Invariance of a recovery capital scale across gender, ethnicity, and sexual orientation in a substance use disorder treatment program.
Behavioral health care providers aim to see their clients achieve lifelong recovery from substance use disorders (SUDs). To do so, they must accurately assess incoming resources and barriers to recovery to identify areas of need for their clients. A recovery capital scale (RCS) is one way to identify these resources and barriers. However, there is limited evidence that RCSs are invariant across different demographics. To evaluate whether a short 10-item RCS (SRCS-10) is invariant across gender (male versus female), ethnicity (white versus African American, Hispanic, and other racial identities) and sexual orientation (heterosexual versus non-heterosexual). The SRCS-10 is a shortened version of White's original unpublished 35-item RCS scale that was matched on items similar to the Brief Assessment of Recovery Capital (BARC-10). We used confirmatory factor analysis (CFA) to confirm unidimensionality and then conducted measurement invariance tests. This study included 2751 females (67%) and 1341 males (33%) totaling 4092 clients from six large residential treatment centers. Using both exploratory factor analysis (EFA) and CFA the SRCS-10 has a large first to second eigenvalue ratio and had a CFI and TLI close to and above .9 with an SRMR of below .05 and an omega of .85. Additionally, we saw limited changes in key indicators such as the CFI and RMSEA across gender, race, and sexual orientation. These findings provide evidence that the SRCS-10 is a valid and reliable assessment across gender, race, and sexual orientation.


Splenic abscess after arterial embolization: a rare cause of acute abdomen.
Splenic abscess is a rare disease and a diagnostic challenge for the medical team. Attributable to its high mortality, prompt diagnosis and treatment are essential. A high degree of clinical awareness is required in conjunction with aggressive treatment, as misleading symptoms may delay treatment and worsen the patient's prognosis. The management of splenic abscess is based on medical therapy, antibiotics and splenectomy or percutaneous drainage. We present the case of a 58-year-old patient presented with a splenic abscess after arterial embolization. He underwent surgery and completely recovered.


Cadmium chloride induces the expression of metallothionein mRNA by endometrial stromal cells and amnion-derived (WISH) cells.
Metallothionein (MT) is known to bind to metals with high affinity. The potential for MT-1 mRNA expression in endometrial stromal cells (ESC) and amniotic cells in response to cytokines and cadmium chloride (CdCl(2)) was evaluated. Human ESC were cultured and treated with interleukin-1α, 12-O-tetradecanoylphobol 13-acetate (TPA), forskolin, transforming growth factor-β, and CdCl(2). Amnion-derived (WISH) cells were also cultured and treated with the same reagents. The levels of MT mRNA were evaluated by Northern blot analysis in ESC and WISH cells. In response to treatment with CdCl(2) (0.01-10 μM), the expression of MT mRNA markedly increased in ESC and WISH cells in a dose-dependent manner. On the other hand, the expression of MT mRNA did not increase after treatment with interleukin-1α (1 nM), TPA (10 nM), forskolin (1 μM) or transforming growth factor-β (1 nM) in these cells. These findings indicate that MT expression in ESC and WISH cells is sensitive to the CdCl(2) concentration, which is known to be evaluated in cigarette smokers. The present results suggest that increased levels of MT may affect metal metabolism at the feto-maternal interface.


Treatment of chronic kidney disease in the elderly: diet or conservative management.
The elderly constitute the fastest-growing group of patients reaching end-stage renal disease and requiring renal replacement therapy. In this group of patients renal failure is only one of the many comorbidities affecting them, and for the nephrologist the decision whether to commence renal replacement therapy when patients present multiple comorbidity is a challenge. In fact, many elderly patients with severe comorbidity have a poor prognosis once dialysis is started, and a conservative management or a low protein diet can be less harmful. Information on survival of elderly patients on these therapies is limited, but in the last years a large body of literature has been published in this field. Rates of dialysis withdrawal are highest among the oldest patients, raising the possibility that the standard information given to patients for dialysis warrant an age-sensitive approach. For the elderly, the information should include risk, benefit and burden associated with dialysis, age-specific estimates of prognosis with dialysis or with conservative management, and potential for loss of independence and decline in functional status and cognitive impairment. Dialysis can impair quality of life of the elderly, and when decision makers choose a treatment they have to keep in mind that specialists should add life to years, and not years to life. When a "no dialysis" option is chosen, an active renal disease management as treatment of anemia, acidosis, fluid balance, hypertension, and active end of life care is required. This approach requires devoted attention from patients, families and caregivers, and a multidisciplinary approach.


A Case of Legg-Calvé-Perthes Disease due to Transient Synovitis of the Hip.
Transient synovitis (TS) of the hip develops spontaneously in childhood; it usually has a good prognosis and is a self-limiting disease. However, its pathology is not well known. We describe a case of Legg-Calvé-Perthes disease (LCPD) that seemingly developed due to TS. Even if TS is diagnosed on the basis of the patient's medical history and imaging findings, physicians should consider the possibility of LCPD and perform a careful observation if joint effusion continues and/or a symptom does not improve within 4 weeks.


[Malignant peripheral T-cell lymphomas: morphologic and immunopathologic bases of the classification proposed by Lennert and Suchi].
In the last few years advances in immunopathology have demonstrated the T cell origins of some malignant lymphoma (ML). Histopathological criteria have been suggested for classifying several varieties of T cell ML. Peripheral T cell ML are the result of proliferation of T cell lymphocytes with markers which distinguish between the enhancing-inducer and suppressor-cytotoxic forms. The diagnosis is made from the appearances of the cell, the presence of vascular hyperplasia and associated lesions. The numbers of small, medium and large cells and clinical follow-up of these tumors have provided a means of distinguishing between low and highly malignant tumors. Some peripheral T cell ML have associated lesions due to the secretion of lymphokines which give characteristic histopathological appearances (lympho-epithelioid T cell ML, AIL type T cell ML). The authors discuss the respective places of each variety of peripheral T cell ML in Lennert and Suchi's classification which is an extension of that proposed by Kiel, and their prognostic signification.


Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex.
The RING finger protein 213 (RNF213) is an important susceptibility gene for moyamoya disease (MMD) and is also implicated in other types of intracranial major artery stenosis/occlusion (ICAS); however, the role of RNF213 in the development of ICAS including MMD is unclear. The constitutive expression of the RNF213 gene is relatively weak in brain tissue, while information regarding the expression patterns of the RNF213 gene under cerebral ischemia, which is one of characteristic pathologies associated with ICAS, is currently limited. Our objective was to address this critical issue, and we investigated Rnf213 mRNA expression in rat brains after 5 minutes of transient global cerebral ischemia (tGCI) by occluding the common carotid arteries coupled with severe hypotension. Rnf213 gene expression patterns were investigated with in situ RNA hybridization and a real-time polymerase chain reaction (PCR) from 1 to 72 hours after tGCI. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the hippocampus CA1 sub-region 48 hours after tGCI. The significant induction of the Rnf213 gene was also evident in the ischemic cortex. Double staining of Rnf213 mRNA with NeuN immunohistochemistry revealed Rnf213 hybridization signal expression exclusively in neurons. The real-time PCR analysis confirmed the induction of the Rnf213 gene after tGCI. The up-regulation of the Rnf213 gene in vulnerable neurons in the hippocampus CA1 after tGCI suggests its involvement in forebrain ischemia, which is an underlying pathology of MMD. Further investigations are needed to elucidate its exact role in the pathophysiology of ICAS including MMD.


Managing Multiple Generations in the Workplace.
Today's workplace often includes workers from 4 distinct generations, and each generation brings a unique set of core values and characteristics to an organization. These generational differences can produce benefits, such as improved patient care, as well as challenges, such as conflict among employees. This article reviews current research on generational differences in educational settings and the workplace and discusses the implications of these findings for medical imaging and radiation therapy departments.


Human papillomavirus E7 protein deregulates mitosis via an association with nuclear mitotic apparatus protein 1.
We previously observed that high-risk human papillomavirus type 16 (HPV16) E7 expression leads to the delocalization of dynein from mitotic spindles (C. L. Nguyen, M. E. McLaughlin-Drubin, and K. Munger, Cancer Res. 68:8715-8722, 2008). Here, we show that HPV16 E7 associates with nuclear mitotic apparatus protein 1 (NuMA) and that NuMA binding and the ability to induce dynein delocalization map to similar carboxyl-terminal sequences of E7. Additionally, we show that the delocalization of dynein from mitotic spindles by HPV16 E7 and the interaction between HPV16 E7 and NuMA correlate with the induction of defects in chromosome alignment during prometaphase even in cells with normal centrosome numbers. Furthermore, low-risk HPV6b and HPV11 E7s also associate with NuMA and also induce a similar mitotic defect. It is possible that the disruption of mitotic events by HPV E7, via targeting of the NuMA/dynein complex and potentially other NuMA-containing complexes, contributes to viral maintenance and propagation potentially through abrogating the differentiation program of the infected epithelium. Furthermore, in concert with activities specific to high-risk HPV E6 and E7, such as the inactivation of the p53 and pRB tumor suppressors, respectively, the disruption of the NuMA/dynein network may result in mitotic errors that would make an infected cell more prone to the accumulation of aneuploidy even in the absence of supernumerary centrosomes.


