[Apnea of prematurity - characteristic and treatment].
Apnea of prematurity (AOP) can affect even 85-100% of premature newborns and is related to lack of full maturity of organs. AOP is manifesting by 15-20 seconds cessations of breathing accompanied by bradycardia and oxygen desaturation, what can lead to hypoxia or death. Therefore it is very important to implement the effective and safe treatment immediately after birth. Widely used caffeine citrate, which stimulates the respiratory system, improving the working of the respiratory muscles. However the metabolism of caffeine citrate is difficult in preterm infants due to the immaturity of the hepatic enzyme system, what can lead to the occurrence of side effects and toxicity. To avoid the toxic effects of caffeine, and at the same time the lack of efficacy associated with administration of too low doses, this therapy should be monitored by measuring the concentration of caffeine in the plasma of treated infants. This would provide the maintenance of therapeutic levels of caffeine and optimization of the treatment.


Combined Effect of Body Mass Index and Waist Circumference in Predicting Nonalcoholic Fatty Liver Disease.
Background: Body mass index (BMI) and waist circumference (WC) are the most widely used anthropometric indices for identifying obesity. This study aimed to compare and clarify the usefulness of BMI, WC, and the combination of these two indicators in predicting nonalcoholic fatty liver disease (NAFLD). Methods: This cross-sectional study included 15,267 Korean adults. We defined four obesity categories using BMI and WC as follows: BMI nonobese and WC nonobese (BNWN); BMI obese and WC nonobese (BOWN); BMI nonobese and WC obese (BNWO); and BMI obese and WC obese (BOWO). Analysis of variance was used to compare fatty liver severity across each category. The odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated using multiple logistic regression. Results: Compared with BNWN, participants with BNWO were 3.235 (95% CI: 2.774-3.773) times more likely and participants with BOWN were 2.344 (95% CI: 2.045-2.687) times more likely to have NAFLD. Participants with BNWO had higher OR for NAFLD than those with BOWN. Moreover, BOWO participants had the highest OR of 4.788 (95% CI: 4.350-5.270) for NAFLD among all obesity categories. Conclusion: Combined obesity classification by BOWO is the most reliable indicator for NAFLD presence in Korean adults.


Animal welfare: European legislation and future perspectives.
Although animals are central to the life of all societies, substantial differences exist in the level of understanding or attitudes toward animal-welfare issues between agrarian and urban societies in developing or industrial countries. These differences are largely dependent on people's degree of contact with animals. Other than domestic species, people in industrialized nations tend to have limited contact with farm and wild animals. With this reduced or lack of daily animal contact, there can be a parallel lack of understanding of or appreciation for animal-welfare issues. As a result, different nations have adopted various policies, procedures, and laws to ensure that their societies protect the welfare of animals. In this article, we chronicle 30 years of actions by European nations through the European Commission to enact legislation that ensures uniform standards of animal-welfare practices to protect farm animals, animals used in research, and wild animals held in captivity.


[Clostridium septicum aortitis : case report and update on infectious aortitis].
A case of Clostridium septicum aortitis is reported. The patient did not present any colon tumor. She died in spite of surgery and i.v. antibiotics. To date C. septicum has been reported only in about 40 cases of infectious aortitis, a disease with unspecific clinical presentation and a high mortality rate. A high index of suspicion is warranted for an early diagnosis which can be made mainly by blood cultures and contrast-enhanced CT-scan. Only starting without delay a treatment that combines antibiotics with surgery can improve a prognosis that remains nevertheless globally bad.


Immune Responses to Plant-Derived Recombinant Colorectal Cancer Glycoprotein EpCAM-FcK Fusion Protein in Mice.
Epidermal cell adhesion molecule (EpCAM) is a tumor-associated antigen (TAA), which has been considered as a cancer vaccine candidate. The EpCAM protein fused to the fragment crystallizable region of immunoglobulin G (IgG) tagged with KDEL endoplasmic reticulum (ER) retention signal (EpCAM-FcK) has been successfully expressed in transgenic tobacco (Nicotiana tabacum cv. Xanthi) and purified from the plant leaf. In this study, we investigated the ability of the plant-derived EpCAM-FcK (EpCAM-FcKP) to elicit an immune response in vivo. The animal group injected with the EpCAM-FcKP showed a higher differentiated germinal center (GC) B cell population (~9%) compared with the animal group injected with the recombinant rhEpCAM-Fc chimera (EpCAM-FcM). The animal group injected with EpCAM-FcKP (~42%) had more differentiated T follicular helper cells (Tfh) than the animal group injected with EpCAM-FcM (~7%). This study demonstrated that the plant-derived EpCAM-FcK fusion antigenic protein induced a humoral immune response in mice.


Drug Allergy.
Drug allergy is commonly encountered in clinical practice. It is an immunological response to a pharmaceutical agent. The clinical presentation can vary from mild cutaneous reactions to life-threatening conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Diagnosis is most often clinical, but investigations such as measurement of immunoglobulin E, patch testing, and skin biopsy may be required. In patients with a known drug allergy, the offending drug should be avoided. [Pediatr Ann. 2018;47(10):e419-e425.].


Lessons Learned in Clinical Research Recruitment of Immigrants and Minority Group Members with First-Episode Psychosis.
Recruitment of immigrants and racial and ethnic minorities with first-episode psychosis (FEP) for research studies presents numerous challenges. We describe methods used to recruit 43 U.S. Latinos with FEP and their family caregivers (n = 41) participating in a study to reduce duration of untreated psychosis. A key challenge was that patients were not continuing treatment at an outpatient clinic, as initially expected. To facilitate identification of patients prior to outpatient care, we collaborated with clinic and hospital administrators. Many patients and families were grappling with the aftermath of a hospitalization or adjusting to a diagnosis of a serious mental illness. A considerable amount of time was devoted to addressing participants' concerns and when possible, facilitating needed services. Our experience underscores the importance of establishing long-term relationships through multiple contacts with patients, families, and stakeholders to address recruitment barriers among underserved groups with FEP.


A Systematic Review: The Effect of Cancer on the Divorce Rate.
Research on the impact of cancer on close relationships brings up conflicting results. This systematic review collects empirical evidence on the research questions whether a cancer diagnosis in general or the type of cancer affects the divorce rate. This systematic review was conducted according to the guidelines of the Cochrane Collaboration and the PRISMA statement. The following electronic databases were searched: Web of Science, Ovid SP MEDLINE, PsycINFO, PsyINDEX, CINAHL, ERIC. Risk of bias assessment was performed with the preliminary risk of bias for exposures tool template (ROBINS-E tool). The grading of methodological quality was assessed with the Newcastle-Ottawa Scale. Of 13,929 identified records, 15 were included in the qualitative synthesis. In 263,616 cancer patients and 3.4 million healthy individuals, we found that cancer is associated with a slightly decreased divorce rate, except for cervical cancer, which seems to be associated with an increased divorce rate. According to this systematic review, cancer is associated with a tendency to a slightly decreased divorce rate. However, most of the included studies have methodologic weaknesses and an increased risk of bias. Further studies are needed.


A rare case of heterotopic ossification in a newborn: a case report.
Heterotopic ossification (HO) is the growth of bone in soft tissue, and can be broadly classified into neurogenic, genetic and traumatic causes. The pathophysiology of HO remains unknown. This disorder is extremely rare in infants and can mimic or coexist with thrombophlebitis, cellulitis or osteomyelitis. Most importantly, HO has to be differentiated from bone-forming tumours such as osteosarcoma and osteochondroma. We report a case of traumatic HO in a fiveday- old newborn following intravenous cannulation of the right wrist and left ankle, with the latter complicated with osteomyelitis. We highlight the clinical and radiological features of HO and differential diagnoses of soft tissue ossification in early childhood. Heterotopic ossification, newborn.


Promotion of tumor cell metastasis and vasculogenic mimicry by way of transcription coactivation by Bcl-2 and Twist1: a study of hepatocellular carcinoma.
The antiapoptotic protein Bcl-2 plays multiple roles in apoptosis, immunity, and autophagy. Its expression in tumors correlates with tumor grade and malignancy. The recapitulation of the normal developmental process of epithelial-mesenchymal transition (EMT) contributes to tumor cell plasticity. This process is also a characteristic of metastatic cells and vasculogenic mimicry. In the present study we report functional and structural interactions between Bcl-2 and the EMT-regulating transcription factor Twist1 and the relationship with metastasis and vascular mimicry. Bcl-2 and Twist1 are coexpressed under hypoxia conditions. The Bcl-2 can bind to Twist1 in vivo and in vitro. This interaction involves basic helix-loop-helix DNA binding domain within Twist1 and through two separate domains within Bcl-2 protein. Formation of the Bcl-2/Twist1 complex facilitates the nuclear transport of Twist1 and leads to transcriptional activation of wide ranges of genes that can increase the tumor cell plasticity, metastasis, and vasculogenic mimicry. Finally, nuclear expression of Bcl-2 and Twist1 is correlated with poor survival of these patients in a cohort of 97 cases of human hepatocellular carcinoma. The results describe a novel function of Bcl-2 in EMT induction, provide insight into tumor progression, and implicate the Bcl-2/Twist1 complex as a potential target for developing chemotherapeutics.


Economic analysis of ALK testing and crizotinib therapy for advanced non-small-cell lung cancer.
The economic outcome of crizotinib in advanced non-small-cell lung cancer harboring anaplastic lymphoma kinase rearrangement would be investigated. Based on a mathematical model, the economic outcome of three techniques for testing ALK gene rearrangement combing with crizotinib would be evaluated and compared with traditional regimen. The impact of the crizotinib patient assistance program (PAP) was assessed. Ventana immunohistochemistry, quantitative real-time reverse transcription-polymerase chain reaction and IHC testing plus fluorescent in situ hybridization confirmation for anaplastic lymphoma kinase testing following crizotinib treatment leaded to the incremental cost-effectiveness ratios of US$16,820 and US$223,242, US$24,424 and US$223,271, and US$16,850 and US$254,668 per quality-adjusted life-year gained with and without PAP, respectively. Gene-guided crizotinib therapy might be a cost-effective alternative comparing with the traditional regimen in the PAP setting.


