The Keap1-Nrf2 system and diabetes mellitus.
Nrf2 (NF-E2-related factor 2) plays a key role in the protection of vertebrates against environmental stress by contributing to the inducible expression of detoxification and antioxidant enzymes. Keap1 (Kelch-like ECH-associated protein 1) is a sensor for oxidative and electrophilic stresses. Keap1 also acts as an E3 ubiquitin ligase substrate-recognition subunit that specifically targets Nrf2. Keap1 causes Nrf2 to be degraded through the ubiquitin-proteasome pathway and thus ensures that Nrf2 is constitutively suppressed under unstressed conditions. Upon exposure to oxidative or electrophilic stress, Keap1 loses its ability to ubiquitinate Nrf2. Many lines of evidence have recently clarified that the Keap1-Nrf2 system also plays critical roles in the maintenance of cellular homeostasis. One of the most salient examples is the contribution of Keap1-Nrf2 to metabolic and energy-balance regulation. In particular, how the Keap1-Nrf2 system protects the body against diabetes mellitus and how perturbations in this system provoke the disease condition are now under intense investigation. This review will summarize the recent progress made in this area.


Differential sodium fluoride sensitivity of alpha-naphthyl acetate esterase in human, bovine, canine, and murine monocytes and lymphocytes.
The sensitivity of alpha-naphthyl acetate esterase (ANAE) activity of human, bovine, canine, and murine leukocytes to low (42 micrograms/ml incubation mixture) and high (1.5 mg/ml incubation mixture) concentrations of sodium fluoride (NaF) was compared. The ANAE activity of bovine and canine monocytes was only slightly inhibited by the low concentration of NaF, whereas that of murine peritoneal macrophages was moderately inhibited and that of human monocytes was completely inhibited. Human and canine monocytic ANAE was completely inhibited by the high concentration of NaF, whereas the ANAE activity in 1% of bovine monocytes and murine peritoneal macrophages was not inhibited. The ANAE activity of human and murine lymphocytes in nonenriched venous blood samples showed no or negligible NaF sensitivity to the low concentration of NaF, whereas bovine lymphocytic ANAE showed slight and canine lymphocytic ANAE moderate NaF sensitivity. The ANAE of murine T-lymphoma L5178Y cells was resistant to the low concentration of NaF, but the ANAE of both murine T-lymphoma L5178Y cells and murine lymphocytes was completely inhibited by the high concentration of NaF. Human, bovine, and canine lymphocytic ANAE showed marked NaF sensitivity toward the high concentration of NaF, showing 73%, 86%, and 93% inhibition, respectively. The neutrophils in murine venous blood and ascites were positive for ANAE activity, which was only slightly inhibited by the low concentration of NaF but completely inhibited by the high concentration. Results of this investigation demonstrate that the ANAE of leukocytes of various species show remarkable differences in its sensitivity to low and high concentrations of NaF, indicating that appropriate concentrations of NaF are required for distinguishing the ANAE of lymphocytes and monocytes of different species.


[Histochemical and immunohistochemical localization of choline acetyltransferase in the nuclei oblongata rat brain].
ChAT-positive neurons in the nuclei of the medulla oblongata of Wistar rats have been studied with the use of histochemical and immunohistochemical methods. We have found that the topography and the number of cholinergic neurons at the projection nuclei studied largely depend on the method of detection of these neurons. Histochemical method always revealed more neurons than immunohistochemistry. Such a feature of ChAT-positive neurons detection was clearly seen among the majority of nuclei in the medial region and in some of the nuclei in the lateral region of the medulla oblongata. The number of immunoreactive cells in the nuclei varied from 17 to 26%, whereas the histochemical reaction determined 1.5-3 times more neurons in the same nuclei. ChAT-positive cells in the nuclei of the back seam were detected mainly by a histochemical method.


Cerebral vasoreactivity in children and adolescents with type 1 diabetes mellitus.
It is well established in clinical and experimental settings that diabetes mellitus, especially if long lasting, impairs autoregulation of cerebral blood flow (CBF). However, the onset and the course of development of this dysfunction remain unknown. We hypothesized that assessment of autoregulatory functions of cerebral arteries in children with relatively short duration of type 1 diabetes mellitus may provide an insight into the pathophysiology of the development of impaired autoregulation of CBF. Such a dysfunction of vasodilation of cerebral arteries can be assessed by transcranial Doppler. Therefore, to examine whether and when autoregulation of CBF becomes affected by diabetes, we used transcranial Doppler and a pCO2 challenge in 17 males between the ages of 12-20 years with type 1 diabetes mellitus of 0.2-16 years duration and with varying degrees of glucose control. The results were compared with age-matched, healthy, nondiabetic controls. The CO2 challenge increased cerebral blood-flow velocities and decreased the pulsatility index. These changes were not influenced by the presence or duration of diabetes, insulin dose, or degree of diabetic control.


Disorder and function: a review of the dehydrin protein family.
Dehydration proteins (dehydrins) are group 2 members of the late embryogenesis abundant (LEA) protein family. The protein architecture of dehydrins can be described by the presence of three types of conserved sequence motifs that have been named the K-, Y-, and S-segments. By definition, a dehydrin must contain at least one copy of the lysine-rich K-segment. Abiotic stresses such as drought, cold, and salinity cause the upregulation of dehydrin mRNA and protein levels. Despite the large body of genetic and protein evidence of the importance of these proteins in stress response, the in vivo protective mechanism is not fully known. In vitro experimental evidence from biochemical assays and localization experiments suggests multiple roles for dehydrins, including membrane protection, cryoprotection of enzymes, and protection from reactive oxygen species. Membrane binding by dehydrins is likely to be as a peripheral membrane protein, since the protein sequences are highly hydrophilic and contain many charged amino acids. Because of this, dehydrins in solution are intrinsically disordered proteins, that is, they have no well-defined secondary or tertiary structure. Despite their disorder, dehydrins have been shown to gain structure when bound to ligands such as membranes, and to possibly change their oligomeric state when bound to ions. We review what is currently known about dehydrin sequences and their structures, and examine the various ligands that have been shown to bind to this family of proteins.


Natural Radioactivity of Granitic Rocks and Their Health Risk around Ingesana Mountains, Sudan.
This work was carried out mainly to analyze radioactive elements 40 K, 232 Th, and 226 Ra and non-radioactive elements in some granitic rocks and study their health risk for humans and non-humans. Radioisotope activity was evaluated using a high-purity germanium (HPGe) detector, and various radiological hazard indices were calculated. We also measured some non-radioactive elements using x-ray fluorescence analysis and performed Pearson correlation analysis to examine the relationships between the radionuclides and the non-radioactive elements. Furthermore, we used the ERICA software to estimate the total dose rate per organism for some non-human biota. The means of 226 Ra, 232 Th, and 40 K are 25.13 ± 5.22 Bq kg -1 , 29.01 ± 6.95 Bq kg -1 , and 323.07 ± 97.83 Bq kg -1 , respectively. Hence, 226 Ra, 232 Th, and 40 K radioactivities were lower than the worldwide average limits. The 226 Ra, 232 Th, and 40 K levels were under the global average values. The hazardous radiometric variables were computed, and the findings observed that the mean absorbed dosage was 23.48 ± 7.36 nGy h -1 , the yearly effective dose rate was 29.82 ± 10.46 μSv y -1 , and the radium equivalent activity was 88.88 ± 18.64 Bq kg -1 . The average dose and yearly effective dose rates were lower than the global average absorbed dose rate of 60 nGy h -1 and the ICRP standard of 1.0 mSv y -1 . The results of Ra-equivalent activity were lower than the recommended maximum criterion for building materials limit of Ra-equivalent activity (370 Bq kg -1 ) proposed by UNSCEAR. Tests of Pearson correlation coefficients indicate a substantial positive relationship between 226 Ra and 232 Th and a modest correlation between 226 Ra and 40 K. Meanwhile, no association between 226 Ra and 40 K and non-radioactive components has been identified. Thorium-232 exhibits a moderately favorable connection with Ti, Fe, and Ni. The estimated total dose rate per organism for the studied non-human is less than the ambient dose rate. However, the total dose rate for small burrowing mammals and reptiles exceeds the background exposure rate. In accordance with the findings, granite rocks may be safe to use as construction materials and pose no threat to human health.


Site specific ligand substitution in cubane-type Mo3FeS(4)(4+) clusters: kinetics and mechanism of reaction and isolation of mixed ligand Cl/SPh complexes.
The synthesis, crystal structure and solution characterization of the cubane-type [Mo(3)(FeCl)S(4)(dmpe)(3)Cl(3)] (1) (dmpe = 1,2-bis(dimethylphophane-ethane)) cluster are reported and the ligand substitution processes of chloride by thiophenolate investigated. The kinetics and the intimate mechanism of these substitutions reveal that compound 1 undergoes a number of Fe and Mo site specific ligand substitution reactions in acetonitrile solutions. In particular, PhS(-) coordination at the tetrahedral Fe site proceeds in a single resolved kinetic step whereas such substitutions at the Mo sites proceed more slowly. The effect of the presence of acids in the reaction media is also investigated and reveals that an acid excess hinders substitution reactions both at the Fe and Mo sites; however, an acid-promoted solvolysis of the Fe-Cl bonds is observed. Electrospray ionization (ESI) and tandem (ESI-MS/MS) mass spectrometry allow the identification of all the reaction intermediates proposed on the basis of stopped-flow measurements. The distinctive site specific reactivity made it possible to isolate two new clusters of the Mo(3)FeS(4)(4+) family featuring mixed chlorine/thiophenolate ligands, namely Mo(3)S(4)(FeSPh)(dmpe)(3)Cl(3) (2) and [Mo(3)S(4)(FeSPh)(dmpe)(3)(SPh)(3)] (3). A detailed computational study has also been carried out to understand the details of the mechanism of substitution at the M-Cl (M = Mo and Fe) bonds as well as the solvolysis at the Fe-Cl sites, with particular emphasis on the role of acids on the substitution process. The results of the calculations are in agreement with the experimental observations, thus justifying the non-existence of an accelerating effect of acids on the thiophenolate substitution reaction, which differs from previous proposals for the Fe(4)S(4) and MoFe(3)S(4) clusters and some related compounds.


