients had a risk factor of developing thrombosis, 19 patients had a malignancy, and 22 did not have an obvious risk factor. To diagnose IJVT, ultrasound alone was used in 11 patients, Ct alone was used in 13 patients, and a combination of CT and ultrasound was used in 21 patients. Conclusion: IJVT thrombosis is a rare condition, but its diagnosis requires reasonable radiological and laboratory investigations; early treatment is warranted to avoid fetal complications.


Hypermethylation of the RUNX3 gene in hepatocellular carcinoma.
Methylation events play a critical role in various cellular processes including regulation of gene transcription and proliferation. Recently, RUNX3 gene, one of TGF-beta-Smads signaling transduction pathway genes, showed strong tumor-suppressor activity by regulation of epithelial proliferation and apoptosis. To elucidate the potential etiological role of the RUNX3 gene in the development of hepatocellular carcinoma (HCC), we have analyzed the methylation status of 5' CpG island of the RUNX3 gene in a series of 73 HCC tissues and 11 liver cell lines. Expectedly, promoter methylation of RUNX3 gene was found in 2 (2.7%) of 73 corresponding normal liver, whereas 30 (41.1%) of 73 HCCs and 4 (40%) of 10 liver cancer cell lines showed hypermethylation of the gene, respectively. There was no significant difference between promoter hypermethylaion and clinicopathologic parameters of primary HCC samples, including histologic grade, microvascular invasion, and clinical stage. Interestingly, demethylating agent 5-aza-2-deoxycytidine induced reactivation and more potent expression of RUNX3 gene in HCC cell lines. Our findings indicate that promoter hypermethylation of RUNX3 gene may occur as an early event in the development of HCC and that methylation may be a major mechanism for inactivation of RUNX3 gene in HCC.


Orthostatic blood pressure response, carotid intima-media thickness, and plasma fibrinogen in older nondiabetic adults.
Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension (OHTN) independently predict cardiovascular events, the underlying mechanisms are still debatable. A total of 700 nondiabetic adults (43% men, age 64 years) were examined by orthostatic blood pressure (BP) test, carotid artery ultrasonography, and biochemical tests including plasma fibrinogen and lipid profile. Multivariate-adjusted logistic regression was applied to assess association of intima-media thickness (IMT) and P-fibrinogen with orthostatic hypotension and OHTN. In addition, distribution of IMT and P-fibrinogen across quintiles of orthostatic systolic BP (SBP) response was analyzed. Orthostatic hypotension and OHTN were found in 40 (5.7%) and 45 (6.4%) study participants, respectively. Both IMT [odds ratio (OR), 95% confidence interval (CI) per one-SD increment: 1.27, 1.01-1.60; P = 0.04] and P-fibrinogen (OR 1.44, 1.07-1.93; P = 0.02) were associated with orthostatic hypotension in a crude model. After adjustment relationship between orthostatic hypotension and IMT was slightly attenuated (OR 1.26, 0.96-1.65; P = 0.09) but was substantially unchanged in regard to P-fibrinogen (OR 1.45, 1.06-1.99; P = 0.02). In contrast, OHTN showed no association with either IMT or P-fibrinogen (adjusted OR 1.09, 0.78-1.52; P = 0.61, and 0.97, 0.70-1.34; P = 0.84, respectively). Distribution of IMT across quintiles of orthostatic SBP response was U-shaped, whereas that of fibrinogen was more linear but none of borderline quintiles (with pronounced hypertensive or hypotensive response) significantly differed from the middle quintiles in a fully adjusted model. In older nondiabetic adults only orthostatic hypotension seems to independently correlate with increased carotid atherosclerosis and systemic inflammation.


Research on polycystic ovary syndrome: a bibliometric analysis from 2009 to 2019.
Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disease. However, there have not been any bibliometric studies on the latest scientific results and research trends of PCOS. This study aimed to review the state of research in PCOS worldwide. Publications on PCOS from 2009 to 2019 were identified and evaluated from the database Web of Science. A total of 7814 articles were retrieved. Shanghai Jiao Tong University published the most articles, with 218 publications. Gynecol Endocrinol had the greatest number of publications (n = 541). J Clin Endocr Metab was cited the most, with a total of 32,207 times. An article written by March et al. in 2010 had the most global citations (737 times) and local citations (463 times). From 2009 to 2019, the number of PCOS global publications gradually increased. Gynecol Endocrinol and Endocr Metab were popular journals for PCOS research. Research trends gradually shifted from treatment and methodology to genetics and basic research. The terms 'microrna,' 'rt qpcr,' 'lncrna,' and 'histological examination' may be hotspots that should be focused on in PCOS research.


Tyrosinase-functionalized polyhydroxyalkanoate bio-beads as a novel biocatalyst for degradation of bisphenol analogues.
Bisphenol compounds are emerging contaminants of high concerns with known endocrine-disrupting effects. Biocatalysis provides a green chemistry alternative for advanced treatment in water reclamation. This study createda novel biocatalyst through genetically immobilizing the Bacillus megaterium tyrosinase enzyme (BmTyr) on the surface ofself-assembled polyhydroxyalkanoate (PHA) biopolymer beads (termed PHA-BmTyr) by using synthetic biology techniques and demonstrated one-pot in vivo production of the biocatalyst for effective degradation and detoxification of various bisphenol analogues for the first time. The degradation pathway of bisphenols was determined to be mediated by the monophenolase and diphenolase activity of BmTyr. Notably, biocatalytic bisphenol degradation by PHA-BmTyr could substantially reduce or eliminate estrogenic activity of the contaminants, and the degradation products had remarkably lower acute and chronic toxicity than their parent compounds. Furthermore, the PHA-BmTyr biocatalyst had high reusability for multiple bisphenol degradation reaction cycles and showed excellent stability that retained 100% and 86.6% of the initial activity when stored at 4 °C and room temperature, respectively for 30 days. Also, the PHA-BmTyr biocatalyst could efficiently degrade bisphenol analogues in real wastewater effluent matrix. This study provides a promising approach to develop innovative biocatalysis technologies for sustainable water reclamation.


