bluuebunny/crossref_metadata_2025 huggingface dataset:
DMBT1 expression in biliary carcinogenesis with correlation of clinicopathological data
Authors: Goeppert Benjamin , Roessler Stephanie , Becker Natalia , Zucknick Manuela , Vogel Monika N , Warth Arne , Pathil‐Warth Anita , Mehrabi Arianeb , Schirmacher Peter , Mollenhauer Jan , Renner Marcus
Published: January 2017

Aims

Deleted in malignant brain tumours 1 (DMBT1) exerts functions in the regulation of epithelial differentiation and inflammation and has been proposed as a tumour suppressor. Because chronic inflammation is a hallmark of cholangiocarcinogenesis, the aim of this study was to investigate the expression of DMBT1 in biliary tract cancer (BTC) and to correlate this expression with clinicopathological data.

Methods and results

The expression of DMBT1 protein was examined immunohistochemically in 157 BTC patients [41 intrahepatic (ICC), 60 extrahepatic cholangiocarcinomas (ECC) and 56 adenocarcinomas of the gallbladder (GBAC)]. Additionally, 56 samples of high‐grade biliary intraepithelial neoplasia (BilIN 3) and 92 corresponding samples of histological non‐neoplastic biliary tract tissues were included. DMBT1 expression was increased significantly in BilIN 3 compared to normal tissue (P < 0.0001) and BTC (P < 0.0001). BTC showed no significant difference in DMBT1 expression compared to non‐neoplastic biliary tissue (P = 0.315). Absent DMBT1 expression in non‐neoplastic biliary tissue of BTC patients was associated with poorer survival (P = 0.027). DMBT1 expression was correlated significantly with patients’ age (P < 0.001).

Conclusion

DMBT1 is expressed differently in cholangiocarcinogenesis and poorer patients’ survival rates are associated with absent DMBT1 expression in non‐neoplastic biliary tissue, suggesting a tumour‐suppressive role of DMBT1 in early cholangiocarcinogenesis.
Abnormal p53 and p16 staining patterns distinguish uterine leiomyosarcoma from inflammatory myofibroblastic tumour
Authors: Schaefer Inga‐Marie , Hornick Jason L , Sholl Lynette M , Quade Bradley J , Nucci Marisa R , Parra‐Herran Carlos
Published: January 2017

Aims

Uterine myxoid leiomyosarcoma may show relatively bland histological appearances, despite its aggressive behaviour. Distinguishing uterine leiomyosarcoma from the more indolent inflammatory myofibroblastic tumour (IMT), which is amenable to targeted therapies, can be challenging. A significant subset of leiomyosarcomas harbour TP53 and/or CDKN2A genomic alterations. Here, we examined the diagnostic value of p53 and p16 immunohistochemistry in the distinction of uterine conventional and myxoid leiomyosarcoma from IMT, in correlation with targeted sequencing of TP53 and CDKN2A.

Methods and results

We performed p53 and p16 immunohistochemistry in 49 tumours, including 23 uterine leiomyosarcomas (12 myxoid, 11 conventional) and 26 IMT (12 uterine, 14 extrauterine). TP53 and CDKN2A coding regions were sequenced in 20 cases (four myxoid, 11 conventional uterine leiomyosarcomas; four uterine, one extrauterine IMT). Abnormal p53 staining patterns (strong/diffuse or null) were observed in six of 12 (50%) myxoid and six of 11 (55%) conventional leiomyosarcomas but none of the IMT (P < 0.0001), correlating with TP53 mutation/deletion (P = 0.0001). P16 loss was detected in five of 10 (50%) myxoid and two of 11 (18%) conventional leiomyosarcomas, but none of the IMT (P = 0.0005), correlating with CDKN2A deletion (P = 0.014). Strong/diffuse p16 staining in six of 21 (29%) leiomyosarcomas and three of 26 (12%) IMT did not correlate with CDKN2A alterations.

Conclusions

Abnormal p53 staining and p16 loss are observed frequently in uterine leiomyosarcomas, with 100% specificity and 70% sensitivity against IMT, and correlating with genomic alterations. Conversely, IMT shows normal p53 and p16 staining, highlighting the use of these markers in the differential diagnosis of uterine mesenchymal neoplasms.
A longitudinal study of changes and associations in dental fear in parent/adolescent dyads
Authors: Luoto Anni , Tolvanen Mimmi , Pohjola Vesa , Rantavuori Kari , Karlsson Linnea , Lahti Satu
Published: January 2017

Background

Dental fear seems to fluctuate, but concordance of changes in dental fears between parent/adolescent dyads has not been reported.

Aim

To study longitudinally the associations between adolescent and parental dental fears and their changes.

Design

Adolescents and parents reported their dental fear independently of each other when adolescents were between 11–12 and 15–16‐year‐olds. Eight hundred and seventeen eligible parent/adolescent dyads were included in the analyses. Dental fear was measured with a single question using five response alternatives. Associations between adolescent and parental dental fears and their changes were analysed using χ2 tests and correlation coefficients.

Results

Prevalence of dental fear remained rather similar during the study. There was a positive association between adolescent and parental dental fears in early adolescence (P < 0.001) but at middle adolescence only among parent/girl dyads (P = 0.007 for girls, P = 0.341 for boys). Changes in dental fear among parent/adolescent dyads did not correlate statistically significantly. Difference between girls’ and boys’ change in dental fear was statistically significant (P = 0.001). Dental fear increased more often among girls than among boys. Boys had stable low/no dental fear more often than girls did.