Comparison of Inflammation-Based Prognostic Scores in a Cohort of Patients with Resectable Esophageal Cancer.
A number of studies have revealed that inflammation-based prognostic scores, such as Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein and albumin ratio (C/A ratio), are associated with poor outcome in cancer patients. However, until now, no study has investigated the role of these prognostic scores in a cohort of neoadjuvant-treated esophageal adenocarcinomas (nEAC) and squamous cell carcinomas (nESCC). Patients had laboratory measurements within three days before resection. GPS, mGPS, and C/A ratio were tested together with established clinicopathological factors in simple and multiple Cox regression analysis of overall survival (OS) and disease-free survival (DFS). A total of 283 patients (201 EAC and 82 ESCC) with locally advanced esophageal cancer were enrolled. 167 patients received neoadjuvant treatment (59.0%). Simple analysis revealed that there were significant differences in cancer-specific survival in relation to elevated C-reactive protein (p = 0.011), lymph node status (p < 0.001), UICC stage (p < 0.001), and nEAC (p = 0.005). mGPS (p = 0.024) showed statistical significance in simple analysis. No statistical significance could be found for GPS (p = 0.29), mGPS (p = 0.16), and C/A ratio (p = 0.76) in multiple analysis. The investigated prognostic scores should be used and interpreted carefully, and established factors like histology, including tumor size and differentiation, lymph node involvement, and status of resection margin remain the only reliable prognostic factors for patients suffering from resectable EC.


Biodegradation of distal shunt catheters.
In a review of pediatric and adult distal cerebrospinal fluid shunt failures, the distal catheters were found to have deteriorated to the point of malfunction in 7 individuals after intervals of over 7 years. All cases presented in the first two decades of life with a duration of symptoms ranging from 1 to 62 days. The mechanism of shunt failure was assessed by radionuclide shuntogram study and at surgery. Degradation of catheter material led to irregular attenuation and fracture of the catheter wall with diffuse leakage of radionuclide into surrounding tissues. The catheter length of most chronic duration following implant was inevitably affected. Radionuclide shuntogram study of the distal catheter clearly identified the nature of the problem by showing an irregular outline of the catheter lumen due to spread of radioactivity into the surrounding soft tissues. Occasionally, intense foci of activity were identified at single or multiple sites where the catheter wall was grossly attenuated or fractured, resulting in cessation of catheter flow further distally. The biodegradability of distal shunt catheters leading to malfunction must be considered when assessing a young individual with features of hydrocephalus and a chronically implanted catheter length. Radionuclide shuntogram study is a convenient means of assessing the problem.


Orotic acid enhancement of preneoplastic and neoplastic lesions induced in the pancreas and liver of hamsters by N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine.
The effect of dietary orotic acid (OA) in liver-pancreas carcinogenesis induced in female Syrian hamsters by N-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP) was evaluated. All animals infused with the carcinogen received the same doses. Results of the control group which received no OA or carcinogen were compared with the results of: (a) hamsters treated with HPOP and fed a regular 20% protein synthetic diet (group 1); (b) hamsters fed the OA diet for a brief time period during initiation with the carcinogen (group 2); and (c) hamsters in which OA was administered after carcinogen infusion for life (group 3). All animals of the control group were normal at autopsy, while those in group 1 (HPOP alone) revealed the spectrum of lesions accepted as classical in the multistep hyperplasia-dysplasia-carcinoma in situ (CIS) sequence of carcinogenesis. Results of group 2, in light of group 1, revealed an increased incidence of the following lesions in the common pancreatic duct: dilatation, 2.5 times; flat and papillary hyperplasia, 2 times; and dysplasia (atypical hyperplasia), 12 times. No significant increase of CIS and invasive cancer in the body and tail of the pancreas was observed; in addition, the incidence, nature, and location of pancreatic adenocarcinomas were not affected. Yet, the effect of OA administered after carcinogen infusion (group 3) when compared to group 1 seemed to enhance a further increase in the incidence of practically all lesions throughout the pancreas. An obvious overall step-up incidence along the multistep hyperplasia-dysplasia-CIS-invasive cancer process in the pancreas was observed. The increase in incidence of flat, papillary, and atypia of the epithelium of the common pancreatic duct in group 3 was mild compared to that found in the same duct of group 2, but the increase in incidence of these same three lesions when found in the main ducts was marked: flat hyperplasia, 3-fold; papillary hyperplasia, 2.5-fold; atypical hyperplasia, 3-fold. The increase in incidence of CIS in this group was 5-fold and papillary adenocarcinomas, 3-fold, when compared to 5% found in groups 1 and 2. Hepatic malignancies (cholangiocarcinomas) occurred in 6% of the cases in group 3 compared to none in group 2; the incidence of malignancy in the gallbladder was the same in groups 2 and 3 but three times greater than that in group 1.(ABSTRACT TRUNCATED AT 400 WORDS)


CircRNA_001569 promotes cell proliferation through absorbing miR-145 in gastric cancer.
Gastric cancer severely threatens human life, while its pathogenesis is still unclear. The present study was to explore the potential pathogenic mechanism underlying gastric cancer. Real-time PCR was performed to detect the expression of circRNA_001569 and miR-145; western blot was performed to detect the expression of NR4A2. Cell cycle and apoptosis was determined using flow cytometry, and cell viability was determined using Cell counting kit-8 (CCK-8) assay. Luciferase reporter assay was carried out to validate the relationship between miR-145 and NR4A2. Both circRNA_001569 and NR4A2 were overexpressed in tissues and cells of gastric cancer, while miR-145 was down-regulated. Overexpressed circRNA_001569 significantly increased cell viability, and decreased cell apoptosis, while down-regulated circRNA_001569 dramatically decreased cell viability and promoted cell apoptosis. CircRNA_001569 regulated the expression of miR-145, the effect of pcDNA-circRNA_001569 was abolished by miR-145 mimic and the effect of si-circRNA_001569 was abolished by miR-145 inhibitor. MiR-145 targets NR4A2 to regulate its expression. Overexpressed miR-145 suppressed cell viability and promoted cell apoptosis. Taken together, the present study indicated that overexpressed circRNA_001569 promoted cell viability of gastric cancer through suppressing the expression of miR-145, which was mediated by NR4A2. The research will provide great theoretical basis for further clinical diagnosis and therapy.


Acute Kidney Injury in Obstetric Patients.
Obstetric-related acute kidney injury (obstetric AKI) is an important and complex public health problem; its early recognition and proper treatment are key in preventing maternal and fetal adverse outcomes. While the incidence of obstetric AKI has drastically declined in some developing countries due to reduction of sepsis-related causes, the opposite has been observed in other developed nations in the last decade due to advanced maternal age and the presence of comorbidities. The diagnosis of obstetric AKI has been made difficult by the physiologic decrease in serum creatinine of pregnancy as well as the absence of a uniform definition for AKI in this population. The most common causes of obstetric AKI include pre-renal etiologies such as hyperemesis gravidarum and post-abortal sepsis, intra-renal causes which comprise the thrombotic microangiopathies (preeclampsia/HELLP, thrombotic thrombocytopenic purpura, pregnancy associated-hemolytic uremic syndrome, lupus nephritis), and post-renal causes due to obstruction from kidney stones or iatrogenic injuries during delivery. A kidney biopsy is rarely required and should be reserved for cases where the diagnosis will change management, preferably before the third trimester. A multidisciplinary approach with the maternal-fetal-medicine specialist and nephrologist, along with the intensivist and hematologist may be needed. In this review, we will present the latest updates on the global epidemiology, focus on the most challenging thrombotic microangiopathy diagnoses, summarize treatment recommendations, and delineate the ongoing challenges as well as novel strategies to tackle this public health burden which does not seem to be disappearing.


Construction and validation of a virtual learning object on intestinal elimination stoma.
To construct and validate a virtual learning object (VLO) on intestinal elimination stoma. Applied, descriptive and quantitative study. In 2014, eight stoma therapists and eight experts in computer science took part of the research. The VLO included four steps: i) planning, ii) construction of VLO and changes of content; iii) development of dynamic, and iv) conclusion and analysis. The VLO was inserted into the Moodle virtual learning environment. The ergonomic and pedagogical validation of the VLO was performed. The experts appreciated the VLO satisfactorily, and scored it between good and full agreement. The VLO on intestinal elimination stoma is a tool that can be implemented at undergraduate programs in nursing and continuing education programs for nurses in clinical practice, contributing significantly to improve the theoretical skills necessary for the care of ostomized people safely, with quality and enabling self-care.


Evaluation of the exoantigen test for identification of Histoplasma species and Coccidioides immitis cultures.
Recently it was demonstrated that certain fungal pathogens could be rapidly and accurately identified on the basis of their exoantigens. Mycelial-form cultures of the Histoplasma species consistently appear to produce either H or M antigens, or both, whereas cultures of Coccidioides immitis produce tube precipitinogen, heat-labile precipitinogen, or heat-labile F antigens. Three laboratories each evaluated 48 cultures by the exoantigen procedure for the identification of Histoplasma spp. and C. immitis. One hundred forty-four cultures were tested, and 143 (99.3%) were correctly identified as Histoplama spp. or C. immitis, or neither. The simple and rapid exoantigen test appears to be a sensitive and specific method for identification of these fungi.


Maternal blood concentration of tadalafil in pregnancy: Comparison of pregnant and non-pregnant women.
In this study, the drug kinetics of tadalafil were compared between pregnant and non-pregnant women to determine the ideal dosage to promote uterine blood flow. We recruited five pregnant and five non-pregnant women, all of which were administered tadalafil (20 mg/day). The blood concentration of tadalafil was measured 1, 2, 4, 6, 8, and 24 h after administration. We investigated the side effects within 4 days of tadalafil administration and compared the cumulative frequency between the two groups. The mean area under the concentration-time curve and maximum blood concentration of tadalafil were not different between the pregnant and non-pregnant groups. Time to maximum blood concentration was delayed by 1 min on average in the pregnant group compared with the non-pregnant group. The cumulative frequency of side effects was significantly lower in the pregnant group than in the non-pregnant group (P = 0.026). No side effects were observed in either group after the fifth day of the tadalafil administration. Although there was no difference in maximum blood concentration between non-pregnant and pregnant women, the rate of side effects was lower in pregnant women than in non-pregnant women. Therefore, pregnant women may tolerate tadalafil better.


