[Hydrothorax as a complication of subclavian vein catheterization. Pathogenetic mechanism and description of a clinical case].
We report a case of possible detouring and malfunctioning of the left subclavian catheter in the homolateral internal mammary vein or of perforation form its tip of the wall of the left innominate vein. The tip of the catheter was rigid and sharp, may be the contractions of the heart or turbulent flow impinged it against the vein wall and have enhanced the perforation. The result was a hydrothorax that allowed a severe cardiac simile tamponed syndrome. The pathophysiology was also discussed.


Staged Hybrid Repair of an Intrathoracic Subclavian Artery Aneurysm Associated with a Long Segment Dissection.
Intrathoracic subclavian artery aneurysms (ISAAs) are infrequently seen in clinical practice. We report the repair of a left ISAA associated with a long segment dissection from the ostia extending to the axillary artery. A hybrid approach was used. Carotid-to-axillary bypass using a reversed greater saphenous vein was first performed, followed by coverage of the origin of the subclavian artery using a thoracic stent graft. Finally, percutaneous access of the radial artery with coil embolization was performed to successfully thrombose the ISAA.


Homeostatic maintenance via degradation and repair of elastic fibers under tension.
Cellular maintenance of the extracellular matrix requires an effective regulation that balances enzymatic degradation with the repair of collagen fibrils and fibers. Here, we investigate the long-term maintenance of elastic fibers under tension combined with diffusion of general degradative and regenerative particles associated with digestion and repair processes. Computational results show that homeostatic fiber stiffness can be achieved by assuming that cells periodically probe fiber stiffness to adjust the production and release of degradative and regenerative particles. However, this mechanism is unable to maintain a homogeneous fiber. To account for axial homogeneity, we introduce a robust control mechanism that is locally governed by how the binding affinity of particles is modulated by mechanical forces applied to the ends of the fiber. This model predicts diameter variations along the fiber that are in agreement with the axial distribution of collagen fibril diameters obtained from scanning electron microscopic images of normal rat thoracic aorta. The model predictions match the experiments only when the applied force on the fiber is in the range where the variance of local stiffness along the fiber takes a minimum value. Our model thus predicts that the biophysical properties of the fibers play an important role in the long-term regulatory maintenance of these fibers.


An essential active-site histidine residue in human prostatic acid phosphatase. Ethoxyformylation by diethyl pyrocarbonate and phosphorylation by a substrate.
Human prostatic acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 126.96.36.199) is a dimeric (alpha 2) protein that catalyses the hydrolysis of phosphomonoesters. Several reports suggest that a phosphoenzyme intermediate is involved in the mechanism of acid phosphatase. Chemical modification studies and trapping experiments were therefore undertaken in order to ascertain the identity of the amino acid residue(s) involved in the formation of this intermediate. Human prostatic acid phosphatase is inactivated by diethyl pyrocarbonate (second-order rate constant of 7 M-1. min-1 at pH 6.2) with an accompanying increase in absorbance at 242 nm due to formation of ethoxyformylhistidyl derivatives. In the presence of competive inhibitors the rate of inactivation is decreased. Inactivation can be partially reversed by hydroxylamine. The pH curve of inactivation indicates the involvement of a residue having a pK alpha of 6.5. Direct evidence for the involvement of a histidine residue in the mechanism was obtained by trapping a covalent phosphohistidyl-enzyme intermediate. Incubation of the enzyme with p-nitrophenyl [32 P] phosphate leads to incorporation of 0.44 mol 32P/mol enzyme. The denatured phosphoenzyme,which was acid labile but base stable, was hydrolyzed in 3 M KOH and the radioactivity was found to cochromatograph with synthetic tau-phosphohistidine on Dowex-1 ion-exchange resin. These results are consistent with a catalytic mechanism involving histidine as a nucleophile in the formation of a covalents phosphoenzyme intermediate.


The potential effect of ambrisentan as monotherapy and combined with tadalafil on diabetic erectile dysfunction in rats.
This study investigated the role of ambrisentan; the selective endothelin type-A receptor (ETAR) blocker on experimental diabetic erectile dysfunction in rats. Eighty-four adult male Sprague Albino rats were divided randomly into 7 groups. Three control groups received 1 mL saline, 0.2 mg/kg/d ambrisentan and 1.5 mg/kg/d tadalafil, respectively orally for 4 weeks. The remaining four groups were fed high fat diet for 14 days. Diabetes was induced by a single intra-peritoneal injection of 40 mg/kg streptozotocin. After 72 h, diabetes was confirmed by plasma glucose level ⩾250 mg/dL. Diabetic rats were divided randomly into four groups, numbered from 4 to 7. The fourth group was the diabetic-control group, while the fifth and sixth groups received ambrisentan and tadalafil respectively. The seventh group received a combination of both drugs. Treatment continued for 4 weeks then, copulatory, intracavernous pressure measurement, and laboratory tests were conducted. In diabetic rats, ambrisentan and tadalafil improved fasting glucose, insulin, insulin resistance, testosterone, nitric oxide, and rho kinase (ROCK) values compared to diabetic group with the maximum improvement achieved in ambrisentan/tadalafil group (p < 0.05). Ambrisentan also enhanced ICP and improved latency to erection and number of mounts with a tolerable SBP. Yet, ambrisentan/tadalafil combined therapy resulted in deterioration in SBP with consecutive worsening in ICP and mating indices. Ambrisentan showed significant therapeutic potential to prevent and improve diabetic ED in rats comparable to tadalafil.


Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid.
Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 < 5.0 μg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field.


Feasibility of electronic patient-reported outcome monitoring and self-management program in aplastic anemia and paroxysmal nocturnal hemoglobinuria-a pilot study (ePRO-AA-PNH).
Electronic patient-reported outcomes (ePRO) are increasingly recognized in health care, as they have been demonstrated to improve patient outcomes in cancer, but have been less studied in rare hematological diseases. The aim of this study was to develop and test the feasibility of an ePRO system specifically customized for aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). After performing a user-centered design evaluation an ePRO system for AA and PNH patients could be customized and the application was tested by patients and their medical teams for 6 months. Symptom-reporting triggered self-management advice for patients and prompts them to contact clinicians in case of severe symptoms, while the medical team received alerts of severe symptoms for patient care. All nine included patients showed a high adherence rate to the weekly symptom-reporting (72%) and reported high satisfaction. The system was rated high for usage, comprehensibility, and integration into daily life. Most patients (78%) would continue and all would recommend the application to other AA/PNH patients. Technical performance was rarely a barrier and healthcare providers saw ePRO-AA-PNH as a useful supplement, but the lacking integration into the hospital information system was identified as a major barrier to usage. An ePRO system customized for AA and PNH was feasible in terms of adherence, satisfaction, and performance, showing a high potential for these rare conditions in terms of data collection and patient guidance. However, the integration into clinical workflows is crucial for further routine use. ClinicalTrials.gov NCT04128943.


Prevention of radiation enteritis after abdominoperineal resection and radiotherapy.
The method described, aimed at preventing radiation enteritis in patients undergoing radiotherapy, postabdominoperineal resection is simple enough, does not materially prolong the time of operation and in our experience, thus far, seems to be effective.


[Dignity in terminal illness - confronting loss of dignity and suffering at the end of life].
How can we act in a dignity-oriented way when we usually only have an abstract idea of dignity? How can we fundamentally strengthen dignity so that we do not focus on it in a deficit-oriented way only when the sense of dignity is threatened?Looking at the concept of dignity in the health care system can be done from two angles: First, we can direct our gaze to abuses, violations of dignity, and rightly become outraged about it. Moreover, we have gained collective experience of dignity violations through the Covid-19 pandemic and continue to experience this. The second focus is on enhancing the dignity, dignified, and dignity-oriented aspirations of people working in the health care system. The following article is intentionally devoted to this second view, opening up possibilities for dignity-strengthening care in the health care system. In doing so, we draw substantially on the research and interventions developed by Harvey M. Chochinov and his research team from Canada. The article offers an overview of theoretical foundations, food for thought for self-reflection, and action aids for practical application.


Are both color-flow duplex scanning and cerebral arteriography required prior to carotid endarterectomy?
In an attempt to eliminate the morbidity, mortality, and cost associated with arteriography, surgeons are relying increasingly on duplex scanning of the extracranial arteries as the primary preoperative evaluation prior to carotid endarterectomy (CEA). This study was initiated to evaluate the need for cerebral arteriography in the preoperative evaluation of patients for CEA. One hundred five patients undergoing 114 CEA procedures are included in a retrospective review to determine whether the addition of cerebral arteriography changed the operative management of these patients. In 58 of 105 patients (55%), color-flow duplex scanning and cerebral arteriography were performed in the workup prior to CEA. In four patients a discrepancy was found between the duplex results and the arteriogram, leading to a change in the operative approach in two. The remaining 47 patients (45%) underwent color-flow duplex scanning as the definitive preoperative study; the surgical management was altered because of the operative findings in one patient. Although color-flow duplex scanning does not provide absolute concordance with cerebral arteriography, in most instances it can be used as the definitive preoperative study prior to CEA. We define the indications for cerebral arteriography in patients undergoing CEA.


The Allen test--an investigation of its accuracy by fluorescein angiography.
Six consecutive patients whose clinical Allen test suggested a non-patent radial artery have been investigated by intra-arterial fluorescein angiography. Cannulation of the radial artery and injection of fluorescein typically perfused only the thumb and thenar eminence. Occlusion of the ulnar artery, leaving the radial artery as the dominant supply, resulted in fluorescein perfusion of the entire hand. It is concluded that the Allen test is of no clinical value.


Purification of human T and B cells by a discontinuous density gradient of percoll.
A simple technique for isolating human peripheral B and T cells is described. This method is based on the different mobility of cells in a discontinuous density gradient of Percoll. A population with a mean of 72.8% of surface stable Ig (B cells) is found in the top layer (fraction I) whereas T cells with less than 3% of Ig are distributed in the two lower layers (fractions II and III). B cells obtained by this method were highly viable and reacted strongly with anti-DRw specific sera, whereas T cells did not respond. The clear-cut difference between positive and negative reactions makes this technique very suitable for DRw typing. The proliferative response to PHA is decreased in fractions I and III while greatly increased in fraction II. The different mitogenic responses in the two fractions containing T cells probably represent two functionally distinct T cell subsets. Cells from all fractions are less activated than unseparated cells when Con A and PWM are used as mitogen. The technique is very rapid, avoids the interaction of cells with their specific receptors and gives both T and B cells in one step, all advantages over other methods commonly used.