Conclusion

Adolescents’ and parents’ dental fears seemingly change independently of each other.
Sarcopenia is associated with incident albuminuria in patients with type 2 diabetes: A retrospective observational study
Authors: Bouchi Ryotaro , Fukuda Tatsuya , Takeuchi Takato , Minami Isao , Yoshimoto Takanobu , Ogawa Yoshihiro
Published: January 2017

Sarcopenia, defined as age‐related loss of skeletal muscle mass and function, increases the risk of albuminuria. However, it has still unknown whether sarcopenia could increase the risk for the progression of albuminuria. A total 238 patients with type 2 diabetes (mean age 64 ± 12 years; 39.2% women) were studied in the present retrospective observational study. The prevalence of sarcopenia was 17.6%. During the median follow‐up period of 2.6 years, albuminuria was measured 5.8 ± 1.8 times, and progression of albuminuria was observed in 14.9% of patients with normoalbuminuria, as was 11.5% in those with microalbuminuria. Sarcopenia was significantly associated with both progression (hazard ratio 2.61, 95% confidence interval 1.08–6.31, P = 0.034) and regression (hazard ratio 0.23, 95% confidence interval 0.05–0.98, P = 0.048) of albuminuria by multivariate Cox regression analysis. The present data suggest that sarcopenia is an important determinant of both progression and regression of albuminuria in patients with type 2 diabetes.
Minnesota field population of western corn rootworm (Coleoptera: Chrysomelidae) shows incomplete resistance to Cry34Ab1/Cry35Ab1 and Cry3Bb1
Authors: Ludwick D. C. , Meihls L. N. , Ostlie K. R. , Potter B. D. , French L. , Hibbard B. E.
Published: January 2017

In the United States of America, the western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), is commonly managed with transgenic corn (Zea mays L.) expressing insecticidal proteins from the bacteria Bacillus thuringiensis Berliner (Bt). Colonies of this pest have been selected in the laboratory on each commercially available transformation event and several resistant field populations have also been identified; some field populations are also resistant. In this study, progeny of a western corn rootworm population collected from a Minnesota corn field planted to SmartStax® corn were evaluated for resistance to corn hybrids expressing Cry3Bb1 (event MON88017) or Cry34/35Ab1 (event DAS‐59122‐7) and to the individual constituent proteins in diet‐overlay bioassays. Results from these assays suggest that this population is resistant to Cry3Bb1 and is incompletely resistant to Cry34/35Ab1. In diet toxicity assays, larvae of the Minnesota (MN) population had resistance ratios of 4.71 and >13.22 for Cry34/35Ab1 and Cry3Bb1 proteins, respectively, compared with the control colonies. In all on‐plant assays, the relative survival of the MN population on the DAS‐59122‐7 and MON88017 hybrids was significantly greater than the control colonies. Larvae of the MN population had inhibited development when reared on DAS‐59122‐7 compared with larvae reared on the non‐Bt hybrid, indicating resistance was incomplete. Overall, these results document resistance to Cry3Bb1 and an incomplete resistance to Cry34/35Ab1 in a population of WCR from a SmartStax® performance problem field.
A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection
Authors: Zhu M.‐Y. , Zou X. , Li Q. , Yu D.‐M. , Yang Z.‐T. , Huang D. , Chen J. , Gong Q.‐M. , Zhang D.‐H. , Zhang Y. , Chen L. , Chen P.‐Z. , Zhang X.‐X.
Published: January 2017

Several noninvasive blood biomarkers have been established for the assessment of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection, but their clinical performance remains inconclusive. Here, we compared the diagnostic performance of these biomarkers and developed a novel algorithm for assessing liver fibrosis. Six hundred and sixteen chronically HBV‐infected and treatment‐naïve patients who underwent liver biopsy were enrolled and randomly divided into training (N=410) and internal validation cohorts (N=206). One hundred and fifty‐nine patients from another centre were recruited as an external validation cohort. Receiver operating characteristic (ROC) curves were used to analyse the performance of the gamma‐glutamyltransferase‐to‐platelet ratio (GPR), red cell volume distribution width‐to‐platelet ratio (RPR), FIB‐4 index, aspartate aminotransferase‐to‐platelet ratio index (APRI) and HBV DNA level against liver histology, and a novel algorithm was developed using the recursive partitioning and regression tree (RPART) method. In the training cohort, the area under the ROC curve of FIB‐4 was significantly higher than that of APRI (P=.038) but was comparable to those of GPR, RPR and HBV DNA; however, the performance of the biomarkers was similar among the validation cohort. The established RPR‐HBV DNA algorithm performed better in the training cohort than any individual blood biomarker, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 63%, 90%, 72% and 80%, respectively. In the internal and external validation cohorts, the performance of the algorithm in assessing liver fibrosis was also superior to that of other biomarkers. These results suggest that the established RPR‐HBV DNA algorithm might improve the diagnostic accuracy of liver fibrosis in treatment‐naïve patients with chronic HBV infection, although additional studies are warranted to confirm these findings.
Imidazole‐dicarboxylic Acid Nickel Complex as a Novel Grafting Agent for Pearl Oyster, Pinctada martensii
Authors: Ji Lili , Song Wendong , Guo Jian , Wang Yaning , Cai Lu
Published: February 2017