Reinventing an Organelle: The Reduced Mitochondrion in Parasitic Protists.
Mitochondria originated from the endosymbiotic event commencing from the engulfment of an ancestral α-proteobacterium by the first eukaryotic ancestor. Establishment of niches has led to various adaptations among eukaryotes. In anaerobic parasitic protists, the mitochondria have undergone modifications by combining features shared from the aerobic mitochondria with lineage-specific components and mechanisms; a diversified class of organelles emerged and are generally called mitochondrion-related organelles (MROs). In this review we summarize and discuss the recent advances in the knowledge of MROs from parasitic protists, particularly the themes such as metabolic functions, contribution to parasitism, dynamics, protein targeting, and novel lineage- specific proteins, with emphasis on the diversity among these organelles.


Comparing two-dimensional ultrasonography with three-dimensional ultrasonography and MRI for the levator ani defects grading.
Levator ani defect (LAD) closely correlates with pelvic floor disorders (PFD). In general, LAD was graded by three-dimensional ultrasonography (3D-US) and MRI, which could be used hardly in some developing area. Our objective was to determine whether two-dimensional ultrasonography (2D-US), a method that is almost universally accessible, could be used to diagnose the LAD. 129 Chinese women with PFD were recruited for the LAD grading by 2D-US and 3D-US and MRI. LAD was classified into intact, partial and complete avulsions. The puborectalis attachment width (PAW) was measured by 2D-US and with the software on the three-dimensional MRI-based LAD models. The results were compared and analyzed using the weighted kappa and the Pearson's coefficient. Of the 119 patients, 64 were diagnosed with LAD by 2D-US, 70 were identified by 3D-US while 68 were confirmed by MRI. The LAD grading of 2D-US showed good agreement with MRI (kappa = 0.78, 95% CI 0.71-0.86) and 3D-US (kappa = 0.77, 95% CI 0.70-0.84). In regard to the consensus of partial or complete avulsions, 2D-US showed excellent good agreement with MRI (kappa = 0.86, 95% CI 0.73-0.97), superior than 3D-US with MRI (kappa = 0.55, 95% CI 0.36-0.71). Additionally, iliococcygeus avulsions detected by MRI (n = 7) were accompanied by complete puborectalis avulsions. The averaged PAW was 10.42 ± 5.57 mm measured by 2D-US, which correlated well with the results measured by MRI (Pearson's coefficient = 0.90). 2D-US, 3D-US and MRI showed the good agreement on LAD diagnosis. Compared with MRI and 3D-US, 2D-US was comparable in grading LAD, especially complete avulsions.


Genes, environment, and exercise.
The definition of the term "environment" has broadened in the past 40 years to include knowledge generated from sequencing genes. Studies on animal responses to the environment have expanded to include selective lifestyle behaviors. Environmental lifestyle components interact with susceptibility genes to pass a threshold of biological significance such that a disease requires clinical treatment. Examples of environmental-gene interactions producing cystic fibrosis and asthma are described. The contributing role of physical inactivity to the epidemic of type 2 diabetes is presented with some of its underlying effectors. A lack of contractile activity by skeletal muscle is associated with less GLUT4 protein in the sarcolemma and a lower glucose uptake into the muscle. The pathways by which contractile activity signals an increase in glucose uptake differs from insulin signaling, but is remarkably similar to how hypoxia stimulates muscle to increase its glucose uptake.


Retroperitoneal robot-assisted laparoscopic partial nephrectomy for posterior located renal tumours: Technique and early term outcomes.
Traditionally, the trans-peritoneal approach is preferred for robot-assisted partial nephrectomy (RPN). However, retroperitoneal RPN (RP-RPN) has recently become widespread because of the advantages of easier access to the hilum, ease dissection of posterior tumours, and lower probability of intra-peritoneal organ injury. We aimed to present our initial experience of the RP-RPN series in posteriorly located renal tumours. Twenty-one patients were included in the study, who underwent RP-RPN by a single surgeon between July 2019 and January 2020. RP-RPN was carried out only in posteriorly located renal tumours with ischemic (on-clamp) or zero ischemic (off-clamp) techniques. Patients with solitary kidney and a history of previous retroperitoneal surgery in the lumbodorsal region were excluded from the study. All cases completed without any operative complication and conversion to open or radical nephrectomy. Seven cases were completed as zero ischemic and 14 cases as ischemic technique. The mean operation time was 157.86 ± 64.24 minutes and estimated blood loss was 173.81 ± 136.84 mL. The mean warm ischemia time was 15.81 ± 12.42 minutes. Positive surgical margin observed in 4.8% of the patients. The mean length of stay was 3.33 ± 0.79 days. The mean estimated glomerular filtration rate (eGFR) change in the 3rd postoperative month was -3.71 ± 8.57 ml/min/1.73 m2 (4.6%). Mean follow-up period was 10.29 ± 4.86 months. New-onset stage 3-4 chronic kidney disease (eGFR < 60 m /min/1.73m2 ) was not observed during the follow-up period. RP-RPN is a safe and feasible approach with acceptable oncological and functional results. We think that RP-RPN can be applied as an alternative to the trans-peritoneal approach for selected cases, especially in renal tumours with the posterior location.