Methadone-related deaths. A ten year overview.
Over the last 10 years we have registered in our district (about 500,000 inhabitants) 36 cases of fatal methadone poisoning, involving both patients on treatment and naive subjects: this is a significant increase of deaths due to methadone use, misuse or abuse compared with previous years. Twenty-four patients (66.7%) were on methadone maintenance programs for heroin detoxification, while 12 (33.3%) were taking the drug without a medical prescription. The average blood concentration of methadone in patients undergoing a maintenance program was 1.06 mg/L (0.21-3.37 mg/L), against 0.79 mg/L (0.2-3.15 mg/L) in those taking the non-prescribed drug. Since 111 heroin-related deaths were recorded in our district in the same period, the fact that there appear to be many methadone deaths (about a third of heroin-related deaths) cannot be overlooked. The aim of this work is to understand the possible reasons for such a large number of methadone-related deaths. On this subject, we have noticed that risks associated with methadone intake are often underestimated by clinicians prescribing the drug: sometimes methadone is prescribed without taking into account patient's tolerance to opiates, and a large number of subjects enrolled in methadone maintenance programs in Italy, have also been given take-home doses, thus increasing the risk of abuse and diversion.


Psychopathological profile and sagittal alignment in low-back pain.
Low-back pain requires comprehensive care using a biopsychosocial model. The psychologic dimension plays an important role, but the link between sagittal alignment and a given psychopathological profile is little studied. The aim of this study was to analyze the psychopathological profiles and sagittal parameters of a population with low-back pain and to assess the link. 205 patients, with a mean age of 49.6 years (range, 18-70 years), presenting chronic common low-back pain without radicular involvement, were included prospectively. Mood scores comprised: the self-administered "Hospital Anxiety and Depression Scale" (HAD), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D) and Young Mania Rating Scale (YMRS). Radiological parameters, measured on lateral full-spine radiographs, included: L1-S1 lordosis, T1-T12 kyphosis, pelvic incidence, pelvic tilt, sacral slope, sagittal vertical axis (SVA), T1 slope, and Roussouly type. Mean HAM-A score was 16.1; 54% of patients had scores ≥14, indicating anxiety disorder. Mean HAM-D score was 10.8; 55% of patients had scores ≥10, indicating depressive disorder. Mean YMRS score was 2.6; only 1 patient had a score ≥20, indicating manic disorder. The 112 patients with HAM-A score >14 showed mean 51.6° L1-S1 lordosis (p=0.356), 48.3° T1-T12 kyphosis (p=0.590), -4.3mm C7 SVA (p=0.900), and 29.3° T1 slope (p=0.451). In case of HAM-A <14, there were no significant differences. The 113 patients with HAM-D score >10 showed significant differences in T1-T12 kyphosis (mean 49.0°; p<0.05) and T1 slope (30.2°; p<0.05); mean L1-S1 lordosis was 50.5° (p=0.861) and C7 SVA 1.6mm (p=0.462). In case of HAM-D <10, T1-T12 kyphosis was 45.5° (p<0.05) and T1 slope 26.2° (p<0.05); mean lordosis was 50.9° (p=0.861) and mean C7 SVA -7.1mm (p=0.259). Multivariate analysis found no significant link between Roussouly type and psychiatric scores: HAD (p=0.715), HAM-A (p=0.652), and HAM-D (p=0.902). More than 50% of patients with common low-back pain presented a mood disorder. Depressive disorder was associated with greater T1-T12 kyphosis and T1 slope. There was no relationship between psychiatric scores and overall sagittal alignment. II.


Neuromuscular conditions associated with malignant hyperthermia in paediatric patients: A 25-year retrospective study.
Malignant Hyperthermia (MH) is a rare pharmacogenetic syndrome that can be fatal and the risk of MH in non RYR1-related disorders is unknown. We conducted a retrospective study to determine the prevalence of neuromuscular disorders among patients with MH at our centre. Patients who were admitted to the Hospital for Sick Children during the study period of January 1, 1990 to April 1, 2015 with a CK level > 8000 IU/L, or who received dantrolene, or who had a clinical diagnosis of MH were included. Medical records of 166 patients who met the inclusion criteria were reviewed and 13 patients were identified with MH-like reactions. Nine patients were classified as having true MH after review of the anaesthesia record and genetic testing results were available for 7 patients, 5 of whom had mutations in RYR1. Of the four patients who had severe reactions to anaesthesia but did not meet the criteria for true MH, two had Duchenne muscular dystrophy (DMD). In this retrospective study over 25 years, RYR1 mutations were the most common cause of MH in our cohort, and of these, one third had an underlying neuromuscular diagnosis. Genetic testing of RYR1 is indicated for all patients with MH, and anaesthetic precautions should be considered for any child with symptoms of neuromuscular disease.


The risk of malignant melanoma, internal malignancy and mortality in xeroderma pigmentosum patients.
Mortality and malignancy were studied in a series of 32 patients with xeroderma pigmentosum presenting during the period 1950-84. Twenty-nine of the patients were followed to the end of 1984 using the National Health Service Central Register, and hospital case records and correspondence with referring physicians; three patients had incomplete follow-up. Three of the patients developed malignant melanoma during follow-up, but none developed internal malignancy. Two males and one female died [standardized mortality ratio (SMR) = 971, P less than 0.05, for males; SMR = 1931, not significant, for females]. All three deaths were from non-malignant causes: severe neurological involvement with terminal infection. This high mortality from neurological complications in xeroderma pigmentosum patients contrasts with previously reported mortality, particularly from actinic-induced cutaneous tumours.


Challenges and strategies in developing nursing research capacity: a review of the literature.
This paper reports the findings of a critical overview of the development of nursing research capacity in academic departments. It examines the major barriers to developing research capacity, the capacity building strategies adopted (or proposed) within the literature, and considers the wider context within which such endeavours take place. The literature review forms part of a longitudinal project utilising case study methodology. A key word search was used to locate relevant journal articles for the period 1999-2004, derived from the project's research question and an earlier literature review. A number of manual 'shelf searches' were conducted. Bibliographic data were retrieved from The Cumulative Index of Nursing and Allied Health literature, The Social Science Citation Index, and Medline. Approximately 150 articles were retrieved, of which 47 were included in the study. Given the paucity of work in this area papers were not excluded on the grounds of methodological weakness. Major themes were identified in each paper and an analytical framework was developed. Two main challenges affecting research capacity development were identified-material constraints and organisational contexts, and the changing roles and expectations of nurse educators. The importance of developing an overall strategic approach, clearly communicated, and accompanied by effective leadership was a point of common agreement. Debate existed on how research support should be managed, particularly the merits of inclusivity and the reconcilement of individual and organisational needs. Specific capacity strategies identified in the literature were the creation of infrastructures, the fostering of research cultures and environments, and the facilitation of training and collaboration. The literature offers many examples of capacity building strategies. However, more empirical studies are needed to understand the situated process of implementing and evaluating capacity building in individual academic departments, and how this process differs between geographical settings.


VPA inhibits breast cancer cell migration by specifically targeting HDAC2 and down-regulating Survivin.
Cell migration plays major roles in human breast cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers including breast cancer. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human breast cancer MDA-MB-231 cells. Mechanistic studies found that VPA significantly inhibited the expression of Survivin. Knockdown of Survivin could obviously inhibited cell migration, while over-expression of Survivin markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on Survivin and cell migration, and over-expression of Survivin could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that HDAC2 may be the specific target of VPA in breast cancer cells, and specific inhibition of HDAC2, especially by small molecular chemicals may lead to less side-effects and provide a better strategy than VPA application for human breast cancer treatment.


"I have never talked to anyone to free my mind" - challenges surrounding status disclosure to adolescents contribute to their disengagement from HIV care: a qualitative study in western Kenya.
Adolescents living with HIV (ALHIV, ages 10-19) experience complex barriers to care engagement. Challenges surrounding HIV status disclosure or non-disclosure to adolescents may contribute to adolescent disengagement from HIV care or non-adherence to ART. We performed a qualitative study to investigate the contribution of disclosure challenges to adolescent disengagement from HIV care. This was a qualitative study performed with disengaged ALHIV and their caregivers, and with healthcare workers (HCW) in the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya. Inclusion criteria for ALHIV were ≥1 visit within the 18 months prior to data collection at one of two clinical sites and nonattendance ≥60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Analysis was conducted by multiple independent coders, and narratives of disclosure and care disengagement were closely interrogated. Overarching themes were elucidated and summarized. Interviews were conducted with 42 disengaged ALHIV, 32 caregivers, and 28 HCW. ALHIV were average age 17.0 (range 12.9-20.9), and 95% indicated awareness of their HIV diagnosis. Issues surrounding disclosure to ALHIV presented important barriers to HIV care engagement. Themes centered on delays in HIV status disclosure; hesitancy and reluctance among caregivers to disclose; struggles for adolescents to cope with feelings of having been deceived prior to full disclosure; pervasive HIV stigma internalized in school and community settings prior to disclosure; and inadequate and unstructured support after disclosure, including for adolescent mental health burdens and for adolescent-caregiver relationships and communication. Both HCW and caregivers described feeling inadequately prepared to optimally handle disclosure and to manage challenges that may arise after disclosure. Complex challenges surrounding HIV status disclosure to adolescents contribute to care disengagement. There is need to enhance training and resources for HCW, and to empower caregivers to support children and adolescents before, during, and after HIV status disclosure. This should include counseling caregivers on how to provide children with developmentally-appropriate and accurate information about their health from an early age, and to support adolescent-caregiver communication and relationships. Optimally integrating peer support can further promote ALHIV wellbeing and retention in care.