In the pearl cultivation industry, the implantation of the nucleus is a critical step in the production process. The surgical insertion of the nucleus and the mantle results in a wound and stress that affect not only the survival chances of the pearl oysters but also the quality of the pearls produced. This study proposes a synthesized imidazole‐dicarboxylic acid nickel complex that may hold potential in assisting the wound healing and nacre formation processes. The acute toxicity of the complex to pearl oysters, Pinctada martensii, was examined in a dose–response study over a 90‐h exposure. The safe concentrations of the nickel complex determined using probit analysis were 0.916 mg/L and 0.471 mg/L for 72‐h and 96‐h treatments, respectively. The reliability of the regression was verified using the chi‐square test. The alkaline phosphatase (ALP) activity in different regions of the treated and control oysters, along with relevant blood biochemical indices, were measured over a 90‐d period to predict the potential effects of the nickel complex on wound healing and nacre formation. A significant increase in ALP activity in the mantle, together with elevated blood levels of Mg (II) and globulin, and reduced blood levels of Zn (II) and blood urea nitrogen were observed. These results indicate that the prepared nickel complex may hold promise in helping wound healing post mantle implantation, promote the secretion of nacre, and enhance the immunity of the oysters, thus ultimately improving the yield and quality of the pearls.
Bias in phylogenetic measurements of extinction and a case study of end‐Permian tetrapods
Authors: Soul Laura C. , Friedman Matt
Published: January 2017

Extinction risk in the modern world and extinction in the geological past are often linked to aspects of life history or other facets of biology that are phylogenetically conserved within clades. These links can result in phylogenetic clustering of extinction, a measurement comparable across different clades and time periods that can be made in the absence of detailed trait data. This phylogenetic approach is particularly suitable for vertebrate taxa, which often have fragmentary fossil records, but robust, cladistically‐inferred trees. Here we use simulations to investigate the adequacy of measures of phylogenetic clustering of extinction when applied to phylogenies of fossil taxa while assuming a Brownian motion model of trait evolution. We characterize expected biases under a variety of evolutionary and analytical scenarios. Recovery of accurate estimates of extinction clustering depends heavily on the sampling rate, and results can be highly variable across topologies. Clustering is often underestimated at low sampling rates, whereas at high sampling rates it is always overestimated. Sampling rate dictates which cladogram timescaling method will produce the most accurate results, as well as how much of a bias ancestor–descendant pairs introduce. We illustrate this approach by applying two phylogenetic metrics of extinction clustering (Fritz and Purvis's D and Moran's I) to three tetrapod clades across an interval including the Permo‐Triassic mass extinction event. These groups consistently show phylogenetic clustering of extinction, unrelated to change in other quantitative metrics such as taxonomic diversity or extinction intensity.
Ecological implications of the correlation of avian footprints with wing characteristics: a mathematical approach
Authors: Tanaka Ikuko
Published: January 2017

The characteristics of avian wings that evolved for flying appear to show a distinct relationship to the shape of the pes and walking abilities as reflected in footprints. Wing area, wing span and body weight data of modern birds were collected and analysed in order to quantify the possible correlation, which was previously only inferred from empirical data. Discriminant analysis demonstrated that avian wings can be divided into three habitat groups, in a similar way to footprints. Multiple regression analyses revealed that the avian wing loading and aspect ratio were correlated with the parameters of footprint shape and can be expressed by a simple equation. The results may reflect the adaptation of avian locomotion to habitat. The relationships between wing area and wing span, and between wing area and footprint area, which are apparent in modern avians, were derived and used to estimate wing area and wing span from the footprints of extinct Cretaceous avian taxa. The estimated values of body weight, wing span and wing area suggest that the trackmakers of Archaeornithipus meijidei, Hwangsanipes choughi and Yacoraitichnus avis had bodies similar to herons (or cranes), large sandpipers (or small sea birds) and medium‐sized gull‐like birds, respectively.
Photodynamic therapy for dermatologic conditions in the pediatric population: a literature review
Authors: Kumar Neha , Warren Christine B.
Published: January 2017

Photodynamic therapy (PDT), using topical aminolevulinic acid (ALA), has been used for years to treat a variety of dermatologic conditions, including actinic keratosis, superficial basal cell carcinoma, and in situ squamous cell carcinoma. While there is a wide range of neoplastic and non‐neoplastic skin diseases for which ALA‐PDT is used in adults, there is a knowledge gap when it comes to its use in children. This review highlights what is currently known regarding the use and efficacy of this therapy in the pediatric population. A PubMed search was conducted to identify studies including pediatric patients undergoing monotherapy PDT with topical aminolevulinate (published 2005–2016). Twenty pediatric articles were identified. ALA‐PDT has been used successfully in children to reduce the number and size of basal cell tumors, inflammatory acne lesions, plantar warts, and linear porokeratoses. ALA‐PDT may be an attractive alternative to surgery for children with basal cell nevus syndrome, or to conventional destructive and/or topical methods used for plantar warts or linear porokeratoses. PDT can be considered for inflammatory acne when topical treatments have failed and systemic medications are not an option. Pain associated with treatment and insurance coverage may be a barrier to use.
Increased bacterial endophyte populations in Nicotiana benthamiana with a branched‐chain alkane mixture
Authors: Goodwin P. H. , Gao W.
Published: January 2017