Environmental opportunities facilitating cognitive development in preschoolers: development of a multicriteria index.
Access to environmental opportunities can favor children's learning and cognitive development. The objectives is to construct an index that synthesizes environmental learning opportunities for preschoolers considering the home environment and verify whether the index can predict preschoolers' cognitive development. A quantitative, cross-sectional, exploratory study was conducted with 51 preschoolers using a multi-attribute utility theory (MAUT). The criteria used for drawing up the index were supported by the literature and subdivided in Group A "Resources from the house" extracted from HOME Inventory including: (1) to have three or more puzzles; (2) have at least ten children's books; (3) be encouraged to learn the alphabet; (4) take the family out at least every 2 weeks. Group B "Screens" (5) caution with using television; (6) total screen time in day/minutes. Group C "Parental Schooling" (7) maternal and paternal education. Pearson correlation analyses and univariate linear regression were performed to verify the relationship between the established index with cognitive test results. The index correlated with the total score of the mini-mental state exam (MMC) and verbal fluency test (VF) in the category of total word production and word production without errors. Multicriteria index explained 18% of the VF (total word production), 19% of the VF (total production of words without errors) and 17% of the MMC. The present multicriteria index has potential application as it synthesizes the preschooler's environmental learning opportunities and predicts domains of child cognitive development.


Aeration of the shell membranes of avian eggs.
The inner and outer shell membranes (ISM, OSM) of fertile hen's eggs become aerated during the first ten days of incubation. The volume of gas in the compound membrane increases from 0 to 65% by day 11 when practically all of the space between the fibers is gas filled. The amount of gas depends on a balance between the capillary tension produced by fluid menisci in the interstices between fibers and the colloid osmotic tension of the albumen. Capillary tension, measured directly with a pressure plate apparatus, and colloid osmotic pressure, measured with a new technique, are in virtual equilibrium during aeration. These tensions increase from 0.15 bar at laying to 2.25 bar on day 11 because of evaporation from the membranes and active removal of water from the albumen by the embryo. Water leaving the membranes by evaporation is only partly replaced from the albumen. Thus the water contents of the membranes and albumen decrease (ISM: 79 to 56%, OSM: 71 to 52%, albumen: 86 to 58%). As the membranes dry, gas enters the larger pores first. Physiological estimates of effective radius show smaller (x = 1.3 micrograms), bimodally distributed pores in the ISM and larger (x = 3.4 micrograms), unimodally distributed pores in the OSM.


Heavy chain binding protein (BiP/GRP78) and endoplasmin are exported from the endoplasmic reticulum in rat exocrine pancreatic cells, similar to protein disulfide-isomerase.
Previously we found that in rat exocrine pancreatic cells, protein disulfide-isomerase (PDI), one of the major resident proteins in the lumen of the endoplasmic reticulum (ER) of many cells, is localized not only in the ER but also in the Golgi apparatus, secretory granules, plasma membranes, and even in the glandular lumens, despite possessing the ER retention signal KDEL (Lys-Asp-Glu-Leu) at the carboxyl terminus. In this report, we examined whether other ER luminal proteins bearing the KDEL signal at their C-termini, such as BiP/GRP78 and endoplasmin/GRP94 are also exported from the ER. We prepared two kinds of affinity-purified polyclonal antibodies; one against a synthetic peptide with 12 amino acids which is identical to the carboxyl terminus of BiP and another against purified endoplasmin. Immunoblot analysis using these two antibodies showed that BiP and endoplasmin exist in both the plasma membrane and the microsomal fractions, similar to the intracellular distribution of PDI in rat exocrine pancreas. The ratios of the amount of the three proteins in the two fractions, however, were variable, suggesting that the KDEL-bearing proteins such as PDI, BiP, and endoplasmin are exported from the ER with different efficiencies. Postembedding protein A-immunogold electron microscopy revealed that endoplasmin was exported from the ER and secreted to the extracellular space. The secretion of PDI in rat pancreatic lobules was inhibited by Brefeldin A (BFA) and by guanidino acid esters (FOY-305), which are known to be the inhibitors of the intracellular transport. Taken together with the previous immunogold electron microscopic analyses by Akagi et al. (1988), it is strongly suggested that in rat exocrine pancreatic cells PDI and the other KDEL-bearing proteins found in the extracellular space were not artificially released by cell damage during incubation but were secreted via the normal secretory pathway.


Molecular characterization and elucidation of the function of Hap38 MAPK in the response of Helicoverpa armigera (Hübner) to UV-A stress.
The cotton bollworm Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), an important pest of cotton, is detrimental to cotton production. Light from UV-A ultraviolet lamps is regarded as a form of environmental stress for insects. In order to investigate the response of H. armigera exposed to UV-A, we explored Hap38 MAPK expression and functions. We hope that the findings of this study will lay the foundation for future investigations into the insect's phototaxis mechanism. A p38 MAPK was cloned and named Hap38 MAPK. A phylogenetic tree showed that Hap38 MAPK was highly conserved. The gene was highly expressed in the thorax and females. Under UV-A stress, the expression of the gene decreased significantly. After silencing Hap38 MAPK, the activity of the antioxidant enzymes SOD, POD, CAT, and GR decreased. This study suggested that Hap38 MAPK responds to UV-A irradiation and plays critical roles in the defense response to environmental stresses.