Isolation and localization of phosphoprotein pp 135 in the nucleoli of various cell lines.
Phosphoprotein pp 135 is one of the dominant proteins endogenously phosphorylated in cellular sonicates during short-time exposure to [gamma-32P]ATP. Mouse cells growing exponentially show the highest pp 135 level as determined by endogenous phosphorylation and immunobinding assays. Disruption of cells in the absence of calcium at low magnesium concentration renders more than 90% pp 135 into the cytosolic fraction. A five-step purification yields greater than 95% pure pp 135. The cellular location of pp 135 was determined with a rat anti-(mouse pp 135) serum by immunofluorescence in mouse cell lines and cryostat sections of normal mouse tissue. We observed fluorescence predominantly of nucleolar structures, confirmed by studies of isolated nuclei and nucleoli. Cross-reacting nucleolar phosphoproteins were identified in cell lines of other species with molecular masses of 128 kDa (human), 135 kDa (hamster) and 118 kDa (Drosophila). Endogenous phosphorylation of pp 135 investigated with purified mouse nucleoli showed optimal activity at isotonicity, pH 7.3, in the presence of 10 mM magnesium ions.


Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary and metastatic head and neck cancer and its modulation by celecoxib.
Eicosanoid metabolism through cyclooxygenases (COXs) and lipoxygenases (LOXs) generates various lipids that play a role in squamous cell carcinogenesis. We used pairs of head and neck squamous cell carcinoma (HNSCC) cell lines derived from primary and metastatic tumors of the same patient to analyze eicosanoid metabolites by ESI-LC/MS/MS and COX/LOX expression by western immunoblotting. The effects of celecoxib on eicosanoid synthesis and HNSCC cell growth were examined. Prostaglandin E2 (PGE2) was the major metabolite in three of six cell lines. COX-2 was detected in three cell lines, which produced PGE2 (two from metastases). We found low expression of COX-1 at similar intensities for each pair of cell lines. 5-LOX was detected in all cells. Some expressed 12-LOX, 15-LOX-1, and 15-LOX-2, but there was no correlation between enzyme expression and endogenous product content. Exogenous arachidonic acid did not change the profile of eicosanoid biosynthesis. Low doses of celecoxib inhibited formation of PGE2 in UMSCC-14A cells by 84% as early as 6 hours. In contrast, 5-HETE, 12-HETE, and 15-HETE levels were increased by approximately 40-, 5- and 3-fold, respectively, with a decline to baseline levels within 24 hours. High dose celecoxib increased the 12-HETE level 2.3-fold after 3 days of incubation. Celecoxib inhibited growth of all HNSCC cell lines in a concentration-dependent manner regardless of their COX expression (IC50 values after 3 days; 33 to 62 microM). Our findings provide new informations about individual eicosanoids produced by HNSCC cells and their differential regulation by the selective COX-2 inhibitor celecoxib.


Pembrolizumab Plus Chemotherapy in Metastatic Thymic Carcinoma: A Case Report.
Metastatic thymic carcinomas have a poor prognosis. Pembrolizumab, an anti-PD-1 antibody, has recently been evaluated for patients with metastatic thymic carcinomas progressing after at least one line of platinum-based chemotherapy. The antitumor activity of immunotherapy appears to be promising for these patients and pembrolizumab in monotherapy is actually a treatment option in second metastatic line. To the best of our knowledge, we report the first case of a patient treated for metastatic thymic adenocarcinoma with a combination of chemotherapy-immunotherapy. The patient is a 46-year-old man with metastatic thymic adenocarcinoma treated in third metastatic line with a combination of pembrolizumab plus platinum-based chemotherapy with a very good metabolic tumor response. He had a progression-free survival of 7.9 months and did not experience any severe side effects related to pembrolizumab. The association of immunotherapy and chemotherapy, as in non-small cell and small cell lung cancers, could be of interest for future therapeutic trials evaluating the survival of patients with metastatic thymic carcinoma.


A protein chemical approach to channel structure and function: the proton channel of the vacuolar H(+)-ATPase.
The vacuolar H(+)-ATPase provides a channel through which protons can be pumped across the bilayer. It is a complex assembly of about 20 subunits made up from 13 different polypeptide chains. The proton channel is located in the bilayer and therefore must be formed from one or both of the two intramembraneous subunits, called in yeast Vphlp (100 kDa) and Vma3p (16 kDa). Electron microscopy and the use of water soluble and hydrophobic chemical probes in conjunction with mutagenesis to cysteine or glutamic acid residues, suggest that the membrane sector consists of a single Vphlp subunit in association with a hexameric complex of the four-helical bundle Vma3p subunit. This hexamer encloses a large central pore lined by the first transmembrane helix. This pore appears to be impermeable, however; instead, a glutamic acid residue critical to transport function is located on the outside of the hexamer, deeply buried in the membrane and accessible to probes and inhibitors resident in the hydrophobic phase of the bilayer. The stoichiometry and chemistry of inhibitor binding supports the postulate that the mechanism of action involves rotation of the hexamer in the plane of the bilayer. Mutagenesis data on the Vphlp subunit indicate that it is vital to proton transport. It is likely, therefore, that the proton channel is formed at the interface of the Vphlp and Vma3p subunits, the protons moving via a network of interacting charged amino acid side-chains.


Successive Ionic Layer Absorption and Reaction for Postassembly Control over Inorganic Interdot Bonds in Long-Range Ordered Nanocrystal Films.
Epitaxially connected assemblies of nanocrystals (NCs) present an interesting new class of nanomaterial in which confinement of charge carriers is intermediate between that of a quantum dot and a quantum well. Despite impressive advances in the formation of high-fidelity assemblies, predicted collective properties have not yet emerged. A critical knowledge gap toward realizing these properties is the current lack of understanding of and control over the formation of epitaxial interdot bonds connecting the NCs within the assemblies. In this work we demonstrate successive ionic layer absorption and reaction (SILAR) to enhance the interdot bonding within the NC assembly. SILAR treatment improved the fraction of interdot bonds from 82% to 91% and increased their width from 3.1 to 4.0 nm. Absorption spectra and charge transport measurements indicate that the effect of postassembly growth on quantum confinement in this system depends on the composition of the SILAR shell material. Increased NC film conductance following SILAR processing indicates that building and strengthening interdot bonds lead to increased electronic coupling and doping in the assemblies. The postassembly film growth detailed here presents an opportunity to repair structural defects and to tailor the balance of quantum confinement and interdot coupling in epitaxially connected NC assemblies.


Perioperative radiotherapy in rectal carcinoma.
Surgery alone is not sufficient for a large group of patients with adenocarcinoma of the rectum. With a combination of surgery and radiotherapy a significantly decreased local recurrence rate has been found, provided that the dose level has been sufficiently high. Whether a combined treatment has an impact on survival is too early to determine. An essential question is whether this additional treatment with irradiation should be given to all patients with rectal carcinoma, i.e. preoperatively or only to patients in Dukes' stage B or C, i.e. postoperatively. For several reasons mentioned in this paper preoperative radiotherapy is to be preferred. Furthermore, a postoperative regime is more difficult to handle within the desired schedule times. Also, data obtained in the Uppsala trial further indicate that a brief, convenient and apparently safe preoperative regime may result in a lower rate of local recurrence than an optimized postoperative regime. It is too early, however, to state that all patients with rectal carcinoma should have combined treatment. Further controlled trials, preferably with preoperative high-dose irradiation schedules, have to be carried out before the benefit of radiotherapy can be said to be conclusively proved. It is also important, however, that the surgical procedure be optimal, since irradiation cannot, and should not, serve as a substitute for poor surgery.


Employees' Environmental Protection and Charitable Donation and Ethical Leadership: An Empirical Study.
The sustainable development of the environment and society depends not only on firms' social responsibility initiatives, but also on employees' socially responsible behavior during their daily work life. Hence, it is important to study why and how employees go about the socially responsible behaviors (SRB), such as environmental protection and charitable donations. Although research has been done on the antecedents of employees' SRB from personal, contextual and leadership perspectives, little is known about the mechanism through which they affect these behaviors. Moreover, compared with the other two perspectives, research from the leadership perspective is relatively scarce. In this paper, we aim to fill these research gaps. Based on 936 respondents from 109 corporations, we empirically test the cross-level direct effect of ethical leadership on employees' SRB and the cross-level mediating effect of perceived organizational virtuousness. In our empirical analyses, we adopt statistical methodologies such as hierarchical linear modeling and multilevel mediation analysis. Our results show that perceived organizational virtuousness partly mediates the influence of ethical leadership on employees' environmental protection and charitable donation. In other words, ethical leadership enables employees to form the perception of organizational virtuousness, and therefore employees are more engaged in environmental protection and charitable donations. This research provides important insights for firms and their employees to become more socially and environmentally responsible.


Left ventricular pseudoaneurysm after myocardial infarction detected by cardiac MRI.
Left ventricular free wall rupture (LVFWR) is a grave complication of acute myocardial infarction. Acutely, it has an extremely high rate of mortality, especially if undetected. Chronically, there is paucity of data on how to manage the pathology, especially if detected as an incidental finding. We present a unique case of initially undetected LVFWR in a patient who presented with repeated chest pain. Cardiac MRI enabled the diagnosis and localisation of the original site of LVFWR and provided highly relevant volume calculations. Measurement of both absolute and virtual volumes indicated that aneurysm resection, including the original site of rupture, was surgically feasible without reducing postoperative stroke volume.


Crystallization and preliminary X-ray crystallographic studies of the rho-class glutathione S-transferase from the Antarctic clam Laternula elliptica.
Glutathione S-transferases are involved in phase II detoxification processes and catalyze the nucleophilic attack of the tripeptide glutathione on a wide range of endobiotic and xenobiotic electrophilic substrates. The rho-class glutathione S-transferase from Laternula elliptica was overexpressed in Escherichia coli, purified and crystallized with two substrates: glutathione and 1-chloro-2,4-dinitrobenzene (CDNB). Diffraction data were collected to 2.20 A resolution for the glutathione-complex crystals and to 2.00 A resolution for the CDNB-complex crystals using a synchrotron-radiation source. Both crystals belonged to the C-centred monoclinic space group C2. The unit-cell parameters for the CDNB-complex crystals were a = 89.66, b = 59.27, c = 55.45 A, beta = 124.52 degrees . The asymmetric unit contained one molecule, with a corresponding V(M) of 2.36 A(3) Da(-1) and a solvent content of 47.8%.