Pregnancy planning, timing, happiness and depressive symptoms among low-income women living with and without HIV.
This study assessed associations of sociodemographic factors and pregnancy intent and wantedness with pregnancy happiness and prenatal depressive symptoms and the relationship between prenatal depressive symptoms and pregnancy happiness. Depression is the leading cause of disability world-wide and more so for women. Women are most likely to experience depression in their child bearing years, including during pregnancy. Untreated prenatal depression, associated with unwanted pregnancies endangers the health and wellbeing of the mother and her child. Research on the association of prenatal depression with pregnancy happiness among women with low incomes in the U.S.A. is limited. For women living with HIV, associations among family planning factors, pregnancy feelings and prenatal depression have been understudied. Sixty-four women living with HIV and 194 HIV-negative low-income pregnant women receiving care in a public university-based ob-gyn clinic with integrated HIV-care in Philadelphia between 2009 and 2012 participated in the study. The women completed a questionnaire on sociodemographic and pregnancy factors and the Center for Epidemiological Studies Depression Scale (CES-D). The independent associations of sociodemographic and pregnancy factors with pregnancy happiness and associations of these factors and pregnancy happiness with the CES-D were assessed using multivariable linear regressions. Women who felt the pregnancy was too soon were less happy being pregnant (p < 0.01). Prenatal depressive symptoms were inversely associated with happiness with being pregnant and completing high school (p < 0.001 for both). Health care professionals need to provide reproductive counselling and mental health for prenatal depression should explore feelings about being pregnant and being a mother.


Why prescribe short-burst oxygen?
In previous reviews of domiciliary oxygen therapy, we have commented on the lack of evidence to justify use of short-burst oxygen therapy, which is expensive and can be difficult to withdraw from patients once they are established on it. For these reasons, we concluded that short-burst oxygen therapy should not be started without objective evidence of benefit for the individual patient, and its use should be under the supervision of a specialist. In February 2006, the supply process for all forms of home oxygen in England and Wales was changed, with the aim of giving patients more appropriate treatment through proper clinical assessment and correct ordering and monitoring of oxygen therapy. Here we reassess the role of short-burst oxygen therapy within these new supply arrangements.


Analysis of matrix-assisted laser desorption/ionization quadrupole time-of-flight collision-induced dissociation spectra of simple precursor ions and isobaric oligosaccharide ion mixtures based on product ion intensities and pattern recognition.
Qualitative analysis of glycomic tandem mass spectrometry (MS/MS) data based on m/z values of product ions alone is widely used, and often sufficient for analysis of single analytes. However, most complex glycomic mixtures contain multiple isobaric oligosaccharides, in which case this approach is often limited. Here we show how ion intensity information can be used in order to enhance MS/MS data analysis, and extract both qualitative and semiquantitative information from complex glycomic MS/MS datasets. A matrix-assisted laser desorption/ionization quadrupole time-of-flight (MALDI QTOF) mass spectrometer was used in this study. We compared the intensities of product ions within a single product ion series, determined by their length, across the whole glycomic MS/MS dataset. In order to detect discernable patterns, the intensity data was normalized to the intensity of each product ion within the series. In most cases, normalized data yielded easily discernable patterns, relevant either for analysis of specific glycomic structure types, or mechanistic MS studies. We used our approach on a glycomic sample consisting of human milk oligosaccharides. The approach yielded useful results for both qualitative and semiquantitative analyses. All normalizations performed were not equally rich in information and the information content of generated tables was not possible to predict. These analyses were shown to be independent of instrument manufacturer. Our approach enabled more detailed qualitative analysis of MS/MS spectra of precursor ions containing isobaric oligosaccharide structures. While limited semiquantitative information could be extracted from the raw data as well, the accuracy of this method should be significantly enhanced when standard calibration mixtures can be prepared. Copyright © 2017 John Wiley & Sons, Ltd.


Cembrane diterpenes from the gorgonian Lophogorgia peruana.
The chemical study of the gorgonian Lophogorgia peruana collected at the Gulf of California has led to the isolation of the new diterpenes lophodienone (2), lophodiol A (3), lophodiol B (4), 17-acetoxylophotoxin (5), 15,16-epoxylophotoxin (6), 17-acetoxy-15,16-epoxylophotoxin (7), and isoepoxylophodione (8), together with the known compounds lophotoxin (1), rubifolide (9), lopholide (10), deoxylophotoxin (11), and the lophotoxin analogues 12 and 13. The structures of the new metabolites have been established by spectroscopic techniques and chemical correlation. The in vitro cytotoxicity has been tested against three tumor cell lines.


Genital necrosis secondary to warfarin therapy.
Several adverse dermatologic effects have been reported with the use of warfarin. Among these is the rare complication of drug-induced necrosis. Approximately 150 cases had been reported by 1976, and a review of the literature since 1943 revealed only 4 reported cases of penile necrosis. We present the fifth case of genital necrosis reported with coumarin anticoagulants and the third such case associated with warfarin.


Is independence of older adults safe considering the risk of falls?
Falls affect approx. 30% of elderly population per year. They cause major injuries and reduce independence of the older adults' functioning. The main objective of the study was to evaluate the degree of independence and find the fall risk factors in the study group. The study included 506 - older adults. The study group included patients from GP clinics and members of two senior centers. The study duration was 12 months. Our study tools included EASY- Care Standard 2010 questionnaire, Abbreviated Mental Test Score (AMTS), Index Barthel, Instrumental Activities of Daily Living Scale (IADL), Geriatric Depression Scale (GDS), Timed Up and Go (TUG). The study included 357 (70.6%) female and 149 (29.4%) male subjects. The mean age of the study group patients was 75.7 years ± 8.0. Most of the older adult subjects were independent in both basic (Index Barthel) and instrumental (IADL) activities. Gait fluency evaluated in TUG scale found slow and unsteady gait in 33.7% of the subjects. 27.5% of the subjects used mobility aids when walking. In the Risk of falls scale, 131 subjects (25.89%) were at risk of falls. According to logistic regression the main risk of fall determinants (p <0.05) in the study group were: age, previous falls, feet problems, lack of regular care, impaired vision, urinary incontinence, pain, sleeping disorders, and lowered mood. Risk of falls increases in people less independent in terms of basic and complex life activities and in people with depression. Most of the risk factors can be modified. It is necessary to develop a standard procedure aimed at preventing falls in the elderly.


Evidence available to guide care during labor and birth for women and their partners who know their baby will be stillborn: a scoping review protocol.
The aim of the proposed scoping review is to explore and summarize the range of available evidence for bereavement care, specifically in relation to labor and birthing experiences of a stillborn baby. Clinical practice guidelines for bereavement care following pregnancy loss have been developed. However, there remains a lack of evidence to guide recommendations for providing appropriate care to parents at the time of diagnosis, and during the labor and birth of a stillborn baby. The proposed review will consider studies, reports, guidelines, evidence syntheses, and other relevant literature that explore the experiences, needs, and care provided to bereaved parents during labor and birth of a stillborn baby. The search strategy for the proposed scoping review will aim to locate both published and unpublished documents, using a three-step search strategy. An initial search will be conducted using the databases MEDLINE and CINAHL to identify relevant articles; a second search will be conducted across all included databases, incorporating identified keywords and index terms; and finally the reference lists of included studies will be screened for additional sources. Google Scholar and Web of Science will be searched for relevant gray literature. The search will restrict documents from 2000 to present to maintain clinical relevancy. Only studies published in English will be included. Results of the search will be exported into a template, where data will be categorized using five key domains (communication, recognition of parenthood, effective support, shared decision-making, and organizational response) summarized into positive, negative, or neutral outcomes, and further refined into common issues across these domains. Open Science Framework "birthing in grief: a scoping review" https://osf.io/xw9md.


A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities.
Gene expression profiles provide an opportunity to dissect the heterogeneity of solid tumors, including colon cancer, to improve prognosis and predict response to therapies. Bayesian binary regression methods were used to generate a signature of disease recurrence in patients with resected early stage colon cancer validated in an independent cohort. A 50-gene signature was developed that effectively distinguished early stage colon cancer patients with a low or high risk of disease recurrence. RT-PCR analysis of the 50-gene signature validated 9 of the top 10 differentially expressed genes. When applied to two independent validation cohorts of 55 and 73 patients, the 50-gene model accurately predicted recurrence. Standard Kaplan-Meier survival analysis confirmed the prognostic accuracy (P < 0.01, log rank), as did multivariate Cox proportional hazard models. We tested potential targeted therapeutic options for patients at high risk for disease recurrence and found a clinically important relationship between sensitivity to celecoxib, LY-294002 (PI3kinase inhibitor), retinol, and sulindac in colon cancer cell lines expressing the poor prognostic phenotype (P < 0.01, t test), which performed better than standard chemotherapy (5-FU and oxaliplatin). We present a genomic strategy in early stage colon cancer to identify patients at highest risk of recurrence. An ability to move beyond current staging by refining the estimation of prognosis in early stage colon cancer also has implications for individualized therapy.


Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers.
This investigation was carried out to evaluate the bioavailability of a new suspension formulation of cefixime (100 mg/5 ml), Winex, relative to the reference product, Suprax (100 mg/5 ml) suspension. The bio-availability study was carried out in 24 healthy male volunteers who received a single oral dose (200 mg) of the test (A) and the reference (B) products on 2 treatment days after an overnight fast of at least 10 hours. The treatment periods were separated by a one-week washout period. A randomized, balanced two-way crossover design was used. After dosing, serial blood samples were collected over a period of 16 hours. Plasma concentrations of cefixime were analyzed using a sensitive high-performance liquid chromatographic assay. The pharmacokinetic parameters for cefixime were determined using standard non-compartmental method. The parameters AUC(0-t), AUC(0-infinity), Cmax, Kel, t1/2 and Cmax/AUC(0-infinity) were analyzed statistically using raw and log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pnfinity harmacokinetic parameters: AUC(0-t), AUC(0-infinity) Cmax, and Cmax/AUC(0-infinity) were within the range 80 - 125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax, and Cmax/AUC(0-infinity) were 88.93 - 107.10%, 89.09 - 107.11%, 89.63 - 108.58% and 96.85 - 105.29%, respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), and Cmax using the Schuirmann's two one-sided t-tests. Therefore, the two formulations were considered to be bioequivalent.