Type IV collagen reduces mucin 5AC secretion in three-dimensional cultured human primary airway epithelial cells.
Mucin 5AC (MUC5AC) hypersecretion induces airway narrowing in patients with asthma, which leads to breathing problems. We investigated the regulation of MUC5AC secretion by extracellular matrix (ECM) proteins in human primary airway epithelial cells from patients with asthma. The addition of type IV collagen to three-dimensional cultured human primary airway epithelial cells, which mimics the airway surface, reduced MUC5AC secretion in the medium, while the addition of laminin increased MUC5AC secretion. Furthermore, the addition of fibronectin did not affect MUC5AC secretion. In particular, the repeated addition of a low concentration of type IV collagen demonstrated a cumulative effect on the reduction in MUC5AC secretion. Human primary cells incubated with type IV collagen showed downregulated extracellular signal-regulated kinase (ERK) activity, which induced MUC5AC hypersecretion but did not affect Akt activity. These results suggest that the addition of type IV collagen to the apical surface of primary cells downregulates MUC5AC secretion and has a cumulative effect on MUC5AC secretion which might be effected via the ERK signaling pathway.


Neutropenia management with granulocyte colony-stimulating factors: from guidelines to nursing practice protocols.
Neutropenia, a problem that oncology nurses face in daily practice, is the major dose-limiting toxicity in patients with cancer who are treated with myelosuppressive chemotherapy. The incidence of chemotherapy dose reductions or treatment delays, which can impact overall dose intensity and compromise treatment outcomes, may be reduced by the proactive use of granulocyte colony-stimulating factor (G-CSF). National and international guidelines have been developed to promote the cost-effective use of G-CSF. Nursing care protocols for the management of chemotherapy-induced neutropenia (CIN) can be developed based on the national guidelines and modified for use by individual clinical practices. Risk assessment for CIN, which considers the prescribed chemotherapy regimen, patient risk factors, and treatment intent, should be a key component of the practice guidelines. Because most neutropenic events occur in the first cycle of chemotherapy, risk assessments should be conducted before the initiation of chemotherapy. Patients identified as at high risk for neutropenic complications should be given G-CSF in the first and subsequent cycles to allow the delivery of chemotherapy at full dose and on schedule. Nurses are instrumental in the development and implementation of neutropenia management protocols, which have the potential to markedly improve the quality of care and outcomes for patients with cancer.


Characterization of anti-porcine epidemic diarrhea virus neutralizing activity in mammary secretions.
Porcine epidemic diarrhea virus (PEDV) causes a severe clinical enteric disease in suckling neonates with up to 100% mortality, resulting in devastating economic losses to the pork industry in recent years. Maternal immunity via colostrum and milk is a vital source to neonates of passive protection against diarrhea, dehydration and death caused by PEDV. Comprehensive information on neutralizing activity (NA) against PEDV in mammary secretions is critically important for assessing the protective capacity of sows. Therefore, the objectives of this study were to characterize anti-PEDV neutralizing activity in mammary secretions. Anti-PEDV NA was present in colostrum, milk and serum from PEDV-infected sows as determined both by immunofluorescence and ELISA-based neutralizing assays, with neutralization levels higher in colostrum and milk than in serum. The highest NA was observed in colostrum on day 1, and decreased rapidly in milk at day 3, then gradually declined from day 3 to day 19 post-farrowing. Notably, the NA in mammary secretions showed various patterns of decline over time of lactation that may contribute to variation in sow protective capacities. The kinetics of NA decline were associated with total IgA and IgG antibody levels. Neutralizing activity significantly correlated with specific IgA primarily to spike domain 1 (S1) and domain 2 (S2) proteins of PEDV rather than to specific IgG in colostrum. Subsequently, the NA in milk was mainly related to specific IgA to S1 and S2 during lactation.


Genetic variations of the hepatic lipase gene in Korean patients with coronary artery disease.
To investigate the association between the HL gene (LIPC) polymorphism, plasma lipid levels and coronary artery disease (CAD). One hundred thirty-seven subjects with CAD and 124 age-matched controls were examined by polymerase chain reaction (PCR). The PCR products were analyzed for LIPC genotyping by enzyme digestion. The allele frequencies of the three polymorphisms in the LIPC gene were not significantly different between the controls and CAD patients. The + allele of the -514 promoter polymorphism was associated with higher total cholesterol (p = 0.05), apolipoprotein (apo) AI (p = 0.04) levels in the men of the normal group, and the apoB level (p = 0.03) in the women of the CAD group without allele effect. The allele frequencies of the -250 and -514 promoter polymorphisms of Koreans were significantly different from those of the white and African American populations studied (p < 0.05). The -514 promoter polymorphism may fluctuate on the lipid levels due to linkage disequilibria with other polymorphisms of the LIPC gene or nearby genes. The difference of the -250 promoter allele frequencies among the different populations may partially explain the variation of the HDL levels in ethnic groups. To elucidate the more exact associations of LIPC polymorphism with the plasma lipid levels, the precise biochemical mechanisms of the LIPC alleles are required.


Antireflection TiO x Coating with Plasmonic Metal Nanoparticles for Silicon Solar Cells.
It is known that the light scattering from the metal particles deposited on the surfaces of cells can be used for increasing light trapping in the solar cells. In this work, plasmonic structures are composite materials that consisted of silver nanoparticles embedded in dielectric films of TiO x -used as cell antireflection coating. The films are deposited by sol-gel method using spin-on technique. Microstructure of prepared samples is analyzed by SEM observation. Good homogenity and particles density was obtained by this simple, cheap, and short time-demanding method. We demonstrate that due to light scattering by metal particles, the plasmonic-ARC layer is more effective than TiO x layer without Ag nanoparticles. Implementation of nanoparticles on bare cell surface was carried out too. The influence of the plasmonic structures on the silicon solar cells parameters is presented as well. We announce about 5 % additional growth in short circuit current for cells with nanoparticles.