The aim of this study was to determine if treatment of soil with a branched‐chain alkane mixture known to induce resistance against Colletotrichum orbiculare also changes populations of bacterial endophytes from Nicotiana benthamiana. Eight culturable bacterial endophyte types matching six species of Bacillus and two species of Pseudomonas were found in roots, stem + petioles and/or leaves. Application of the branched‐chain alkane mixture resulted in significantly higher endophyte populations compared to the water or emulsifier controls for the Pseudomonas sp. LW3, Bacillus simplex LW4 and Bacillus pumilis LW5 colony types in roots and the B. simplex LW4 colony type in stem + petioles. The Pseudomonas sp. LW3 and B. simplex LW4 colony types also had higher populations in pure cultures under in vitro conditions with the branched‐chain alkane mixture compared to the controls. Inoculation with each of the eight colony types increased their population in the plant and induced resistance against C. orbiculare, with the most effective being Pseudomonas sp. LW3 and Pseudomonas alcaligenes SW1. Most of the endophytes could inhibit C. orbiculare growth in vitro, but the level of resistance in planta was not correlated to the ability of the colony type to inhibit C. orbiculare in culture. Thus, a branched‐chain alkane mixture can selectively affect the biomass of a subset of bacterial endophytes, demonstrating that it is a novel in planta endophyte growth promoter.
Neural correlates of apathy in late‐life depression: a pilot [18F]FDDNP positron emission tomography study
Authors: Eyre Harris A. , Siddarth Prabha , van Dyk Kathleen , St. Cyr Natalie , Baune Bernhard T. , Barrio Jorge R. , Small Gary W. , Lavretsky Helen
Published: January 2017

Background

Neurotoxicity associated with amyloid and tau protein aggregation could represent a pathophysiological cascade that, along with vascular compromise, may predispose individuals to late‐life depression (LLD). In LLD, apathy is common, leads to worsening of functioning, and responds poorly to antidepressant treatment. Better understanding of the pathophysiological mechanisms of apathy in LLD would facilitate development of more effective diagnostic and treatment approaches. In this cross‐sectional pilot study, we performed positron emission tomography scans after injection of 2‐(1‐{6‐[(2‐[18
F]fluoroethyl)(methyl)‐amino]‐2‐naphthyl}ethylidene) malononitrile ([18
F]FDDNP), an in vivo amyloid and tau neuroimaging study, in patients with LLD to explore neural correlates of apathy.

Methods

Sixteen depressed elderly volunteers received clinical assessments and [18
F]FDDNP positron emission tomography scans. The cross‐sectional relationship of [18F]FDDNP binding levels with depression (Hamilton Depression Rating Scale) and apathy (Apathy Evaluation Scale) were studied using Spearman's correlation analyses because of the relatively small sample size. Age, sex, and years of education were partialed out. Significance levels were set at P ≤ 0.05.

Results

[18
F]FDDNP binding in the anterior cingulate cortex was negatively associated with the Apathy Evaluation Scale total (r = −0.62, P = 0.02; where low Apathy Evaluation Scale score equals greater severity of apathy). This suggests that apathy in LLD is associated with higher amyloid and/or tau levels in the anterior cingulate cortex. None of the regional [18
F]FDDNP binding levels was significantly associated with the Hamilton Depression Rating Scale total.

Conclusion

This pilot study suggests that increased apathy in subjects with LLD may be associated with greater amyloid and/or tau burden in certain brain regions. Future studies in larger samples would elucidate the generalizability of these results, which eventually could lead to improved diagnostic and treatment methods in LLD.
Serum tumour necrosis factor‐α and interleukin‐6 levels in Alzheimer's disease and mild cognitive impairment
Authors: Kim Yo Sup , Lee Kang Joon , Kim Hyun
Published: January 2017

Background

Neuroinflammation has been recognized as a feature of Alzheimer's disease (AD), and mild cognitive impairment (MCI) is believed to share several pathological features with AD. The aim of the present study was to compare serum cytokine levels between patients with AD, subjects with MCI, and healthy controls, and to assess the correlation between cytokine levels and cognitive performance in these subjects.

Methods

Participants included 35 patients with AD, 29 subjects with MCI, and 28 healthy controls from the Department of Psychiatry of IIlsan Paik Hospital in South Korea. Demographic and neuropsychological information were obtained, and peripheral cytokine levels, specifically tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 levels, were measured for all subjects.

Results

After adjustment for age, a significant difference in IL‐6 levels (P = 0.045), but not in TNF‐α (P = 0.082) levels, was observed among the three groups. IL‐6 levels were higher in patients with AD than in subjects with MCI and healthy controls. TNF‐α and IL‐6 levels negatively and positively correlated with Mini‐Mental State Examination and Global Deterioration Scale scores, respectively. TNF‐α and IL‐6 levels were also positively correlated with each other.