L-NAME- and ADMA-induced sympathetic neural activation in conscious rats.
Although studies in anesthetized, sino-aortic denervated animals indicate that inhibition of central nitric oxide (NO) causes an excitatory influence on efferent sympathetic nerve activity (SNA) that is normally offset by baroreflex activation, studies in conscious animals have not provided clear-cut evidence for a sympathoexcitatory effect of N(omega)-nitro-l-arginine methyl ester (L-NAME) or the endogenous circulating NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). Thus our goals were to 1) use surgical sino-aortic denervation to test for a sympathoexcititatory effect of intravenous l-NAME in conscious rats, and 2) to determine whether SNA responses to intravenous L-NAME can be extrapolated directly to intravenous ADMA. We recorded mean arterial blood pressure and renal SNA in both intact and sino-aortic-denervated conscious rats during 3 h of continuous intravenous infusion with either L-NAME or ADMA. When we eliminated the confounding influence of the sino-aortic baroreceptors, L-NAME produced a progressive increase in SNA with the peak response exceeding the baseline level of nerve firing by 150%. The same type of frank sympathetic activation was observed with intravenous ADMA. Taken together, these data offer straightforward evidence for l-NAME, as well as ADMA-induced sympathetic activation with direct recordings of SNA in conscious animals. These data confirm and extend the concept that circulating endogenous NOS inhibitors can constitute an excitatory signal to SNA.


Clostridium perfringens Type A Isolates of Animal Origin with Decreased Susceptibility to Metronidazole Show Extensive Genetic Diversity.
Metronidazole (MTZ) is a first-line drug for the treatment of human infections caused by anaerobic bacteria. Although most Clostridium perfringens isolates are susceptible to metronidazole, a number of strains with decreased susceptibility have been obtained in clinical and environmental surveys. However, little is known yet about the toxinotype and genetic diversity of metronidazole-resistant C. perfringens strains. We tested for susceptibility to metronidazole and assessed the toxigenic status and amplified fragment length polymorphism (AFLP) diversity of a collection of 80 C. perfringens isolates of animal origin. In vitro susceptibility testing by the standard agar dilution technique revealed that 22 isolates (27.5% of total) were susceptible to metronidazole, 54 (67.5%) intermediate susceptible, and four (5%) resistant. All isolates belonged to toxinotype A, and two, 41 and 17, of them yielded a positive PCR result for presence of the gene encoding for enterotoxin (cpe), the consensus form of β2 toxin (cpb2) and the atypical form of β2 toxin, respectively. AFLP fingerprinting classified isolates into 65 genotypes indicating a high molecular diversity among isolates in this study, and this diversity was reflected among isolates from each susceptibility category. In conclusion, the results of this study revealed extensive genetic diversity among C. perfringens type A isolates regardless of their susceptibility to metronidazole.


Self-healing of surfactant surface micelles on millisecond time scales.
We study the dynamics of surfactant micelles at the solid-liquid interface using a new atomic force-microscopic imaging mode to visualize the nanometer-level structural features of the micelles and the picometer-level lattice of the substrate simultaneously. We find that defects created in a crystalline micellar array by the scanning probe tip self-heal flawlessly in less than 6 ms.


Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma.
The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is pivotal to the pathophysiology of widespread allergic diseases mediated by type 2 helper T cell (Th2) responses, including asthma and atopic dermatitis. The emergence of human TSLP as a clinical target against asthma calls for maximally harnessing its therapeutic potential via structural and mechanistic considerations. Here we employ an integrative experimental approach focusing on productive and antagonized TSLP complexes and free cytokine. We reveal how cognate receptor TSLPR allosterically activates TSLP to potentiate the recruitment of the shared interleukin 7 receptor α-chain (IL-7Rα) by leveraging the flexibility, conformational heterogeneity and electrostatics of the cytokine. We further show that the monoclonal antibody Tezepelumab partly exploits these principles to neutralize TSLP activity. Finally, we introduce a fusion protein comprising a tandem of the TSLPR and IL-7Rα extracellular domains, which harnesses the mechanistic intricacies of the TSLP-driven receptor complex to manifest high antagonistic potency.


Long-range Fourier ptychographic imaging of the dynamic object with a single camera.
Fourier ptychographic imaging technology is a new imaging method proposed in recent years. This technology captures multiple low-resolution images, and synthesizes them into a high-resolution image in the Fourier domain by a phase retrieval algorithm, breaking through the diffraction limit of the lens. In the field of macroscopic Fourier ptychographic imaging, most of the existing research generally focus on high-resolution imaging of static objects, and applying Fourier ptychographic imaging technology to dynamic objects is a hot research area now. At present, most of the researches are to use camera arrays combined with multiplexed lighting, deep learning or other algorithms, but the implementation of these methods is complicated or costly. Based on the diffraction theory of Fourier optics, this paper proposes that by expanding and focusing the illumination area, we can apply Fourier ptychographic imaging technology with a single camera to moving objects within a certain range. Theoretical analysis and experiments prove the feasibility of the proposed method. We successfully achieve high-resolution imaging of the dynamic object, increasing the resolution by about 2.5 times. This paper also researches the impact of speckles in the illuminated area on imaging results and proposes a processing method to reduce the impact of speckles.


[Stable remission of early active rheumatoid arthritis treated with etanercept (Enbrel)].
Regarding to the role of cytokines in ethiology of rheumatoid arthritis, the treatment with anti-TNFalpha is coming to be reasonable in early aggressive rheumatoid arthritis. Studies of etanercept in early stage of disease indicate the sustained efficacy and decreased rate of radiographic progression with significant improvement of life quality.


Perinatal exposure to a high-fat diet alters proopiomelanocortin, neuropeptide Y and dopaminergic receptors gene expression and the food preference in offspring adult rats.
Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation - Control (C) and High-fat (H). Post-weaning - Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life's day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.


Effect of nisoldipine on electrophysiological parameters in patients pretreated with beta-blockers.
The effect of the new 1,4-dihydropyridine calcium antagonist nisoldipine on electrophysiological parameters was investigated in 10 patients who were pretreated with a beta-blocker. 9 patients received atenolol (75 mg/d) and 1 patient pindolol (15 mg/d) at least for three days prior to the electro-physiological study. Before and after the intravenous injection of nisoldipine (1.5 micrograms/kg body weight) the sinus node function (spontaneous sinus node cycle length, sinus node recovery time, rate corrected sinus node recovery time), the conduction times from the high right atrium to the apex of the right ventricle, and the refractoriness of the different compartments of the heart were assessed. Arterial blood pressure was measured with the cuff method. Nisoldipine induced a slight but significant increase of the heart rate without effecting the blood pressure significantly. All other measured electrophysiological parameters remained unaltered, especially the conduction time of the av node. It is concluded that concerning electrophysiology nisoldipine can safely be combined with beta-blockers because this calcium antagonist does not exert an electrophysiological effect.


[Preliminary study on genotyping of Mycobacterium tuberculosis strains isolated in Tibet with multiple locus variable numbers of tandem repeats].
To investigate the application of the multiple locus variable numbers of tandem repeats (MLVA) in genotype Mycobacterium tuberculosis strains isolated from Tibet, and to understand the characteristics of genotype and distribution. 217 M. tuberculosis strains were collected from six regions of Tibet. Twenty tandem repeats loci in the total genome of M. tuberculosis (MTB) were analyzed by PCR and agarose gel electrophoresis method. The characteristics on polymorphism of DNA fingerprinting of 217 MTB strains were analyzed with BioNumerics 3.0 software. 217 M. tuberculosis strains detected with 20 MLVA loci were classified to 19 genotypes with 87.6% of the stains belonging to Beijing genotype and the other 18 genotypes were scattered,accounted for 1.38% and 0.92% strains, respectively. Beijing genotype was not significantly associated with the resistance to all of the four drugs and BCG vaccination. It is concluded that the strains of MTB isolated in Tibet present definite polymorphism and most of the epidemic strains belonged to Beijing family genotype and MTB genotyping. The Beijing genotype was not recognized as the one transferred from some of the drug resistance strains or from BCG vaccination. Being a fast and simple technique, MLVA method, seemed a better molecular typing method and could be used for genotyping in M. tuberculosis and monitoring pathogen.


Displacement behaviour is associated with reduced stress levels among men but not women.
Sex differences in the ability to cope with stress may contribute to the higher prevalence of stress-related disorders among women compared to men. We recently provided evidence that displacement behaviour--activities such as scratching and face touching--represents an important strategy for coping with stressful situations: in a healthy population of men, displacement behaviour during a social stress test attenuated the relationship between anxiety experienced prior to this test, and the subsequent self-reported experience of stress. Here, we extend this work to look at physiological and cognitive (in addition to self-reported) measures of stress, and study both men and women in order to investigate whether sex moderates the link between displacement behaviour and the response to stress. In a healthy study population, we quantified displacement behaviour, heart rate and cognitive performance during the Trier Social Stress Test, and used self-report questionnaires to assess the experience of stress afterwards. Men engaged in displacement behaviour about twice as often as women, and subsequently reported lower levels of stress. Bivariate correlations revealed that for men, higher rates of displacement behaviour were associated with decreased self-reported stress, fewer mistakes in the cognitive task and a trend towards lower heart rate; no relationships between displacement behaviour and stress measures were found for women. Moreover, moderation analyses revealed that high rates of displacement behaviour were associated with lower stress levels in men but not in women, and that high displacement behaviour rates were associated with poorer cognitive performance in women, but not men. These results point to an important sex difference in coping strategies, and highlight new avenues for research into sex biases in stress-related disorders.