Parkinson's disease and intensive exercise therapy--a systematic review and meta-analysis of randomized controlled trials.
To evaluate and compare the effect of 3 intensive exercise therapy modalities - Resistance Training (RT), Endurance Training (ET) and Other Intensive Training Modalities (OITM) - in Parkinson's Disease (PD). Design A systematic review and meta-analysis of randomized controlled trials. A systematic literature search was conducted (Embase, Pubmed, Cinahl, SPORTDiscus, Cochrane, PEDro), which identified 15 studies that were categorized as RT, ET or OITM. The different exercise modalities were reviewed and a meta-analysis evaluating the effect of RT on muscle strength was made. In PD intensive exercise therapy (RT, ET and OITM) is feasible and safe. There is strong evidence that RT can improve muscle strength in PD, which is underlined by the meta-analysis (g'=0.54 [95%CI 0.22;0.86]). There is moderate evidence that ET can improve cardio-respiratory fitness in PD. RT, ET and OITM may have beneficial effects on balance, walking performance, Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score and quality of life in PD, but findings are inconsistent. No studies find deterioration in any outcomes following exercise therapy. RT, ET and OITM all represent feasible, safe and beneficial adjunct rehabilitation therapies in PD.


Glucose transporters in chromaffin cells: subcellular distribution and characterization.
The glucose transporter was identified and characterized by cytochalasin B binding in subcellular membrane fractions of chromaffin tissue. The binding was saturable with Kd of about 0.3 microM for each subcellular fraction. The Bmax capacity was 12-16 pmol/mg protein for enriched plasma membrane fractions, 6.3 pmol/mg protein for microsomal membrane preparations and 5.4 pmol/mg protein for chromaffin granule membranes. Irreversible photoaffinity labelling of the glucose-protectable binding sites with [3H]cytochalasin B followed by solubilization and polyacrylamide gel electrophoresis from enriched plasma membrane preparations demonstrated the presence of three molecular species: 97 +/- 10, 51.5 +/- 6 and 30 +/- 4 kDa. The chromaffin granule membranes showed only a molecular species of 80 +/- 10 kDa.


Alterations in white matter fiber in Parkinson disease across different cognitive stages.
Cognitive impairment in Parkinson disease (PD) leads to substantial disability. Unlike external manifestations such as tremor, the decay of cognitive function is often an underlying process, and its neuroanatomic substrates are not yet fully elucidated. Knowledge regarding cognitive-related alterations in white matter (WM) pathways helps us understand the mechanisms of cognitive decline in patients with PD. Previous voxel-based analyses with Diffusion tensor imaging (DTI) metrics, such as fractional anisotropy (FA) and mean diffusivity (MD) have uncovered white matter differences in groupwise, but the conclusions were inconsistent. That was partially due to white matter fibers that are known to affect cognition, such as the corpus callosum (CC) and superior longitudinal fasciculus that cross in voxel, and are hard to interpreted by the abovementioned metrics. Furthermore, cognitive decay is a continuous process, it is difficult to reflect the continuous changes of white matter fibers between groups comparison. In the present work, we chose the constrained spherical deconvolution (CSD) and the fixel model, which avoided the effect of crossing fibers. To compare the white matter fiber in different cognitive stages of patients with PD, the results found that the CC, the cingulum bundle (CB), and the corticospinal tract (CST) showed the same trend in the decline of cognitive function, and this change may lead to the impairment of cognitive function. Our findings can help physicians determine the cognitive stage of PD from the perspective of white matter fiber and provide a reference for clinical trials and predictions.


ORF in sheep and goats in Nigeria.
Orf virus was demonstrated in biopsy material taken from lambs during an outbreak of the disease on the University of Ibadan Teaching and Research Farm. Clinical cases were also seen in goats. The confirmation of orf in Nigeria is discussed in relation to peste des petits ruminants, an important virus disease of small ruminants in West African countries.


Laparoscopic management of large retroperitoneal lymphoceles complicating aortic surgery.
Retroperitoneal lymphocele is a rare but debilitating complication of aortic replacement with synthetic graft. The only effective treatment reported to date is surgical reexploration and ligation of leaking lymphatics. This report illustrates the successful management of two patients with large retroperitoneal lymphoceles formed after aortic surgery using laparoscopic techniques. The available literature is reviewed. Laparoscopic fenestration of the lymphocele and laparoscopically assisted ligation of the leaking lymphatics combined with internal drainage resulted in long-term relief of compression symptoms, as observed, respectively, over the 5-year and 3-month follow-up periods. Percutaneous catheter drainage before laparoscopic management was unsuccessful in both cases. In addition, the unique presentation of a large retroperitoneal lymphocele with intestinal obstruction is reported, and currently available treatment options are discussed.


Cyclin-dependent kinase inhibitor fadraciclib (CYC065) depletes anti-apoptotic protein and synergizes with venetoclax in primary chronic lymphocytic leukemia cells.
Fadraciclib (CYC065) is a second-generation aminopurine CDK2/9 inhibitor with increased potency and selectivity toward CDK2 and CDK9 compared to seliciclib (R-roscovitine). In chronic lymphocytic leukemia (CLL), a disease that depends on the over-expression of anti-apoptotic proteins for its survival, inhibition of CDK9 by fadraciclib reduced phosphorylation of the C-terminal domain of RNA polymerase II and blocked transcription in vitro; these actions depleted the intrinsically short-lived anti-apoptotic protein Mcl-1 and induced apoptosis. While the simulated bone marrow and lymph node microenvironments induced Mcl-1 expression and protected CLL cells from apoptosis, these conditions did not prolong the turnover rate of Mcl-1, and fadraciclib efficiently abrogated the protective effect. Further, fadraciclib was synergistic with the Bcl-2 antagonist venetoclax, inducing more profound CLL cell death, especially in samples with 17p deletion. While fadraciclib, venetoclax, and the combination each had distinct kinetics of cell death induction, their activities were reversible, as no additional cell death was induced upon removal of the drugs. The best combination effects were achieved when both drugs were maintained together. Altogether, this study provides a rationale for the clinical development of fadraciclib in CLL, either alone or in combination with a Bcl-2 antagonist.