First Report of Neofusicoccum ribis Causing Cankers and Dieback Diseases on Apricot Trees in Canada and Worldwide.
Apricot trees (Prunus armeniaca L.) with cankers, gummosi and dieback symptoms were observed in a commercial orchard in Niagara-on-the-Lake, Ontario, Canada. In October 2018, up to 44.9% disease incidence (n = 318) was observed on 2-year-old 'Harostar™' trees grafted onto 'Haggith' rootstocks. Fungal colonies were consistently isolated and purified from small sections of wood collected from canker margins of symptomatic trunk and shoot tissue, as described by Ilyukhin et al. (2023). Purified mycelial isolates sharing similar morphological characteristics were categorized into five distinct morphotypes. One representative isolate from each morphotype was used to inoculate excised apricot shoots as described by Ilyukhin and Ellouze (2023). One morphotype displayed necrotic lesions on the shoots consistently yielded abundant white aerial mycelium that turned grey-brown on PDA after 7 days (Figure S1) and produced black pycnidia three weeks following incubtion at 22°C in the dark. Conidia were hyaline, one-celled, fusiform, with dimensions of 19.7 - 24.2 × 3.6 - 4.8 μm (average 22.1 × 4.3 μm, n = 30), the typical morphology of a Neofusicoccum sp. (Crous et al. 2006). Species identification was verified by extracting genomic DNA of the representative isolate M1-105, amplifying and sequencing the internal transcribed spacer (ITS), translation elongation factor 1-α (EF1-α) and β-tubulin (TUB2) gene regions with primers ITS1/ITS4, EF1-728F/EF1-986R and Bt2a/Bt2b. Nucleotide sequences (GenBank Accession No. ITS: OK287034; EF1-α: OK346636; TUB2: OK346633) have 100%, 99.61% and 99.55% identity with Neofusicoccum ribis isolates from different hosts and countries (MT587514, DQ235142, OL455952, respectively). Randomized accelerated maximum likelihood analysis (Stamatakis et al. 2008), using ITS, EF1-α and TUB2 sequence data, clustered M1-105 with the highest bootstrap support values with the N. ribis ex-epitype CBS 115475 (Figure S2). A living culture of M1-105 was deposited in the Canadian Collection of Fungal Cultures (DAOMC 252247). Pathogenicity was verified using 5 potted healthy 1-year-old 'Haroblush™' apricot cultivar grafted onto 'Krymsk® 86' rootstocks. Trunks and shoots were inoculated in a shallow wound made by a scalpel with mycelial plugs from a 5-day-old culture of M1-105. Five control trees were inoculated with sterile plugs. Trees were put in an open-air area and watered as needed. Canker symptoms appeared 7 days after inoculation, and spread above and below the inoculation point. Fifteen days post-inoculation, the upper portion of inoculated shoots showed necrosis, gummosis and wilt (Fig. S1). Neofusicoccum ribis was re-isolated from all infected trees and species identity was confirmed by sequencing as described above. Controls remained symptom-free and no fungi were isolated from the wood. Therefore, Koch's postulates were completed. Neofusicoccum ribis was reported to cause branch dieback of olive trees in Spain (Romero et al. 2005) and pistachio in Italy (Corazza et al. 1986), stem blight and dieback of blueberry in Michigan (Heger et al. 2023) and Florida (Wright and Harmon 2010) and postharvest decay of apple fruit from cold storage in Pennsylvania (Jurick et al. 2013). To the best of our knowledge, this is the first report of N. ribis causing canker and shoot dieback of apricot trees in Canada and worldwide. This report reveals N. ribis as a potential threat, causing canker and dieback. Without proper management, it could lead to significant losses in apricot orchards and the stone fruit industry. This study paves the way for crucial research on N. ribis outbreaks and effective disease control.


Environmental factors and suicide in Australian farmers: A qualitative study.
Farmers and farm workers have been recognized as a group at high risk of suicide in Australia. This study aims to identify and better understand environmental factors associated with suicide among Australian farmers and farm workers. Qualitative analysis was undertaken in accordance with the Consolidated Criteria for Reporting Qualitative Research. Male and female focus groups were conducted separately with people who lived or worked on a farm in six farming communities. Qualitative analyses showed that a number of environmental influences may contribute to the increased risk of suicide: extreme climatic events; isolation; service availability; access to, and frequent use of firearms; death and suffering of animals; government and legislation; technology; and property values. Both the physical and socio-cultural environments in which farmers operate appear to contribute to farmer suicide and need to be considered in suicide prevention.


Differential expression of mitochondria-encoded genes in a hibernating mammal.
A cDNA library constructed from kidney of the thirteen-lined squirrel, Spermophilus tridecemlineatus, was differentially screened for genes that were upregulated during hibernation. A clone encoding cytochrome c oxidase subunit 1 was found and confirmed to have been upregulated by northern blotting. Differential expression of Cox1 mRNA occurred in multiple organs during hibernation; in hibernating animals transcript levels were twofold higher in kidney and fourfold higher in heart and brown adipose tissue than in euthermic animals, but were unchanged in skeletal muscle. Transcript levels of mitochondrial-encoded ATP synthase 6/8 were similarly upregulated in these tissues whereas transcript levels of the nuclear encoded subunits Cox4 and ATP synthase alpha did not change during hibernation. Immunoblot analysis revealed a 2.4-fold increase in Cox 1 protein and a slight decrease in Cox 4 protein in kidney of hibernating squirrels, compared with euthermic controls. Hibernating mammals may increase the expression of the mitochondrial genome in general, and Cox1 specifically, to prevent or minimize the damage to the electron transport chain caused by the cold and ischemia experienced during a hibernation bout.


Tight junctions potentiate the insulative properties of small CNS myelinated axons.
Claudin family proteins form the physical barriers of tight junctions (TJs) and regulate paracellular diffusion across polarized epithelia. In addition to these heterotypic TJs, claudin 11 forms autotypic TJs comprising the radial component of central nervous system myelin. The exact function of these TJs has been unclear, although their location at the membrane perimeter is well sited to regulate diffusion between the interstitium and intramyelinic space. In this study, we demonstrate that claudin 11 affords rapid nerve conduction principally for small diameter myelinated axons. Claudin 11-null mice have preserved myelin and axonal architecture, but as much as a 60% decrease in conduction. They also have increased action potential thresholds and activated internodal potassium channels. These data indicate that TJs modulate the biophysical properties of myelin. Computational modeling reveals that claudin 11 reduces current flow through myelin and moderates its capacitive charging. Together, our data shed new light on myelin structural components and our understanding of the biology and pathophysiology of this membrane.


Evaluation of acridine orange stain for detection of Trichomonas vaginalis in vaginal specimens.
Vaginal exudates from 105 patients were examined by direct wet-mount microscopy and acridine orange stain for the presence of Trichomonas vaginalis. Both procedures demonstrated greater than 90% agreement in both sensitivity and specificity. When specimens can be examined immediately after collection, it appears that wet-mount microscopy is almost as sensitive as acridine orange staining for detection of T. vaginalis.


An evaluation of propofol toxicity on mouse oocytes and preimplantation embryos.
Mouse biological assays were used to investigate potential adverse effects of propofol on the oocyte's competence to fuse with spermatozoa and on the embryo's ability to develop to the blastocyst stage. Cumulus-enclosed metaphase II oocytes were exposed for 1 h to 0.01, 0.1, 0.4, 1 and 10 microg/ml propofol (Diprivan) and subjected to a sperm-oocyte fusion test based on the dye (Hoechst 33342) transfer technique. Oocytes exposed to 0.4, 1 and 10 microg/ml propofol showed a significant reduction in the rate of sperm fusion and underwent pronuclei formation at a rate similar to that of sperm fusion. In a second trial, mouse 1-cell and 2-cell embryos were exposed to varying propofol concentrations for 14h and then checked for subsequent development. Although adverse effects were not observed in 2-cell embryos, treatment of 1-cell embryos with propofol concentrations ranging from 0.01 to 10 microg/ml resulted in the inhibition of cleavage to blastocyst stage. We conclude that propofol can negatively influence fertilization in the mouse by impairing the oocyte's ability to fuse with spermatozoa, without interfering with the sperm-induced activation of the cell cycle. Moreover, we document the peculiar sensitivity to propofol of mouse 1-cell embryos as compared with 2-cell embryos.


Difficult-to-treat-pediatric Crohn's disease: focus on adalimumab.
Adalimumab is a fully humanized anti-tumor necrosis factor alpha monoclonal antibody that was recently granted regulatory approval in the USA for the treatment of moderate to severe Crohn's disease (CD) in children. Like infliximab, the first biologic agent used to treat pediatric CD, regulatory approval was secured many years following approval for adults. The long delay between adult and pediatric approval has led to many years of off-label use of adalimumab, although it is anticipated that the use of adalimumab may further increase with official regulatory approval. To date, pediatric literature on the use of adalimumab for treatment of CD is limited, and pediatric practitioners have mostly extrapolated from research and experience provided by the adult literature. The aim of this paper is to review the literature regarding adalimumab for the treatment of pediatric CD, and includes a review of landmark adult studies as well as the pivotal pediatric study that facilitated regulatory approval. We also discuss the role of anti-tumor necrosis factor alpha agents including adalimumab in the current treatment paradigm for pediatric CD.


Acetabular labrum tear in a 15-year-old male: diagnosis with correlative imaging.
A 15-year-old male with unresolved hip pain after minor trauma is presented. The diagnosis of an acetabular labral tear was made using correlative scintigraphic and magnetic resonance (MR) imaging, obviating the more invasive investigations of arthrography or arthroscopy of the hip. The clinical and radiological features of this lesion are reviewed. Undiagnosed, acetabular labral tears may result in considerable morbidity. Appropriate operative or conservative management of the condition usually provides symptomatic relief.


Ovarian carcinoma presenting as cutaneous nasal metastasis.
Metastatic ovarian cancer uncommonly presents with skin metastasis. When present, skin metastases of ovarian cancer are usually localized in the vicinity of the primary tumor. We report a case of a 58-year-old woman with a rapid growing erythematous, well-defined nodule localized on the left nasal ala. A skin biopsy was performed and histopathological and immunohistochemical findings were compatible with a cutaneous metastasis of adenocarcinoma. A systematic investigation revealed a bilateral ovarian cystadenocarcinoma associated with visceral dissemination, likely associated with nose cutaneous metastasis. We report a very uncommon case because of the presentation of ovarian carcinoma as cutaneous metastasis. To our knowledge, this atypical localization on the nose has not been described yet in the literature.