Molecular and functional assessment of bacterial community convergence in metal-amended soils.
Species diversity and the structure of microbial communities in soils are thought to be a function of the cumulative selective pressures within the local environment. Shifts in microbial community structure, as a result of metal stress, may have lasting negative effects on soil ecosystem dynamics if critical microbial community functions are compromised. Three soils in the vicinity of a copper smelter, previously contaminated with background, low and high levels of aerially deposited metals, were amended with metal-salts to determine the potential for metal contamination to shape the structural and functional diversity of microbial communities in soils. We hypothesized that the microbial communities native to the three soils would initially be unique to each site, but would converge on a microbial community with similar structure and function, as a result of metal stress. Initially, the three different sites supported microbial communities with unique structural and functional diversity, and the nonimpacted site supported inherently higher levels of microbial activity and biomass, relative to the metal-contaminated sites. Amendment of the soils with metal-salts resulted in a decrease in microbial activity and biomass, as well as shifts in microbial community structure and function at each site. Soil microbial communities from each site were also observed to be sensitive to changes in soil pH as a result of metal-salt amendment; however, the magnitude of these pH-associated effects varied between soils. Microbial communities from each site did not converge on a structurally or functionally similar community following metal-salt amendment, indicating that other factors may be equally important in shaping microbial communities in soils. Among these factors, soil physiochemical parameters like organic matter and soil pH, which can both influence the bioavailability and toxicity of metals in soils, may be critical.


First-episode psychosis in a 15 year-old female with clinical presentation of anti-NMDA receptor encephalitis: a case report and review of the literature.
Anti-NMDA receptor encephalitis is an autoimmune disease that was identified in 2007, and manifests in a stepwise manner with psychiatric, neurological and autonomic symptoms. The disease is caused by autoantibodies against NMDA receptors. It can have a paraneoplastic origin, mainly secondary to ovarian teratomas, but it can also be unrelated to the tumor. This disease can affect both sexes and all ages. Here, we present a case of a 15 year-old female adolescent with first-episode psychosis with anti-NMDA receptor encephalitis not related to tumor, which manifested with delusion, hallucinations, panic attacks, agitation, and neurological symptoms, and later with autonomic instability. She was treated with immunotherapy and psychiatric medication resulting in improvement of her main psychiatric and neurological symptoms. Our main objective in presenting this case is to alert clinicians to this challenging and recent disease that has a clinical presentation that might resemble a functional psychiatric condition and can be underdiagnosed in the context of child and adolescent psychiatry.


An ex vivo RNA trans-splicing strategy to correct human generalized severe epidermolysis bullosa simplex.
Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is a genetic blistering skin disease in which autosomal dominant mutations in either the keratin KRT5 or KRT14 genes lead to impaired function of the intermediate filament cytoskeleton in the basal epidermis. Here we present an ex vivo RNA trans-splicing-based therapeutic approach to correct the phenotype. To correct a mutation within exon 1 of the KRT14 gene, using a 5'-trans-splicing approach, where any mutation within the first seven exons could be replaced by a single therapeutic molecule. A therapeutic RNA trans-splicing molecule containing wild-type exons 1-7 was stably transduced into an EBS patient-derived keratinocyte line. Trans-splicing was confirmed via reverse-transcriptase polymerase chain reaction, Western blotting and immunofluorescence microscopy. Skin equivalents generated from corrected keratinocytes were grafted onto nude mice and analysed about 8 weeks post-transplantation for regular epidermal stratification, trans-splicing-induced green fluorescent protein expression and blistering. Transplanted skin equivalents generated from trans-splicing-corrected patient keratinocytes showed a stable and blister-free epidermis. KRT14 correction disrupted EBS-gen sev-associated proinflammatory signalling, as shown at the mRNA and protein levels. Disruption of the pathogenic feedback loop in addition to overall downregulation of KRT14 expression highlighted the effect of KRT14 correction on the EBS pathomechanism. Our data demonstrate that trans-splicing-mediated mRNA therapy is an effective method for the correction of dominantly inherited KRT14 mutations at the transcriptional level. This results in the rescue of the EBS-gen sev phenotype and stabilization of the epidermis in a xenograft mouse model.


FeF3@Thin Nickel Ammine Nitrate Matrix: Smart Configurations and Applications as Superior Cathodes for Li-Ion Batteries.
Iron fluorides (FeFx) for Li-ion battery cathodes are still in the stage of intensive research due to their low delivery capacity and limited lifetime. One critical reason for cathode degradation is the severe aggregation of FeFx nanocrystals upon long-term cycling. To maximize the capacity and cyclability of these cathodes, we propose herein a novel and applicable method using a thin-layered nickel ammine nitrate (NAN) matrix as a feasible encapsulation material to disperse the FeF3 nanoparticles. Such core-shell hybrids with smart configurations are constructed via a green, scalable, in situ encapsulation approach. The outer thin-film NAN matrix with prominent electrochemical stability can keep the FeF3 nanoactives encapsulated throughout the cyclic testing, protecting them from adverse aggregation into bulk crystals and thus leading to drastic improvements of electrode behaviors (e.g., high electrode capacity up to ∼423 mA h g(-1), greatly prolonged cyclic period, and promoted rate capabilities). This present work may set up a new and general platform to develop intriguing core-shell hybrid cathodes for Li-ion batteries, not only for FeFx but also for a wide spectrum of other cathode materials.


Role of oral food challenges in the diagnostic work-up of food allergy in atopic eczema dermatitis syndrome.
The diagnosis of food allergy in infants and children is still a challenging task for the pediatrician. While immediate-type allergic reactions to foods can be diagnosed quite easily, late-phase reactions, e.g. in atopic dermatitis, often represent a diagnostic challenge. Once classical diagnostic procedures such as history, skin prick tests, atopy patch test, and specific immunoglobulin E in serum have been exhausted, double-blind, placebo-controlled food challenges represent the state of the art. After an oligo-allergenic diet, suspected foods or placebo are given in a titrated manner until a clear clinical reaction or the highest dose. The observation period should be 48 h in the case of atopic dermatitis. Constant clinical monitoring is mandatory. Dietetic recommendations are given for 12 months. The effort involved in such a procedure is justified because it can help to avoid clinically relevant food allergens in some cases and in others can prevent children from being exposed unnecessarily to diets that may be harmful to them.


Repeat gamma knife surgery for regrowth of vestibular schwannomas.
Gamma knife surgery (GKS) has become established as a minimally invasive treatment modality for patients with vestibular schwannomas. Treatment failure and/or tumor regrowth, however, is occasionally encountered, and microsurgical resection is usually warranted in such cases. The role of repeat GKS in these situations is still unclear. The goal of this study was to investigate whether repeat GKS is an effective treatment for recurrent vestibular schwannomas and to assess the conservation of residual neurological function. Between July 1992 and December 2007, 1951 patients harboring a unilateral vestibular schwannoma were treated with GKS. Of these, 48 patients (2.5%) had to undergo a subsequent intervention because of progression or regrowth of the tumor. Repeat GKS was performed in a total of 15 patients, 8 of whom had more than 2 years of follow-up and were eligible to be enrolled in the present study. The median follow-up period after repeat GKS was 64 months, and the median interval between these interventions was 46 months. The median tumor volume was 0.51 and 1.28 mL at the initial and second GKS treatments, respectively. Patients received a median prescription dose of 12.0 Gy at both interventions. We report no cases of failure. Six patients demonstrated a significant reduction in tumor volume. In 1 patient, the final tumor volume was less than the initial volume. The other 2 patients showed stabilization of tumor growth. Useful hearing ability was preserved in only 1 of the 3 patients who had serviceable hearing ability at the time of the second GKS. Neither aggravation of facial nerve dysfunction nor other neurological deficits secondary to GKS were observed. This is the first report to address repeat GKS for vestibular schwannomas. After long-term follow-up, repeat GKS with a low marginal dose seems to be a safe and effective treatment in selected patients harboring regrowth of small vestibular schwannomas that have previously been treated with GKS.


Bilateral Parainfectious Optic Neuritis in Young Patient.
Parainfectious optic neuritis arises from infectious aetiology either from pathogen direct invasion or after an infectious disease which can be immunologically mediated demyelination of optic nerve or, from inflammation of optic disc vasculature. We report a case of bilateral optic neuritis in a young patient. A 13-year-old boy presented with painless profound vision loss in both eyes preceded by an episode of fever two weeks prior. Visual acuity in both eyes was a perception of light. Fundoscopy showed a bilateral hyperemic swollen disc. Blood investigations were normal except for C-reactive protein and ESR was elevated. CSF analysis was also normal with no growth of micro-organisms. Both CT scans and MRIs of the brain and orbit showed normal findings. The patient was diagnosed to have parainfectious optic neuritis. He was started on intravenous methylprednisolone for five days followed by a tapering dose of oral prednisolone for a total of one month. His final visual acuity improved to 6/6 in both eyes with a normal optic disc appearance.


Robust technique using an imaging plate to detect environmental radioactivity.
The Fukushima Daiichi Nuclear Power Plant was severely damaged by the Great East Japan Earthquake on 11 March 2011. Consequently, a large amount of radioactive material was accidentally released. Recently, the focus has been on quantification of environmental radioactive material. However, conventional techniques require complicated and expensive measurement equipment. In this research, the authors developed a simple method to detect environmental radioactive material with an imaging plate (IP). Two specific measurement subjects were targeted: measurements for the depth distribution of radioactive material in soil and surface contamination of a building roof. For the measurement of depth distribution of radioactive material in soil, the authors ascertained that the concentration of environmental radioactivity was highest at 5 cm below the surface, and it decreased with depth. For the measurement of surface contamination of the building roof, the authors created a contamination map of the building roof. The detector developed could contact the ground directly, and unlike other survey meters, it was not influenced by peripheral radioactivity. In this study, the authors verified the feasibility of measurement of environmental radioactivity with an IP. Although the measured values of the IP were relative, further work is planned to perform evaluations of absolute quantities of radioactive material.


Combining natriuretic peptides and necrosis markers in the assessment of acute coronary syndromes.
Management of patients with acute coronary syndromes (ACS) is becoming more complex as the array of treatment options available to patients and physicians continues to expand. Cardiac biomarkers play an important role in risk stratification in ACS, and results of cardiac biomarker tests can be used to help guide choices between alternative therapies. In addition to biomarkers of myocyte necrosis, markers of neurohormonal activation, such as B-type natriuretic peptide (BNP), provide important prognostic information in ACS. In the future, multimarker strategies that incorporate panels of cardiac biomarkers are likely to be used for risk stratification and for pathophysiology-guided treatment in patients with ACS.