A randomized controlled trial of a brief intervention for families of patients with a first episode of psychosis.
Carers' satisfaction with psychiatric services related to information and advice is generally poor. This may be particularly true for services trying to meet the needs of ethnically diverse communities. It is important that services attempt to ameliorate carers' concerns as early as possible. The authors aimed to assess the impact of a brief educational and advice support service on carers of patients with a first episode of psychotic illness. Carers of all patients identified with a first episode of psychosis in a defined psychiatric catchment area of North London were invited to participate. Following consent from patients and relatives, relatives were randomly allocated to receive (in addition to usual services) a brief intervention comprising education and advice about the disorder from a support team or to usual care from community psychiatric services. One hundred and six carers were recruited to the study. Take-up of the intervention was less than expected and the intervention had little impact. The authors found no differences over time between the randomized arms for relatives' satisfaction (F = 23, p = 0 .4, df = 1) or number of days spent by patients in hospital over nine months from entry to the trial (F= 1.7, p= 0.18, df = 1). It was found that the support and advice intervention for families had little impact on their satisfaction or on patients' outcomes. However, failure to take up the intervention threatens the conclusions as the power to show an effect was reduced. Although family interventions, in general, are considered an important adjunct to the treatment of patients with chronic psychosis, there may be difficulties in providing an educational and support intervention shortly after first onset. How and when psychiatric services provide information and advice to carers of people newly diagnosed with a psychosis requires further study.


The effect of ethanol on the release of opioids from oral prolonged-release preparations.
Recent experience has prompted the US FDA to consider whether ethanol ingestion may modify the release characteristics of prolonged-release formulations, where dose dumping may be an issue for patient safety. The influence of ethanol on the in vitro release of opioid drugs from some prolonged-release formulations utilizing different release technologies was examined. Results indicated that the prolonged-release mechanisms remained intact under the testing conditions, although one product showed initial sensitivity to ethanol in its release characteristics. Nevertheless, in this case, extrapolation of the findings to likely outcome in vivo indicated no risk of dose-dumping. It is proposed that prolonged-release medicinal products should be tested during development to ensure robustness to the effects of ethanol on drug release.


Sonication-assisted fabrication and post-synthetic modifications of graphene-like materials.
Chemistry of and with graphene constitutes a rapidly evolving field that holds much promise for the generation of advanced materials with salient, and often unique, properties and potential applications in different fields. However, reliable, mild, and scalable methods to produce this layered carbonaceous material represent an important bottleneck and are critical for progress in this research area to continue. In this context, the use of ultrasound has become a routine and indispensable step in numerous synthetic protocols, even though most researchers usually overlook the science behind it. This minireview provides some fundamentals on the interaction of sound waves with matter and equally illustrates how sonication assists further synthetic decorations under benign conditions.


New records of one of the least known snakes, Telescopus pulcher (Squamata: Colubridae) from the Horn of Africa.
Telescopus pulcher is an enigmatic colubrid snake only known from the holotype and paratype specimens described from 'Migiurtinia' in Puntland (Somalia) in 1935. Herein we recorded the third and fourth-ever known specimens of this species from the Toon village, Woqooyi Galbeed Region, and 15 km southeast of Sheikh, Saahil Region, Somaliland. The species is endemic to Somaliland and adjoining parts of Ethiopia and Puntland. Data on morphology and natural history, as well as the first photographs of live specimens are provided. We also provide a detailed description of the paratype. The coloration of the species resembles that of the vipers of the genus Echis and we hypothesize that T. pulcher mimics these common and sympatric vipers in the Horn of Africa.


Clinical Utility and Cost of Postoperative Hemoglobin Level Testing Following Robotic-assisted Hysterectomy for Endometrial Cancer.
Our aim was to assess the clinical utility of postoperative hemoglobin testing following hysterectomy. We carried out a retrospective cohort study of patients who underwent robotic surgery at an academic center during a 44-month study period. Data included demographics and perioperative outcomes. The mean postoperative decrease in hemoglobin level was evaluated using numerical and categorical variables. A total of 201 women were included. A total of 45 (22.4%) developed symptoms suggestive of hemodynamic compromise. When compared to asymptomatic patients, these patients were no different in operative time, estimated blood loss, pre- or post-operative hemoglobin levels, or the change in hemoglobin levels. Symptomatic patients did receive less fluid intraoperatively (1.2 vs. 1.5 l; p<0.0001). Perioperative outcomes were not associated with a greater postoperative decrease in hemoglobin (Hb). Postoperative anemia was associated with preoperative anemia (0% vs. 45%; p<0.0001). Patients with postoperative anemia were also more likely to be re-admitted within 30 days after surgery (7% vs. 23%; p=0.025). Of the three patients who received blood transfusions postoperatively, all three had preoperative Hb<9.5 g/dl, compared to 2.5% of those who were not transfused (p<0.0001). Using Institutional charges and Medicare reimbursement rates for blood hemoglobin testing, savings were estimated to be $3,629 and $1,236, respectively, during the study period. Postoperative Hb testing may be safely avoided unless starting Hb is less <10 g/dl. Clinical practice change can reduce healthcare costs without hindering patient care.


Diverse effects of stimulus history in waking mouse auditory cortex.
Responses to auditory stimuli are often strongly influenced by recent stimulus history. For example, in a paradigm called forward suppression, brief sounds can suppress the perception of, and the neural responses to, a subsequent sound, with the magnitude of this suppression depending on both the spectral and temporal distances between the sounds. As a step towards understanding the mechanisms that generate these adaptive representations in awake animals, we quantitatively characterize responses to two-tone sequences in the auditory cortex of waking mice. We find that cortical responses in a forward suppression paradigm are more diverse in waking mice than previously appreciated, that these responses vary between cells with different firing characteristics and waveform shapes, but that the variability in these responses is not substantially related to cortical depth or columnar location. Moreover, responses to the first tone in the sequence are often not linearly related to the suppression of the second tone response, suggesting that spike-frequency adaptation of cortical cells is not a large contributor to forward suppression or its variability. Instead, we use a simple multilayered model to show that cell-to-cell differences in the balance of intracortical inhibition and excitation will naturally produce such a diversity of forward interactions. We propose that diverse inhibitory connectivity allows the cortex to encode spectro-temporally fluctuating stimuli in multiple parallel ways.NEW & NOTEWORTHY Behavioral and neural responses to auditory stimuli are profoundly influenced by recent sounds, yet how this occurs is not known. Here, the authors show in the auditory cortex of awake mice that the quality of history-dependent effects is diverse and related to cell type, response latency, firing rates, and receptive field bandwidth. In a cortical model, differences in excitatory-inhibitory balance can produce this diversity, providing the cortex with multiple ways of representing temporally complex information.


Atropine and testosterone propionate induced atretic changes in granulosa cells of house rat (Rattus rattus) ovary.
Degenerative changes in membrana granulosa of ovaries in R. rattus have been studied using scanning electron microscopy. Ovaries from rats treated with atropine (300 mg/kg body weight) and testosterone propionate (10 IU) were used to study sequential course of atresia in granulosa cells. Granulosa cells undergoing atresia showed degenerative changes in following order i) loosening of intercellular matrix, ii) changed morphology and texture of secretory granules, iii) destabilization of granulosa cell membranes, iv) erosion of cell membrane, v) formation of specific degenerative belts, vi) pycnosis, vii) ghost cell formation and their subsequent mixing in hazzy follicular fluid of cyst. Phenomenon of atresia, its duration, course and underlying causes have been discussed.


Hand dystonia secondary to cervical demyelinating lesion.
Dystonia is generally considered a disease of basal ganglia. We report two patients with definite MS who acutely developed hand dystonia and athetoid movements. In both patients: 1) dystonia was electrophysiologically demonstrated by lack of reciprocal inhibition between antagonistic forearm muscles; 2) SEP from median nerve stimulation showed delayed cervical N13 and absent frontal and parietal components; 3) the long latency response after stimulation of median nerve of the affected hand was absent or delayed; 4) MRI showed lesions in the posterolateral cervical spine but no involvement of basal ganglia and thalami. We think that, in these cases, dystonia and athetoid movements could be ascribed respectively to the involvement of descending pathways regulating reciprocal inhibition of motoneurons and to the involvement of large diameter afferents due to the demyelinating lesion at the cervical level.