Arch Height Index, Arch Rigidity Index, and Arch Stiffness Values in a Symptomatic Population.
Studies of arch height index (AHI), arch rigidity index (ARI), and arch stiffness have primarily focused on healthy populations. Normative values of the aforementioned measurements in a pathologic sample may be useful in identifying relationships between arch structure and pathology. AHI was obtained bilaterally at 10% and 90% weightbearing conditions using the AHI measurement system. ARI and arch stiffness were calculated using AHI measurements. Dependent t tests compared right and left, dominant and nondominant, and injured and noninjured limbs. Dominant feet were compared between sexes using independent t tests. Relationships between arch stiffness and subcategories were examined using the coefficient of determination (R2). One-way analyses of variance determined differences between arch structure and number of pathologies or body mass index (BMI). A total of 110 participants reported one (n = 55), two (n = 38), or three or more (n = 17) pathologies. Plantar fasciitis (n = 31) and hallux valgus (n = 28) were the most common. AHI, ARI, and arch stiffness did not differ between limbs or sexes for any comparisons. Between subgroups of BMI and number of pathologies, BMI influenced AHI (10% weightbearing) and arch stiffness (P < .05). Arch stiffness showed a weak relationship to AHI, where a higher AHI was associated with a stiffer arch (R2 = 0.06). Normative arch structure values were established in a pathologic sample with a large incidence of plantar fasciitis and hallux valgus. Understanding relationships between arch structure and pathology is helpful for clinicians and researchers.


5-Cyano substituted diarylpyridines as potent HIV-1 NNRTIs: Rational design, synthesis, and activity evaluation.
To develop more potent HIV-1 inhibitors against a variety of NNRTIs-resistant strains, a series of 5-cyano substituted diarylpyridines was designed based on the cocrystal structural analysis. Among them, I-5b showed the greatest potency (EC50 = 5.62-171 nM) against the wild-type (WT) and mutant HIV-1 strains. Especially for K103 N, I-5b exhibited outstanding activity with EC50 values of 9.37 nM, being much superior to that of NVP (EC50 = 5128 nM) and EFV (EC50 = 114 nM) and comparable to that of ETR (EC50 = 3.45 nM). In addition, the target of all compounds was turned out to be HIV-1 RT with moderate RT enzyme inhibitory activity (IC50 = 0.094-12.0 μM). Moreover, the binding mode of representative compounds with RT was elaborated via molecular docking.


Clear cell sarcoma of kidney: morphoproteomic analysis reveals genomic correlates and therapeutic options.
We used the morphoproteomic approach to analyze clear cell sarcoma of kidney (CCSK), a rare pediatric renal tumor, for which the exact pathogenesis and reliable diagnostic markers remain inexplicable. The tumor, currently being treated with chemotherapy and radiation therapy before or after radical nephrectomy, has demonstrated improved survival rates after introduction of doxorubicin. Three cases of CCSK were studied. We attempted to decipher the possible pathological mechanisms involved in CCSK and to explore the therapeutic targets and plausible less-toxic chemotherapeutic agents. We propose that cyclin D1 may be a central molecule in the pathogenesis of CCSK, driven mainly by the sonic hedgehog and the nuclear factor-kappa B pathways and secondarily by the mammalian target of rapamycin complex mTORC2/PI3K/Akt pathway, heat shock protein 90, and possibly phospholipase D1. Inclusion of relatively less toxic but effective therapies in the form of statins, 13-cis retinoic acid, curcumin, and 17-AAG in the combinatorial treatment strategies, which can target the involved subcellular pathways, may be considered.


Research on health risk assessment of heavy metals in soil based on multi-factor source apportionment: A case study in Guangdong Province, China.
Environmental problems caused by heavy metal pollution in soil have attracted widespread attention worldwide. Identifying and quantifying the heavy metal pollution sources and risks is crucial for subsequent soil management. In this study, an integrated source-risk method for source apportionment and risk assessment based on the PMF model, the geodetector model and the health risk assessment model (HRA) was proposed and applied. Analysis of Hg, As, Pb, Cd, Cu, Ni, Cr, and Zn in 208 topsoils showed that the average contents of eight heavy metals were 1.87-5.86 times greater than corresponding background values, among which Cd and As were relatively high, which were higher than the specified soil risk screening values, high-value areas of heavy metals are mainly concentrated in the central part of the study area. The source apportionment showed that the accumulation of heavy metals was affected by five sources: atmospheric deposition (16.3 %), natural sources (33.1 %), industrial activities dominated by metal mining (15.1 %), industrial activities dominated by metal smelting (12.6 %) and traffic sources (22.9 %). The results of the health risk assessment showed that the carcinogenic risks (adult: 4.74E-05, children: 7.41E-05) of heavy metals in soil to the study population were both acceptable, the non-carcinogenic risk of adult (THI = 0.277) was within the limit, while the non-carcinogenic risk of children (THI = 1.70) was higher than the limit value. Ingestion (89.5 %-95.9 %) contributed the greatest health risk among all exposure routes. Source 3 (arsenic-related industrial activities dominated by metal mining) contributed the most to the HI and CRI of adults and children (all above 50 %), therefore, in the formulation stage of soil management strategy in this area, priority should be given to the control and management of this pollution source. These results can provide more detailed support for environmental protection departments to propose targeted soil pollution control measures.


Seroconversion of calves following intravenous injection with embryos exposed to bovine viral diarrhea virus (BVDV) in vitro.
Two recent studies demonstrated that a high-affinity isolate of BVDV (SD-1), remained associated with a small percentage of in vivo-derived bovine embryos following artificial exposure to the virus and either washing or trypsin treatment. Further, the embryo-associated virus was infective in an in vitro environment. Therefore, the objective of this study was to determine if the quantity of a high-affinity isolate of BVDV associated with single-washed or trypsin-treated embryos could cause infection in vivo. Twenty zona-pellucida-intact morulae and blastocysts (MB) were collected on day 7 from superovulated cows. After collection, all MB were washed according to International Embryo Transfer Society (IETS) standards, and all but 4 MB (negative controls) were exposed for 2 h to 10(5)-10(6) cell culture infective doses (50% endpoint) per milliliter (CCID(50)/mL) of viral strain SD-1. Following exposure, according to IETS standards, one half of the MB were washed and one half were trypsin treated. All MB were then individually sonicated, and sonicate fluids were injected intravenously into calves on day 0. Blood was drawn to monitor for viremia and(or) seroconversion. Seroconversion of calves injected with sonicate fluids from washed and trypsin-treated embryos occurred 38% and 13% of the time, respectively. Therefore, the quantity of a high-affinity isolate of BVDV associated with single-washed or trypsin-treated embryos was infective in vivo.


Utility of point-of-care diagnostic testing in patients with chest pain and suspected acute myocardial infarction.
Advances over the past few years have led to the use of hand-held point-of-care diagnostic tests to expedite testing for cardiac enzymes indicative of acute myocardial infarction. Although cardiac enzymes such as troponin I and CKMB are reliable markers of acute myocardial infarction, they cannot be detected until several hours after the insult and patients are often tested for up to 24 hours before acute myocardial infarction can be ruled out. A better understanding of early events in thrombus formation, specifically the role of P-selectin in platelet aggregation, should soon allow even more rapid diagnosis and improve pharmacological treatment. In addition, early ruling-out of patients with non-cardiac chest pain would reduce unnecessary hospital admissions and associated healthcare costs.


DNA-PKcs kinase activity orchestrates both end-processing and end-ligation.
Recent structural studies have revealed the atomic details of how the DNA-PKcs kinase protects DNA ends, recruits and activates Artemis endonuclease for end-processing, and phosphorylates itself for end-ligation, revealing the molecular details from end-processing to end-ligation, two critical phases of the non-homologous end-joining (NHEJ) DNA-double strand break repair pathway.


Monoclonal antibody against diphtheria toxin. Effect on toxin binding and entry into cells.
A number of monoclonal antibodies against diphtheria toxin were isolated. Some of their properties were determined. Antibody 2 reacts with the region of between 30 and 45 kDa from the NH2 terminus of toxin. Antibody 7 reacts with the COOH-terminal 17-kDa region of toxin. These two antibodies show sharp contrasts in their effects on toxin action in cultured cells. When antibody 2 or 7 and toxin were mixed, incubated at 37 degrees C, and then added to sensitive Vero cells, antibody 7 blocked toxin action, but antibody 2 did not. When antibody 2 or 7 was added to cells to which toxin had been prebound at 4 degrees C, and the cells were then shifted to 37 degrees C, antibody 7 did not block toxin action, but antibody 2 inhibited intoxication. Antibody 7 blocked binding of 125I-toxin to cells and did not block degradation of toxin associated with cells. Antibody 2 did not block binding of 125I-toxin to cells, and was able to bind to cells in the presence of toxin. The results obtained from the effect of antibody 2 on degradation of 125I-toxin associated with cells resemble those seen with amines, which block toxin action but do not inhibit binding of toxin to cells. These facts show that antibody 2 does not block binding of toxin to cell surfaces, but blocks the entry of toxin into the cytosol at a step after binding of toxin to the receptor. Antibodies 14 and 15 react with fragment A of diphtheria toxin, but have no effect on any activity of toxin. The other monoclonal antibodies have effects on toxin binding and entry intermediate between those of 2 and 7.


Brain inflammation and hypertension: the chicken or the egg?
Inflammation of forebrain and hindbrain nuclei controlling the sympathetic nervous system (SNS) outflow from the brain to the periphery represents an emerging concept of the pathogenesis of neurogenic hypertension. Angiotensin II (Ang-II) and prorenin were shown to increase production of reactive oxygen species and pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)) while simultaneously decreasing production of interleukin-10 (IL-10) in the paraventricular nucleus of the hypothalamus and the rostral ventral lateral medulla. Peripheral chronic inflammation and Ang-II activity seem to share a common central mechanism contributing to an increase in sympathetic neurogenic vasomotor tone and entailing neurogenic hypertension. Both hypertension and obesity facilitate the penetration of peripheral immune cells in the brain parenchyma. We suggest that renin-angiotensin-driven hypertension encompasses feedback and feedforward mechanisms in the development of neurogenic hypertension while low-intensity, chronic peripheral inflammation of any origin may serve as a model of a feedforward mechanism in this condition.


Identification of a BRCA2 mutation in a Turkish family with early-onset breast cancer.
We used a multi-gene panel testing to identify the germline variants in a mother-daughter pair with early-onset breast cancer, and detected one pathogenic protein-truncating variant in BRCA2. Our results highlight the importance of genetic testing in identifying the pathogenic mutation running in cancer families.