Insulin and jejunal electrical activity in dogs and sheep.
The effect of insulin on jejunal myoelectric activity was studied in conscious dogs and sheep by injection of insulin and stimulation of insulin release. In dogs, the migrating myoelectric complex (MMC), characteristic of fasting, was replaced by a continuous pattern of activity after feeding, injection of insulin, or infusion of D-glucose, L-leucine, or L-arginine. The response to feeding was reduced in alloxan-diabetic dogs and completely abolished following additional vagotomy when only exogenous insulin induced the "fed" pattern. Vagotomy alone had only minor effects on the response to feeding. Sheep exhibit a continuous sequence of MMC, regardless of feeding, but infusion of insulin or volatile fatty acids produced activity similar to that seen after feeding in dogs. In alloxan-diabetic sheep the recurrence and intensity of the MMC were decreased, and the effect of volatile fatty acids was eliminated. Insulin injection restored the pattern to normal. Thus, insulin levels are of importance in the control of the jejunal motor profile and may mediate the postprandial disappearance of MMC in dogs.


Recombinant poxviruses: versatile tools for immunological assays.
The study of antigen processing and presentation is critical to our understanding of the mechanisms that govern immune surveillance. A typical requirement of assays designed to examine antigen processing and presentation is the de novo biosynthesis of a model antigen. Historically, Vaccinia virus (VACV), a poxvirus closely related to Cowpox, has enjoyed widespread use for this purpose. Recombinant poxvirus-based expression has a number of advantages over other systems. Poxviruses accommodate the insertion of large pieces of recombinant DNA into their genome, and recombination and selection are relatively efficient. Poxviruses readily infect a variety of cell types, and they drive rapid and high levels of antigen expression. Additionally, they can be utilized in a variety of assays to study both MHC class I-restricted and MHC class II-restricted antigen processing and presentation. Ultimately, the numerous advantages of poxvirus recombinants have made the Vaccinia expression system a mainstay in the study of processing and presentation over the past two decades. In an attempt to address one shortcoming of VACV while simultaneously retaining the benefits inherent to poxviruses, our laboratory has begun to engineer recombinant Ectromelia viruses. Ectromelia virus, or mousepox, is a natural pathogen of murine cells and performing experiments in the context of a natural host-pathogen relationship may elucidate unknown factors that influence epitope generation and host response. This chapter describes several recombinant poxvirus system protocols used to study both MHC class I and class II antigen processing and presentation, as well as provides insight and troubleshooting techniques to improve the reproducibility and fidelity of these experiments.


Evaluation of fracture stability. A mechanical simulator for assessment of clinical judgement.
To test the surgeon's clinical ability to detect small movements in fractures, a simulator with elastic behaviour was constructed. The bending moment required to produce a certain deflection was adjusted at four different levels. With the lowest stiffness, all surgeons in the test series reported that the fracture was unstable at a deflection of 3-4 degrees. With increasing stiffness, an increase in stability was reported--the registered deflection, however, was always 3-4 degrees. These observations confirm that manual tests of fracture stability are uncertain.


Exploring the impact of oral diseases and disorders on quality of life of preschool children.
To assess the impact of oral health outcomes on Oral Health-Related Quality of Life (OHRQoL) in a school-based sample of Brazilian preschool children and their families. A cross-sectional study was conducted in 1036 children aged 2-5 years attending all the public nurseries in Canoas, Brazil. Caregivers were asked to complete questionnaire on socioeconomic status and the Early Childhood Oral Health Impact Scale (ECOHIS) on their perception of the children's OHRQoL. Clinical assessment included dental caries, traumatic dental injuries (TDI) and malocclusion. Multivariable Poisson regression models with robust variance were fitted to assess covariates for the prevalence of impacts on OHRQoL following a theoretical hierarchical framework. 17.4% of the caregivers reported that their child had an impact on at least one ECOHIS item. Negative impacts were more prevalent on items related to pain, difficult drinking and eating some foods. The multivariable Poisson regression analysis showed that dental caries, TDI and malocclusion were associated with the outcome. The prevalence of having any impact on OHRQoL was almost three times higher for children with dental caries (PR 2.74 95% CI 2.02-3.72) compared to those who were caries free; and approximately 1.5 times higher for those who presented TDI (PR 1.70 95% CI 1.27-2.27) and malocclusion (PR 1.42 95% CI 1.04-1.94). The findings showed that caregivers of young children with oral disease and disorders perceived that both the children and other family members had poorer quality of life. Oral health policies should be included into general health programs based on common risk approach.


Identification and characterization of functional intermediates of stem bromelain during urea and guanidine hydrochloride unfolding.
By comparing changes in enzyme activity with changes in spectral features for stem bromelain (EC.22.214.171.124) in the absence and presence of urea, Guanidine hydrochloride and ethanol; four intermediate states could be identified: two activity-enhanced state obtained in the presence of 5 M urea and 2 M GnHCl, termed X and X', respectively, and a third, similarly active state closely resembling the native protein in the presence of 8-9 M urea, termed Y. The enhanced activity of these states is due to local conformational changes accompanied by increased dynamics in the active site. Further, the enzyme does not lose its activity after substantial tertiary structure changes in 8-9 M urea (Y state), suggesting that active site containing domain is more resistant to chemical denaturation than the other structural domain. This makes stem bromelain and in general cysteine proteases an exception to the hypothesis that active site is the most labile part of enzyme.


Dietary Glutamine and Glutamate in Relation to Cardiovascular Disease Incidence and Mortality in the United States Men and Women with Diabetes Mellitus.
Evidence regarding the potential health effects of dietary amino acids glutamine and glutamate among individuals with type 2 diabetes (T2D) is limited. The aim was to examine dietary glutamine and glutamate in relation to subsequent risk of cardiovascular disease (CVD) and mortality among individuals with T2D. We prospectively followed 15,040 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1980-2014 and Health Professionals Follow-Up Study: 1986-2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 y. Associations of energy-adjusted glutamine and glutamate intake, as well as their ratio, with CVD risk and mortality, were assessed using Cox proportional-hazards models with adjustments for demographics, dietary and lifestyle factors, and medical history. During 196,955 and 225,371 person-years of follow-up in participants with T2D, there were 2927 incident CVD cases and 4898 deaths, respectively. Higher intake of glutamine was associated with lower risk of CVD incidence, CVD mortality, and total mortality: comparing extreme quintiles, the hazard ratios (HRs) (95% confidence intervals [CIs]) were 0.88 (0.77, 0.99), 0.78 (0.65, 0.92), and 0.84 (0.76, 0.92), respectively (all P-trend < 0.05). In contrast, higher intake of glutamate was associated with a higher risk of CVD incidence, CVD mortality, and total mortality; the HRs were 1.30 (1.15, 1.46), 1.46 (1.24, 1.72), and 1.20 (1.09, 1.32), respectively (all P-trend < 0.05). Furthermore, comparing extreme quintiles, a higher dietary glutamine-to-glutamate ratio was associated with a lower risk of CVD incidence (0.84 [0.75, 0.95]), CVD mortality (0.66 [0.57, 0.77]), and total mortality (0.82 [0.75, 0.90]). In addition, compared with participants with stable or decreased consumption of glutamine-to-glutamate ratio from prediabetes to postdiabetes diagnosis, those who increased the ratio had a 17% (5%, 27%) lower CVD mortality. In adults with T2D, dietary glutamine was associated with a lower risk of CVD incidence and mortality, whereas the opposite was observed for glutamate intake.


Meta-analysis of the influence of Parkin p.Asp394Asn variant on the susceptibility of Parkinson's disease.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The Parkin p.Asp394Asn variant (c.1281G>A) has been investigated as a potential genetic hallmark of PD, but studies investigating the association between the variant and PD have reported conflicting results. Therefore, we conducted this meta-analysis to assess whether pooled results show the association. We performed structured literature searches in MEDLINE, EMBASE, Cochrane Library, and China Academic Journals databases for studies addressing the association between Parkin p.Asp394Asn variant and PD. The meta-analysis was conducted in five genetic models: additive, dominant, recessive, heterozygous, and homozygous, with the odds ratio (OR) as the measure of association. When all 7 studies involving 2425 subjects (1213 cases and 1212 controls) were pooled into the analysis, there was no evidence for significant association between Parkin p. Asp394Asn variant and PD risk in additive genetic model (OR=1.06, 95% confidence interval (CI)=0.66-1.70, P=0.825). The OR for the dominant model was 1.07 (95% CI=0.69-1.67) while the OR for the recessive model was 0.84 (95% CI=0.16-4.35). The OR for the heterozygote was 1.08 (95% CI=0.73-1.60) while the OR for the homozygote was 0.85 (95% CI=0.16-4.61). Concluding, our study does not support an association between the Parkin p.Asp394Asn variant and PD risk.


Amelioration of Nephrotoxicity in Mice Induced by Antituberculosis Drugs Using Ensete ventricosum (Welw.) Cheesman Corm Extract.
Antituberculosis drugs are antimicrobial agents important for treating a communicable disease called tuberculosis. Despite their importance, antituberculosis drugs such as isoniazid and rifampicin have severe adverse effects like nephrotoxicity with acute renal failures. Ensete ventricosum (Welw.) Cheesman is a nutritional herbaceous perennial plant, and it has indigenous ethnomedicinal values for the society. This study aimed to evaluate the protective role of the Ensete ventricosum (Welw.) Cheesman corm extract (EVCE) against nephrotoxicity induced by isoniazid and rifampicin in mice. The present study was conducted on thirty Swiss albino mice randomly allocated into five groups. Group-I (only distilled water), Group-II (only isoniazid 75 mg/kg and rifampicin150 mg/kg), Group-III (isoniazid and rifampicin along with 200 mg/kg EVCE), Group-IV (isoniazid and rifampicin along with 400 mg/kg EVCE), and Group-V (isoniazid and rifampicin along with silymarin) were treated for thirty days. At the end of the study, the experimental animals were sacrificed after being injected with anesthetic drug, blood was drawn for a kidney function test, and the kidney was also taken from each experimental animal for histopathological evaluation. Data were entered and analyzed by using one-way ANOVA of SPSS version 25. Results and Conclusion. Serum levels of creatinine, blood urea nitrogen (BUN), and uric acid of the Group-II mice were significantly (P < 0.01) elevated, and serum levels of total proteins and albumin of Group-II mice were significantly (P < 0.01) decreased as compared to Group-I. The group of mice treated with an EVCE reinstated those derangements. The kidney section of Group-II mice showed an abnormality in kidney structure; however, these deformities were not detectable in group-IV mice. The EVCE has sufficient nephroprotective potential against antituberculosis drug-induced kidney injury.