Personal Retirement Accounts and Saving.
Aging populations are leading countries worldwide to social security reforms. Many countries are moving from pay-as-you-go to personal retirement account (PRA) systems because of their financial sustainability and positive impact on private savings. PRA systems boost private savings at a macro level by converting a government liability into financial wealth managed by private fund managers. However, at a micro level, changes in retirement wealth affect individuals' saving and consumption patterns through their working lives. Retirement wealth increased for lower-income workers after Mexico introduced PRAs, crowding out saving, increasing consumption, and offsetting some of the PRA effect on private savings. (JEL D14, E21, H55, J26, O16).


Current Perspective of Plant-Based Diets on Communicable Diseases Caused by Viruses: A Mini Review.
Communicable diseases are illnesses caused by pathogenic biological agents, including viruses, bacteria, fungi, parasites, and protozoa. Such diseases spread among people through contact with contaminated surfaces, bodily fluids, or blood products, or through the air, insect bites, or consuming contaminated food and beverages. Although some communicable diseases can be treated or prevented by taking medication and vaccines, there has been an increase in awareness of adopting a healthy diet to aid in the prevention and reversal of these diseases. One popular diet is a plant-based diet. Plant-based diets generally consist of vegetables, grains, nuts, seeds, legumes, and fruits, without any animal-source foods or artificial ingredients. Over the years, this diet has continuously increased in popularity. Reasons for following a plant-based diet are varied but include health benefits, such as improving immunity, and reducing the risk of heart disease, diabetes, and some cancers. Scientific evidence even shows that just an increased vegetable intake can decrease the occurrence of chronic diseases caused by viruses, such as hepatitis viruses, and reduce the risk of severe coronavirus disease 2019. Therefore, this mini review discusses the effectiveness of adopting a plant-based diet in ameliorating diseases caused by selected viruses and its limitations.


Anemia and mortality in hemodialysis patients: accounting for morbidity and treatment variables updated over time.
The objective of this study was to gain insight into the associations of anemia with mortality among maintenance hemodialysis (HD) patients and patient subgroups by an analysis that more comprehensively represents hemoglobin (Hb) level, morbidity, and treatment characteristics over time than was possible in prior observational studies. A cohort study was conducted among 5517 subjects in the American arm of the Dialysis Outcomes and Practice Patterns Study Phase I. We used proportional hazard analysis to model all-cause mortality as a function of Hb level measured 1, 3, and 6 months previously. Forty-five potentially confounding patient-level characteristics were considered, including demographics, comorbidities, and time-updated levels of erythropoietin and parenteral iron dosing, medical events, and laboratory and dialysis measures. Compared to Hb 11 to <12 g/dL, subjects with Hb <11 g/dL had increased mortality [adjusted hazard ratios (95% confidence interval) in the 3-month-lagged model = 1.74 (1.24 to 2.43) for <9 g/dL, 1.25 (0.96 to 1.63) for 9 to <10 g/dL, and 1.22 (0.99 to 1.49) for 10 to <11 g/dL categories]. Mortality rates for subjects with Hb 12 to <13 g/dL and > or = 13 g/dL did not differ significantly from those with Hb 11 to <12 g/dL. The relationships between Hb and mortality varied modestly with changes in the time interval between Hb measurement and the time at risk for mortality, but did not vary according to ESRD vintage or health status indicators. Our findings confirm the associations of Hb levels > or =11 g/dL with longer survival among maintenance HD patients, but show no additional survival advantage for patients with Hb levels > or =12 g/dL. Further investigation of the relationships among anemia, treatment of anemia, and survival is warranted.


Chimeric multispecific DNA methyltransferases with novel combinations of target recognition.
DNA target recognizing domains of different multispecific DNA-cytosine-methyltransferases can be rearranged through engineering of the corresponding genes to generate enzymes with novel combinations of target recognition.


An intravenous radionuclide method to evaluate hypoxemia caused by abnormal alveolar vessels. Limitation of conventional techniques.
Using conventional concepts, it is possible that a single pathologic entity, pulmonary telangiectases, can produce hypoxia by 3 physiologic mechanisms; shunt, diffusion defect, and ventilation-perfusion abnormalities. The estimation of shunt or shunt-like effect is traditionally calculated by measuring the Po2 of arterial blood during the breathing of 100 per cent 02. This method, however, did not determine blood flow through large alveolar vessels in a patient with familial hemorrhagic telangiectasis who was severely hypoxemic while breathing air. This case served to test the concept that blood flowing through large vessels in the airspaces may be hypoxemic when the patient breathes air, but not 02. Blood flow through these vessles can be estimated by use of radionuclide lung perfusion techniques and estimation of the quantity of radioactive particles that pass through an abnormal pulmonary vascular bed and lodge in kidney and brain. Conventional approaches to estimating blood flow through these fistulas underestimated their effect.


Assessing the Performance of GPT-3.5 and GPT-4 on the 2023 Japanese Nursing Examination.
Purpose The purpose of this study was to evaluate the changes in capabilities between the Generative Pre-trained Transformer (GPT)-3.5 and GPT-4 versions of the large-scale language model ChatGPT within a Japanese medical context. Methods The study involved ChatGPT versions 3.5 and 4 responding to questions from the 112th Japanese National Nursing Examination (JNNE). The study comprised three analyses: correct answer rate and score rate calculations, comparisons between GPT-3.5 and GPT-4, and comparisons of correct answer rates for conversation questions. Results ChatGPT versions 3.5 and 4 responded to 237 out of 238 Japanese questions from the 112th JNNE. While GPT-3.5 achieved an overall accuracy rate of 59.9%, failing to meet the passing standards in compulsory and general/scenario-based questions, scoring 58.0% and 58.3%, respectively, GPT-4 had an accuracy rate of 79.7%, satisfying the passing standards by scoring 90.0% and 77.7%, respectively. For each problem type, GPT-4 showed a higher accuracy rate than GPT-3.5. Specifically, the accuracy rates for compulsory questions improved from 58.0% with GPT-3.5 to 90.0% with GPT-4. For general questions, the rates went from 64.6% with GPT-3.5 to 75.6% with GPT-4. In scenario-based questions, the accuracy rates improved substantially from 51.7% with GPT-3.5 to 80.0% with GPT-4. For conversation questions, GPT-3.5 had an accuracy rate of 73.3% and GPT-4 had an accuracy rate of 93.3%. Conclusions The GPT-4 version of ChatGPT displayed performance sufficient to pass the JNNE, significantly improving from GPT-3.5. This suggests specialized medical training could make such models beneficial in Japanese clinical settings, aiding decision-making. However, user awareness and training are crucial, given potential inaccuracies in ChatGPT's responses. Hence, responsible usage with an understanding of its capabilities and limitations is vital to best support healthcare professionals and patients.


[Expression and characterizations of a novel full-length gene PKIbeta related to human glioma].
To obtain differentially expressed genes related to human glioma using cDNA microarray and to characterization of one novel full-length gene. Four samples of human glioma samples, 1 fetal brain tissue sample, and 2 normal brain tissue samples were used to extract the total RNA, and the mRNA was used to make probes. After hybridization and washing procedure, the products of hybridization were scanned using computer system. One gene, named 436F11 clone, was subsequently analyzed by Northern blotting, bioinformatics, and protein expression. Fifteen differentially expressed new genes related to human glioma were obtained through four times of hybridization and scanning. Northern blotting confirmed that over-expression of 436F11 gene in the normal human brain tissue and low-expression in the human glioma tissues. The analysis of BLASTn and BLASTx showed that the clone of 436F11 was a novel full-length gene coding 78 amino acids of protein with a theoretical relative molecular weight of 8648 and an isoelectric point of 4.69 and that it was 60% identical to mouse PKIbeta amino acid, so it was called human PKIbeta gene. After it was transfected into Escherichia coli, higher-expressed protein of PKIbeta was obtained which yielded a major clear band on an SDS-PAGE gel after purification. The products obtained from amino acid sequencing and molecular weight detection were exactly the same as the products performed by bioinformatic analysis. cDNA microarray technology can be successfully applied to identify differentially expressed genes. PKIbeta may be a novel full-length gene related to human glioma and may provide a new way to gene therapy of glioma.


Radioimmunological comparison of the DNA polymerases of avian retroviruses.
125I-labeled DNA polymerases of avian myeloblastosis virus and spleen necrosis virus were used in a radioimmunological characterization of avian retrovirus DNA polymerases. It was shown that avian leukosis virus and reticuloendotheliosis virus DNA polymerases do not cross-react in radioimmunoassays. Within the avian leukosis virus species, species-specific and type-specific antigenic determinants of the DNA polymerase were defined. The previous finding of genus-specific antigenic determinants in avian myeloblastosis virus and Amherst pheasant virus DNA polymerases was confirmed and extended to members of all subgroups of avian leukosis virus. It was shown that there is little immunological variation between the DNA polymerases of the four members of the reticuloendotheliosis virus species. Particles with RNA-dependent DNA polymerase activity from the allantoic fluid of normal chicken eggs and from the medium of a goose cell culture did not compete for the antibodies directed against any of the sets of antigenic determinants defined in this study.