Conclusions

The present study suggests that serum IL‐6 levels of patients with AD might be higher than those of subjects with MCI and healthy controls. Serum TNF‐α and IL‐6 levels might be negatively correlated with cognitive function, and we suspect that serum IL‐6 levels could be biomarkers for AD.
The usefulness of combined brain perfusion single‐photon emission computed tomography, Dopamine‐transporter single‐photon emission computed tomography, and 123I‐metaiodobenzylguanidine myocardial scintigraphy for the diagnosis of dementia with Lewy bodies
Authors: Kobayashi Seiju , Makino Kanae , Hatakeyama Shigeki , Ishii Takao , Tateno Masaru , Iwamoto Tomo , Tsujino Hanako , Kawasaki Kazuhito , Mikuni Kouhei , Ukai Wataru , Murayama Tomonori , Hashimoto Eri , Utsumi Kumiko , Kawanishi Chiaki
Published: January 2017

Background

Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single‐photon emission computed tomography (bp‐SPECT), 123
I‐metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy), and DAT‐SPECT. Taking finances and patient burden into consideration, we compared the tests to determine priority.

Methods

Thirty‐four patients with probable DLB (75.0 ± 8.3 years old; 14 men, 20 women) underwent bp‐SPECT, MIBG scintigraphy, and DAT‐SPECT.

Results

Our comparison of three functional imaging techniques indicated that MIBG scintigraphy (79%) and Dopamine‐transporter (DAT) SPECT (79%) had better sensitivity for characteristic abnormalities in DLB than bp‐SPECT (53%). The combination of the three modalities could increase sensitivity for diagnosis of DLB to 100%. Additionally, the ratio of patients with rapid eye movement sleep behaviour disorder was significantly higher in the positive finding group on MIBG scintigraphy than in the negative finding group.

Conclusions

In terms of stand‐alone diagnostic means, priority should be placed on MIBG scintigraphy or DAT‐SPECT for the diagnosis of DLB. However, our results suggest that the combination of bp‐SPECT, MIBG scintigraphy, and DAT‐SPECT increased the accuracy of the clinical diagnosis of DLB.
Analysis of inedible substance ingestion at a Japanese psychiatric hospital
Authors: Yayama So , Tanimoto Chie , Suto Shunji , Matoba Kei , Kajiwara Tomomi , Inoue Masue , Endo Yoshimi , Yamakawa Miyae , Makimoto Kiyoko
Published: January 2017

Background

Inedible substance ingestion increases the risk of ileus, poisoning, and suffocation. Prevention is especially important in a psychiatric setting. This study aimed to analyze the incidence of inedible substance ingestion in a Japanese psychiatric hospital.

Methods

Inedible substance ingestion incidents were extracted from an incident report database spanning 2000–2012 at a 400‐bed psychiatric hospital in Japan. We tabulated the frequencies of incidents in accordance with major diagnosis, ingested materials, incident levels, and time of occurrence.

Results

The incidence rate was 0.09/1000 patient days, and 149 cases in 105 patients were classified as having experienced inedible substance ingestion. The most common diagnosis was dementia (n = 58), followed by schizophrenia (n = 22). Materials ingested by dementia patients were nappies or gauze attached to the patient's body after medical procedures. Materials ingested by schizophrenic patients were liquid soap, detergent or shampoo, and cigarettes. Inedible substance ingestion among dementia patients occurred mostly before or during meals. Among schizophrenic patients, the peak period of incidents was in the evening.

Conclusions

Dementia patients were overrepresented in the inedible substance ingestion incidents. Items they wore or applied to their bodies were often subject to ingestion, and such behaviours mostly occurred around meal time. Therefore, the nursing staff were able to discover them quickly and treat most of the cases free of serious consequences. In contrast, schizophrenic patients were underrepresented in the incidents, and most cases involved ingestion of detergent powder or cigarettes, resulting in more serious consequences and requiring treatment.
Caregiver burden in older adults with bipolar disorder: relationship to functionality and neuropsychiatric symptoms
Authors: dos Santos Glenda D. , Forlenza Orestes V. , Ladeira Rodolfo B. , Aprahamian Ivan , Almeida Jouce G. , Lafer Beny , Nunes Paula V.
Published: January 2017

Background

There are few studies addressing caregivers of bipolar disorder (BD) patients, especially patients who are older adults with an increased need for care, often given by a relative. The aim of this study was to describe which factors increase caregiver burden among caregivers of elderly BD outpatients.

Methods

Patients were older than 60 years and met the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for BD. They were evaluated for current mood, cognitive and other neuropsychiatric symptoms, functionality, medical comorbidities, quality of life, years since BD diagnosis, and number of psychiatric admissions. The caregiver who spent the greatest time with each patient was evaluated with the Zarit Caregiver Burden Interview. The caregivers' global health, mood symptoms, quality of life, and tasks performed for the patient were also assessed.

Results

Thirty‐six BD patients and their caregivers were assessed. The Zarit Caregiver Burden Interview was positively correlated with patients' neuropsychiatric symptoms (r = 0.508, P = 0.002) and functional impairment (r = 0.466, P = 0.004). The Zarit Caregiver Burden Interview was also correlated with caregivers' own depression (r = 0.576, P < 0.001), anxiety (r = 0.360, P = 0.031), quality of life (r = −0.406, P = 0.014), medical comorbidities (r = 0.387, P = 0.020), and number of tasks that they completed for the patient (r = 0.480, P = 0.003).