Rapid profiling and pharmacokinetic studies of major compounds in crude extract from Polygonum multiflorum by UHPLC-Q-TOF-MS and UPLC-MS/MS.
A reliable, rapid analytical method was established for characterization of constituents in the ethanol extract of Polygonum multiflorum by combining an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). 131 constituents which including phenolic acids, stilbenes, flavones, anthraquinones, naphthalenes and their derivatives were identified or tentatively identified by using characteristic diagnostic fragment ions and references. The established method was further applied to analyze blood samples, and successfully identified 41 compounds which were absorbed through the gastrointestine in rats after administration the extract of P. multiflorum. Moreover, the pharmacokinetic studies of some major compounds in blood were investigated by using ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method. This study showed a comprehensive research of P. multiflorum, which could provide a meaningful basis for further quality control, pharmacological as well as toxicological researches.


Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericum ascyron L.
Hypericum ascyron L. (Great St. Johnswort), which belongs to the Hypericaceae family, has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China. The aim of the present study was to clarify the anticancer activity compounds from H. ascyron L. and the underlying molecular mechanism. Anticancer activity of H. ascyron L. extract was evaluated using an MTT assay. To confirm the anticancer mechanism of activity compounds, Hoechst 33258, Annexin V-fluorescein isothiocyanate/propidium iodide, 2',7'-dichlorodihydrofluorescein diacetate, rhodamine 123 staining and caspase-3 activity analysis were performed. The results demonstrated that the anti-proliferative action of the mixture of kaempferol 3-O-β-(2″-acetyl) galactopyranoside (K) and quercetin (Q) (molar ratio, 1:1) was significantly increased compared with either of these two compounds separately, and the active fraction of the H. ascyron L. extract |(HALE). HALE, indicating that the anti-proliferative function of H. ascyron L. may be a synergic effect of K and Q. Furthermore, the inhibitory effect of KQ on the growth of HeLa cells was mediated by the induction of apoptosis. To the best of our knowledge, the present study is the first to identify that KQ exhibits significant anti-proliferation activity on HeLa cells via the apoptotic pathway, and is also the first to evaluate the anticancer potential of H. ascyron L. The results of the present study may provide a rational base for the use of H. ascyron L. in the clinic, and shed light on the development of novel anticancer drugs.


Central peptidergic neurons as targets for glucocorticoid action. Evidence for the presence of glucocorticoid receptor immunoreactivity in various types of classes of peptidergic neurons.
By means of double immunolabeling procedures it has been possible to demonstrate glucocorticoid receptor (GR) immunoreactivity (IR) in large numbers of various peptidergic neurons of the brain including neurons containing gastrointestinal peptides, opioid peptides, and peptides with a hypothalamic hormone function. For each peptide system, however, marked heterogeneities exist among brain regions. Thus, in the neocortex and the hippocampal formation most of the brain peptide neurons lack GR IR, while the same types of peptide neurons in the arcuate and paraventricular nucleus [e.g. neuropeptide Y (NPY), somatostatin (SRIF) and the cholecystokinin (CCK) neurons] possess strong GR IR. Furthermore, in the arcuate, parvocellular part of the paraventricular nuclei and the central amygdaloid nucleus practically all the peptidergic neurons are strongly GR IR, while in the lateral hypothalamus, mainly the neurotensin (NT) and galanin (GAL) IR neurons are GR IR. These marked differences among areas probably reflect functional differences dependent upon their participation in stress regulated circuits. All the paraventricular NT, corticotropin-releasing factor (CRF), growth hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) and SRIF IR neurons appear to contain GR IR, while the luteinizing hormone-releasing hormone (LHRH) IR neurons lack GR IR, underlying the importance of glucocorticoids (GC) in controlling endocrine function. Finally, the GC may influence pain and mood control mainly via effects on enkephalin (ENK) neurons especially in the basal ganglia (mood) and on all beta-endorphin (beta-END) neurons of the arcuate nucleus, while most of the dynorphin neurons are not directly controlled by GC.


Major themes for 2010 in cardiothoracic and vascular anesthesia.
Significant variability in transfusion practice persists despite guidelines. Although the lysine analogues are effective antifibrinolytics, safety concerns exist with high doses tranexamic acid. Despite recombinant activated factor VII promising results in massive bleeding after cardiac surgery, it significantly increases arterial thromboembolic risk. Aortic valve repair may evolve to standard of care. Transcatheter aortic valve implantation is an established therapy for aortic stenosis. The cardiovascular anesthesiologist features prominently in the new guidelines for thoracic aortic disease. Although intense angiotensin blockade improves outcomes in heart failure, it might aggravate the maintenance of perioperative systemic vascular tone. Ultrafiltration is an alternative to diuresis for volume overload in heart failure. Management of heart failure titrated to brain natriuretic peptide activity reduces mortality. A major surgical advance has been the significant outcome improvement achieved with continuous-flow left ventricular assist devices. Advanced liver disease is a significant predictor for perioperative bleeding, transfusion and mortality after ventricular assist device insertion. Acquired von Willebrand syndrome is not only common in patients with these devices but often aggravating bleeding and transfusion in this setting. Metabolic myocardial modulation with perhexilene significantly enhances effort tolerance in hypertrophic cardiomyopathy. A landmark report has highlighted future priorities in this disease. Pediatric cardiac surgical trials have revealed the importance of perioperative cerebral oxygen saturation monitoring and the Sano shunt. Advances in pediatric-specific ventricular assist devices will likely revolutionize pediatric heart failure. Recent reports have highlighted the priorities for future perioperative trials and for training models in pediatric cardiac anesthesia.


The biogenetic law and the Gastraea theory: From Ernst Haeckel's discoveries to contemporary views.
More than 150 years ago, in 1866, Ernst Haeckel published a book in two volumes called Generelle Morphologie der Organismen (General Morphology of Organisms) in the first volume of which he formulated his biogenetic law, famously stating that ontogeny recapitulates phylogeny. Here, we describe Haeckel's original idea as first formulated in the Generelle Morphologie der Organismen and later further developed in other publications until the present situation in which molecular data are used to test the "hourglass model," which can be seen as a modern version of the biogenetic law. We also tell the story about his discovery, while traveling in Norway, of an unknown organism, Magosphaera planula, that was important in that it helped to precipitate his ideas into what was to become the Gastraea theory. We also follow further development and reformulations of the Gastraea theory by other scientists, notably the Russian school. Elias Metchnikoff developed the Phagocytella hypothesis for the origin of metazoans based on studies of a colonial flagellate. Alexey Zakhvatin focused on deducing the ancestral life cycle and the cell types of the last common ancestor of all metazoans, and Kirill V. Mikhailov recently pursued this line of research further.


The agotrons: Gene regulators or Argonaute protectors?
Over the last decades, it has become evident that highly complex networks of regulators govern post-transcriptional regulation of gene expression. A novel class of Argonaute (Ago)-associated RNA molecules, the agotrons, was recently shown to function in a Drosha- and Dicer-independent manner, hence bypassing the maturation steps required for canonical microRNA (miRNA) biogenesis. Agotrons are found in most mammals and associate with Ago as ∼100 nucleotide (nt) long RNA species. Here, we speculate on the functional and biological relevance of agotrons: (i) agotrons could serve as non-promiscuous miRNA-like regulators with reduced off-targeting or (ii) agotrons could encompass other putative functions, such as protecting Ago proteins from taking up aberrant short RNAs or by rescuing and stabilizing otherwise unloaded Ago-proteins from degradation. Collectively, agotrons have emerged as a novel class of interesting non-coding RNA molecules, but their full functional potential and biological impact still remain to be disclosed.


Antitussive effect of (+/-) pentazocine in diabetic mice is mediated by delta-sites, but not by mu- or kappa-opioid receptors.
The effects of streptozotocin-induced diabetes on the antitussive effect of (+/-) pentazocine were examined in mice. Intracerebroventricular (i.c.v.) administration of (+/-) pentazocine produced a dose-dependent antitussive effect in both diabetic and non-diabetic mice. There were no significant differences in the antitussive effect of (+/-) pentazocine in diabetic and non-diabetic mice. The antitussive effect of i.c.v. (+/-) pentazocine was partially, but significantly, reduced in non-diabetic mice following pretreatment with either beta-funaltrexamine, a selective mu-opioid antagonist, or rimcazole, a specific sigma-site antagonist. The antitussive effect of (+/-) pentazocine in diabetic mice was significantly antagonized by pretreatment with rimcazole. However, beta-funaltrexamine had no effect on the antitussive effect of (+/-) pentazocine in diabetic mice. Furthermore, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of (+/-) pentazocine in either non-diabetic or diabetic mice. These results suggest that although the antitussive effect of i.c.v. (+/-) pentazocine in non-diabetic mice is mediated by both mu-opioid receptors and sigma-sites, in diabetic mice this effect is mainly mediated by sigma-sites.


Keratometric results of penetrating keratoplasty with the Hessburg-Barron and Hanna trephine systems using a standard double-running suture technique.
To compare final, sutures-out, keratometric results of penetrating keratoplasty using two different suction trephine systems and a standard double-running suture technique. Keratometric data after final suture removal were compared retrospectively for three groups of transplants: Group 1, 7.50-mm Hessburg-Barron recipient trephine and 7.70-mm modified Lieberman donor punch (n = 70); Group 2, 7.50-mm Hessburg-Barron recipient trephine and 8.00-mm modified Lieberman donor punch (n = 18); Group 3, 7.50-mm Hanna recipient trephine and 7.75-mm Hanna donor punch (n = 68). Final average keratometry was 46.7 +/- 2.4 D (mean +/- SD, diopters), and final median keratometric astigmatism was 4.6 D (2.6-7.4 D, interquartile range), with no significant difference between groups. Final average keratometry values increased from preoperative values by 3.3 +/- 2.7 D. The correlation between preoperative average keratometry values and final values was low (rs = 0.2; p = 0.07). Average keratometry values increased by 2.3 D (median) after 10/ 0 suture removal (p < 0.0001) and by 0.2 D (median) after 11/0 suture removal (p = 0.09), with no significant difference between groups. There was a negative correlation between donor age and overall change in average keratometry (rs = -0.3; p = 0.002). Visual acuity improved by a median of 5 lines, with no significant difference between trephine systems. There was no statistically significant difference in keratometric results using these two suction trephines with a standard suture technique. Final graft curvature was greater with both suction trephines compared with previously published results of transplants using hand-held trephines with the same suture technique.