[Investigation on the real herb of Mugwort leaf and the standard of its processing for moxibustion].
Mugwort leaf is the traditional herb being used for moxibustion. Although its place of production and the course of making Mugwort floss have been described in detail, there is no unified standard about the quality and processing of Mugwort floss until now, which seriously affect on the popularity and application of moxibustion. In accordance with the real herb of Mugwort leaf and floss as well as its processing and quality judgment, this paper thoroughly analyze the related data including ancient documents, modern research results and clinical applications. The authors consider that the Mugwort floss in the market is lack of regulations for its processing, and it needs to be discussed the way to judge the quality of Mugwort leaf by volatile oil, suggesting that the further study on the quality control of Mugwort leaf and floss has to be carried out from multiple aspects, such as physical attributes and chemical characteristics.


Aged rats lose vasoprotective and anti-inflammatory actions of estrogen in injured arteries.
17beta-estradiol (E2) negatively modulates neointima formation, leukocyte infiltration, and proinflammatory mediator expression after vascular injury in young (10-wk-old) ovariectomized (OVX) rats. Trials of E2 in elderly postmenopausal women have not confirmed a vasoprotective effect. This study tested the hypothesis that responsiveness to E2 is lost in injured arteries of aged (12-mo-old) OVX rats. E2- or vehicle-treated OVX rats underwent balloon injury of the carotid artery and were killed after 2 weeks for morphometric examination of arteries, after 24 hours for assessment of leukocyte infiltration, and after 2 hours for quantification of proinflammatory mediator mRNA expression. Neointima formation was significantly reduced in aged compared with young vehicle-treated rats. E2 treatment had directionally opposite effects on intima/media ratios in aged (+75%) and young (-40%) rats. Injury induced increases in infiltrating total leukocytes, neutrophils, monocytes/macrophages, and expression of proinflammatory mediators in arteries of aged rats; E2 had no effect on these inflammatory responses to injury. Estrogen receptor alpha and beta protein expression were similar in carotid arteries of young and aged rats on immunofluorescence testing. Aged OVX rats lose the vasoprotective and anti-inflammatory responses to exogenous E2 seen in younger animals. These results may be relevant to the lack of vasoprotection observed in outcome trials of estrogen therapy in postmenopausal women.


Activity-Guided Design of HDAC11-Specific Inhibitors.
Mammalian histone deacetylases (HDACs) are a class of enzymes that play important roles in biological pathways. Existing HDAC inhibitors target multiple HDACs without much selectivity. Inhibitors that target one particular HDAC will be useful for investigating the biological functions of HDACs and for developing better therapeutics. Here, we report the development of HDAC11-specific inhibitors using an activity-guided rational design approach. The enzymatic activity and biological function of HDAC11 have been little known, but recent reports suggest that it has efficient defatty-acylation activity and that inhibiting it could be useful for treating a variety of human diseases, including viral infection, multiple sclerosis, and metabolic diseases. Our best inhibitor, SIS17, is active in cells and inhibited the demyristoylation of a known HDAC11 substrate, serine hydroxymethyl transferase 2, without inhibiting other HDACs. The activity-guided design may also be useful for the development of isoform-specific inhibitors for other classes of enzymes.


Transition State Gauche Effects Control the Torquoselectivities of the Electrocyclizations of Chiral 1-Azatrienes.
Hsung et al. have reported a series of torquoselective electrocyclizations of chiral 1-azahexa-1E,3Z,5E-trienes that yield functionalized dihydropyridines. To understand the origins of the torquoselectivities of these azaelectrocyclizations, we modeled these electrocyclic ring closures using the M06-2X density functional. A new stereochemical model that rationalizes the observed 1,2 stereoinduction emerges from these computations. This model is an improvement and generalization of the "inside-alkoxy" model used to rationalize stereoselectivities of the 1,3-dipolar cycloaddition of chiral allyl ethers and emphasizes a stabilizing hyperconjugative effect, which we have termed a transition state gauche effect. This stereoelectronic effect controls the conformational preferences at the electrocyclization transition states, and only in one of the allowed disrotatory electrocyclization transition states is the ideal stereoelectronic arrangement achieved without the introduction of a steric clash. Computational experiments confirm the role of this effect as a stereodeterminant since substrates with electropositive groups and electronegative groups have different conformational preferences at the transition state and undergo ring closure with divergent stereochemical outcomes. This predicted reversal of stereoselectivity for the ring closures of several silyl substituted azatrienes have been demonstrated experimentally.


Settlement and Metamorphosis of Capitella Larvae Induced by Juvenile Hormone-Active Compounds Is Mediated by Protein Kinase C and Ion Channels.
The signal transduction pathway by which juvenile hormone-active compounds induce settlement and metamorphosis of metatrochophore larvae of the polychaete annelid Capitella sp. 1 was investigated. The known protein kinase C (PKC) activator phorbol-12, 13-dibutyrate was an active inducer of settlement and metamorphosis, whereas H-7, an inhibitor of PKC, inhibited settlement and metamorphosis in response to juvenile hormone III (JH III). JH III and methyl farnesoate (MF) also directly activated, in vitro, both a PKC-like enzyme present in Capitella homogenates and PKC purified from rat brain. In addition, binding studies using the fluorescent PKC inhibitor RIM-1 revealed the presence of a PKC-like enzyme in intact Capitella larvae and juveniles. Settlement and metamorphosis of the larvae was also stimulated by membrane-depolarizing concentrations of KCI. This response to KCl was inhibited by tetraethylammonium. The potassium channel blocker 4-aminopyridine induced settlement and metamorphosis, whereas settlement and metamorphosis in response to JH III was inhibited by the potassium channel ionophore nigericin. Settlement and metamorphosis induced by JH III was inhibited by the calcium channel blockers Ni2+, Zn2+, and verapamil, whereas settlement and metamorphosis was induced by the calcium ionophore A23187. These results suggest that in mediating this response, juvenile hormones may cause activation of PKC, leading to subsequent modulation of potassium and calcium channels.


Emergency cholecystectomy and hepatic arterial repair in a patient presenting with haemobilia and massive gastrointestinal haemorrhage due to a spontaneous cystic artery gallbladder fistula masquerading as a pseudoaneurysm.
Haemobilia usually occurs secondary to accidental or iatrogenic hepatobiliary trauma. It can occasionally present with cataclysmal upper gastrointestinal haemorrhage posing as a life threatening emergency. Haemobilia can very rarely be a complication of acute cholecystitis. Here we report a case of haemobilia manifesting as massive gastrointestinal haemorrhage in a patient without any prior history of biliary surgery or intervention and present a brief review of literature. A 22 year old male admitted with history suggestive of acute cholecystitis subsequently developed waxing waning jaundice and recurrent episodes of upper gastrointestinal bleed. Endoscopy showed an ulcer in the first part of duodenum with a clot, no active bleed was visible. Angiography was suggestive of a ruptured pseudoaneurysm in the vicinity of the right hepatic artery probably originating from the cystic artery. Coil embolization was tried but the coil dislodged into the right branch of hepatic artery distal to the site of pseudoaneurysm. Review of angiographic video in light of operative findings demonstrated a fistulous communication between cystic artery and gallbladder as the cause, a simultaneous cholecystoduodenal fistula was also noted. Retrograde cholecystectomy, closure of cholecystoduodenal fistula and right hepatic arteriotomy with retrieval of the endo-coil and hepatic arterial repair was performed. Fistula between the cystic artery and gallbladder has been commonly reported to occur after laparoscopic cholecystectomy. Spontaneous fistulous communication, i.e. in the absence of any prior trauma or intervention, between cystic artery and gallbladder is rare with very few reports in literature. Aetiopathogenesis of the disease, in the context of current literature is reviewed. The diagnostic dilemma posed by the confounding finding of an ulcer in the duodenum, the iconic video angiographic depiction as also the therapeutic challenge of a failed embolization with consequent microcoil migration and primary hepatic arterial repair in the emergency situation is discussed.


Physical performance and physical activity in grown-up congenital heart disease.
To review exercise performance and exercise habits in patients with congenital heart disease (CHD). Physical exercise and physical activity has shown beneficial effects on the physical, psychological and social level in adult patients with cardiovascular disease. Favourable effects have also been documented in children with CHD. Exercise testing is preferentially performed on a treadmill in children, with the measurement of gas exchange. An overview of the literature showed that formal exercise testing has frequently documented reduced or suboptimal values for aerobic exercise performance in children with left-to-right shunts (atrial septal defect, ventricular septal defect), valvular heart disease and obstructive anomalies (aortic stenosis, pulmonary stenosis, coarctation of the aorta). Subnormal values for exercise tolerance have also been observed in patients with successfully repaired cyanotic heart disease (tetraology of Fallot, transposition of the great arteries, Fontan operation). An important contributing factor to the impaired exercise performance is the hypoactive lifestyle, as often observed in patients with CHD. This frequently results from parental or environmental overprotection. These patients should be stimulated to be physically active, unless medical restriction is imposed. Fortunately, this represents only a small fraction of the total number of congenital heart defects for which sports participation is allowed.


The Stimulatory Effect of Notochordal Cell-Conditioned Medium in a Nucleus Pulposus Explant Culture.
Notochordal cell-conditioned medium (NCCM) has previously shown to have a stimulatory effect on nucleus pulposus cells (NPCs) and bone marrow stromal cells (BMSCs) in alginate and pellet cultures. These culture methods provide a different environment than the nucleus pulposus (NP) tissue, in which the NCCM ultimately should exert its effect. The objective of this study is to test whether NCCM stimulates NPCs within their native environment, and whether combined stimulation with NCCM and addition of BMSCs has a synergistic effect on extracellular matrix production. Bovine NP tissue was cultured in an artificial annulus in base medium (BM), porcine NCCM, or BM supplemented with 1 μg/mL Link N. Furthermore, BM and NCCM samples were injected with 10(6) BMSCs per NP sample. Samples were cultured for 4 weeks, and analyzed for biochemical contents (water, glycosaminoglycan [GAG], hydroxyproline, and DNA), gene expression (COL1A1, COL2A1, ACAN, and SOX9), and histology by Safranin O/Fast Green staining. Culture in NCCM resulted in increased proteoglycan content compared to day 0 and BM, similar to Link N. However, only minor differences in gene expression compared to day 0 were observed. Addition of BMSCs did not result in increased GAG content, and surprisingly, DNA content in BMSC-injected groups was not higher than in the other groups after 4 weeks of culture. This study shows that, indeed, NCCM is capable of stimulating NPC matrix production within the NP environment. The lack of increased DNA content in the BMSC-injected groups indicates that BMSCs have died over time. Identification of the bioactive factors in NCCM is crucial for further development of an NCCM-based treatment for intervertebral disc regeneration.