Noninvasive determination of the pulmonary artery input impedance.
A reliable noninvasive method for the estimation of pulmonary function in healthy and diseased subjects should be of great importance in the prognosis, diagnosis, and treatment of pulmonary hypertension. Here we propose such a method, which is based on the parameter identification of the five-element Windkessel model of pulmonary circulation. The method requires the following input variables: the heart rate, the stroke volume, the Doppler echocardiographic measurements of the tricuspid regurgitation and the pulmonary valve velocity profiles, and estimations of the right atrium and the pulmonary vein pressure. The stroke volume is calculated as a product of the left ventricle outflow tract area and the velocity-time integral measured at the same place. The model parameter identification procedure is based on minimization of the root mean square error between the pulmonary artery root pressure calculated from the aforementioned Doppler velocity profiles (from the Bernoulli equation applied during the ejection phase) and the pressure from the Windkessel model during the same period. The output from the model contains the calculated pulmonary artery input impedance (i.e. the model parameters: pulmonary vascular resistance, pulmonary artery proximal and distal compliances, inertance, and characteristic impedance) and the pulmonary artery pressure profile during the whole heart period. Our method is applied to a subject with pulmonary hypertension. The right heart Swan-Ganz catheterization has been performed in this subject. The results obtained by using this method show that the five-element Windkessel model reconstructs the main features of the pulmonary artery input impedance very well: its modulus shows the minimum where the phase angle changes its sign. The pulmonary vascular resistance, the systolic, diastolic and mean pulmonary artery pressures obtained from the method are in good agreement with the values obtained invasively from the catheterization. Sensitivity analysis shows that the mean pulmonary pressure is fairly insensitive to slight overestimation/ underestimation of all input parameters, except for the right atrium pressure. The absolute error in the mean pulmonary artery pressure is nearly the same as the error in the right atrium pressure. Since the proposed method offers a deeper insight into the pulmonary circulation than the catheterization itself because it provides the proximal and distal compliance, the inertance and the characteristic impedance, it seems that it can serve in clinical practice as a good substitute for catheterization.


Ureteral obstruction secondary to retained ovarian remnants: a case report and review of the literature.
A case is reported of ureteral obstruction from retained retroperitoneal corpus luteum. Previously, the patient had undergone a hysterectomy and salpingo-oophorectomy with incomplete removal of ovarian tissue on the affected side. The ureteral obstruction was treated by excision of the mass and ureterolysis.


Two-dimensional gel electrophoretic analyses of Kentucky bluegrass and rye grass pollen allergens. Detection with a murine monoclonal anti-Poa p I antibody and amino terminal amino acid sequence of Poa p I allergen.
Allergenic extracts of Kentucky bluegrass (Poa pratensis) and rye grass (Lolium perenne) pollen were shown by 2-dimensional (2-D) gel electrophoresis to consist of several hundred protein components. The pollen extracts of the two related grasses had unique 2-D gel patterns. Two major grass pollen allergens, Poa p I and Lol p I, and their isoforms (i.e. isoallergens) were detected and localized on 2-D gels by immunoblotting with anti-Poa p I antibody mAb 60. Poa p I isoallergens were less acidic than Lol p I isoallergens. The relative proportion of four Poa p I isoallergens was (in decreasing pI): A, 13%; B, 37%; and D, 15%. The amino terminal amino acid sequences of the two major isoallergens of Poa p I were identical. However, the amino acid composition of these isoallergens showed enough differences to account for their charge differences. The amino terminal amino acid sequence of two major Poa p I isoallergens had a 70% homology in 20 amino acid overlap with the previously published amino terminal amino acid sequence of rye grass pollen allergen R-7.


Prognostic Value of Negative Emotions on the Incidence of Breast Cancer: A Systematic Review and Meta-Analysis of 129,621 Patients with Breast Cancer.
Breast cancer (BC) is one of the common malignant tumors in women and affects 1.6 million new cases globally each year. Investigators have recently found that negative emotions (NEs) and their impacts have greatly influenced the incidence and risk of BC. The present study aims to provide an association between NEs and the incidence of BC with possible risk factors. A total of 9343 studies were screened; nine studies met all inclusion criteria that were considered for the meta-analysis. The qualitative studies were measured by the Newcastle-Ottawa Scale; the observational studies were included with relative risks (RR) and corresponding 95% confidence intervals (CI). Besides the NEs and BC, the possible risk factors were evaluated. We analyzed data from 129,621 women diagnosed with NEs of which 2080 women were diagnosed with BC and their follow-up year ranges were from 4-24 years. NEs were significantly (p < 0.0001) associated with a higher incidence of BC with RR = 1.59, 95% CI:1.15-2.19, with other high-risk factors including, geographical distribution, emotion types, standard diagnosis of NEs, and follow-up duration. This study suggests that NEs significantly increase the risk for the incidence of BC, which can be supportive of the prognosis of the disease.