Transport of through a Thick Vadose Zone.
Livestock manure applications on fields can be a source of contamination in water resources, including groundwater. Although fecal indicators like have often been detected in tile drainage systems, few studies have monitored groundwater at depth after manure treatments, especially at sites with a deep, heterogeneous vadose zone. Our hypothesis was that microbial transport through a thick vadose zone would be limited or nonexistent due to attenuation processes, subsurface thickness, and heterogeneity. This study tested this hypothesis by monitoring concentrations beneath a 12-m-thick vadose zone of coarse, heterogeneous glacial sediments after surface application of liquid swine manure. was detected on all 23 sample dates over the 5-mo period (4 Apr. 2012-13 Aug. 2012), with particularly elevated concentrations 1 wk after application and lasting for 5 wk. Variable low-level concentrations before and after the elevated period suggest remobilization and delayed transport of microorganisms to the water table without additional loadings within the flow field. These findings suggest preferential flow pathways allowing deep infiltration of manure bacteria as well as a continued source of bacteria, with variable retention and travel times, over several months. Preferential flow pathways at this site include soil macropores, depression focused infiltration, and pathways related to subsurface heterogeneity and/or fracture flow through finer-grained diamict beds. Further research is needed to confirm the relative contribution of sources, constrain travel times, and define specific transport pathways.


Application of an interactive water simulation model in urban water management: a case study in Amsterdam.
Water simulation models are available to support decision-makers in urban water management. To use current water simulation models, special expertise is required. Therefore, model information is prepared prior to work sessions, in which decision-makers weigh different solutions. However, this model information quickly becomes outdated when new suggestions for solutions arise and are therefore limited in use. We suggest that new model techniques, i.e. fast and flexible computation algorithms and realistic visualizations, allow this problem to be solved by using simulation models during work sessions. A new Interactive Water Simulation Model was applied for two case study areas in Amsterdam and was used in two workshops. In these workshops, the Interactive Water Simulation Model was positively received. It included non-specialist participants in the process of suggesting and selecting possible solutions and made them part of the accompanying discussions and negotiations. It also provided the opportunity to evaluate and enhance possible solutions more often within the time horizon of a decision-making process. Several preconditions proved to be important for successfully applying the Interactive Water Simulation Model, such as the willingness of the stakeholders to participate and the preparation of different general main solutions that can be used for further iterations during a work session.


Establishing an interventional nephrology suite.
Procedures related to dialysis access are best performed in a center or suite designated specifically for that purpose. The facility can either be within a hospital or be a free-standing unit. Feasibility depends largely on the size of the end-stage renal disease population. Alternatives include existing interventional radiology or cardiac catheterization suites. Success of a dialysis access center requires attention to proper physician training, design, staffing, equipment and supplies, and regulations related to procedures, licensing for fluoroscopy, privileges for sedation, and outcome assessment. A successful dialysis access center improves the management of dialysis access and allows the nephrologist to function more efficiently.


Semi-probabilistic coastal flood impact analysis: From deterministic hazards to multi-damage model impacts.
Coastal flood impact assessments are important tools for risk management and are performed by combining the hazard component with the vulnerability of exposed assets, to quantify consequences (or impacts) in terms of relative or absolute (e.g. financial) damage. The process generates uncertainties that should be taken into account for the correct representation of the consequences of floods. This study presents a coastal flood impact application at the spatial level of the Stavanger municipality (Norway), based on a multi-damage model approach able to represent impacts, and their overall uncertainty. Hazard modelling was performed using the LISFLOOD-FP code, taking into account historical extreme water level events (1988-2017) and relative sea level rise scenarios. Direct impacts were calculated in the form of relative and financial damage for different building categories, using flood damage curves. The results showed that the expected impacts are fewer than 50 flooded receptors and less than €1 million in damage in the current sea level scenario. The impacts could double by the end of the century, considering the most optimistic relative sea level scenario. The results were discussed considering the limitations of the approach for both hazard and impact modelling, that will be improved in future implementations. The outcome of this study may be useful for cost-benefit analyses of mitigation actions and local-scale plans for adaptation.


Angiogenesis in hematologic malignancies and its clinical implications.
Angiogenesis is defined as a neoformation of blood vessels of capillary origin. Hematopoiesis is closely linked with angiogenesis, for they share a common ancestor, the hemangioblast. Although it is well established that growth in solid tumors is dependent on angiogenesis, its role in hematologic malignancies has not yet been clarified. In this review, the direct evidence, ie, increased microvessel density, and the indirect evidence, ie, elevated level of angiogenic factors or overexpression of messenger RNA or protein of angiogenic factors, for and against the role of angiogenesis in the development and progression of hematologic malignancies are presented.


The benefits and challenges of the computerized electronic medical record.
Data from aggregate individual patient records can be gathered to answer many clinical and nursing research questions about quality assurance and resource allocation, assisting in the measurement and evaluation of patient care outcomes. The use of standardized nursing language, large integrated computer databases, and information management processes provide for the use of patient-specific data and information to facilitate patient care. The use of aggregated data can also facilitate the comparison of nursing practice across populations, demonstrate and project nursing care trends, serve as a financial and legal record, aid in clinical research, support decision analysis, and guide professional and organization performance improvement.


Diet, cellular, and systemic homeostasis control the cycling of potassium stable isotopes in endothermic vertebrates.
The naturally occurring stable isotopes of potassium (41K/39K, expressed as δ41K) have the potential to make significant contributions to vertebrate and human biology. The utility of K stable isotopes is, however, conditioned by the understanding of the dietary and biological factors controlling natural variability of δ41K. This paper reports a systematic study of K isotopes in extant terrestrial endothermic vertebrates. δ41K has been measured in 158 samples of tissues, biofluids, and excreta from 40 individuals of four vertebrate species (rat, guinea pig, pig and quail) reared in two controlled feeding experiments. We show that biological processing of K by endothermic vertebrates produces remarkable intra-organism δ41K variations of ca. 1.6‰. Dietary δ41K is the primary control of interindividual variability and δ41K of bodily K is +0.5-0.6‰ higher than diet. Such a trophic isotope effect is expected to propagate throughout trophic chains, opening promising use for reconstructing dietary behaviors in vertebrate ecosystems. In individuals, cellular δ41K is related to the intensity of K cycling and effectors of K homeostasis, including plasma membrane permeability and electrical potential. Renal and intestinal transepithelial transports also control fractionation of K isotopes. Using a box-modeling approach, we establish a first model of K isotope homeostasis. We predict a strong sensitivity of δ41K to variations of intracellular and renal K cycling in normal and pathological contexts. Thus, K isotopes constitute a promising tool for the study of K dyshomeostasis.


Mesothelin gene expression and promoter methylation/hypomethylation in gynecological tumors.
Mesothelin is a cell surface glycoprotein that is present on normal mesothelial cells and overexpressed in several cancers. In this study, we investigated the methylation/hypomethylation status in the promoter region of the mesothelin gene in gynecological tumors. Forty-four ovarian tumor specimens and 16 cases of uterine endometrial carcinoma, and normal tissue specimens were used. Monoclonal antibody (5B2) was employed for the immunohistochemical analysis. The methylation-sensitive single-nucleotide primer extension (Ms-SNuPE) technique was used to quantify the methylation/hypomethylation status at 20 CpG sites in the mesothelin promoter region. Mesothelin was expressed in 100% of serous cystadenocarcinoma and 100% of serous borderline tumor of the ovary. None of the germ cell tumors and sexcord-stromal tumors was immunoreactive. Fifty percent of endometrial carcinoma was immunoreactive for mesothelin. The average methylation of CpG sites in ovarian tumors ranged from 6-56% (median: 31%) in mesothelin-positive and 13-79% (median: 43%) in mesothelin-negative samples. In endometrial tumors, the average methylation ranged from 5-52% (median: 28%) in mesothlin-positive and from 15-67% (median: 22%) in mesothlin-negative samples. A correlation was found between mesothelin expression and the average methylation/hypomethylation status as well as methylation/hypomethylation status at four of 20 CpG sites in ovarian samples. No correlation was found in endometrial samples. We detected diverse levels of methylation/hypomethylation at CpG sites in the mesothelin promoter region in ovarian and endometrial tumors. We speculate that, although methylation/hypomethylation changes may affect its transcription, other mechanisms may synergically operate in tissue-specific expression and tumor-related mesothelin overexpression.