Bird-headed dwarf of Seckel.
Seckel syndrome is an extremely rare inherited disorder characterized by growth delays prior to birth resulting in low birth weight. Growth delays continue after birth resulting in short stature (dwarfism). This syndrome is associated with an abnormally small head, varying degrees of mental retardation and unusual "beak like" protrusion of nose. Other facial features may include abnormally large eyes, a narrow face, malformed ears and an unusually small jaw. This syndrome has an autosomal recessive pattern of inheritance. A case of the Seckel syndrome is presented.


Neck dissection prior to radiation therapy for squamous cell carcinoma of tongue base.
Squamous cell carcinoma of the tongue base can be treated with comparable control and survival rates when neck dissection (ND) is performed before radiation therapy (RT). Fourteen patients were treated between 1990 and 2000. Tumor stage on presentation was: T2, 6; T3, 4; T4, 4. Average radiation dose was 7,268 cGy. Follow-up ranged from 2 to 11 years (median, 50 months). Ten patients (71.4%) who presented with cervical metastases underwent neck dissection. All neck dissections were performed prior to RT. The initial local control rate was 85.7%. The 10-year survival rate was 62.8%. Patients tolerated their procedure well and were ready for RT within 2 to 4 weeks. Our preliminary data indicate that our treatment protocol results in control and survival rates which are comparable with other regimens. It is our impression that in contrast to patients undergoing ND after radiation, our patients tolerated their initial ND well and were better prepared for the second part of the treatment. Future studies will use quality-of-life research methods to study this aspect of the treatment protocol.


Long-term follow-up after percutaneous coronary intervention with polytetrafluoroethylene-covered Symbiot stents compared to bare metal stents, with and without FilterWire embolic protection, in diseased saphenous vein grafts.
The long-term clinical outcome of covered stents in the percutaneous treatment of diseased saphenous vein graft (SVG) has been disappointing. The single self-expanding polytetrafluoroethylene (PTFE)-covered Symbiot stent with a unique profile may present advantages that translate into superior long-term clinical outcomes. This study evaluated the safety, effectiveness and clinical outcome of the Symbiot covered stent system (Boston Scientific, Natick, Mass.) and FilterWire EX (Boston Scientific, Natick, Mass.) versus bare metal stents (BMS) in SVG intervention. Between January 2003 and August 2005, 90 patients with degenerative SVG lesions were prospectively randomized at 6 study sites to Symbiot implantation (n = 30), BMS with FilterWire as embolic protection device (EPD, n = 30), or BMS without EPD (control group, n = 30). The primary end point was reduction in peri-procedural cardiac enzyme rise. The major secondary end points were in-hospital, 6-month and long-term target vessel failure rates, defined as the cumulative of death, myocardial infarction and clinically driven target lesion revascularization. There was no significant reduction in median [IQR] post-procedural troponin-I rise in the Symbiot group compared to the FilterWire or the control group (0.08 [0-1.40] microg/l; 0.06 [0-0.28] microg/l; and 0.04 [0-0.31] microg/l, P = 0.58). At 7.4 +/- 1.3 (mean +/- SD) years, there were numerically less deaths in the Symbiot group, although this did not reach statistical significance (P = 0.20). There was no significant difference in TVF-free survival between the treatment groups (P = 0.98). This study failed to show a procedural or long-term clinical advantage for the Symbiot PTFE-covered stent in the treatment of degenerated SVG.


General population knowledge about osteoarthritis and its related risk factors in Jeddah Saudi Arabia.
To identify the knowledge gap and misconceptions about osteoarthritis (OA) and its risk factors among the general population of Jeddah, Saudi Arabia. This is a cross-sectional study conducted Jeddah, Saudi Arabia, between 11-13 April, 2019. The study was approved by King Abdullah International Medical Research Center. A representative sample of the public in well-known mall was asked to complete the questionnaire to assess their knowledge regarding OA. The questionnaire consisted of 3 parts: 1) demographic data, 2) general knowledge regarding OA, and 3) a quiz of 20 questions. A descriptive analysis was carried out with t-test and F-test-based method. The study had 1238 respondents. Approximately 55% of them were females, with 51.8% between the ages of 18 to 29. Approximately 62% held a bachelor's degree and 63% had a family member or a friend afflicted with OA. Relatives and friends were the main source of information regarding OA. Only 37% correctly identified the mechanism behind OA. The mean score for the 20-item quiz was 9.84. No significant differences were found when comparing scores of males and females or those of age groups. However, significant differences in scores were identified between respondents of varying educational levels (p less than 0.001), participants' knowledge of the mechanism leading to OA (p less than 0.001), information sources (p less than 0.001), and knowing someone with it (p less than 0.001). The results of our study suggest a low level of knowledge regarding OA among Jeddah population. Many misconceptions regarding OA were identified, so more information be brought to the public.


Leukocyte adhesion molecule expression during intense resistance exercise.
We hypothesized that expression of L-selectin and very late antigen-4 (VLA-4) integrin adhesion molecules would influence cell type-specific redistribution during exercise. Women subjects performed six sets of 10-repetition maximum squats. L-selectin and VLA-4 integrin were measured by using flow cytometry pre- and postexercise on peripheral blood neutrophils and lymphocytes (n = 29 subjects) and lymphocyte subsets (n = 70 subjects), respectively. Neutrophil concentration increased 41.8% (P < 0.001), whereas the percent expressing L-selectin was unchanged (79%). Lymphocyte concentration increased 61.8% (P < 0.001). The percent of T cells expressing L-selectin decreased from 73.5 +/- 8.9 to 68.2 +/- 11.4% (P < 0.001); the combined population of natural killer and B cells expressing L-selectin decreased from 80.4 +/- 22.5 to 62.7 +/- 25.8% (P < 0.001). VLA-4 integrin was expressed by nearly all lymphocytes both pre- and postexercise. The proportional decrease in L-selectin positive cells could have resulted from 1) shedding of L-selectin, 2) selective entry of L-selectin-negative subsets, or 3) selective removal of L-selectin-positive subsets.


Approach to genetic analysis in the diagnosis of hereditary autoinflammatory syndromes.
Hereditary autoinflammatory syndromes are characterized by recurrent episodes of fever and inflammation. Seven subtypes have been described, caused by mutations in four different genes. Apart from a common phenotype of lifelong recurrent inflammatory attacks, all subtypes have distinct features and specific therapeutic options, which emphasizes the need for a specific diagnosis in each case. Our aim was to examine whether genetic screening would allow classification of previously unclassified patients, and whether individual patients suffering from an autoinflammatory syndrome carry additional mutations in one of the other autoinflammatory genes. We included 60 patients with an unclassified autoinflammatory syndrome, 87 patients diagnosed with either hyper-IgD syndrome, familial Mediterranean fever (FMF) or tumour necrosis factor (TNF)-receptor-associated periodic syndrome and 50 healthy controls. Deoxyribonucleic acid samples were screened for the most prevalent mutations in the MEFV, TNFRSF1A, MVK and CIAS1 genes. We found only one possible diagnosis of FMF in the 60 previously unclassified patients. Two low-penetrance mutations were found in equal numbers in the groups of patients and controls. Screening of highly prevalent mutations in known genes involved in these disorders does not yield additional relevant information. Differential diagnosis of hereditary autoinflammatory syndromes can be made by thorough clinical examination followed by targeted genetic analysis of the one or two most likely syndromes. High-prevalence low-penetrant mutations from autoinflammatory genes do not occur more frequently in patients with hereditary autoinflammatory syndromes compared with the general population.


Current Challenges and Achievements in Maternal Immunization Research.
Maternal immunization has the potential to significantly improve maternal and child health worldwide by reducing maternal and infant morbidity and mortality associated with disease caused by pathogens that are particularly relevant in the perinatal period and in early life, and for which no alternative effective preventive strategies exist. Research on all aspects related to vaccines for administration during pregnancy is ongoing with support of multiple stakeholders and global participation. Substantial progress has been made, and the availability of new vaccines licensed exclusively for use in pregnant women to protect their infants has become an achievable goal. This review provides an update of the current challenges and achievements in maternal immunization research, focusing on recent milestones that advance the field and the prospects to make maternal immunization a feasible and accessible strategy to improve global health.


Synchronized GABAergic IPSPs recorded in the neocortex after blockade of synaptic transmission mediated by excitatory amino acids.
1. Intracellular and extracellular recordings were carried out in guinea pig neocortical slices to examine the effects of blockade of excitatory amino acid (EAA) synaptic transmission on population discharges elicited by 4-aminopyridine (4-AP; 50-100 microM). 2. After the introduction of 4-AP, two distinct types of rhythmic spontaneous field potentials were recorded in neocortical slices. Type I consisted of multiple spike discharges lasting 20-90 s. These events occurred at a frequency of 0.4-0.2/min. Type II were single field potential spikes (3-6 s in duration) occurring at a higher frequency (2-4/min). 3. Blockade of amino acid-mediated excitatory synaptic transmission with D-2-amino-5-phosphonovaleric acid (D-AP5; 10-30 microM) or 3-(2-carboxypiperazin-4-yl)propyl-l-phosphonic acid (CPP, 10 microM) and 6-cyano-7nitroquinoxaline-2,3-dione (CNQX; 10 microM) abolished the first type of 4-AP-induced field potential, whereas type II events persisted. 4. Type II field events, occurring in the presence of EAA blockers, were further characterized by paired recordings. Events recorded along an axis orthogonal to the pia surface occurred simultaneously without measurable delay. Recordings made along a plane parallel to the pia surface showed that type II discharges propagated over distances of greater than or equal to 3 mm at an estimated velocity of 7.5 mm/s. 5. Intracellular recordings show that during type II field discharges all cells exhibited phasic depolarizations or hyperpolarizations, depending on the resting membrane potential. When resting potentials were more depolarized than -68 mV, events became mostly hyperpolarizing.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of glutamate and aspartate on ataxic gait induced by 3-acetyl pyridine in rats.
The main purpose of this study was to examine the effects of intraventricular injections of glutamate and aspartate on the walking gait of rendered ataxic by the administration of 3-acetyl pyridine. Both amino acids significantly improved the walking gait of these animals. The effects of other substances known to have a stimulatory influence on locomotor activity in rats were also investigated. Amphetamine, apomorphine and thyrotropin releasing hormone (TRH) had no effect on the ataxic gait of 3-AP treated animals. Substance P significantly improved the gait of ataxic animals, but to a lesser extent than that seen with glutamate and aspartate.