Quantifying the cleanliness of glass capillaries.
I used capillary rise methods to investigate the lumenal surface properties of quartz (fused silica, Amersil T-08), borosilicate (Corning 7800), and high-lead glass (Corning 0010) capillaries commonly used to make patch pipets. I calculated the capillary rise and contact angle for water and methanol from weight measurements. The capillary rise was compared with the theoretical maximum value calculated by assuming each fluid perfectly wetted the lumenal surface of the glass (i.e., zero contact angle, which reflects the absence of surface contamination). For borosilicate, high-lead, and quartz capillaries, the rise for water was substantially less than the theoretical maximum rise. Exposure of the borosilicate, lead, and quartz capillaries to several cleaning methods resulted in substantially better--but not perfect--agreement between the theoretical maximum rise and calculated capillary rise. By contrast, the capillary rise for methanol was almost identical in untreated and cleaned capillaries, but less than its theoretical maximum rise. The residual discrepancy between the observed and theoretical rise for water could not be improved on by trying a variety of cleaning procedures, but some cleaning methods were superior to others. The water solubility of the surface contaminants, deduced from the effectiveness of repeated rinsing, was different for each of the three types of capillaries examined: Corning 7800 > quartz > Corning 0010. A surface film was also detected in quatz tubing with an internal filament. I conclude that these borosilicate, quartz, and high-lead glass capillaries have a film on the lumenal surface, which can be removed using appropriate cleaning methods. The surface contaminants may be unique to each type of capillary and may also be hydrophobic. Two simple methods are presented to quantitate the cleanliness of glass capillary tubing commonly used to make pipets for studies of biological membranes. It is not known if the surface film is of importance in electrophysiological studies of biological membranes.


Improvement of the nutritive value of rye for broiler chickens by gamma irradiation-induced viscosity reduction.
A study was undertaken with chickens to determine the effect of irradiation treatment on the viscosity-inducing properties of polysaccharide components of rye. Three-week body weight, food utilisation, fat retention, and bone ash of chicks were substantially improved by irradiating rye (0 to 10 Mrad) and were maximal at 6 Mrad. Irradiation of the entire diet resulted in no further improvement over irradiating the rye fraction alone. The improved performance coincided with radiation-induced damage to rye polysaccharides, as indicated by reduced viscosity and increased concentrations of reducing sugars.


Expert Characteristics: Implications for Expert Systems.
While expert systems are artificial intelligence (AI) agents, they share many common characteristics with human experts. As technology progresses, such systems are not just able to make simple decisions following "simplistic" linear logical protocols; they "behave" as real experts in at least two ways: by demonstrating superb decision-making skills and by conforming to the social norms for expertise, i.e., they "feel" as human experts. A review of the common characteristics of human experts may have important implications for the direction of the development for such systems. Implications for bioinformatics and future research (especially concerning the accompanying concept of "expert generalist") are also discussed.


C9orf72 poly(PR) aggregation in nucleus induces ALS/FTD-related neurodegeneration in cynomolgus monkeys.
Poly(PR) is a dipeptide repeat protein comprising proline and arginine residues. It is one of the translational product of expanded G4C2 repeats in the C9orf72 gene, and its accumulation is contributing to the neuropathogenesis of C9orf72-associated amyotrophic lateral sclerosis and/or frontotemporal dementia (C9-ALS/FTD). In this study, we demonstrate that poly(PR) protein alone is sufficient to induce neurodegeneration related to ALS/FTD in cynomolgus monkeys. By delivering poly(PR) via AAV, we observed that the PR proteins were located within the nucleus of infected cells. The expression of (PR)50 protein, consisting of 50 PR repeats, led to increased loss of cortical neurons, cytoplasmic lipofuscin, and gliosis in the brain, as well as demyelination and loss of ChAT positive neurons in the spinal cord of monkeys. While, these pathologies were not observed in monkeys expressing (PR)5, a protein comprising only 5 PR repeats. Furthermore, the (PR)50-expressing monkeys exhibited progressive motor deficits, cognitive impairment, muscle atrophy, and abnormal electromyography (EMG) potentials, which closely resemble clinical symptoms seen in C9-ALS/FTD patients. By longitudinally tracking these monkeys, we found that changes in cystatin C and chitinase-1 (CHIT1) levels in the cerebrospinal fluid (CSF) corresponded to the phenotypic progression of (PR)50-induced disease. Proteomic analysis revealed that the major clusters of dysregulated proteins were nuclear-localized, and downregulation of the MECP2 protein was implicated in the toxic process of poly(PR). This research indicates that poly(PR) expression alone induces neurodegeneration and core phenotypes associated with C9-ALS/FTD in monkeys, which may provide insights into the mechanisms of disease pathogenesis.


Characterization of pyridine nucleotide binding site of UDP-glucose 4-epimerase from Saccharomyces fragilis.
UDP-glucose 4-epimerase from Saccharomyces fragilis has 1 mol of NAD firmly bound per mol of the dimeric apoenzyme. This prevents a direct study of the coenzyme binding site of the protein. Dissociation of the dimer with p-chloromercuribenzoate and its reconstitution with exogenous NAD or one of its analogues and 2-mercaptoethanol provides an indirect method of study of the site. Depending on the reconstitution properties, the analogues can be classified in the following groups: (i) analogues that have no affinity for the site; (ii) analogues that have affinity but are not incorporated into the apoenzyme; (iii) analogues that produce catalytically inactive holoenzymes; and (iv) analogues that produce catalytically active holoenzymes. Minimum structural requirements that lead to affinity for the coenzyme site and to binding to the apoenzyme can also be discerned from these studies. Reconstitution with etheno-NAD, a fluorescent analogue of NAD, indicates the presence of a hydrophobic pocket for the adenosine subsite.


Severe combined immunodeficiency syndrome, tissue transplant, leukaemia, and Q fever.
A child born with severe combined immunodeficiency, who was immunoreconstituted by a fetal liver and thymus transplant, developed acute lymphoblastic leukaemia in the donor cell line. During remission she contracted acute Q fever, which gave rise to unexpected complications. Early treatment of the Q fever might have altered the subsequent events and prevented her death.


Ocular hypotony after laser suture lysis following trabeculectomy with mitomycin C.
To report our experience with laser suture lysis (LSL) following trabeculectomy with mitomycin C, its timing, effectiveness and related complications. We retrospectively examined 38 consecutive eyes of 36 patients that underwent LSL following trabeculectomy with mitomycin C. The mean preLSL intraocular pressure (IOP) was 27.0 mm Hg (SD 6.3, range 16-39 mm Hg) and the postLSL IOP (IOP 1 h after the last session of LSL) was 16.0 mm Hg (SD 7.2, range 3-31 mm Hg). Following the LSL in 7 eyes (7 of 38) hypotony (IOP<6 mm Hg, lasting more than 24 h) developed. Two groups were defined. In group I no hypotony was found after LSL and group II went through a period of hypotony. The time interval between surgery and LSL was significantly shorter in group II (mean 5.7, SD 7.5, range 1-19 days), compared to group I ( mean 14.7, SD 13.0, range 1-44 days) (p=0.041). The mean final IOP (IOP measured at the last visit) was 13.3 mm Hg (SD 3.4, range 6-20 mm Hg) and mean follow-up was 6.1 months (SD 3.9, range 2.0-15.2 months). No hypotony was found at final examination. PostLSL IOP and final IOP were significantly lower in group II (p=0.002 and p=0.024 respectively). IOP reduction by LSL was significantly greater in group II (p=0.046). LSL is an effective and safe procedure to lower the IOP following trabeculectomy with mitomycin C. Early application of LSL results in lower final IOPs, but has a higher risk of hypotony.


Relation between the degree of procedural anticoagulation and complications after coronary stent implantation.
The impact of the degree of anticoagulation in patients who underwent stent implantation without glycoprotein IIb/IIIa inhibitors was examined in 1,020 patients. High levels of procedural anticoagulation with heparin were found to increase hemorrhagic complications without improving clinical or angiographic outcomes.


MCMV exploits the spleen as a transfer hub for systemic dissemination upon oronasal inoculation.
Murine cytomegalovirus (MCMV) infection in mice is a commonly used animal model for studying human cytomegalovirus (HCMV) infections. In our previous studies, a mouse model based on an oronasal MCMV infection was set up for mimicking a natural infection, and the spleen was hypothesized to regulate viremia and virus dissemination to distal organs such as submandibular glands. Here, the role of the spleen during an MCMV infection was investigated by the comparison of intact and splenectomized Balb/c mice. Both highly passaged MCMV Smith and low passaged MCMV HaNa1 were used. Various samples were collected at 7, 14, and 21 days post inoculation (dpi) for analyses by virus isolation/titration, co-cultivation and qPCR. The results showed that for both virus strains, 1) cell-associated virus in PBMC (determined by co-cultivation) was detected in intact mice but not in splenectomized mice; 2) the mean viral DNA load in PBMC of splenectomized mice was 4.4-(HaNa1)/2.7-(Smith) fold lower at the peak viremia (7dpi) in contrast to that of intact mice; and 3) infectious virus in the submandibular glands was detected later in splenectomized mice (14dpi) than in intact mice (7dpi). Moreover, the average virus titers in submandibular glands of splenectomized mice were 10-(HaNa1)/7.9-(Smith) fold lower at 14dpi and 1.7-(HaNa1)/2.1-(Smith) fold lower at 21dpi compared with that of intact mice. Upon inoculation with MCMV Smith, infectious virus was found in the kidneys and liver of intact mice, but not in splenectomized mice. Taken together, all these data clearly demonstrate that virus dissemination to distant organs is reduced in splenectomized mice, further confirming the importance of the spleen as a viremia booming site for a natural MCMV infection.