[Combinatorial CRISPR inversions of CTCF sites in HOXD cluster reveal complex insulator function].
CTCF (CCCTC-binding factor) is a zinc-finger protein which plays a vital role in the three-dimensional (3D) genome architecture. A pair of forward-reverse convergent CTCF binding sites (CBS elements) mediates long-distance DNA interactions to form chromatin loops with the assistance of the cohesin complex, while CBS elements at the chromatin domain boundaries show reverse-forward divergent patterns and function as insulators to discriminate against DNA interaction between chromatin domains. However, there are still many unresolved problems regarding CTCF-mediated insulation function. In order to study the connections between chromatin loops and the insulation function of CBS elements, we combinatorically inverted CBS elements at the HOXD locus by using CRISPR/Cas9 DNA-fragment editing methods in the HEK293T cell line and obtained five different kinds of single-cell CRISPR clones. By performing quantitative high-resolution chromosome conformation capture copy (QHR-4C) experiments, we found that boundary CBS inversions abolish original chromatin loops and establish new loops from the opposite direction, thus shifting the insulator boundary to the new divergent CTCF sites. Furthermore, tandem CBS elements block cohesin permeated from the opposite orientation to function as insulators. RNA-seq experiments showed that alterations of local three-dimensional genome architecture would further influence gene expression of the HOXD cluster. In conclusion, a pair of divergent CBS elements function as insulators by forming chromatin loops within chromatin domains to block cohesin sliding.


Bovine Anaplasmosis: Will there ever be an almighty effective vaccine?
Bovine anaplasmosis is a tick-borne bacterial disease with a worldwide distribution and the cause of severe economic losses in the livestock industry in many countries, including México. In the present work, we first review the elements of the immune response of the bovine, which allows ameliorating the clinical signs while eliminating the majority of the blood forms and generating an immunologic memory such that future confrontations with the pathogen will not end in disease. On the other hand, many vaccine candidates have been evaluated for the control of bovine anaplasmosis yet without no commercial worldwide effective vaccine. Lastly, the diversity of the pathogen and how this diversity has impaired the many efforts to control the disease are reviewed.


Optimizing irrigation and nitrogen fertilization for seed yield in western wheatgrass [Pascopyrum smithii (Rydb.) Á. Löve] using a large multi-factorial field design.
It is crucial for agricultural production to identify the trigger that switches plants from vegetative to reproductive growth. Agricultural sustainability in semiarid regions is challenged by nitrogen (N) fertilizer overuse, inadequate soil water, and heavy carbon emissions. Previous studies focused on the short-term effects of a single application of N and water but have not investigated the long-term effects of different irrigation and N fertilizer regimens on crop yields and yield components. N application is routinely coupled with water availability, and crop yields can be maximized by optimizing both. We examined the growth of western wheatgrass [Pascopyrum smithii (Rydb.) Á. Löve], a temperate-region forage and turf grass, using multiple different combinations of N fertilizer [(NH4)2·CO3] and irrigation levels over 3 years to determine optimal field management. We conducted multifactorial, orthogonally designed field experiments with large sample sizes, and measured fertile tillers m-2 (Y1), spikelets/fertile tillers (Y2), florets/spikelet (Y3), seed numbers/spikelet (Y4), seed weight (Y5), and seed yield (Z) to study factors associated with the switch between vegetative and reproductive growth. Fertilization had a greater effect on seed yield and yield components than irrigation. Y1 had the strongest positive effect on Z, whereas Y5 had a negative effect on Z. Irrigation and fertilization affected Z, Y1, and Y5. Fertilizer concentrations were positively correlated with Z, Y1, and Y5, whereas irrigation levels were negatively correlated. The ridge regression linear model results suggested N application rate and irrigation had antagonistic effects on Y1 (X3 = 867.6-4.23×X2; R2 = 0.988, F = Infinity, P<0.0001). We conclude that the optimal amount of N fertilizer and irrigation was 156 kg ha-1 + 115 mm for seed yield, 120 kg ha-1 + 146 mm for spikelets/fertile tillers, and 108 kg ha-1 + 119 mm for seed numbers/spikelets. These results will improve yield and reduce agricultural inputs for P. smithii in semiarid and arid regions, thereby reducing fertilizer pollution and conserving water.


Purpura fulminans: a disease best managed in a burn center.
Victims of purpura fulminans are overcome by a rapidly progressive and sometimes fatal course involving large amounts of tissue loss and multiple organ system failure. From 1986 to 1995, seven children ranging in age from 10 months to 19 years (mean, 6.2 years) were referred to the Shriners Burns Institute in Cincinnati with purpura fulminans. Neisseria meningitidis was identified as the precipitating pathogen in most of the patients. The mean TBSA full-thickness skin loss was 33%. Fourteen extremities were amputated in the seven patients, including three patients with amputations of all four extremities. Transfer to our institution occurred after a mean delay of 20 days, usually after the demarcation of viable tissue. In one patient, however, fasciotomies obviated multiple impending amputations. Monitoring for elevated compartment pressures, early fasciotomies, and expedient transfer to a burn center for a multidiciplinary approach to care should improve the outcome in patients with purpura fulminans.


Antigenic analysis by immunofluorescence of in vitro-produced metacyclics of Trypanosoma brucei and their infections in mice.
The antigenic types in populations of Metacyclic trypanosomes of Trypanosoma brucei isolated from Glossina morsitans head-salivary gland trypanosome cultures and bloodstream forms in the early parasitemias produced from whole culture supernatant fluids containing metacyclic forms, were analyzed by the indirect fluorescent antibody test using clone-specific antisera. Metacyclic trypanosomes in cultures initiated with cloned bloodstream forms with heterogeneous with respect to their variable antigenic type (VAT). Trypanosomes comprising early parasitemias in immunosuppressed mice infected with metacyclics produced in cultures also had a range of VATs. Three of the VATs detected in the early parasitemias in mice have also been identified by other investigators in tsetse fly-transmitted populations of the same stock.


[A method of photometric measurement of the ciliary beat of cultivated ciliated cells of the upper respiratory tract in the human].
This study was based on a method of microphotometrical measurement of the ciliary beat of cells from the human upper respiratory tract. The ciliated cells were acquired by the tissue cultivation of small pieces of nasal mucosa obtained during surgical interventions in the paranasal sinuses. The experiments were performed in a chamber where the cells were superfused by a tyrode solution. The ciliary beat was measured by a microscope photometer built into an inverted microscope. During the measurements the diaphragm aperture of the photometer was positioned over the cilia in such a manner that the changes of light intensity resulting from the movement of the cilia could be registered. The frequency of the ciliary beat was estimated by counting the individual beats. The ciliary beat during control conditions was studied as well as the influence of temperature. Cooling of the experimental chamber resulted in a significant reduction of the frequency of the ciliary beat. The advantages of this single cell preparation of ciliated epithelia for pharmacological investigations are discussed.


Development and evaluation of anisotropic and nonlinear aortic models made from clinical images for in vitro experimentation.
In this work we developed a methodology to manufacture a new type of arterial model that could be used in experimental setting instead of excised arteries while developing new imaging modalities. CT-images of the descending aorta were used to create molds with patient specific morphology. A polyvinyl alcohol (PVA) solution with a reinforcing cotton mesh was used to generate the models. The mesh is circumferentially elastic while non-compliant longitudinally and is responsible for the non-linear anisotropic mechanical behavior of the models. Two models were fabricated following the same manufacturing procedure. Their circumferential and longitudinal mechanical properties were evaluated and compared to those of excised healthy pig aortas via tensile testing. A very good agreement was found for the circumferential direction, while the longitudinal direction showed to have a more marked anisotropic behavior compared to the excise arteries. An increase from 113 kPa at 2.5% strain, to 914 kPa at 40% strain was obtained for the models, while the arteries showed an increase from 172 kPa at 2.5% strain to 922 kPa at 38% strain. Furthermore, by plugging the models into a cardiovascular simulator their mechanical response in a more realistic setting was evaluated under static and dynamic pressure conditions by using shear wave elastography (SWE). Static and dynamic experiments showed an increase in the shear modulus as a function of pressure from 61 kPa to 263 kPa, between 20 mmHg and 150 mmHg for Model 1 (similar values within 10% were obtained for Model 2). These values are in good agreement with those reported in the literature for healthy human arteries. To our knowledge the models presented in this study are the first morphologically realistic phantoms that have demonstrated nonlinear and anisotropic elastic behaviors close to those of healthy arteries.