Conclusions

In this group of elderly BD patients, caregiver burden was more associated with symptoms frequently seen in others diseases as in dementia than with depressive, manic, or anxiety symptoms, which are often used as treatment outcomes measures goals in BD. Potential treatable and modifiable factors associated with caregiver burden could be caregivers' depression, anxiety, and medical comorbidities, as well as support for caregivers in terms of services and social relationships.
Preprocedural platelet transfusion for patients with thrombocytopenia undergoing interventional radiology procedures is not associated with reduced bleeding complications
Authors: Warner Matthew A. , Woodrum David , Hanson Andrew , Schroeder Darrell R. , Wilson Gregory , Kor Daryl J.
Published: January 2017

BACKGROUND

Platelet (PLT) transfusion before interventional radiology procedures is commonly performed in patients with thrombocytopenia. However, it is unclear if PLT transfusion is associated with reduced bleeding complications.

STUDY DESIGN AND METHODS

This is a retrospective cohort study of adults undergoing interventional radiology procedures between January 1, 2009, and December 31, 2013. Baseline characteristics, coagulation variables, transfusion requirements, and procedural details were evaluated. Propensity‐matched analyses were used to assess relationships between PLT transfusions and the outcomes of interest, including a primary outcome of periprocedural red blood cell (RBC) transfusion during the procedure or within the first 24 hours after procedure.

RESULTS

A total of 18,204 participants met inclusion criteria, and 2060 (11.3%) had a PLT count of not more than 100 × 109/L before their procedure. Of these, 203 patients (9.9) received preprocedural PLTs. There was no significant difference in RBC requirements between those receiving or not receiving preprocedural PLTs in propensity‐matched analysis (odds ratio [OR], 1.45; 95% confidence interval [CI], 0.95‐2.21; p = 0.085). PLT transfusion was associated with increased rates of intensive care unit admission (OR [95% CI], 1.57 [1.07‐2.32]; p = 0.022).

CONCLUSION

In patients with thrombocytopenia undergoing interventional radiology procedures, preprocedural PLT transfusion was not associated with reduced periprocedural RBC requirements. These findings suggest that prophylactic PLT transfusions are not warranted in nonbleeding patients with preprocedural PLT counts exceeding 50 × 109/L. Future clinical trials are needed to further define relationships between prophylactic PLT administration and bleeding complications, especially at more severe levels of thrombocytopenia or in the presence of PLT dysfunction.
Methods for counting residual leukocytes in leukocyte‐depleted plasma—a comparison between a routine hematology instrument, the Nageotte chamber, flow cytometry, and a fluorescent microscopy analyzer
Authors: Petersson Annika , Ekblom Kim
Published: January 2017

BACKGROUND

Counting very low levels of leukocytes is technically challenging but mandatory for quality control of leukocyte‐depleted plasma. Established assays, such as flow cytometry and counting in the Nageotte chamber, are laborious and expensive. The aim of this study was to test two alternative assays, the cerebrospinal fluid program in the routine hematology analyzer ADVIA 2120 and a fluorescence microscopy analyzer, the ADAM‐rWBC.

STUDY DESIGN AND METHODS

Linearity, accuracy, and precision were established for the ADVIA 2120, the ADAM‐rWBC analyzer and the Nageotte chamber with flow cytometry as the reference method. Two hundred consecutive leukocyte‐depleted donor plasma samples were also tested.

RESULTS

The ADAM‐rWBC analyzer and the Nageotte chamber fulfilled all quality requirements. Flow cytometry fulfilled the requirements for linearity and precision. The ADVIA 2120 analyzer did not fully reach the quality criteria, and flow cytometry did not reach quality criteria on accuracy. No false‐positive results on donor plasma samples were recorded.

CONCLUSION

The ADAM‐rWBC is suitable for the purpose of quality control of residual leukocytes in leukocyte‐depleted plasma. For the ADVIA 2120, further improvements and studies are needed to reach the quality requirements stated in this study.
Production of high‐quality islets from goettingen minipigs: Choice of organ preservation solution, donor pool, and optimal cold ischemia time
Authors: Steffen Anja , Kiss Thomas , Schmid Janine , Schubert Undine , Heinke Sophie , Lehmann Susann , Bornstein Stefan , Ludwig Barbara , Ludwig Stefan
Published: January 2017

Background

The transplantation of porcine islets into man might soon become reality for patients with type 1 diabetes mellitus. Therefore, porcine islets of high quality and quantity, and a scalable isolation process with strict quality control will be an unconditional prerequisite to enable the best possible transplantation graft. In this study, we provide a comparative study evaluating islet isolation outcome and in vitro survival based upon donor age, organ preservation solution (OPS), and cold ischemia time (CIT).

Methods

Goettingen minipigs of younger age (1 year) and retired breeder animals (3.5 years) were studied. Pancreata were harvested according to the standards of human organ retrieval including in situ cold perfusion with either Custodiol®‐HTK or Belzer® UW solution. Pancreatic tissue was characterized by quantification of apoptotic cells. Islet isolations were performed according to a modified Ricordi method, and isolation outcome was assessed by determining islet particle numbers (IP), islet equivalents (IEQ), and isolation factor (IF). Isolated islets were cultured for 24 and 48 h for the assessment of in vitro survival.