Set-shifting ability and schizophrenia: a marker of clinical illness or an intermediate phenotype?
Impairments of executive functioning, such as set-shifting ability, are seen as core deficits of schizophrenia and are of interest as candidate intermediate phenotype markers. The Intradimensional/Extradimensional (ID/ED) shift task offers a differentiated assessment of shifting from previously reinforced stimuli as well as shifting from previously reinforced features and has proven to be sensitive to the impairment seen in patients with schizophrenia. We examined ID/ED performance in 147 patients with schizophrenia, 131 of their healthy siblings, and 303 healthy control subjects. Participants were recruited from local and national sources as volunteers for the Clinical Brain Disorders Branch/National Institute of Mental Health "sibling study". Nearly all control subjects (87%) finished the task successfully, as did 80% of siblings. In contrast only 54% of patients with schizophrenia were able to complete the task. Despite the apparent similarity of performance across the sibling and healthy comparison group, the two groups differed significantly in terms of the number of stages until failure. This difference, however, was not present at any particular stage or any other measure of performance. Patients demonstrated robust ID/ED deficits. However, their siblings were minimally impaired, and this impairment did not seem to run in families. These results suggest that impairments on attentional set shifting assessed by ID/ED task are strongly associated with clinical illness, but these impairments are not a promising intermediate phenotype.


Microarray Analysis of Gene Expression Involved in Butyrate-Resistant Colorectal Carcinoma HCT116 Cells.
Resistance to chemotherapeutic agents is usually found in cancer stem cells (CSCs) and cancer stem-like cells that are often regarded as the target for cancer monitoring. However, the different patterns of their transcriptomic profiling is still unclear. This study aims to illustrate the transcriptomic profile of CSCs and butyrate-resistant colorectal carcinoma cells (BR-CRCs), by comparing them with parental colorectal cancer (CRC) cells in order to identify distinguishing transcription patterns of the CSCs and BR-CRCs. Parental CRC cells HCT116 (HCT116-PT) were cultured and induced to establish the butyrate resistant cell model (HCT116-BR). Commercial enriching of the HCT116-CSCs were grown in a tumorsphere suspension culture, which was followed firstly by the assessment of butyrate tolerance using MTT and PrestoBlue. Then their gene expression profiling was analyzed by microarray. The results showed that both butyrate-resistant HCT116 cells (HCT116-BR) and HCT116-CSCs were more tolerant a butyrate effects than HCT116-PT cells. Differentially expressed gene profiles exhibited that IFI27, FOXQ1, PRF1, and SLC2A3 genes were increasingly expressed in CSCs, and were dramatically overexpressed in HCT116-BR cells when compared with HCT116-PT cells. Moreover, PKIB and LOC399959 were downregulated both in HCT116-CSCs and HCT116-BR cells. Our findings shed light on the transcriptomic profiles of chemoresistant CRC cells. This data should be useful for further study to provide guidelines for clinical prognosis to determine the guidelines for CRC treatment, especially in patients with chemoresistance and designing novel anti-neoplastic agents.


[Pulmonary rehabilitation of patients following thoracic and upper abdominal surgery].
The incidence of pulmonary complications is high in patients undergoing thoracic and upper abdominal surgery. Such surgery requires that an incision be made into the patient's respiratory muscles. As a result, each respiration taken induces great pain, which makes patients breathe shallowly and prevents their taking deep breaths and coughing. This article takes a pathophysiological approach in examining the mechanisms involved in the development of pulmonary complications and critiques the effectiveness of rehabilitative interventions that are described in the published literature. Upper arm exercise is suggested as an effective and acceptable intervention to promote pulmonary rehabilitation for this group of patients.


Intrapartum management of insulin-dependent diabetes mellitus (IDDM) gestants. A comparative study of constant intravenous insulin infusion and continuous subcutaneous insulin infusion pump (CSIIP).
Two groups of insulin-dependent diabetes mellitus (IDDM) parturients were managed according to different intrapartum protocols and compared with a control group of normal women in labor. Thirty-seven patients received conventional intensified insulin therapy during pregnancy and intravenous continuous insulin infusion during labor. Twenty-eight women were managed by continuous subcutaneous insulin infusion pump (CSIIP) throughout gestation and this therapeutic approach was continued during labor. When the two glucose control techniques were compared, CSIIP was superior to achieving and maintaining intrapartum optimal metabolic control, reducing significantly the incidence of acute fetal distress, thus lowering the cesarean section rate and neonatal hypoglycemia. Consequently we concur with the recommendation that firm prepartum as well as intrapartum diabetic control is mandatory for successful management of labor in IDDM patients.


[The value of computer tomography in the diagnosis of chest wall tumors].
Conventional roentgen diagnosis of chest wall tumors, especially with reference to the expansion in the soft tissue, is limited. The computed tomographic examinations in 35 patients with tumors of the chest wall and pleura demonstrate the great value of this method for localization and the judgement of tumor spreading. CT-controlled fine-needle biopsy can clarify the diagnosis. Computed tomography is important for decision and planning of surgical and radiation therapy.


The problem of erectile dysfunction following myocardial infarction.
The causes of erection problems after an MI can be physical, psychological, a result of medication or a combination of these factors. This paper examines the causes and considers ways in which nurses can help men experiencing this problem, who may still feel embarrassed to broach this subject even though it is now more publically discussed.


Dipeptidyl peptidase-4 inhibitors in progressive kidney disease.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs approved for the treatment of type 2 diabetes. The main action of DPP-4 inhibitors is to increase the level of incretin hormones such as glucagon-like peptide-1 (GLP-1), thereby stimulating insulin secretion from pancreatic β cells. Recently emerging evidence suggests the pleiotropic extrapancreatic function of GLP-1 or DPP-4 inhibitors, including kidney and cardiovascular protection. Here, we review the effects of DPP-4 inhibitors on progressive kidney disease such as diabetic nephropathy from a therapeutic point of view. A growing number of studies in animal models and human diseases have shown that DPP-4 inhibition ameliorates kidney disease by a process independent of glucose lowering. Possible mechanisms underlying such protective properties include the facilitation of natriuresis and reduction of blood pressure, and also local effects of the reduction of oxidative stress, inflammation and improvement of endothelial function in the kidney. DPP-4 inhibitors may also restore other DPP-4 substrates which have proven renal effects. Treatment of diabetes with DPP-4 inhibitors is likely to involve a variety of extrapancreatic effects including renal protection. Such pleiotropic action of DPP-4 inhibitors might occur by both incretin-dependent and incretin-independent mechanisms. Conclusive evidence is needed to translate the favorable results from animal models to humans.


Adenosine Derivates as Antioxidant Agents: Synthesis, Characterization, in Vitro Activity, and Theoretical Insights.
In this work, we present results about the synthesis and the antioxidant properties of seven adenosine derivatives. Four of these compounds were synthesized by substituting the N6-position of adenosine with aliphatic amines, and three were obtained by modification of the ribose ring. All compounds were obtained in pure form using column chromatography, and their structures were elucidated by infrared spectroscopy (IR) and Nuclear Magnetic Resonance (NMR). All adenosine derivatives were further evaluated in vitro as free radical scavengers. Our results show that compounds 1c, 3, and 5 display a potent antioxidant effect compared with the reference compound ascorbic acid. In addition, the absorption, distribution, metabolism and excretion (ADME) calculations show favorable pharmacokinetic parameters for the set of compounds analyzed, which guarantees their suitability as potential antioxidant drugs. Furthermore, theoretical analyses using Molecular Quantum Similarity and reactivity indices were performed in order to discriminate the different reactive sites involved in oxidative processes.


Dissolved rare earth elements in the central-western sector of the Ross Sea, Southern Ocean: Geochemical tracing of seawater masses.
The present essay contributes to the existing literature on rare earth elements (REEs) in the southern hemisphere by presenting the first data, to our knowledge, on the vertical profiles of dissolved REEs in 71 samples collected in the central-western sector of the Ross Sea (Southern Ocean-SO). The REEs were measured in the water samples collected during the 2002-2003 and 2005-2006 austral summers. 4 samples were collected and analysed in the framework of a test experiment, as part of the WISSARD Project (Whillans Ice Stream Subglacial Access Research Drilling). Our results show significant differences between the REE patterns of the main water masses present in the SO: we could observe specific signature in the High Salinity Shelf Water (HSSW), Ice Shelf Water (ISW) and Low Salinity Shelf Water (LSSW). A significant increase in Terbium (Tb) concentration was observed in the HSSW and ISW, the two principal water masses contributing to the formation of Antarctic Bottom Water (AABW) in the Ross Sea area, and in LSSW. Some of the HSSW samples show enrichment in Neodymium (Nd). Dissolved REE could therefore be used as tracers to understand the deep circulation of the SO (Pacific sector). We hypothesize that: (I) the characteristic dissolved REE pattern may derive from the composition of source area and from the hydrothermal activity of the central-western area of the Ross Sea; (II) the Tb anomaly observed in the AABW on the South Australian platform could be partially explained by the contribution of AABW generated in the Ross Sea region.


Number of freestanding EDs up, helping ease overcrowding, serving rural areas.
Freestanding EDs must look and act exactly like the ED in the main facility to meet Medicare requirements. Facilities must be open 24 hours a day with trained nursing and matching physician credentials. Specialty on-call panel must include the same physicians as the one used by main ED. Moving patients into your main hospital is a direct admit, not an Emergency Medical Treatment and Labor Act-covered transfer.