Dissatisfaction with the dental services and associated factors among adults.
This study aimed to identify factors associated with dissatisfaction with dental services among adults. It analyzed 830 adult participants of an epidemiological survey of oral health. The dependent variable was dissatisfaction with the dental service, and the independent ones were selected according to the theoretical model set forth by Andersen and Davidson (1997). Estimates were corrected by the sample design effect, and Binary Logistic Regression was carried out. It was found that about 11% of adults were dissatisfied with the dental service. In the final model, dissatisfaction with dental services was lower among older adults (OR = 0.559) and among smokers (OR = 0.332). On the other hand, it was higher among adults who self-perceived their chewing as negative (OR = 2,804), who self-perceived some discomfort in the mouth and head and neck region (OR = 2.065), and among those who did not have access to information on how to avoid oral problems (OR = 3.020). Therefore, the services need to access the perceptions and expectations expressed by users, and provide information in appropriate quantity and quality, in the context of "health literacy" in order to achieve greater satisfaction among its users.


Acute Subdural Hematoma: A Rare Manifestation of Cerebral Venous Sinus Thrombosis.
Cerebral venous sinus thrombosis (CVST) usually presents with headaches, seizures, and signs and symptoms of raised intracranial pressure (ICP). Risk factors for CVST commonly include hypercoagulable states such as pregnancy and the peripartum period, dehydration, vitamin B12 deficiency, hyper-homocysteinemia, coagulation factor deficiency, antiphospholipid antibody disease, oral contraceptive pill intake, etc. CVST with venous hemorrhagic infarction is commonly reported, but only a few cases have been reported in the literature of CVST presenting as SDH. Here, we present a case of a 28-year-old female who presented with an acute onset of severe headache, vomiting, and bilateral papilledema on fundus examination. She had a prior history of oral contraceptive pill intake. An MRI brain venogram suggested CVST involving the superior sagittal sinus, right transverse, and a few cortical vein thromboses with subdural hematoma (SDH) in the frontal-parieto-temporo-occipital region on the right side. The patient was treated with anticoagulants and antiepileptics and had significant improvement in symptoms with the resolving SDH on subsequent scans.


Native-like in vivo folding of a circularly permuted jellyroll protein shown by crystal structure analysis.
A jellyroll beta-sandwich protein, the Bacillus beta-glucanase H(A16-M), is used to probe the role of N-terminal peptide regions in protein folding in vivo. A gene encoding H(A16-M) is rearranged to place residues 1-58 of the protein behind a signal peptide and residues 59-214. The rearranged gene is expressed in Escherichia coli. The resultant circularly permuted protein, cpA16M-59, is secreted into the periplasm, correctly processed, and folded into a stable and active enzyme. Crystal structure analysis at 2.0-A resolution, R = 15.3%, shows cpA16M-59 to have a three-dimensional structure nearly identical with that of the parent beta-glucanase. An analogous experiment based on the wild-type Bacillus macerans beta-glucanase, giving rise to the circularly permuted variant cpMAC-57, yields the same results. Folding of these proteins, therefore, is not a vectorial process depending on the conformation adopted by their native N-terminal oligopeptides after ribosomal synthesis and translocation through the cytoplasmic membrane.


Health-related quality of life after surviving intensive care for COVID-19: a prospective multicenter cohort study.
In survivors of severe coronavirus disease 2019 (COVID-19) incomplete mental and physical recovery may considerably impact daily activities and health-related quality of life (HRQoL). HRQoL can be evaluated with the RAND-36 questionnaire, a multidimensional instrument that assesses physical and mental aspects of health in eight dimensions. The objective was to investigate HRQoL in intensive care patients previously treated for COVID-19 at three Nordic university hospitals, in a prospective multi-center cohort study. HRQoL was measured using RAND-36, 3-9 months after discharge from intensive care units (ICU). One hospital performed a second follow-up 12 months after discharge. A score under the lower limit of the 95% confidence interval in the reference cohorts was considered as significantly reduced HRQoL. We screened 542 and included 252 patients. There was more than twice as many male (174) as female (78) patients and the median age was 61 (interquartile range, IQR 52-69) years. Hypertension was the most common comorbidity observed in 132 (52%) patients and 121 (48%) patients were mechanically ventilated for a median of 8 (IQR 4-14) days. In RAND-36 physical functioning, physical role functioning, general health (p < 0.001 for all) and social functioning (p < 0.05) were below reference, whereas bodily pain, emotional role functioning and mental health were not. In a time-to-event analysis female sex was associated with a decreased chance of reaching the reference HRQoL in the physical function, bodily pain and mental health dimensions. Higher body mass index was found in the physical functioning dimension and hypertension in the physical functioning, vitality and social functioning dimensions. Similar results were seen for diabetes mellitus in general health, vitality and mental health dimensions, as well as pulmonary illness in the physical role functioning dimension and psychiatric diagnosis in the social functioning dimension. Mechanical ventilation was associated with a decreased likelihood of achieving reference HRQoL in the bodily pain and physical functioning dimensions. Patients treated in an ICU because of COVID-19 had lower HRQoL 3-9 months after ICU discharge than 95% of the general population. Physical dimensions were more severely affected than mental dimensions. Female sex and several comorbidities were associated with a slower rate of recovery.Study registration: clinicaltrials.gov: NCT04316884 registered on the 13th of March 2020, NCT04474249 registered on the 29th of June 2020 and NCT04864938 registered on the 4th of April 2021.


Thermal diffusivity and specific heat of dental casting alloys at room and elevated temperatures.
Thermal diffusivity and specific heat of four groups of dental casting alloys (Ag-based, Au-Pd, high karat and Ni-based alloys) were determined. Measurements were carried out from room temperature to 750 degrees C in an evacuated electric furnace with a laser flash thermal constant analyzer. There was no significant difference between the values of thermal diffusivity in the Ag-based and high karat alloys; 18-24 and 40-53 mm2/s, at room temperature and at 600 degrees C, respectively. For Au-Pd and Ni-based alloys, diffusivity was 8-12 and 3-4 mm2/s at room temperature, and 19-22 and 5-6 mm2/s at 600 degrees C, respectively. The thermal diffusivity of the alloys was significantly low compared to that of the pure-metals of which they were composed. Specific heat was determined as 0.14-0.16, 0.24-0.34, 0.17-0.19 and 0.45-0.51 kJ/(kg.K) for high karat, Ag-based, Au-Pd and Ni-based alloys, respectively, at room temperature. Oxidation of the Ni-based alloy at elevated temperature affected the value of specific heat measured.


Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica.
Polymyalgia rheumatica (PMR) is an inflammatory disease that typically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients. Synovial expression of neuropeptides was investigated by immunohistochemical analysis, in two groups of PMR patients: the first one at the onset of disease and the second one after corticosteroid treatment, and in other joint diseases, rheumatoid arthritis (RA) and osteoarthritis (OA). The only significant expression of VIP was found in PMR and, to a lesser extent, in RA synovial tissue. In PMR, we observed VIP immunostaining both in the lining layer and in the sublining area. In patients on corticosteroid treatment VIP lining layer expression was not significantly different while VIP positive cells in the sublining area were almost absent. Local VIP production in PMR synovial tissue might contribute to the typical musculoskeletal discomfort and it may have a role in the immunomodulation of synovial inflammation.


Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.
By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.


Focusing of surface plasmon polaritons propagating at the SiO2/Ag interface with 2-level and 4-level Fresnel phase zone pad structures.
We propose and demonstrate dielectric Fresnel phase zone pad (FPZP) structures for focusing surface plasmon polaritons (SPPs) propagating at the SiO2/Ag interfaces. We exploited up-conversion fluorescence microscopy to characterize the SPP focusing. We first report on the SPP focusing with 2-level FPZP structures that introduced a π-phase shift in the SPP wavefront between adjacent zones. We optimized the SPP focusing by fine-tuning the longitudinal width of the FPZP structure. This led to the enhancement of the peak intensity of the SPP focal spot and the reduction of the focal spot size in both the longitudinal and transverse directions. Such focusing was also demonstrated with different focal lengths. To further improve the SPP focusing, we developed a 4-level FPZP structure, which introduced a π/2-phase shift in the SPP wavefront between adjacent zones. With the optimized 4-level FPZP structure, the SPP focal spot peak intensity is further improved, and the spot size is reduced. To assist the design of the FPZP structures, we carried out theoretical analysis and numerical calculations to determine the SPP wavelengths at various oxide/Ag interfaces. We also carried out finite difference time domain (FDTD) calculations to simulate the SPP focusing with the FPZP structures. The results of the FDTD simulation agree with the experimental results qualitatively.


[Cases of posterior inferior cerebellar artery aneurysms].
The authors described two cases of aneurysms of the posterior inferior cerebellar artery (PICA) successfully operated on. The possibilities of surgical approaches and methods of obliteration of the aneurysm and review of PICA aneurysms in the literature are presented.


Polyketides with Anti-Inflammatory Activity from Trichoderma koningiopsis, a Rhizosphere Fungus from the Medicinal Plant Polygonum paleaceum.
Twelve new fungal polyketides, koningiopisins I-P (1-8) and trichoketides C-F (9-12), together with six known congeners (13-18), were isolated from Trichoderma koningiopsis, a rhizosphere fungus obtained from the medicinal plant Polygonum paleaceum. Their structures and absolute configurations were established by spectroscopic analysis, single-crystal X-ray diffraction, the modified Mosher's method, chemical derivatization, the octant rule, and 13C NMR and ECD calculations. Compounds 1-5 are tricyclic polyketides possessing an octahydrochromene framework with a 6,8-dioxabicyclo[3.2.1]octane core. Compounds 7 and 8 contain a unique ketone carbonyl group at C-7 and differ from other members of this group of compounds with the ketone carbonyl group at C-1. Compounds 1, 2, and 13 showed inhibitory activity on LPS-induced BV-2 cells on NO production with IC50 values of 14 ± 1, 3.0 ± 0.5, and 8.9 ± 2.7 μM, respectively.