Results

Islet viability was significantly higher in Custodiol®‐HTK preserved pancreas organs compared to Belzer® UW. Furthermore, organs harvested from retired breeder preserved in Custodiol®‐HTK resulted in stable islet isolation yields even after prolonged CIT and showed superior survival rates of islets in vitro compared to the Belzer® UW group. Younger porcine donor organs resulted generally in lower islet yield and survival rates.

Conclusions

In summary, Custodiol®‐HTK solution should be preferred over Belzer® UW solution for the preservation of pancreata from porcine origin. Custodiol®‐HTK allows for maintaining islet viability and promotes reproducible isolation outcome and survival even after longer CIT. The usage of retired breeder animals over young animals for islet isolation is highly advisable to yield high quality and quantity.
The TRPM7 channel kinase regulates store‐operated calcium entry
Authors: Faouzi Malika , Kilch Tatiana , Horgen F. David , Fleig Andrea , Penner Reinhold
Published: January 2017

Key points

Pharmacological and molecular inhibition of transient receptor potential melastatin 7 (TRPM7) reduces store‐operated calcium entry (SOCE).

Overexpression of TRPM7 in TRPM7−/− cells restores SOCE.

TRPM7 is not a store‐operated calcium channel.

TRPM7 kinase rather than channel modulates SOCE.

TRPM7 channel activity contributes to the maintenance of store Ca2+ levels at rest.

The transient receptor potential melastatin 7 (TRPM7) is a protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. In the present study, we report store‐operated calcium entry (SOCE) as a novel target of TRPM7 kinase activity. TRPM7‐deficient chicken DT40 B lymphocytes exhibit a strongly impaired SOCE compared to wild‐type cells as a result of reduced calcium release activated calcium currents, and independently of potassium channel regulation, membrane potential changes or changes in cell‐cycle distribution. Pharmacological blockade of TRPM7 with NS8593 or waixenicin A in wild‐type B lymphocytes results in a significant decrease in SOCE, confirming that TRPM7 activity is acutely linked to SOCE, without TRPM7 representing a store‐operated channel itself. Using kinase‐deficient mutants, we find that TRPM7 regulates SOCE through its kinase domain. Furthermore, Ca2+ influx through TRPM7 is essential for the maintenance of endoplasmic reticulum Ca2+ concentration in resting cells, and for the refilling of Ca2+ stores after a Ca2+ signalling event. We conclude that the channel kinase TRPM7 and SOCE are synergistic mechanisms regulating intracellular Ca2+ homeostasis.
Preliminary Design, Modeling, Production, and First Evaluation Tests of a Ti–Al Gas Turbine Blade
Authors: Brotzu Andrea , Capata Roberto , Felli Ferdinando , Pilone Daniela , Sciubba Enrico
Published: February 2017

The aim of this work is to design a lightweight, creep-resistant blade for an axial single-stage micro-gas turbine. The selected process was casting of an intermetallic titanium/aluminum alloy. All the project phases are described, from the preliminary thermodynamic and geometric stage design, to its three-dimensional (3D) modeling and the subsequent finite element method–computational fluid dynamics (FEM-CFD) analysis, to the manufacturing process of the single rotor blade. The blade making (height 7 cm and chord 5 cm, approximately) consisted in a prototyping phase in which a fully 3D version was realized by means of fused deposition modeling and then in the actual production of a full-scale set of blades by investment casting in an induction furnace. The produced items showed acceptable characteristics in terms of shape and soundness. Metallographic investigations and preliminary mechanical tests were performed on the blade specimens. The geometry was then refined by a CFD study, and a slightly modified shape was obtained whose final testing under operative conditions is though left for a later study. This paper describes the spec-to-final product procedure and discusses some critical aspects of this manufacturing process, such as the considerable reactivity between the molten metal and the mold material, the resistance of the ceramic shell to the molten metal impact at high temperatures, and the maximal acceptable mold porosity for the specified surface finish. The CFD results that led to the modification of the original commercial shape are also discussed, and a preliminary performance assessment of the turbine stage is presented and discussed.
Terrestrial discharges mediate trophic shifts and enhance methylmercury accumulation in estuarine biota
Authors: Jonsson Sofi , Andersson Agneta , Nilsson Mats B. , Skyllberg Ulf , Lundberg Erik , Schaefer Jeffra K. , Åkerblom Staffan , Björn Erik
Published: January 2017

Terrestrial discharge can cause pelagic zone trophic shifts and enhance methylmercury accumulation in plankton three- to sixfold.
Understanding charge transport in lead iodide perovskite thin-film field-effect transistors
Authors: Senanayak Satyaprasad P. , Yang Bingyan , Thomas Tudor H. , Giesbrecht Nadja , Huang Wenchao , Gann Eliot , Nair Bhaskaran , Goedel Karl , Guha Suchi , Moya Xavier , McNeill Christopher R. , Docampo Pablo , Sadhanala Aditya , Friend Richard H. , Sirringhaus Henning
Published: January 2017

Band-like charge transport is observed in lead halide perovskite field-effect transistors.
Distinct Growth and Secretome Strategies for Two Taxonomically Divergent Brown Rot Fungi
Authors: Presley Gerald N. , Schilling Jonathan S.
Published: January 2017