Crossing the front: contrasting storm-forced dispersal dynamics revealed by biological, geological and genetic analysis of beach-cast kelp.
The subtropical front (STF) generally represents a substantial oceanographic barrier to dispersal between cold-sub-Antarctic and warm-temperate water masses. Recent studies have suggested that storm events can drastically influence marine dispersal and patterns. Here we analyse biological and geological dispersal driven by two major, contrasting storm events in southern New Zealand, 2017. We integrate biological and physical data to show that a severe southerly system in July 2017 disrupted this barrier by promoting movement of substantial numbers of southern sub-Antarctic Durvillaea kelp rafts across the STF, to make landfall in mainland NZ. By contrast, a less intense easterly storm (Cyclone Cook, April 2017) resulted in more moderate dispersal distances, with minimal dispersal between the sub-Antarctic and mainland New Zealand. These quantitative analyses of approximately 200 freshly beach-cast kelp specimens indicate that storm intensity and wind direction can strongly influence marine dispersal and landfall outcomes.


Prognostic value of ejection fraction in patients admitted with acute coronary syndrome: A real world study.
There are limited data regarding factors affecting outcomes among acute coronary syndrome (ACS) patients presenting with varying degrees of left ventricle (LV) dysfunction. We aimed to identify factors associated with mortality according to LV ejection fraction (LVEF) at 1st admission in ACS patients.A total of 8983 ACS patients prospectively enrolled in the Acute Coronary Syndrome Israeli Survey (2000-2010) were categorized according to their LVEF at admission: severe LV dysfunction (LVEF < 30% [n = 845]), mild-moderate LV dysfunction (LVEF 30%-49% [n = 4470]); preserved LV function (LVEF ≥ 50% [n = 3659]). Multivariable Cox proportional hazards regression modeling was used to assess the risk factors for 1-year mortality according to LVEF on admission.Over the past decade there was a gradual decline in the proportion of patients admitted with low LVEF. Mortality rates were highest among patients with severe LV dysfunction (36%), intermediate among those with mild-moderate LV dysfunction (10%), and lowest among those with preserved LV function (4%, P < 0.001). We recognized different risk factors for mortality according to LVEF at admission. Admission clinical features (syncope, anterior myocardial infarction, and ST elevation myocardial infarction [STEMI]) predicted mortality risk in patients with severe LV dysfunction (all P < 0.05), whereas the presence of comorbidities (hypertension, diabetes mellitus, chronic renal failure, and peripheral arterial disease) predicted mortality risk in patients with more preserved LV function. Age and admission Killip class ≥II were consistent predictors in all LVEF subsets.LVEF at admission is a strong predictor of mortality in ACS, and prognostic factors differ according to LVEF during admission. In patients with severe LV dysfunction signs of clinical instability are related to 1-year mortality; in patients with a more preserved LV function the prognosis is related to the presence of co-morbidities.


Evaluation of a 36-item measure of ICD-11 and DSM-5 personality disorder trait domains and facets in Russian inpatients.
The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and International Classification of Diseases 11th revision (ICD-11) have introduced a new dimensional approach to personality disorder (PD) classification that relies on the global level of PD severity and individual expressions of personality dysfunction in terms of specified trait domains (i.e., negative affectivity, detachment, antagonism, disinhibition, anankastia, and psychoticism). This study sought to evaluate the psychometric qualities of the DSM-5 and ICD-11 trait domains and facets in 570 Russian psychiatric inpatients using the Modified 36-Item Personality Inventory for DSM-5 and ICD-11 Brief Form Plus-Modified (PID5BF + M). The expected six-factor structure of the DSM-5 and ICD-11 trait domains was replicated using exploratory factor analysis. The six domain scores showed expected convergence with normal five-factor model scores, and the 18 subfacets showed acceptable scale reliability. Our findings overall support the psychometric properties of the six PID5BF + M domain scores and 18 subfacet scores covering both the ICD-11 and the DSM-5 trait models. Consequently, clinicians and researchers in Russian-speaking mental health services are now able to perform a combined and facet-level assessment of the DSM-5 and ICD-11 trait models in a feasible and psychometrically sound manner. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Cardiogenic and myogenic gene expression in mesenchymal stem cells after 5-azacytidine treatment.
5-Azacytidine is a hypomethylating agent that is used for the treatment of myelodysplastic syndrome. This histone modifier is widely employed and plays a nonspecific role in influencing the differentiation capability of stem cells. The ability of bone marrow mesenchymal stem cells to differentiate into cardiomyocyte- and myocyte-like cells after exposure to 3 different doses of 5-azacytidine has been evaluated and compared. The aim of the study was to optimize the effective dose of 5-azacytidine for promoting the cardiomyocyte and myocyte differentiation capabilities of human mesenchymal stem cells (MSCs). Human bone marrow aspirations were collected from healthy donors. MSCs were used for the study of mesodermal differentiation. MSCs were cultured to promote osteoblast differentiation and adipocyte differentiation. The evaluation of osteogenic or adipogenic properties was then performed through immunocytochemical staining. BMMSCs were trypsinized into single-cell suspensions and then prepared for flow cytometric analysis. The MSCs were treated with 5, 10, or 15 μM 5-azacytidine for 24 h and then cultured for 3 weeks. Total RNA was extracted from untreated and 5-azacytidine-treated cells. Troponin T and GATA4 antibodies were used as cardiogenic markers, whereas myogenin and MyoD antibodies were used as myocyte markers. The morphology and growth rate of MSCs that were treated with any of the 3 doses of 5-azacytidine were similar to the morphology and growth rate of control MSCs. An immunofluorescence analysis examining the expression of the cardiac-specific markers GATA4 and troponin T and the skeletal muscle-specific markers MyoD and myogenin revealed that cells treated with 15 μM 5-azacytidine were strongly positive for these markers. Real-time RT-PCR results were examined; these amplifications indicated that there were higher expression levels of cardiac- and skeletal muscle-specific mRNAs in MSCs treated with 15 μm 5-azacytidine than in MSCs that had either been treated with lower doses of 5-azacytidine or left untreated. MSCs treated with 5-azacytidine demonstrated the capacity to differentiate into both cardiomyocytes and skeletal myocytes, and 15 μM 5-azacytidine could be the optimal dose of this drug. Other promoting factors should be examined to investigate the possibility of promoting the differentiation of MSCs into specific cell types. None declared.


Mechanisms of joint damage in an experimental model of hemophilic arthritis.
Autologous whole blood was injected into the knee joints of rabbits 3 times each week for 12 weeks. The resulting destructive arthritis showed macroscopic and microscopic changes similar to those described in hemophilic arthritis in humans. Immunofluorescence studies indicated that a specific immune response is probably not involved in the pathogenesis of hemophilic arthritis. Detailed histopathologic examinations of knee joints in both the early and the late phase of arthritis revealed an obvious synovial and cartilage iron load, in the absence of inflammatory changes. The implications of these findings in the pathogenesis of destructive cartilage changes are discussed.


Regulation of NF-kappaB responses by epigenetic suppression of IkappaBalpha expression in HCT116 intestinal epithelial cells.
Intestinal epithelial cells play critical roles in regulating mucosal immunity. Since epigenetic factors such as DNA methylation and histone modifications are implicated in aging, carcinogenesis, and immunity, we set out to assess any role for epigenetic factors in the regulation of intestinal epithelial cell immune responses. Experiments were conducted using the HCT116 cell line, and a subclone was genetically engineered to lack DNA methyltransferases (DNMT). The induction of the chemokine interleukin-8 and the antiapoptotic protein cFLIP by tumor necrosis factor-alpha were markedly less in HCT116 cells lacking DNMT than in parental cells. These effects were accompanied by lower monocyte chemotaxis and higher caspase signaling in HCT116 cells lacking DNMT than parental cells. Tumor necrosis factor-alpha-induced NF-kappaB activation was blocked and IkappaBalpha expression was higher in HCT116 cells lacking DNMT than in parental cells. A CpG island in the IkappaBalpha gene promoter region was found to contain variable levels of methylation in parental HCT116 cells. Chromatin immunoprecipitation analysis of histone proteins bound to the IkappaBalpha gene promoter revealed that higher levels of IkappaBalpha expression in HCT116 cells lacking DNMT compared with parental cells were accompanied by more chromatin marks permissive to gene transcription. These findings show that epigenetic factors influence the NF-kappaB system in intestinal epithelial cells, resulting in a previously unrecognized mechanism of innate immune regulation.


Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease.
Human actin-related protein 2/3 complex (Arp2/3), required for actin filament branching, has two ARPC1 component isoforms, with ARPC1B prominently expressed in blood cells. Here we show in a child with microthrombocytopenia, eosinophilia and inflammatory disease, a homozygous frameshift mutation in ARPC1B (p.Val91Trpfs*30). Platelet lysates reveal no ARPC1B protein and greatly reduced Arp2/3 complex. Missense ARPC1B mutations are identified in an unrelated patient with similar symptoms and ARPC1B deficiency. ARPC1B-deficient platelets are microthrombocytes similar to those seen in Wiskott-Aldrich syndrome that show aberrant spreading consistent with loss of Arp2/3 function. Knockout of ARPC1B in megakaryocytic cells results in decreased proplatelet formation, and as observed in platelets from patients, increased ARPC1A expression. Thus loss of ARPC1B produces a unique set of platelet abnormalities, and is associated with haematopoietic/immune symptoms affecting cell lineages where this isoform predominates. In agreement with recent experimental studies, our findings suggest that ARPC1 isoforms are not functionally interchangeable.