[Mitrofanoff continent urinary diversions: The opinion of 57 patients].
To evaluate the psychological repercussions and degree of adaptation in daily living of patients with a Mitrofanoff continent external urinary diversion. Fifty seven patients were questioned about their Mitrofanoff continent urinary diversions, using a questionnaire translated into their spoken language (Arabic). The mean age was 29 years (range: 10 to 72 years). The indication for the diversion was a neurological cause in 91% of cases. Continence was achieved in every case, but after surgical revision in 3 cases. Self-catheterization was considered to be easy and not especially bothersome in 49 cases (86%). The diversion had occasional and moderate repercussions on activities of daily living, estimated between 3.5 and 17.5%. Sixteen patients (94%) returned to work and another fifteen (79%) successfully resumed their schooling. Nineteen patients (83%) who were sexually active preoperatively reported a satisfactory sex life after the operation. Finally, this operation was highly appreciated by the patients in 96.5% of cases for hygienic and psychological reasons. The Mitrofanoff urinary diversion allows satisfactory social, work and family rehabilitation provided the patient adapts to diversion management.


Emergency transcatheter arterial embolization for massive gastrointestinal arterial hemorrhage.
To evaluate the different arteriographic manifestations of acute arterial massive hemorrhage of the gastrointestinal (GI) tract and the efficacy of emergency transcatheter arterial embolization (ETAE).A total of 88 patients with acute massive GI bleeding who experienced failure of initial endoscopy and/or conservative treatment were referred to our interventional department for acute GI arteriography from January 2007 to June 2015. After locating the source of bleeding, appropriate embolic agents, such as spring coil, hydroxyl methyl acrylic acid gelatin microspheres, polyvinyl alcohol (PVA) particles, etc., were used to embolize the targeted vessels. The angiographic manifestations and the effects of embolization of acute arterial massive hemorrhage of the GI tract were retrospectively analyzed.Of the 88 patients, 54 were diagnosed with arterial hemorrhage of the upper GI tract and 34 with arterial hemorrhage of the lower GI tract. Eighty cases were associated with positive angiography, which showed the following: contrast extravasation (only); gastroduodenal artery stenosis; pseudoaneurysm (only); pseudoaneurysm rupture with contrast extravasation; pseudoaneurysms merged with intestinal artery stenosis; GI angiodysplasia; and tumor vascular bleeding. Eight cases were diagnosed with negative angiography. Seven-two patients underwent successful hemostasis, and a total of 81 arteries were embolized. The technical and clinical success rates (no rebleeding within 30 days) in performing transcatheter embolization on patients with active bleeding were 100% and 84.71%, respectively (72 of 85). Within 30 days, the postoperative rebleeding rate was 15.29% (13/85). Of these rebleeding cases, 2 patients were formerly treated with "blind embolization," 7 underwent interventional embolic retreatment, and 3 had surgical operations. All cases were followed-up for 1 month, and 3 patients died from multiple organ failure. No serious complications such as bowel ischemia necrosis were observed.ETAE is a safe, effective, and minimally invasive treatment; because of the diversified arteriographic manifestations of acute GI hemorrhage, the proper selection of embolic agents and the choice of reasonable embolization method are essential for successful hemostasis.


Measurement of D{0}-D[-over]{0} mixing from a time-dependent amplitude analysis of D{0}-->K+pi{-}pi{0} decays.
We present evidence of D{0}-D[-over ]{0} mixing using a time-dependent amplitude analysis of the decay D{0}-->K+pi{-}pi;{0} in a data sample of 384 fb{-1} collected with the BABAR detector at the PEP-II e+e{-} collider at the Stanford Linear Accelerator Center. Assuming CP conservation, we measure the mixing parameters x{Kpipi{0}}{'}=[2.61{-0.68}{+0.57}(stat)+/-0.39(syst)]%, y{Kpipi;{0}}{'}=[-0.06{-0.64}{+0.55}(stat)+/-0.34(syst)]%. This result is inconsistent with the no-mixing hypothesis with a significance of 3.2 standard deviations. We find no evidence of CP violation in mixing.


Cytocompatible, Photoreversible, and Self-Healing Hydrogels for Regulating Bone Marrow Stromal Cell Differentiation.
Photo-crosslinking and self-healing have received considerable attention for the design of intelligent materials. A novel photostimulated, self-healing, and cytocompatible hydrogel system is reported. A coumarin methacrylate crosslinker is synthesized to modify the polyacrylamide-based hydrogels. With the [2+2] cyclo-addition of coumarin moieties, the hydrogels exhibit excellent self-healing capacity when they are exposed to light with wavelengths at 280 and 365 nm, respectively. To enhance cell compatibility, a poly (amidoamine) crosslinker is also synthesized. Variations in light exposure times and irradiation wavelengths are found to alter the self-healing property of the hydrogels. The hydrogels are shown to induce a regular cellular pattern. The hydrogels are used to regulate bone marrow stromal cells differentiation. The relative mRNA expressions are recorded to monitor the osteogenic differentiation of the cells.


Population Growth Parameters of Tuta absoluta (Lepidoptera: Gelechiidae) on Tomato Plant Using Organic Substrate and Biofertilizers.
The tomato leafminer, Tuta absoluta (Meyrick) is a devastating pest associated with tomato. In this study, effects of tomato plants treated with vermicompost (20, 40, and 60%), humic fertilizer (2, 4 and 6 g/kg soil) and plant growth promoting rhizobacteria (Pseudomonas fluorescens and Bacillus subtilis) were investigated on the life table parameters of T. absoluta in a growth chamber at 25 ± 2 °C, 65 ± 5% RH, and 16:8 (L:D) h. Significant differences were found for the total developmental time, fecundity, and oviposition period of T. absoluta on the treatments tested. The net reproductive rate (R0), intrinsic rate of natural increase (rm), finite rate of increase (λ), mean generation time (T), and doubling time (DT) of T. absoluta were significantly different among treatments tested. We found that in all vermicompost, humic fertilizer and plant growth promoting rhizobacteria treatments, values of R0, rm, and λ were lower than control treatment. However, the lowest values of these parameters were obtained on 2 g/kg humic fertilizer and 40% vermicompost. Furthermore, T. absoluta had longest T and DT values on 2 g/kg humic fertilizer treatment. Data obtained showed that the addition of 2 g/kg humic fertilizer and 40% vermicompost to the growing soil reduced T. absoluta populations in tomato cultures. In addition, these levels of fertilizers improved growth parameters of tomato seedlings (plant height, wet weight, and dry weight) compared with other treatments. These results could be useful in improving the sustainable management of the moth.


Comparison of inactivated poliovirus vaccine and oral poliovirus vaccine programs in Israel.
In spite of high vaccination coverage, paralytic poliomyelitis still occurs in Israel, either in sporadic form in the urban area or in small outbreaks in the rural, non-Jewish segment. At high risk are mainly very young infants, not yet protected by poliovirus vaccine and children who have failed to seroconvert after a full course of oral poliovirus vaccine ( OPV ). In these circumstances, a new program for vaccination of young infants early in life with a quadruple vaccine containing inactivated poliovirus vaccine (IPV) and diphtheria, tetanus, and pertussis vaccines (DTP) has been tested. Administration of two doses of IPV up to the age of three and one-half months followed by a booster at the age of 10 months has produced a very satisfactory antibody response (100% seroconversion and high geometric mean titers of antibody to the three antigens), which has occurred early in life and persisted up to two years after booster. This response was similar to that observed after four doses of trivalent OPV ( TOPV ) reinforced with one dose of monovalent type 1 OPV . Two doses of the quadruple vaccine have also induced an antibody response to pertussis antigen in greater than 90% of the infants. After booster, a greater than 99% conversion rate has been recorded, which has remained unchanged at one year of follow-up. The above data have led to the modification of the poliovirus vaccination schedule in the areas at risk.


Ethnic differences in physiological responses to fear conditioned stimuli.
The idea that emotional expression varies with ethnicity is based largely on questionnaires and behavioral observations rather than physiological measures. We therefore compared the skin conductance responses (SCR) of Hispanic (Puerto Rican) and White non-Hispanic subjects in a fear conditioning and fear extinction task. Subjects were recruited from two sites: San Juan, Puerto Rico (PR), and Boston, Massachusetts (MA), using identical methods. A total of 78 healthy subjects (39 from PR, 39 from MA) were divided by sex and matched for age and educational level. Females from the two sites did not differ in their SCRs during any experimental phase of fear conditioning (habituation, conditioning, or extinction). In contrast, PR males responded significantly to the conditioned stimulus than MA males or PR females. Subtracting ethnic differences observed during the habituation phase (prior to conditioning) eliminated differences from subsequent phases, suggesting that PR males are elevated in their response to novelty rather than fear learning. Our findings suggest that, in addition to sex differences, there are ethnic differences in physiological responses to novel stimuli at least in males, which could be relevant for the assessment and treatment of anxiety disorders.


Cues of intraguild predators affect the distribution of intraguild prey.
Theory on intraguild (IG) predation predicts that coexistence of IG-predators and IG-prey is only possible for a limited set of parameter values, suggesting that IG-predation would not be common in nature. This is in conflict with the observation that IG-predation occurs in many natural systems. One possible explanation for this difference might be antipredator behaviour of the IG-prey, resulting in decreased strength of IG-predation. We studied the distribution of an IG-prey, the predatory mite Neoseiulus cucumeris (Acari: Phytoseiidae), in response to cues of its IG-predator, the predatory mite Iphiseius degenerans. Shortly after release, the majority of IG-prey was found on the patch without cues of IG-predators, suggesting that they can rapidly assess predation risk. IG-prey also avoided patches where conspecific juveniles had been killed by IG-predators. Because it is well known that antipredator behaviour in prey is affected by the diet of the predator, we also tested whether IG-prey change their distribution in response to the food of the IG-predators (pollen or conspecific juveniles), but found no evidence for this. The IG-prey laid fewer eggs on patches with cues of IG-predators than on patches without cues. Hence, IG-prey changed their distribution and oviposition in response to cues of IG-predators. This might weaken the strength of IG-predation, possibly providing more opportunities for IG-prey and IG-predators to co-exist.