Neurochemistry of myenteric plexus neurons of bank vole (Myodes glareolus) ileum.
The neurochemistry of enteric neurons differs among species of small laboratory rodents (guinea-pig, mouse, rat). In this study we characterized the phenotype of ileal myenteric plexus (MP) neuronal cells and fibers of the bank vole (Myodes glareolus), a common rodent living in Europe and in Northern Asia which is also employed in prion experimental transmission studies. Six neuronal markers were tested: choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), calbindin (CALB), calcitonin gene-related peptide (CGRP) and substance P (SP), along with HuC/D as a pan-neuronal marker. Neurons expressing ChAT- and nNOS-immunoreactivity (IR) were 36 ± 12% and 24 ± 5%, respectively. Those expressing CGRP-, SP- and CALB-IR were 3 ± 3%, 21 ± 5% and 6 ± 2%, respectively. Therefore, bank vole MPs differ consistently from murine MPs in neurons expressing CGRP-, SP- and CALB-IR. These data may contribute to define the prion susceptibility of neuron cell populations residing within ileal MPs from bank voles, along with their morpho-functional alterations following oral experimental prion challenge.


[New endovascular biological approaches to the treatment of arterial restenoses (review of literature)].
This review analyzes the reported data on the most pressing problem of modern interventional radiology, namely the problem of restenoses after angioplasty and of the possibilities of their treatment. Reverberates the basic methods for the treatment of restenosis based on biological approaches. Describes the principles and mechanisms of the medical action of intravascular sonotherapy, cryotherapy, photoangioplasty , and soft rays. Presents the results of the multi-center clinical trials which have demonstrated that the methods based on biological approaches are effective and promising.


[Changes in the hand in Ehlers-Danlos syndrome type IV].
The authors report a lethal course of Ehlers-Danlos syndrome type IV. In this patient hypermobility of the finger joints had been seen. The patho-biochemical structure of fibrous tissue is discussed.


Comparison of bone marrow dosimetry and toxic effect of high dose 131I-labeled monoclonal antibodies administered to man.
131I-labeled monoclonal antibodies were used in therapeutic trials in two potentially useful clinical situations: disseminated melanoma (intravenously administered Fab fragments; 21 patients) and disseminated peritoneal adenocarcinomatosis (intraperitoneal injection of IgG; 5 patients). Acute toxicity observed is consistent with mild bone marrow suppression of acute radiation syndrome and the observed toxicity is dose related in a manner that conforms to the expected human response to total body irradiation. For single doses of both i.p. administered and intravenously administered 131I-labeled anti-tumor antibodies, 100 rad to red marrow, calculated by the absorbed dose fraction method (MIRD), appeared to be a threshold below which significant acute toxicity was unlikely.


Signature of nonadiabatic transitions on the pump-probe infrared spectra of a hydrogen-bonded complex dissolved in a polar solvent: a computational study.
The mixed quantum-classical Liouville equation provides a unified and self-consistent platform for modeling the spectral signatures of nonequilibrium solvation dynamics, non-Condon effects, and nonadiabatic transitions. These features are demonstrated in this paper in the context of the pump-probe infrared spectra of the hydrogen stretch in a moderately strong hydrogen-bonded complex dissolved in a polar solvent. Particular emphasis is put on incorporating nonadiabatic transitions and accounting for their unique spectral signature.


Tumor necrosis factor-alpha in peripical tissue exudates of teeth with apical periodontitis.
The aim of this study was to determine tumor necrosis factor-alpha (TNF-alpha) levels in periapical exudates and to evaluate their relationship with radiological findings. Periapical exudates were collected from root canals of 60 single-rooted teeth using absorbent paper points. TNF-alpha levels were determined by enzyme-linked immunosorbent assays. The samples were divided into three groups according to the periapical radiolucent area. Nonparametric Kruskal-Wallis test revealed significant differences between TNF-alpha concentrations in control group (40, 57+/-28, 15 pg/mL) and group with larger radiolucent areas (2365, 79+/-582, 95 pg/mL), as well as between control and canals with small radiolucent areas (507, 66+/-278, 97) (P<.05). The levels of TNF-alpha increase significantly in teeth with periapical pathosis, from smaller to bigger lesions. This research and its results have shown that objective analysis of the TNF-alpha levels enables establishment of a relationship between different concentrations of TNF-alpha and different radiological changes.


Improved Cr (VI) adsorption performance in wastewater and groundwater by synthesized magnetic adsorbent derived from Fe3O4 loaded corn straw biochar.
This work developed an easy method to utilize corn straw (CS) waste for sustainable development and reduce the volume of waste volume as well as bring value-added. The magnetic adsorbent was prepared by loading Fe3O4 onto biochar derived from corn straw (Fe@CSBC), then used for capturing Cr (VI) in groundwater and wastewater samples. The characterization of adsorbents showed that Fe3O4 was successfully loaded on corn straw biochar (CSBC) and contributed to the improvement of the surface area, and surface functional groups like Fe-O, Fe-OOH, CO, and O-H. The presence of iron oxide was further confirmed by XPS and XRD analysis and a magnetization value of 35.6 emu/g was obtained for Fe@CSBC. The highest uptake capacity of Cr (VI) onto Fe@CSBC and CSBC by monolayer were 138.8 and 90.6 mg/g, respectively. By applying magnetic adsorbent Fe@CSBC for the treatment of groundwater and wastewater samples, the chromium could be removed up to 90.3 and 72.6%, respectively. The remaining efficiency of Cr (VI) was found to be 84.5% after four times reused Fe@CSBC, demonstrating the great recyclable ability of the adsorbent. In addition, several interactions between Cr (VI) and Fe@CSBC like ion exchange, complexation, and reduction reaction were discussed in the proposed adsorption mechanism. This study brings an efficient method to turn corn straw biomass into an effective magnetic adsorbent with high adsorption performance and good reusability of Cr (VI) in groundwater as well as in wastewater.


Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm.
The mechanisms of brain tissue damage in stroke are strongly linked to the phenomenon of excitotoxicity, which is defined as damage or death of neural cells due to excessive activation of receptors for the excitatory neurotransmitters glutamate and aspartate. Under physiological conditions, ionotropic glutamate receptors mediate the processes of excitatory neurotransmission and synaptic plasticity. In ischemia, sustained pathological release of glutamate from neurons and glial cells causes prolonged activation of these receptors, resulting in massive depolarization and cytoplasmic Ca(2+) overload. High cytoplasmic levels of Ca(2+) activate many degradative processes that, depending on the metabolic status, cause immediate or delayed death of neural cells. This traditional view has been expanded by a number of observations that implicate Cl(-) channels and several types of non-channel transporter proteins, such as the Na(+),K(+),2Cl(-) cotransporter, Na(+)/H(+) exchanger, and Na(+)/Ca(2+) exchanger, in the development of glutamate toxicity. Some of these ion transporters increase tissue damage by promoting pathological cell swelling and necrotic cell death, while others contribute to a long-term accumulation of cytoplasmic Ca(2+). This brief review is aimed at illustrating how the dysregulation of various ion transport processes combine in a 'perfect storm' that disrupts neural ionic homeostasis and culminates in the irreversible damage and death of neural cells. The clinical relevance of individual transporters as targets for therapeutic intervention in stroke is also briefly discussed.


Enhanced mortality of rat pups following inductions of epileptic seizures after perinatal exposures to 5 nT, 7 Hz magnetic fields.
While investigating the effects of weak complex magnetic fields upon neuroplasticity following induction of early epilepsy, an unprecedented increase in post-seizure mortality (76%) was observed for young rats that had been exposed perinatally to 7 Hz magnetic fields with maximum intensities around 5 nT. Pups exposed to less intense or more intense fields of this frequency did not display this magnitude of significant mortality. Perinatal exposure through the maternal water supply to either a putative nitric oxide donor or inhibitor did not affect this mortality. The non-linear relationship between perinatal 7 Hz magnetic field intensity and post-seizure mortality may be considered analogous to the non-linear relationship between the molarity of ligands and their sequestering to receptor subtypes. These unexpected results suggest that exposure to apparently innocuous stimuli during early development may affect vulnerability to stimuli presented later in ontogeny.


Analysis of subjective perception and influencing factors of different inclusive education models among prelingually deaf children with a cochlear implant.
We aimed to explore the educational outcome and influencing factors of ongoing verbal rehabilitation training together with inclusive education among prelingually deaf children with a cochlear implant. Prelingually deaf children who underwent cochlear implantation, rehabilitation, and had inclusive education placement were randomly divided into two groups: one group received continuous verbal rehabilitation training under inclusive education status; the other group did not receive this training. Speech discrimination scores were determined. Among 60 included children, subjectively perceived academic adaptability, peer relations, initiative communication, and teacher's involvement under inclusive education, as well as speech discrimination scores, were all significantly different between groups. Continuous verbal rehabilitation training influenced the subjective perception of children and resulted in higher speech discrimination scores and more positive subjective perception. Subjective perception was not significantly correlated with chronological age, sex, age at the time of cochlear implantation, or duration of inclusive education. Ongoing verbal rehabilitation training within inclusive education can largely improve the education placement outcomes of prelingually deaf children with cochlear implants.


MicroRNA-302d targets IRF9 to regulate the IFN-induced gene expression in SLE.
Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs). In keeping with the reduced expression of miR-302d in SLE patient monocytes, IRF9 levels were increased, as was expression of a number of ISGs including MX1 and OAS1. In vivo evaluation revealed that miR-302d protects against pristane-induced inflammation in mice by targeting IRF9 and hence ISG expression. Importantly, patients with enhanced disease activity have markedly reduced expression of miR-302d and enhanced IRF9 and ISG expression, with miR-302d negatively correlating with IFN score. Together these findings identify miR-302d as a key regulator of type I IFN driven gene expression via its ability to target IRF9 and regulate ISG expression, underscoring the importance of non-coding RNA in regulating the IFN pathway in SLE.


Clinico-pathological profile of 12 cases of chorangiosis.
Chorangiosis is one of the vascular lesions that involves terminal chorionic villi. It is commonly associated with various feto-maternal conditions like pre-eclampsia, diabetes etc. However, the clinical significance of this pathological finding has not been studied extensively. The aim of this study was to identify the various conditions associated with chorangiosis and to determine its clinical significance. A retrospective study to identify the cases of placentas diagnosed with chorangiosis was carried out and the clinical and morphological details of these cases were reviewed. Immunostaining for CD34 and muscle-specific actin was also performed to confirm chorangiosis and to exclude chorangiomatosis. A total of 12 cases of chorangiosis were retrieved, most of them were of term gestation. Five of these 12 cases were associated with various maternal conditions including syphilis (2 cases) and single cases of pre-eclampsia, diabetes and jaundice. One case in each had abruptio placenta and non-immune hydrops. Of these 12 cases, seven were stillborn. Microscopically, all 12 cases showed extensive chorangiosis involving terminal villi. In addition, two cases showed focal infarction and one had extensive calcification. Immunostaining for CD34 confirmed increased number of capillaries while muscle-specific actin was negative, excluding chorangiomatosis. The clinico-pathological profile presented in this study suggests that chorangiosis has characteristic pathological features for its recognition and needs to be differentiated from similar conditions like chorangioma and chorangiomatosis. Also, chorangiosis has potential clinical significance and should be mentioned in the pathology report and the patient should be investigated for associated conditions like syphilis, pre-eclampsia, diabetes etc.