Brown rot fungi are wood-degrading fungi that employ both oxidative and hydrolytic mechanisms to degrade wood. Hydroxyl radicals that facilitate the oxidative component are powerful nonselective oxidants and are incompatible with hydrolytic enzymes unless they are spatially segregated in wood. Differential gene expression has been implicated in the segregation of these reactions in
Postia placenta
, but it is unclear if this two-step mechanism varies in other brown rot fungi with different traits and life history strategies that occupy different niches in nature. We employed proteomics to analyze a progression of wood decay on thin wafers, using brown rot fungi with significant taxonomic and niche distances:
Serpula lacrymans
(Boletales; “dry rot” lumber decay) and
Gloeophyllum trabeum
(order Gloeophyllales; slash, downed wood). Both fungi produced greater oxidoreductase diversity upon wood colonization and greater glycoside hydrolase activity later, consistent with a two-step mechanism. The two fungi invested very differently, however, in terms of growth (infrastructure) versus protein secretion (resource capture), with the ergosterol/extracted protein ratio being 7-fold higher with
S. lacrymans
than with
G. trabeum
. In line with the native substrate associations of these fungi, hemicellulase-specific activities were dominated by mannanase in
S. lacrymans
and by xylanase in
G. trabeum
. Consistent with previous observations,
S. lacrymans
did not produce glycoside hydrolase 6 (GH6) cellobiohydrolases (CBHs) in this study, despite taxonomically belonging to the order Boletales, which is distinguished among brown rot fungi by having CBH genes. This work suggests that distantly related brown rot fungi employ staggered mechanisms to degrade wood, but the underlying strategies vary among taxa.

IMPORTANCE
Wood-degrading fungi are important in forest nutrient cycling and offer promise in biotechnological applications. Brown rot fungi are unique among these fungi in that they use a nonenzymatic oxidative pretreatment before enzymatic carbohydrate hydrolysis, enabling selective removal of carbohydrates from lignin. This capacity has independently evolved multiple times, but it is unclear if different mechanisms underpin similar outcomes. Here, we grew fungi directionally on wood wafers and we found similar two-step mechanisms in taxonomically divergent brown rot fungi. The results, however, revealed strikingly different growth strategies, with
S. lacrymans
investing more in biomass production than secretion of proteins and
G. trabeum
showing the opposite pattern, with a high diversity of uncharacterized proteins. The “simplified”
S. lacrymans
secretomic system could help narrow gene targets central to oxidative brown rot pretreatments, and a comparison of its distinctions with
G. trabeum
and other brown rot fungi (e.g.,
Postia placenta
) might offer similar traction in noncatabolic genes.
Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida
Authors: Bojanovič Klara , D'Arrigo Isotta , Long Katherine S.
Published: January 2017

Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of
Pseudomonas putida
KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which
P. putida
responds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings.

IMPORTANCE
This study maps the complete transcriptional response of
P. putida
KT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one condition, suggesting their involvement in adaptation to stress conditions and identifying interesting candidates for further functional characterization.
CcpA and CodY Coordinate Acetate Metabolism in Streptococcus mutans
Authors: Kim Jeong Nam , Burne Robert A.
Published: January 2017

In the dental caries pathogen
Streptococcus mutans
, phosphotransacetylase (Pta) and acetate kinase (Ack) convert pyruvate into acetate with the concomitant generation of ATP. The genes for this pathway are tightly regulated by multiple environmental and intracellular inputs, but the basis for differential expression of the genes for Pta and Ack in
S. mutans
had not been investigated. Here, we show that inactivation in
S. mutans
of
ccpA
or
codY
reduced the activity of the
ackA
promoter, whereas a
ccpA
mutant displayed elevated
pta
promoter activity. The interactions of CcpA with the promoter regions of both genes were observed using electrophoretic mobility shift and DNase protection assays. CodY bound to the
ackA
promoter region but only in the presence of branched-chain amino acids (BCAAs). DNase footprinting revealed that the upstream region of both genes contains two catabolite-responsive elements (
cre1
and
cre2
) that can be bound by CcpA. Notably, the
cre2
site of
ackA
overlaps with a CodY-binding site. The CcpA- and CodY-binding sites in the promoter region of both genes were further defined by site-directed mutagenesis. Some differences between the reported consensus CodY binding site and the region protected by
S. mutans
CodY were noted. Transcription of the
pta
and
ackA
genes in the
ccpA
mutant strain was markedly different at low pH relative to transcription at neutral pH. Thus, CcpA and CodY are direct regulators of transcription of
ackA
and
pta
in
S. mutans
that optimize acetate metabolism in response to carbohydrate, amino acid availability, and environmental pH.

IMPORTANCE
The human dental caries pathogen
Streptococcus mutans
is remarkably adept at coping with extended periods of carbohydrate limitation during fasting periods. The phosphotransacetylase-acetate kinase (Pta-Ack) pathway in
S. mutans
modulates carbohydrate flux and fine-tunes the ability of the organisms to cope with stressors that are commonly encountered in the oral cavity. Here, we show that CcpA controls transcription of the
pta
and
ackA
genes via direct interaction with the promoter regions of both genes and that branched-chain amino acids (BCAAs), particularly isoleucine, enhance the ability of CodY to bind to the promoter region of the
ackA
gene. A working model is proposed to explain how regulation of
pta
and
ackA
genes by these allosterically controlled regulatory proteins facilitates proper carbon flow and energy production, which are essential functions during infection and pathogenesis as carbohydrate and amino acid availability continually fluctuate.