Health Behavior Change Following Stroke: Recommendations for Adapting the Diabetes Prevention Program-Group Lifestyle Balance Program.
Objective. History of stroke increases risk for recurrent stroke, which is a significant issue faced by survivors. The Diabetes Prevention Program-Group Lifestyle Balance (DPP-GLB) program is an effective lifestyle modification intervention for ameliorating cardiovascular risk factors but has not been adapted to account for common stroke-related deficits. The purpose of this study was to determine appropriate adaptations to the DPP-GLB for adults with stroke. Design and Methods. In this phenomenological qualitative study, a total of 15 community-dwelling adults with stroke and 10 care-partners participated in 4 focus groups to review DPP-GLB curriculum materials and provide recommendations for adaptation. Focus groups were recorded and transcribed. Inductive content analysis was used to identify key themes. Results. Three themes were identified. First, physical, cognitive, sensory, and psychosocial stroke-related deficits could affect DPP-GLB participation. Second, existing DPP-GLB characteristics could facilitate participation by adults with stroke. Third, stroke-specific adaptations were recommended, including modified session content and format, adapted physical activity and dietary recommendations, and inclusion of care-partners. Conclusion. Current DPP-GLB content and structure may be insufficient to meet the unique needs of adults with stroke. The suggested adaptations should be incorporated into a stroke-specific curriculum and tested for preliminary efficacy for reducing recurrent stroke risk.


Perinatal oxycodone exposure causes long-term sex-dependent changes in weight trajectory and sensory processing in adult mice.
In utero opioid exposure is associated with lower weight and a neonatal opioid withdrawal syndrome (NOWS) at birth, along with longer-term adverse neurodevelopmental outcomes and mood disorders. While NOWS is sometimes treated with continued opioids, clinical studies have not addressed if long-term neurobehavioral outcomes are worsened with continued postnatal exposure to opioids. In addition, pre-clinical studies comparing in utero only opioid exposure to continued post-natal opioid administration for withdrawal mitigation are lacking. Here, we sought to understand the impact of continued postnatal opioid exposure on long term behavioral consequences. We implemented a rodent perinatal opioid exposure model of oxycodone (Oxy) exposure that included Oxy exposure until birth (short Oxy) and continued postnatal opioid exposure (long Oxy) spanning gestation through birth and lactation. Short Oxy exposure was associated with a sex-specific increase in weight gain trajectory in adult male mice. Long Oxy exposure caused an increased weight gain trajectory in adult males and alterations in nociceptive processing in females. Importantly, there was no evidence of long-term social behavioral deficits, anxiety, hyperactivity, or memory deficits following short or long Oxy exposure. Our findings suggest that offspring with prolonged opioid exposure experienced some long-term sequelae compared to pups with opioid cessation at birth. These results highlight the potential long-term consequences of opioid administration as a mitigation strategy for clinical NOWS symptomology and suggest alternatives should be explored.


Bioinspired Nanonetwork Hydroxyapatite from Block Copolymer Templated Synthesis for Mechanical Metamaterials.
Inspired by Mantis shrimp, this work aims to suggest a bottom-up approach for the fabrication of nanonetwork hydroxyapatite (HAp) thin film using self-assembled polystyrene-block-polydimethylsiloxane (PS-b-PDMS) block copolymer (BCP) with a diamond nanostructure as a template for templated sol-gel reaction. By introducing poly(vinylpyrrolidone) (PVP) into precursors of calcium nitrate tetrahydrate and triethyl phosphite, which limits the growth of forming HAp nanoparticles, well-ordered nanonetwork HAp thin film can be fabricated. Based on nanoindentation results, the well-ordered nanonetwork HAp shows high energy dissipation compared to the intrinsic HAp. Moreover, the uniaxial microcompression test for the nanonetwork HAp shows high energy absorption per volume and high compression strength, outperforming many cellular materials due to the topologic effect of the well-ordered network at the nanoscale. This work highlights the potential of exploiting BCP templated synthesis to fabricate ionic solid materials with a well-ordered nanonetwork monolith, giving rise to the brittle-to-ductile transition, and thus appealing mechanical properties with the character of mechanical metamaterials.


Amphibian malformations and inbreeding.
Inbreeding may lead to morphological malformations in a wide variety of taxa. We used genetic markers to evaluate whether malformed urodeles were more inbred and/or had less genetic diversity than normal salamanders. We captured 687 adult and 1,259 larval tiger salamanders (Ambystoma tigrinum tigrinum), assessed each individual for gross malformations, and surveyed genetic variation among malformed and normal individuals using both cytoplasmic and nuclear markers. The most common malformations in both adults and larvae were brachydactyly, ectrodactyly and polyphalangy. The overall frequency of adults with malformations was 0.078 compared to 0.081 in larval samples. Genetic diversity was high in both normal and malformed salamanders, and there were no significant difference in measures of inbreeding (f and F), allele frequencies, mean individual heterozygosity or mean internal relatedness. Environmental contaminants or other extrinsic factors may lead to genome alternations that ultimately cause malformations, but our data indicate that inbreeding is not a causal mechanism.


Multiple cytotoxic and genotoxic effects induced in vitro by differently shaped copper oxide nanomaterials.
In nanotoxicology, the capacity of nanoparticles of the same composition but different shape to induce cytotoxicity and genotoxicity is largely unknown. A series of cytotoxic and genotoxic responses following in vitro exposure to differently shaped CuO nanoparticles (CuO NPs, mass concentrations from 0.1 to 100 μg/ml) were assessed in murine macrophages RAW 264.7 and in peripheral whole blood from healthy volunteers. Cytotoxicity, cytostasis and genotoxicity were evaluated by the colorimetric assay of formazan reduction [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)] and by the cytokinesis-block micronucleus cytome (CBMN Cyt) assay. The comet assay was applied for detecting DNA strand breaks and information on oxidative damage to DNA (oxidised purines and pyrimidines). The MTT assay revealed a decrease in cell viability in RAW 264.7 cells and peripheral blood lymphocytes (PBL) with significant dose-effect relationships for the different CuO NP shapes. The comet assay revealed a dose-dependent increase in primary DNA damage, and a significant increase in oxidative damage to DNA was also detectable, as well as increased frequency of micronuclei in binucleated cells, often in a dose-related manner. Proliferative activity, cytotoxicity and apoptotic markers showed a significant trend in the two cell types. Finally, we have differentiated clastogenic events from aneugenic events by fluorescence in situ hybridisation with human and murine pancentromeric probes, revealing for the first time characteristic aneugenic responses related to the shape of CuO NPs and cell type. Independently of size and shape, all CuO NPs revealed a clear-cut cytotoxic and genotoxic potential; this suggests that CuO NPs are good candidates for positive controls in nanotoxicology.


[The protective properties of myelopeptides in the development of infectious processes caused by bacteria of the genus Salmonella].
The protective properties of myelopeptides in the development of bacterial infection in mice and young pigs, caused by S. typhimurium 415, S. cholerae-suis 1422 and 370, have been studied. Myelopeptides have been found to possess protective properties when injected into animals infected with S. typhimurium and S. cholerae-suis in lethal doses. The best protective effect (survival rate of 100%) has been achieved by the injection of myelopeptides 24 hours before challenge. Myelopeptides have also been found to promote the weight gain of young pigs infected with S. cholerae-suis.


Evaluation of radioactive phosphorus in the palliation of metastatic bone lesions from carcinoma of the breast and prostate.
Radioactive phosphorus effected substantial palliation of intractable bone pain in 17 of 33 (51.5%) women with metastatic carcinoma of the breast and in 14 of 15 (93.3%) men with metastatic carcinoma of the prostate. No significant difference in the overall response rate was found between androgen and parathormone priming prior to radiophosphorus therapy. The degree of response was not dependent on total dose of 32P within the range of 9--18 mCi (333--666 MBq). Myelosuppression was a transient complication in 9 of 33 patients with metastatic breast carcinoma and in 7 of 15 patients with metastatic prostate carcinoma. Symptomatic hypercalcemia was an infrequent complication of radiophosphorus therapy irrespective of the priming regimen.