Aboriginal and Torres Strait Islander communities forgotten in new Australian National Action Plan for Human Influenza Pandemic: "Ask us, listen to us, share with us".
The epidemiology of influenza pandemics demands that Aboriginal and Torres Strait Islander people occupy centrestage in future planning.


Lesion dimensions during temperature-controlled radiofrequency catheter ablation of left ventricular porcine myocardium: impact of ablation site, electrode size, and convective cooling.
It is important to increase lesion size to improve the success rate for radiofrequency ablation of ischemic ventricular tachycardia. This study of radiofrequency ablation, with adjustment of power to approach a preset target temperature, ie, temperature-controlled ablation, explores the effect of catheter-tip length, ablation site, and convective cooling on lesion dimensions. In vitro strips of porcine left ventricular myocardium during different levels of convective cooling and in vivo pig hearts at 2 or 3 left ventricular sites were ablated with 2- to 12-mm-tip catheters. We found increased lesion volume for increased catheter-tip length </=8 mm in vitro (P<0.05) and 6 mm in vivo (P<0. 0001), but no further increase was found for longer tips. For the 4- to 10-mm catheter tips, we found smaller lesion volume in low-flow areas (apex) than in high-flow areas (free wall and septum) (P<0.05). Increasing convective cooling of the catheter tip in vitro increased lesion volume (P<0.0005) for the 4- and 8-mm tips but not for the 12-mm tip as the generator reached maximum output. In contrast to power-controlled ablation, we found a negative correlation between tip temperature reached and lesion volume for applications in which maximum generator output was not achieved (P<0. 0001), whereas delivered power and lesion volume correlated positively (P<0.0001). Lesion size differs in different left ventricular target sites, which is probably related to convective cooling, as illustrated in vitro. Longer electrode tips increase lesion size for tip lengths </=6 to 8 mm. For temperature-controlled ablation, the tip temperature achieved is a poor predictor of lesion size.


Association of Pentraxin 3 with Autoimmune Diseases: A Systematic Review and Meta-Analysis.
Pentraxin 3 (PTX3) plays an important role in the inflammatory processes. Recently it has been reported to be involved in autoimmune diseases. Many studies have investigated the serum/plasma levels of PTX3 in autoimmune diseases, but the results are contradictory or inconclusive among those findings. The purpose of this meta-analysis was to investigate whether serum/plasma levels of PTX3 were associated with autoimmune diseases by comparing the serum/plasma levels of PTX3 in the autoimmune diseases and healthy controls. PubMed, ELSEVIER ScienceDirect and Cochrane Library databases (up to December 26, 2015) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. A total of 20 studies including seven studies of systemic lupus erythematosus (SLE), four studies of ankylosing spondylitis (AS), five studies of rheumatoid arthritis (RA), three studies of systemic sclerosis (SSc) and one study of multiple sclerosis (MS) were finally included in the meta-analysis. The results revealed that the serum/plasma levels of PTX3 in autoimmune diseases were significantly higher than in normal controls (SMD = 0.496 ng/mL, 95% CI = 0.107-0.886, p <0.001; I(2) = 91.9, p <0.001). The subgroup analysis showed that the serum/plasma levels of PTX3 in AS and SSc were higher than in healthy controls (pooled SMD = 0.926 ng/mL, 95% CI = 0.174-1.677, p <0.001, I(2) = 77.0, p = 0.013; pooled SMD = 0.546 ng/mL, 95% CI = 0.136-0.957, p <0.001; I(2) = 30.9, p = 0.299, respectively). Serum/plasma levels of PTX3 in autoimmune diseases were higher than in normal controls.


Toxic shock syndrome presenting to a paediatric service.
A case of toxic shock syndrome occurring in a 13-year-old and presenting to a paediatric service is described. Some implications are discussed including an approach to menstrual protection and the question of future contraceptive needs.


Fibroid and myometrial steroid receptors in women treated with gonadotropin-releasing hormone agonist leuprolide acetate.
The reduction in uterine and fibroid volume associated with the chronic administration of a gonadotropin-releasing hormone agonist (GnRH-a) is thought to be secondary to the analogue induced hypoestrogenic state. Our hypothesis was that the concentration of bioactive estrogen receptors (ER) and progesterone receptors (PR) may be important in the regulation of fibroid growth. The purpose of this study was to determine ER and PR content in fibroids and myometria from women pretreated with GnRH-a compared with controls. Tissue was obtained from 20 premenopausal women with uterine fibroids who were randomized to receive either leuprolide acetate depot, 3.75 mg intramuscularly every 28 days for four injections (n = 10) or placebo (n = 10) before myomectomy. The mean fibroid ER and PR content was significantly greater than the mean myometrial ER and PR content. The mean fibroid ER content for GnRH-a-treated patients was significantly greater than in placebo-treated patients (143.3 +/- 22.8 versus 36.1 +/- 14.3 fmol/mg). The mean fibroid PR and the mean myometrial ER and PR content were not significantly different between treatment groups. Clinically, the significant increase in fibroid ER may be an explanation for the rapid regrowth of fibroids observed after the cessation of GnRH-a therapy.


Directed evolution of a thermostable phosphite dehydrogenase for NAD(P)H regeneration.
NAD(P)H-dependent oxidoreductases are valuable tools for synthesis of chiral compounds. The expense of the cofactors, however, requires in situ cofactor regeneration for preparative applications. We have attempted to develop an enzymatic system based on phosphite dehydrogenase (PTDH) from Pseudomonas stutzeri to regenerate the reduced nicotinamide cofactors NADH and NADPH. Here we report the use of directed evolution to address one of the main limitations with the wild-type PTDH enzyme, its low stability. After three rounds of random mutagenesis and high-throughput screening, 12 thermostabilizing amino acid substitutions were identified. These 12 mutations were combined by site-directed mutagenesis, resulting in a mutant whose T50 is 20 degrees C higher and half-life of thermal inactivation at 45 degrees C is >7,000-fold greater than that of the parent PTDH. The engineered PTDH has a half-life at 50 degrees C that is 2.4-fold greater than the Candida boidinii formate dehydrogenase, an enzyme widely used for NADH regeneration. In addition, its catalytic efficiency is slightly higher than that of the parent PTDH. Various mechanisms of thermostabilization were identified using molecular modeling. The improved stability and effectiveness of the final mutant were shown using the industrially important bioconversion of trimethylpyruvate to l-tert-leucine. The engineered PTDH will be useful in NAD(P)H regeneration for industrial biocatalysis.


Self-reported number of remaining teeth is associated with bone mineral density of the femoral neck, but not of the spine, in Japanese men and women.
Recent studies suggest that a small number of remaining teeth may be associated with low skeletal bone mineral density (BMD) in postmenopausal women. Estrogen deficiency after menopause is considered potential cause relating to tooth loss accompanied by low skeletal BMD in women. Since estrogen plays a dominant role in regulating the male skeleton, it is likely that a small number of remaining teeth also may be associated with low skeletal BMD in men. However, it remains uncertain whether tooth loss is associated with low skeletal BMD in both men and women. We investigated the association between self-reported number of remaining teeth and BMD of the spine and the femoral neck in a cohort of 1914 Japanese subjects aged 48-95 years who were recruited from the Adult Health Study conducted by the Radiation Effects Research Foundation (RERF). BMD of the spine and the femoral neck was measured by dual energy X-ray absorptiometry (DXA). Tooth count was self-reported in response to a simple question to subjects about the number of remaining teeth they had at the time of the survey. Multiple regression analysis adjusted for age, weight, height, smoking, estrogen use, and years since menopause revealed a significant association between number of remaining teeth and BMD of the femoral neck in both men and women; however, no association was found between number of remaining teeth and BMD of the spine in both sexes. Retention of four teeth was significantly associated with a 0.004 g/cm2 increase in femoral neck BMD in men (P<0.05), which was similar to that observed in women (P<0.01). Our results suggest the presence of common causes, except age and body weight, relating to tooth loss accompanied by low BMD of the femoral neck in both men and women.


Suppression of porcine reproductive and respiratory syndrome virus replication by morpholino antisense oligomers.
Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of a contagious disease characterized by reproductive failure in sows and respiratory disease in piglets. This infectious disease results in significant losses in the swine industry and specific anti-PRRSV drugs are needed. In this study, we evaluated a novel class of antisense compounds, peptide-conjugated phosphorodiamidate morpholino oligomers (P-PMOs), for their ability to suppress PRRSV replication in cell culture. P-PMOs are analogs of single-stranded DNA and contain a modified backbone that confers highly specific binding to RNA and resistance to nucleases. Of six P-PMOs tested, one ('5UP1'), with sequence complementary to the 5'-terminal 21 nucleotides of the PRRSV genome, was found to be highly effective at reducing PRRSV replication in a specific and dose-dependent manner in CRL11171 cells in culture. 5UP1 treatment generated up to a 4.5log reduction in infectious PRRSV yield, while a control P-PMO had no effect on viral titer. Immunofluorescence assay with an anti-PRRSV monoclonal antibody confirmed the titer observations. The sequence-specificity of 5UP1 effect was confirmed in part by a cell-free luciferase reporter assay system, which showed that 5UP1-mediated inhibition of translation decreased if the target-RNA contained mispairings in relation to the 5UP1 P-PMO. Real-time RT-PCR showed that the production of PRRSV negative-sense RNA was reduced if 5UP1 was added to cells at up to 6h post-virus inoculation. Cell viability assays detected no cytotoxicity of 5UP1 within the concentration-range of this study. These results indicate that P-PMO 5UP1 has potential as an anti-PRRSV agent.