Membrane phospholipid reorganization differentially regulates metallothionein and heme oxygenase by heme-hemopexin.
Heme-hemopexin coordinately regulates genes encoding protective proteins including metallothionein-I (MT-I) and heme oxygenase 1 (HO-1). Hexamethylene-bisacetamide (HMBA), which induces differentiation and activates protein kinase C (PKC), synergistically augments the induction of both MT-I and MT-II mRNAs in response to heme-hemopexin, but attenuates the induction of HO-1. HMBA also augments the increase in MT mRNA in response to cobalt protoporphyrin-hemopexin, a hemopexin (HPX) receptor ligand that activates signaling cascades without tetrapyrrole uptake. Unlike the PKC-activating phorbol esters that induce MT-I and HO-1, HMBA has minimal effects on MT-I or HO-1. HMBA is an amphipathic molecule, and is shown here to interact physically with lipids in model membranes using differential scanning calorimetry (DSC). The data are consistent with a stabilization of the lipid bilayer and an HMBA-induced segregation of lipids into separate domains each relatively enriched in one of the lipids. HMBA also perturbs membrane-protein interactions, and causes a loss of PKC and G-protein subunits from plasma membranes in vitro. Taken together, these observations reveal an additional level of complexity in the regulation of protective proteins induced by HPX, and which may take place in vivo in response to natural compounds that reorganize membrane phospholipids. A model is proposed whereby a reorganization of lipids by HMBA alters signaling pathways and fusion events considered to be the etiology of the differential response of the MT-1 (and MT-II) and the HO-1 genes to HMBA and heme-HPX.


Acute renal insufficiency in the rabbit by glycerol.
The appearance of an acute renal insufficiency in the rabbit, after glycerol injection (10, 13 or 15 ml/kg of a 50% solution) is investigated. After a 24 hours of intoxication, especially in the ten following days, cylinders, erythrocytes and renal cells appear in the urine sediment. Proteinuria appears after 24 hours and practically disappears after 72 h. Glucosuria persists from 24 hours to 6 days. Haemoglobinuria is intense after 24 and 48 hours and persists slightly about 6 days. Na, K and Cl elimination in urine diminishes clearly in all animals. Plasma K increases in non-surviving animals and does not change in those surviving. Plasma Na does not change in the dying ones, and decreases in those surviving. In non-surviving animals, pH, pCO2 and CO3H minus decrease sharply. In the surviving ones pCO2 decreases clearly after 24 hours, increasing afterwards slowly to normal values. pH increases, slightly during the first 48 hours, and then neatly during approximately 6 days. Standard CO2H minus does not change during the first 48 hours, increasing afterwards during 6 to 7 days. Histologically, the chief lesion is a vacuolar degeneration of the proximal tubule. The possible mechanisms of such alterations are discussed.


Physiological and pathophysiological aspects of cardiac prostaglandins.
It has now been demonstrated that prostaglandins produce a wide variety of actions on cardiac tissue. These effects are quite complex and are dependent on such factors as type of prostaglandin, animal species, experimental format, as well as the amount of prostaglandin employed. The last factor is of particular concern since the administration of large amounts of prostaglandins may not truly reflect the actual actions of the endogenously synthesized prostaglandins which are likely to be at a very low concentration. In this review we have attempted to analyze the pharmacological properties of prostaglandins on cardiac tissue including coronary arteries and myocardium as well as the subcellular basis for their actions. The possible reasons for the diverse effects of prostaglandins under different experimental conditions have been pointed out. An effort has also been made to synthesize the existing information concerning the actions of prostaglandins on heart in terms of current concepts. A discussion is presented concerning the role of endogenously synthesized prostaglandins in physiological and pathological aspects of cardiac performance and the potential use of prostaglandins and prostaglandin synthesis inhibitors in the treatment of heart disease.


Divergence of variant binding/neutralizing antibodies following SARS-CoV-2 booster vaccines in myeloma: Impact of hybrid immunity.
We characterized virus-neutralization and spike-binding antibody profiles in myeloma patients following monovalent or bivalent-SARS-CoV-2 booster vaccination. Vaccination improves the breadth of binding antibodies but not neutralization activity against current variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity.


Cloning, expression, and fibrin (ogen)olytic properties of a subtilisin DJ-4 gene from Bacillus sp. DJ-4.
Previously, we purified a strong fibrinolytic enzyme (subtilisin DJ-4) from Bacillus sp. DJ-4 and characterized its enzymatic activity. Here, we cloned the gene subtilisin DJ-4, and determines its nucleotide sequence, which showed 97% identity with subtilisin BPN' from B. amyloliquefacens. Recombinant full-subtilisin DJ-4 (rf-subDJ-4) and mature-subtilisin DJ-4 (rm-subDJ-4) were expressed using a pET29 vector system, and their fibrin (ogen)olytic and plasminogen activator activities were studied. rf-subDJ-4 was found to have a higher stability to heat (60 degrees C) and to acidic conditions (pH 3.0-4.0) than the native subtilisin DJ-4 of Bacillus sp. DJ-4. The plasminogen activator activity of rf-subDJ-4 was 2.75 times greater than that of plasmin on a molar basis. And its specific activity (F/C, the ratio of fibrinolytic activity to caseinolytic activity) was 2.67 and 3.97 times higher than those of subtilisin BPN' and subtilisin Carlsberg, respectively. rf-subDJ-4 rapidly hydrolyzed the Aalpha-, Bbeta-, and gamma-chains of fibrinogen within 5 min. But, unlike subtilisin BPN' at a very low concentration (50 ng), the gamma-chain was not cleaved. On the other hand, rm-subDJ-4 did not show enzyme activity.


A femtosecond study of the anomaly in electron injection for dye-sensitized solar cells: the influence of isomerization employing Ru(II) sensitizers with anthracene and phenanthrene ancillary ligands.
In this study, an intriguing difference caused by structural isomerization based on anthracene and phenanthrene stilbazole type ancillary ligands in Ru(ii) sensitizers for dye sensitized solar cells (DSCs) has been investigated using femtosecond transient absorption spectroscopy. Both anthracene and phenanthrene based sensitizers HD-7 and HD-8, respectively, resulted in a similar extinction coefficient, photophysical and thermodynamic free energy of electron injection and dye regeneration as measured by UV-Vis, excited state lifetime and cyclic voltammetry measurements, respectively. However, TiO2 adsorbed HD-7 resulted in up to 45% less photocurrent density than HD-8 although photovoltage was similar owing to comparable thermodynamic characteristics. It was obvious from the measurement of incident photon to current conversion efficiency (IPCE) that excited electrons in HD-7 are prone to internal energy loss before injection into the TiO2 conduction band. Analysis of photo-induced spectral features measured by femtosecond transient absorption spectroscopy showed that excited electrons in HD-7 are prone to ISC (intersystem crossing) much more than HD-8 and those triplet electrons are not injected into TiO2 efficiently. Interestingly, from impedance measurements, HD-7 showed higher recombination resistance than HD-8 and N719, but a shorter lifetime for electrons injected into the TiO2 conduction band.


Isolation of a new polyether antibiotic, lonomycin.
A new polyether antibiotic, lonomycin, was isolated from the culture of Streptomyces ribosidifcus strain TM-481. The antibiotic obtained as a sodium salt is a colorless prism having a molecular formula of C44H75O14Na(M.W. 850), m.p. 188 approximately 189 degrees C, and has no absorption maxima in the ultraviolet region. The infrared and NMR spectra of the antibiotic suggest the presence of a carboxyl and four methoxyl groups. Lonomycin shows antimicrobial activity against gram-positive bacteria.


Quantitation of the pool of cholesterol associated with acyl-CoA:cholesterol acyltransferase in human fibroblasts.
The esterification of cholesterol in homogenates of human fibroblasts was explored as a means of estimating the size of the pool of cholesterol associated with the endoplasmic reticulum (ER) in vivo. The rationale was that the acyl-coenzyme A:cholesterol acyltransferase (ACAT) in homogenates should have access only to cholesterol associated with the (rough) ER membrane fragments in which it resides. Reacting whole homogenates to completion with an excess of [14C]oleoyl-CoA converted approximately 0.1-2% of total cell-free cholesterol to [14C]cholesteryl esters. Control studies indicated that membranes not associated with ACAT did not contribute cholesterol to this reaction. The extent of in vitro cholesterol esterification varied with pretreatment of the cells. Exposing intact cells to serum lipoproteins, oxysterols, or sphingomyelinase increased cholesterol esterification in homogenates severalfold; exposing the cells to mevinolin or cholesterol oxidase had the opposite effect. The variation in cholesterol esterification did not correlate with either the total cellular cholesterol or the intrinsic activity of ACAT, neither of which was changed significantly by the pretreatments. Rather, the total amount of cholesterol esterified in homogenates paralleled the rate of cholesterol esterification in the corresponding intact cells. The pool of cholesterol esterified in vitro therefore appears to reflect that associated with the ER in vivo. Since several of the mechanisms keeping cell cholesterol under tight feedback control are themselves located in the ER, this pool might not only be regulated physiologically, but could, in turn, help to regulate homeostatic effector pathways.


The Value of Computed Tomography in Preoperative N Staging of Early Gastric Cancer Meeting the Endoscopic Resection Criteria.
This study evaluated the value of abdominal computed tomography (CT) in preoperative N staging of early gastric cancers (EGCs) within standard and expanded indications of endoscopic resection (ER) and investigated the factors affecting accuracy. Between March 2009 and March 2016, a total of 268 patients with EGC within the standard and expanded indications of ER underwent preoperative abdominal CT and surgical gastrectomy with lymph node (LN) dissection. Preoperative N staging of CT was compared with the pathologic result. The accuracy of N staging for EGCs within the standard and expanded indications was 86.1% (235/268). There was no LN metastasis in patients with cN1 in CT staging. LN metastasis was found in 7 patients with EGCs that met the expanded ER indication and cN0 in CT staging. According to the univariate analysis, ulcers, including scars, were associated with the false positive of lymph node metastasis in abdominal CT (odds ratio 3.56; 95% confidence interval 1.56-8.15). The present study suggests that the value of abdominal CT is limited for nodal staging of EGCs that meet the ER indication.


The Trans-Contextual Model of Autonomous Motivation in Education: Conceptual and Empirical Issues and Meta-Analysis.
The trans-contextual model outlines the processes by which autonomous motivation toward activities in a physical education context predicts autonomous motivation toward physical activity outside of school, and beliefs about, intentions toward, and actual engagement in, out-of-school physical activity. In the present article, we clarify the fundamental propositions of the model and resolve some outstanding conceptual issues, including its generalizability across multiple educational domains, criteria for its rejection or failed replication, the role of belief-based antecedents of intentions, and the causal ordering of its constructs. We also evaluate the consistency of model relationships in previous tests of the model using path-analytic meta-analysis. The analysis supported model hypotheses but identified substantial heterogeneity in the hypothesized relationships across studies unattributed to sampling and measurement error. Based on our meta-analysis, future research needs to provide further replications of the model in diverse educational settings beyond physical education and test model hypotheses using experimental methods.