Validation of a Comprehensive Measure of the Family Caregiver Experience: The Caregiver Reaction Scale.
The Caregiver Reaction Scale (CRS) is a multi-dimensional measure of the family caregiving experience that assesses role conflict, challenges, and positive aspects of caregiving. The CRS has been validated in a sample of older adult caregivers who sought counseling, but its validity and reliability in a broader population of caregivers had not been established. This study aimed to explore how well the CRS assesses the multiple dimensions of the caregiving experience in a sample of family caregivers who match the national profile of caregivers and to confirm the validity and structure of the subscales. Family caregivers (N = 452), age 18-89 (M = 48.56, SD = 17.15) were recruited online and completed the CRS and questionnaires of burden and positive aspects of caregiving. A confirmatory factor analysis (CFA) was conducted to confirm the underlying factor structure of the CRS, and convergent and discriminant validity was examined. CFA supported the existing structure of the CRS; all subscales demonstrated very good internal consistency reliability (α ≤.88), convergent validity (r ≥.39), and discriminant validity (r ≤.12). The CRS offers a valid and reliable assessment of the caregiving experience as evidenced by the convergent and discriminant validity of CRS subscales with well-validated measures of burden and positive aspects of caregiving. The CRS assesses multiple dimensions of caregiving that can be used to better understand the caregiver's experience, guide clinical interventions and referrals, and identify caregiver strengths.


Outcome of R1 resection in patients undergoing pancreatico-duodenectomy for pancreatic cancer.
Pancreatico-duodenectomy (PD) is the only potentially curative treatment for pancreatic cancer, but most surgeons are reluctant to perform a palliative resection. The aim was to define the outcome for microscopically incomplete PD (R1). Ninety-nine consecutive patients underwent laparotomy to perform PD. Sixty-seven patients were resected and 32 underwent palliative bypass (PSB) because of locally advanced disease. Of the 67 PD, 27 were classified as R0 and 40 as R1. Median survival for R0, R1 and PSB were 24, 18 and 9 months, respectively. Survival in the PSB group was 34% at 1 year and 0% at 2 years. 1-, 2- and 5-year survival in the R0 and R1 groups was 79% and 70%, 48.3% and 39.1%, 21.5% and 9.9%, respectively. Compared to PSB, both other groups were less likely to die over follow-up (p=0.002). Survival was not significantly different between the R0 and R1 groups (p=0.21). Perioperative morbidity and mortality were similar in the PD and PSB groups (29.9% and 3.0% vs 31.3 and 3.1%, respectively, p=1.00). Better survival in the resection group and similar perioperative risk would support the decision to perform PD even when there is the possibility of incomplete microscopic clearance.


The ventral spino-olivocerebellar system in the cat. V. Supraspinal control of spinal transmission.
1. The transmission from the flexor reflex afferents (FRA) and from tracts running in the ipsilateral half of the spinal cord to the spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs; Oscarsson and Sjölund, 1977) was compared with the transmission from these sources to segmental reflex arcs. The climbing fibre responses evoked in Purkinje cells by electrical stimulation of limb nerves and spinal tracts were monitored by recording the mass activity at the cerebellar surface simultaneously from several termination zones, while the activity in flexor motoneurones was recorded from a flexor nerve and the primary afferent depolarization from a dorsal filament. 2. Changes in the segmental reflex response were produced by release from the tonic inhibition of transmission from the FRA in decerebrate preparations and by conditioning electrical stimulation of dissected spinal funiculi containing inhibitory descending tracts. 3. The changes of the transmission from the FRA to two of the paths, the a- and b2-VF-SOCPs, parallelled the changes of the transmission to the segmental reflex arcs. On the other hand, the monosynaptic transmission from the FRA to the c1- and c3-VF-SOCPs was not significantly influenced by the inhibitory descending control systems. 4. The a- and b2-VF-SOCPs but not the c1- and c3-VF-SOCPs received polysynaptic excitation from tracts running in the ipsilateral half of the spinal cord. 5. The suggestion that the a- and b2-VF-SOCPs carry information related to interneuronal activity in segmental centres, whereas the c1- and c3-VF-SOCPs forward information mainly related to peripheral events (Andersson and Sjölund, 1978) is supported by the present findings.


Deletion of the Dishevelled family of genes disrupts anterior-posterior axis specification and selectively prevents mesoderm differentiation.
The Dishevelled proteins transduce both canonical Wnt/β-catenin and non-canonical Wnt/planar cell polarity (PCP) signaling pathways to regulate many key developmental processes during embryogenesis. Here, we disrupt both canonical and non-canonical Wnt pathways by targeting the entire Dishevelled family of genes (Dvl1, Dvl2, and Dvl3) to investigate their functional roles in the early embryo. We identified several defects in anterior-posterior axis specification and mesoderm patterning in Dvl1+/-; Dvl2-/-; Dvl3-/- embryos. Homozygous deletions in all three Dvl genes (Dvl TKO) resulted in defects in distal visceral endoderm migration and a complete failure to induce mesoderm formation. To identify potential mechanisms that lead to the defects in the developmental processes preceding gastrulation, we generated Dvl TKO mouse embryonic stem cells (mESCs) and compared the transcriptional profile of these cells with wild-type (WT) mESCs during germ lineage differentiation into 3D embryoid bodies (EBs). While the Dvl TKO mESCs displayed similar morphology, self-renewal properties, and minor transcriptional variation from WT mESCs, we identified major transcriptional dysregulation in the Dvl TKO EBs during differentiation in a number of genes involved in anterior-posterior pattern specification, gastrulation induction, mesenchyme morphogenesis, and mesoderm-derived tissue development. The absence of the Dvls leads to specific down-regulation of BMP signaling genes. Furthermore, exogenous activation of canonical Wnt, BMP, and Nodal signaling all fail to rescue the mesodermal defects in the Dvl TKO EBs. Moreover, endoderm differentiation was promoted in the absence of mesoderm in the Dvl TKO EBs, while the suppression of ectoderm differentiation was delayed. Overall, we demonstrate that the Dvls are dispensable for maintaining self-renewal in mESCs but are critical during differentiation to regulate key developmental signaling pathways to promote proper axis specification and mesoderm formation.


CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations.
Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive distal limb weakness, ptosis, ophthalmoplegia, bulbar muscle weakness and rimmed vacuoles on muscle biopsy. Recently, CGG repeat expansions in the noncoding regions of two genes, LRP12 and GIPC1, have been reported to be causative for OPDM. Furthermore, neuronal intranuclear inclusion disease (NIID) has been recently reported to be caused by CGG repeat expansions in NOTCH2NLC. We aimed to identify and to clinicopathologically characterize patients with OPDM who have CGG repeat expansions in NOTCH2NLC (OPDM_NOTCH2NLC). Note that 211 patients from 201 families, who were clinically or clinicopathologically diagnosed with OPDM or oculopharyngeal muscular dystrophy, were screened for CGG expansions in NOTCH2NLC by repeat primed-PCR. Clinical information and muscle pathology slides of identified patients with OPDM_NOTCH2NLC were re-reviewed. Intra-myonuclear inclusions were evaluated using immunohistochemistry and electron microscopy (EM). Seven Japanese OPDM patients had CGG repeat expansions in NOTCH2NLC. All seven patients clinically demonstrated ptosis, ophthalmoplegia, dysarthria and muscle weakness; they myopathologically had intra-myonuclear inclusions stained with anti-poly-ubiquitinated proteins, anti-SUMO1 and anti-p62 antibodies, which were diagnostic of NIID (typically on skin biopsy), in addition to rimmed vacuoles. The sample for EM was available only from one patient, which demonstrated intranuclear inclusions of 12.6 ± 1.6 nm in diameter. We identified seven patients with OPDM_NOTCH2NLC. Our patients had various additional central and/or peripheral nervous system involvement, although all were clinicopathologically compatible; thus, they were diagnosed as having OPDM and expanding a phenotype of the neuromyodegenerative disease caused by CGG repeat expansions in NOTCH2NLC.


Attitudes to psychological groups in a paediatric and adolescent diabetes service--implications for service delivery.
To explore the potential interest in psychology support groups in a paediatric and adolescent diabetes service. A short semi-structured interview using both open and closed questions to generate quantitative and qualitative data. Sixty-four parents were interviewed on the telephone by an assistant psychologist. The majority of parents (81%) reported an interest in participating in a psychology group if it was offered, but preferences varied between a child/young person group (33%), parents only (15%) or family groups (11%). Twenty-three percent said that they would prefer individual work rather than a group. Parents identified groups as an opportunity to acquire practical knowledge, exchange ideas in an informal setting, share a common reality with others and gain more confidence in managing diabetes together with their child. Reasons not to attend a group included parents being able to cope well at the moment, school demands, feeling uncomfortable speaking in front of a group and use of online support groups. The majority of parents identified psychological support as having a role for families living with diabetes. The audit highlighted that families have different ideas about how they would prefer this support to look and emphasized the need to consult with service users when designing psychological support for young people and families living with a chronic condition.


Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".
The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.


Degradation of dibenzothiophene and its metabolite 3-hydroxy-2-formylbenzothiophene by an environmental isolate.
Microbial degradation of dibenzothiophene (DBT) beyond 3-hydroxy-2-formylbenzothiophene (HFBT), a commonly detected metabolite of the Kodama pathway for DBT metabolism, and the catabolic intermediates leading to its mineralization are not fully understood. The enrichment cultures cultivated from crude oil contaminated soil led to isolation of ERI-11; a natural mixed culture, selected for its ability to deplete DBT in basal salt medium (BSM). A bacterial strain isolated from ERI-11, and tentatively named A11, degraded more than 90 % of the initial DBT (270 µM), present as the sole carbon and sulfur source, in 72 h. Gas chromatography-mass spectrophotometry (GC-MS) analyses of the DBT degrading A11 culture medium extracts led to detection of HFBT. The metabolite HFBT, produced using A11, was used in degradation assays to evaluate its metabolism by the bacteria isolated in this study. Ultra violet-visible spectrophotometry and high-performance liquid chromatography analyses established the ability of the strain A11 to deplete HFBT, present as the sole sulfur and carbon source in BSM. GC-MS analyses showed the presence of 2-mercaptobenzoic acid in the HFBT degrading A11 culture extracts. The findings in this study establish that the environmental isolate A11 possesses the metabolic capacity to degrade DBT beyond the metabolite HFBT. The compound 2-mercaptobenzoic acid is an intermediate formed on HFBT degradation by A11.


Fetal damage due to maternal phenylketonuria: effects of dietary treatment and maternal phenylalanine concentrations around the time of conception (an interim report from the UK Phenylketonuria Register).
In 94 infants born to women with PKU, birth weight and head circumference were inversely and linearly related to the mothers' phenylalanine concentrations close to conception; with each 200 mumols/L rise in phenylalanine concentrations, birth weight fell by 98 g and head circumference by 0.46 cm. This relationship was highly significant and appeared to be the same whether or not the mother received a low phenylalanine diet. Even in the 28 infants whose mothers conceived on a strict low phenylalanine diet, birth weights and head circumferences, corrected for sex and gestation, were a little below the population norms (3421 g and 34.7 cm compared with 3600 g and 35.2 cm respectively) although the differences were not statistically significant. Optimal fetal growth occurred only in infants whose mothers had phenylalanine concentrations close to the normal range at conception. Dietary treatment started after conception did not appear to confer any benefit.