Photoacoustic mediated multifunctional tumor antigen trapping nanoparticles inhibit the recurrence and metastasis of ovarian cancer by enhancing tumor immunogenicity.
The hypoimmunogenicity of tumors is one of the main bottlenecks of cancer immunotherapy. Enhancing tumor immunogenicity can improve the efficacy of tumor immunotherapy by increasing antigen exposure and presentation, and establishing an inflammatory microenvironment. Here, a multifunctional antigen trapping nanoparticle with indocyanine green (ICG), aluminum hydroxide (Al(OH)3) and oxaliplatin (OXA) (PPIAO) has been developed for tumor photoacoustic/ultrasound dual-modality imaging and therapy. The combination of photothermal/photodynamic therapy and chemotherapy induced tumor antigen exposure and release through immunogenic death of tumor cells. A timely capture and storage of antigens by aluminum hydroxide enabled dendritic cells to recognize and present those antigens spatiotemporally. In an ovarian tumor model, the photoacoustic-mediated PPIAO NPs combination therapy achieved a transition from "cold tumor" to "hot tumor" that promoted more CD8+ T lymphocytes activation in vivo and intratumoral infiltration, and successfully inhibited the growth of primary and metastatic tumors. An in situ tumor vaccine effect was produced from the treated tumor tissue, assisting mice against the recurrence of tumor cells. This study provided a simple and effective personalized tumor vaccine strategy for better treatment of metastatic and recurrent tumors. The developed multifunctional tumor antigen trapping nanoparticles may be a promising nanoplatform for integrating multimodal imaging monitoring, tumor treatment, and tumor vaccine immunotherapy.


[The effect and mechanism of sphingosine kinase-1 knockdown on non-small cell lung cancer cell proliferation and mitochondrial apoptotic pathway].
The purpose of the present study was to investigate the effect and potential mechanism of knockdown of sphingosine kinase-1 (SPHK1) on the proliferation, cell cycle and apoptosis of non-small cell lung cancer (NSCLC) cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect SPHK1 mRNA expression in human healthy lung fibroblasts (MRC-5 cells) and four NSCLC cell lines. Then, A549 and H1299 cells were transfected with SPHK1-shRNA and corresponding negative control. CCK-8, Annexin V-FITC/PI dual staining and cell cycle assay were performed to evaluate cell proliferation, apoptosis and cell cycle distribution, respectively. JC-1 mitochondrial membrane potential measurement kit was adopted to measure mitochondrial membrane potential. Western blot was used to detect the protein expression levels of cell cycle and mitochondrial apoptotic pathway-related proteins, as well as MEK/ERK signaling pathway. The results showed that the mRNA expression of SPHK1 in NSCLC cells was higher than that in MRC-5 cells. SPHK1-shRNA significantly inhibited the proliferation of A549 and H1299 cells, blocked the cell cycle in G0/G1 phase, and promoted cell apoptosis through the mitochondrial pathway. Compared with the control group, the expression of p-MEK and p-ERK proteins in the SPHK1-shRNA group was significantly down-regulated. Moreover, MEK/ERK inhibitor could dramatically suppress cell proliferation and promote cell apoptosis. These results suggest that SPHK1 knockdown can inhibit the proliferation of NSCLC cells and might promote mitochondrial apoptotic pathway by inhibiting MEK/ERK signaling pathway.


How timely can our hand movements be?
The temporal variability of our movements is reduced when we move fast. Here we study whether different sensory information (vision and proprioception) or prior knowledge of final position or travelled distance can affect the temporal precision of movements directed to static targets. We attempted to promote the use of either on-line feedback control (providing visual and proprioceptive information of the movement and maintaining the target position predictable trial-to-trial) or forward control (removing visual feedback and maintaining a predictable target position). In a first experiment, the variability of movement times indicates that temporal precision is affected by the predictability of the target's position and by different feedback conditions. In a second experiment we disentangled the question regarding whether it is the target's position estimate, the travelled distance or the velocity that enhanced the temporal performance. In accordance with previous studies, results indicate that velocity is the main factor in controlling temporal precision across different conditions.


The tumor EPR effect for cancer drug delivery: Current status, limitations, and alternatives.
Over the past three decades, the enhanced permeability and retention (EPR) effect has been considered the basis of tumor-targeted drug delivery. Various cancer nanomedicines, including macromolecular drugs, have been designed to utilize this mechanism for preferential extravasation and accumulation in solid tumors. However, such nanomedicines have not yet achieved convincing therapeutic benefits in clinics. Increasing evidence suggests that the EPR effect is over-represented in human tumors, especially in metastatic tumors. This review covers the evolution of the concept, the heterogeneity and limitation of the EPR effect in clinical realities, and prospects for alternative strategies independent of the EPR effect.


Thermodynamic Surface Analyses to Inform Biofilm Resistance.
Biofilms are the habitat of 95% of bacteria successfully protecting bacteria from many antibiotics. However, inhibiting biofilm formation is difficult in that it is a complex system involving the physical and chemical interaction of both substrate and bacteria. Focusing on the substrate surface and potential interactions with bacteria, we examined both physical and chemical properties of substrates coated with a series of phenyl acrylate monomer derivatives. Atomic force microscopy (AFM) showed smooth surfaces often approximating surgical grade steel. Induced biofilm growth of five separate bacteria on copolymer samples comprising varying concentrations of phenyl acrylate monomer derivatives evidenced differing degrees of biofilm resistance via optical microscopy. Using goniometric surface analyses, the van Oss-Chaudhury-Good equation was solved linear algebraically to determine the surface energy profile of each polymerized phenyl acrylate monomer derivative, two bacteria, and collagen. Based on the microscopy and surface energy profiles, a thermodynamic explanation for biofilm resistance is posited.


Copper removal by dry and re-hydrated biomass of Spirulina platensis.
Dried and re-hydrated biomass of Spirulina platensis was employed as a sorbent in tests of copper removal from water. Biomass re-hydrated for 24 h before use exhibited a shorter adsorption time as well as an increased percentage removal when compared with simply dried biomass. The combined effects of the concentrations of re-hydrated biomass (from 1.0 to 4.0 g l-1) and copper (from 0.1 to 0.4 g l-1) were then investigated. Copper was almost entirely removed (91% removal) at relatively high biomass levels (X0>or=2.0 gDM l-1), while 1.0 gDM l-1 removed only 81% of copper present initially, suggesting a situation of excess metal with respect to the adsorption capacity of biomass. Additional tests performed with biomass re-hydrated for variable time demonstrated that no less than 48 h of this treatment are needed to ensure a satisfactory copper removal, while no significant improvement was detected using biomass re-hydrated for longer times.


Structure of the complete elongation complex of RNA polymerase II with basal factors.
In the early stage of transcription, eukaryotic RNA polymerase II (Pol II) exchanges initiation factors with elongation factors to form an elongation complex for processive transcription. Here we report the structure of the Pol II elongation complex bound with the basal elongation factors Spt4/5, Elf1, and TFIIS. Spt4/5 (the Spt4/Spt5 complex) and Elf1 modify a wide area of the Pol II surface. Elf1 bridges the Pol II central cleft, completing a "DNA entry tunnel" for downstream DNA. Spt4 and the Spt5 NGN and KOW1 domains encircle the upstream DNA, constituting a "DNA exit tunnel." The Spt5 KOW4 and KOW5 domains augment the "RNA exit tunnel," directing the exiting nascent RNA. Thus, the elongation complex establishes a completely different transcription and regulation platform from that of the initiation complexes.


Transient Ischemic Attack, the Initial Presentation of Azygos to Pulmonary Vein Fistula.
There are different sources of cerebral emboli, including cardiac embolism, extracranial arterial embolism, paradoxical embolism, trauma, and iatrogenic embolism. In rare cases, atypical sources should be ruled out. We are reporting a lady who presented with transient ischemic attack and had a fistula between the azygos to the pulmonary vein. (Level of Difficulty: Advanced.).


Recent advances in defined hydrogels in organoid research.
Organoids are in vitro model systems that mimic the complexity of organs with multicellular structures and functions, which provide great potential for biomedical and tissue engineering. However, their current formation heavily relies on using complex animal-derived extracellular matrices (ECM), such as Matrigel. These matrices are often poorly defined in chemical components and exhibit limited tunability and reproducibility. Recently, the biochemical and biophysical properties of defined hydrogels can be precisely tuned, offering broader opportunities to support the development and maturation of organoids. In this review, the fundamental properties of ECM in vivo and critical strategies to design matrices for organoid culture are summarized. Two typically defined hydrogels derived from natural and synthetic polymers for their applicability to improve organoids formation are presented. The representative applications of incorporating organoids into defined hydrogels are highlighted. Finally, some challenges and future perspectives are also discussed in developing defined hydrogels and advanced technologies toward supporting organoid research.


Nasal Melanophoroma in a Captive Green Iguana (Iguana Iguana).
Green iguanas are arboreal lizards, common as pet animals and in captivity. Knowledge of neoplasms in iguanas is scarce, and a challenge to their prevention, treatment, and prognosis. A captive green iguana showed a pigmented nasal exophytic neoplasm. Tumor cells were spindle-shaped to epithelioid with a variable amount of dark-brown or black granular melanin within the cytoplasm, and also presented cytoplasmic positivity for Melan-A and S100. Transmission electron microscopy evidenced intracytoplasmic melanosomes and premelanosomes and provided a definitive diagnosis of a nasal melanophoroma. Full characterization of the clinicopathological and ultrastructural features of the melanophoroma may contribute to the limited knowledge concerning cutaneous neoplasms in green iguanas.


Cell-wall deficient bacteria in inflammatory bowel disease.
Cell wall deficient forms of bacteria were isolated from 40-60% of patients with active inflammatory bowel disease, 15-25% of patients with inactive disease and only 5-7% of controls. The recovery rate from Crohn's disease and ulcerative colitis tissue filtrates did not differ significantly, but was raised in both groups in comparison with controls (p less than 0.01). It is concluded that a range of such bacteria have a possible aetiological role in inflammatory bowel disease.


Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam.
Ro 21-3981 is a newly synthesized water soluble benzodiazepine derivative. Its pharmacological properties are similar to diazepam. This investigation was designed to establish the effective induction dosage of Ro 21-3981 and to compare it with diazepam for induction of anaesthesia. The ED50 for Ro 21-3981 induction is 0.15 mg/kg and ED 100 is 0.2 mg/kg. Ro 21-3981 is one and one-half times as potent as diazepam (0.3 mg/kg) and more rapid in action. There is significantly less pain on injection with Ro 21-3981 as compared to diazepam. Cardiovascular stability and apnoea were observed with both drugs. Ro 21-3981 is a promising anaesthetic induction drug that merits further human study.


Somatosensory evoked potentials during reversible spinal cord ischemia in man.
Somatosensory evoked potentials (SEPs) from peroneal nerve were recorded continuously on 13 patients undergoing extensive aortic replacement of thoracic, abdominal, or thoracico-abdominal aneurysms. During this surgical procedure, the descending aorta is completely occluded, and circulation to the spinal cord may thus be compromised, causing a risk of postoperative paraplegia. This risk may be minimized if changes in the SEP seen during intraoperative monitoring prove to correlate well with clinical outcome. Changes in the SEP observed during complete occlusion of the aorta and subsequent restoration of blood flow included: (1) progressive latency prolongation within the first 10 min of occlusion, (2) coincident and progressive amplitude depression, (3) eventual loss of the SEP, (4) rapid reversal of these changes with restoration of circulation, and (5) preservation of the lumbar response when the cephalic response became abnormal. The degree of prolongation of latency after restoration of blood flow appeared related to the duration of aortic occlusion and to the duration of SEP absence. These findings indicate that conduction through the spinal pathways that mediate the SEP is sensitive to ischemia produced by aortic occlusion. Intraoperative monitoring of SEPs as a means of reducing the neurological morbidity of extensive aortic replacement is discussed.


Active immunization with a Coxsackievirus A16 experimental inactivated vaccine induces neutralizing antibodies and protects mice against lethal infection.
Coxsackievirus A16 (CA16) is one of the main pathogens that cause hand, foot and mouth disease, which frequently occurs in young children. A small percentage of patients infected with CA16 may suffer from severe neurological complications that could also lead to death. Recent epidemiological data shows the increase in both the total number and the incidence rate of severe CA16-associated cases in China, indicating that CA16 should be targeted for vaccine development. In this article, we report the immunogenicity and protective efficacy of experimental inactivated CA16 vaccines in mice. We show that immunization with β-propiolactone-inactivated whole-virus vaccines derived from two CA16 clinical isolates were able to induce CA16-specific antibody and IFN-secreting T-cell responses in mice. The resulting anti-CA16 mouse sera neutralized both homologous and heterologous CA16 clinical isolates, as well as a mouse-adapted strain called CA16-MAV, which is capable of infecting 14-day-old mice. Passive transfer of anti-CA16 neutralizing sera partially protected neonatal mice from lethal challenge by a clinical isolate CA16-G08. More significantly, active immunization of mice with the inactivated vaccines conferred complete protection against lethal infection with CA16-MAV. Collectively, these results provide a solid foundation for further development of inactivated whole-virus CA16 vaccines for human use.


[Unusual causes of biphonation].
Biphonation or diplophonia can be caused by several mechanisms. Although helpful for communication in some animals, biphonation in humans is usually perceived as increased roughness. Herein we report two unusual causes for biphonation. In the first case, a woman suffered from vocal fold bamboo nodes. These decoupled the anterior from the posterior part of the vocal folds, leading to an intermittent anterior-posterior vibration pattern during phonation. In the second case, a patient underwent a pitch-raising operation. Postoperatively we saw a transversal fixation of the vocal fold mucosa caused by a suture. This fixation led to two separated "neo" glottides, one being in the anterior third and the other in the posterior third of the vocal folds.


Structural and biochemical basis for the substrate specificity of Pad-1, an indole-3-pyruvic acid aminotransferase in auxin homeostasis.
Phytohormone indole-3-acetic acid (IAA) plays a vital role in regulating plant growth and development. Tryptophan-dependent IAA biosynthesis participates in IAA homeostasis by producing IAA via two sequential reactions, which involve a conversion of tryptophan to indole-3-pyruvic acid (IPyA) by tryptophan aminotransferase (TAA1) followed by the irreversible formation of IAA in the second reaction. Pad-1 from Solanaceae plants regulates IAA levels by catalyzing a reverse reaction of the first step of IAA biosynthesis. Pad-1 is a pyridoxal phosphate (PLP)-dependent aminotransferase, with IPyA as the amino acceptor and l-glutamine as the amino donor. Currently, the structural and functional basis for the substrate specificity of Pad-1 remains poorly understood. In this study, we carried out structural and kinetic analyses of Pad-1 from Solanum melongena. Pad-1 is a homodimeric enzyme, with coenzyme PLP present between a central large α/β domain and a protruding small domain. The active site of Pad-1 includes a vacancy near the phosphate group (P-side) and the 3'-O (O-side) of PLP. These features are distinct from those of TAA1, which is homologous in an overall structure with Pad-1 but includes only the P-side region in the active site. Kinetic analysis suggests that P-side residues constitute a binding pocket for l-glutamine, and O-side residues of Phe124 and Ile350 are involved in the binding of IPyA. These studies illuminate distinct differences in the active site between Pad-1 and TAA1, and provide structural and functional insights into the substrate specificity of Pad-1.


Investigation of the psychometric properties of the Turkish version Multidimensional Weight Locus of Control Scale (T-MWLCS) in individuals with different body mass index.
The Multidimensional Weight Locus of Control Scale (MWLCS) measures a individuals' focus on body weight or their beliefs about a lack of locus of control. This study was carried out to determine the validity and reliability of the Turkish culture-adapted version of the Multidimensional Weight Locus of Control Scale in adults, which was originally developed by Cebolla et al. METHODS: The sample of the study consists of 700 individuals between the ages of 19-64 who voluntarily agree to participate in online survey. Validity and reliability analyses were performed for the Turkish version Multidimensional Weight Locus of Control Scale. Confirmatory factor analysis (CFA) was performed to evaluate the factor structure of the Turkish version Multidimensional Weight Locus of Control Scale. In addition, reliability analyses and Pearson correlations were also examined. Individuals were divided into two groups as those with normal (18.50-24.99 kg/m2; n = 432) and those with overweight-obese body mass index (≥ 25.0 kg/m2; n = 268) and measurement invariance tested in both the groups. The four-factor structure (internal, chance, doctors, and other people) describing the weight locus of control was supported by confirmatory factor analyses. The sub-factors of the Turkish version Multidimensional Weight Locus of Control Scale were positively associated with the sub-factors of Dutch Eating Behaviour Questionnaire (DEBQ). In addition, the scale showed configural invariance in different body mass index groups. Findings from this study revealed that Turkish version Multidimensional Weight Locus of Control Scale is a valid and reliable measurement tool that can be applied in Turkish culture. It is thought that this scale will contribute to studies that will evaluate the focus of individuals in different body mass index groups related to weight control. Level V, descriptive study.


Segmentation-Based Analysis of T2- and T1-Weighted Dynamic Magnetic Resonance Images Provides Adequate Observer Agreement in the Evaluation of Interstitial Lung Disease.
The aim of the study is to quantify observer agreement in the magnetic resonance imaging (MRI) classification of inflammatory or fibrotic interstitial lung disease (ILD). Our study is a preliminary analysis of a larger prospective cohort. The MRI images of 18 patients with ILD (13 females; mean age, 65 years) were acquired in a 1.5 T scanner and included axial fat-saturated T2-weighted (T2-WI, n = 18) and coronal fat-saturated T1-weighted images before and 1, 3, 5, and 10 minutes after gadolinium administration (n = 16). The MRI studies were evaluated with 2 different methods: a qualitative evaluation (visual assessment and measurement of few regions of interest; evaluations were performed independently by 5 radiologists and 3 times by 1 radiologist) and a segmentation-based analysis with software extraction of signal intensity values (evaluations were performed independently by 2 radiologists and twice by 1 radiologist). Interstitial lung disease was classified as inflammatory or fibrotic, based on previously described imaging criteria. Regarding the qualitative evaluation, intraobserver agreement was excellent (κ = 0.92, P < 0.05) for T2-WI and fair (κ = 0.29, P < 0.05) for T1 dynamic study, while interobserver agreement was moderate (κ = 0.56, P < 0.05) and poor (κ = 0.11, P = 0.18), respectively. In contrast, upon segmentation-based analysis, intraobserver and interobserver agreement were excellent for T2-WI (κ = 0.886, P < 0.001; κ = 1.00, P < 0.001; respectively); for T1-WI, intraobserver agreement was excellent (κ = 0.87, P < 0.05) and interobserver agreement was good (κ = 0.75, P < 0.05). Segmentation-based MRI analysis is more reproducible than a qualitative evaluation with visual assessment and measurement of few regions of interest.


The effect of surface charge property on Escherichia coli initial adhesion and subsequent biofilm formation.
Polyethylene (PE) sheets were modified by radiation-induced graft polymerization (RIGP) of an epoxy-group containing monomer glycidyl methacrylate (GMA). The epoxy group of GMA was opened by introducing sodium sulfite (SS) and diethylamine (DEA) as representatives of negatively and positively charged functional groups, respectively. These modified surfaces by RIGP, termed GMA, SS, and DEA sheets, were investigated to elucidate their effects on initial adhesion and subsequent biofilm formation of Escherichia coli. Initial adhesion test revealed that E. coli density and viability were governed by sheet surface electrostatic property: E. coli cell density on the DEA sheet was 23 times higher than that on the SS sheet after 8 h incubation. The viability of E. coli cells dramatically decreased after contact with the DEA sheet, but remained high on the SS sheet. E. coli biofilm structure on the DEA sheet was dense, homogeneous, and uniform, with biomass higher than that of the GMA and SS sheets by factors of 14.0 and 37.5, respectively. On the contrary, biofilm structure on the SS sheet was sparse, heterogeneous, and mushroom-shaped. More than 40% of E. coli biofilm on the DEA sheet was retained under a high liquid shear force condition (5,000 s(-1)), whereas 97% and 100% of biofilms on the GMA and SS sheets were sloughed, indicating that E. coli biofilm robustness depends on surface charge property of the substratum. This suggests that substratum surface fabrication by RIGP may enhance or suppress biofilm formation, a finding with potentially important practical implications.