Investigation of Adsorption Kinetics and the Isotherm Mechanism of Manganese by Modified Diatomite.
Natural diatomite modified by acetic acid (C-D) and sodium hydroxide (Na-D) for adsorbing manganese (Mn) was studied. The construction and morphology of the modified diatomite were then characterized by different efficient and accurate detection methods (Fourier transform infrared, scanning electron microscopy, and Brunauer-Emmett-Teller), and it was proved that C-D and Na-D increased the surface area and void volume compared to natural diatomite, and the modification of diatomite with acetic acid and alkali also significantly changed the structure of the functional groups of diatomite, especially in Na-D. Therefore, the adsorption rate of Mn by C-D and Na-D was higher than that of natural diatomite. The optimum conditions of Mn adsorption for C-D and Na-D were pH 5.0, 40 °C, 30 min and pH 5.0, 40 °C, 120 min, respectively, and this was best illustrated by pseudo-second-order kinetics. The Mn adsorption isotherm models showed that Mn adsorption on C-D and Na-D was stable, and the Langmuir adsorption isotherm model fitted adsorption processes of natural diatomite, C-D, and Na-D well as their correlation coefficients were 0.931, 0.940, and 0.991, respectively. These results suggested that modified diatomite with acetic acid and sodium hydroxide significantly increased the adsorption rate of Mn, which had an important application prospect for the remediation of Mn pollution in soil and water.


Macrophage-Related Genes Biomarkers in Left Ventricular Remodeling Induced by Heart Failure.
Elevated left ventricular mass index contributes to morbidity and mortality induced by heart failure and M2 macrophages play a critical role in left ventricular remodeling. Here, our aim was to investigate the roles of M2 macrophage-related genes in heart failure. GSE10161 was downloaded and the abundance of immune cells were estimated utilizing the CIBERSORT algorithm. Using the limma test and correlation analysis, differentially expressed plasm B cells and M2 macrophages-related genes (DEBRGs and DEMRGs) were documented. Functional pathways and the protein-protein interaction network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the hub DEMRGs expressions were analyzed using the GSE135055, GSE116250 and GSE74144 datasets. 103 differentially expressed genes were correlated with the abundance of M2 Macrophages and were identified as DEMRGs (PCC >0.4), which were mainly enriched in extracellular matrix organization, cell adhesion molecule binding and postsynaptic membrane. After screening out, 5 hub DEMRGs were obtained, including FN1 (degree = 21), COL3A1 (degree = 13), COL1A2 (degree = 13), FBN1 (degree = 12), and MMP2 (degree = 11). However, no hub DEBRGs were obtained in the network. The expression patterns of the screened DEMRGs were further validated in the patients with heart failure, dilated cardiomyopathy, ischemic cardiomyopathy or hypertension. The results can improve our understanding of the macrophages-associated molecular mechanisms in heart failure induced by dilated cardiomyopathy, ischemic cardiomyopathy or hypertension and 5 hub DEMRGs may help prevent the adverse left ventricular remodeling to decrease mortality and morbidity.


Computing stationary distributions in equilibrium and nonequilibrium systems with forward flux sampling.
We present a method for computing stationary distributions for activated processes in equilibrium and nonequilibrium systems using forward flux sampling. In this method, the stationary distributions are obtained directly from the rate constant calculations for the forward and backward reactions; there is no need to perform separate calculations for the stationary distribution and the rate constant. We apply the method to the nonequilibrium rare event problem proposed by Maier and Stein, to nucleation in a 2-dimensional Ising system, and to the flipping of a genetic switch.


Effect of radiation on the penetration of irinotecan in rat cerebrospinal fluid.
Anticancer agents are useful for treating brain tumors, but sub therapeutic concentrations due to decreased blood-brain barrier (BBB) penetration limit their effectiveness. This study evaluated the effect of cranial radiation on the pharmacokinetics of irinotecan in plasma and cerebrospinal fluid (CSF). Rats (n = 48) were treated with irinotecan (10 mg/kg), and then administered 10 or 20 Gy or sham irradiation as control after drug. The pharmacokinetics for irinotecan, SN-38, and APC were measured in plasma and CSF over 6 h. Up to 7 plasma samples per animal were collected, and one CSF sample was collected per animal (serial sacrifice design). Population pharmacokinetic analysis was performed with NONMEM, and radiation tested as a covariate for the fraction of irinotecan (f(CSF)) entering the CSF. The estimate of f(CSF) (% and RSE) was 0.165 (73.5) for the control group and 0.265 (66.5) for radiation-treated groups, respectively (P < 0.05). Predictive check plots showed that the model adequately described the overall trend and variability in the observed data. The median values of bootstrap parameters were similar to the NONMEM estimates based on the original data set. These results indicate that cranially administered radiation can increase the penetration of anticancer agents such as irinotecan into the CSF. Studies that evaluate radiation-fractionation, radiation-time course effect relationships, blood-brain barrier and blood-tumor barrier effects for irinotecan and other anticancer agents are warranted.


The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.
The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease.


The forgotten nodule: complications of sacral nodules in rheumatoid arthritis.
Nodules commonly occur in rheumatoid arthritis and occasionally give rise to complications. The sacral nodule is easily missed and may ulcerate to produce extensive sacral sores which may lead to serious and even fatal complications in patients with rheumatoid arthritis. Seven cases are reported which illustrate some of these features.


Theoretical study of reaction pathways for the rhodium phosphine-catalysed borylation of C-H bonds with pinacolborane.
The reaction mechanism of the rhodium-phosphine catalysed borylation of methyl-substituted arenes using pinacolborane (HBpin) has been investigated theoretically using DFT calculations at the B3PW91 level. Factors affecting selectivity for benzylic vs. aromatic C-H bond activation have been examined. It was found that [Rh(PR3)2(H)] is the active species which oxidatively adds the C-H bond leading to an eta3-benzyl complex which is the key to determining the unusual benzylic regioselectivity observed experimentally for this catalyst system. Subsequent reaction with HBpin leads to a [Rh(PR3)2(eta3-benzyl)(H)(Bpin)] complex from which B-C reductive elimination provides product and regenerates the catalyst. The electrophilic nature of the boryl ligand assists in the reductive elimination process. In contrast to Ir(L)2(boryl)3-based catalysts, for which Ir(III)-Ir(V) cycles have been proposed, the Rh(I)-Rh(III) cycle is operating with the system addressed herein.


[Successful treatment of an elderly patient with pretreated recurrent breast cancer using low-dose capecitabine].
The author reports the successful treatment of an 85-year-old recurrent breast cancer patient with low-dose capecitabine. Approximately 20 years ago, the patient received a left mastectomy and 2 years later was treated with unspecified chemotherapy for bone metastasis. In November 2001, metastatic tumors in thoracic vertebrae were removed by emergency laminectomy, followed by radiotherapy plus chemotherapy using mitoxantrone, cyclophosphamide and doxifluridine. In June 2005, abdominal computed tomography revealed a single metastatic tumor 20 mm in diameter in the liver. Treatment with paclitaxel at 70 mg/m(2)/day on days 1 and 14 resulted in no change in tumor size while serum levels of cancer antigen 15-3 increased from 22.1 to 98.1 U/ml. Subsequent daily treatment with capecitabine at 1,000 mg/m(2)/day for 21 days was associated with a 50% decrease in tumor size and a reduction in serum cancer antigen of 15-3 to 18.8 U/ml. Grade 2 hand-foot syndrome was noted,but no severe adverse effects were evident. Five months after the induction of capecitabine treatment, a partial response was obtained. These results suggest that low-dose capecitabine may be a safe and efficacious treatment for elderly patients with pretreated recurrent breast cancer. Clinical trials of low-dose capecitabine in such patients are therefore warranted.


Vascular inner ear partition: a concept for some forms of sensorineural hearing loss and vertigo.
The results of a series of scanning electron microscopical studies were used to construct a model for the vascular pathways in the inner ear. Corrosion cast preparations of the vessels of the inner ear of the adult rat were used in this study. The inner ear is, like a hand, an end organ containing four sense organs (cochlea, saccule, utricle and the cristae ampullaris). All these specific inner ear structures have their own vascular supply. We have developed a blood flow diagram of the inner ear. This model was used for a classification of different types of ischemia in the inner ear and forms a concept for some forms of sensorineural hearing loss and vertigo. Four types of inner ear ischemia are proposed. In type I (a or b) of inner ear ischemia only the vessels of the cochlea are involved resulting in two types of hearing loss without vertigo. Type II is characterized by ischemia of a part of the cochlea and a part of the vestibular system. In type III (a or b) only the vestibular system is involved, while in type IV no blood circulation will be present in the inner ear resulting in total deafness and severe vertigo. Inner ear partition at ultramicroscopical level of these structures may be possible in the future and new imaging techniques will probably support the vascular schematic model presented in this study.


Spontaneous intraperitoneal haemorrhage of the gastric vessels.
A male in his 70s presented to the emergency department with sudden-onset abdominal pain and syncope. While in the emergency department, he developed worsening hypotension and anaemia. A CT angiogram was suggestive of abdominal apoplexy (spontaneous intraperitoneal haemorrhage), which was treated successfully with embolisation of the bleeding vessels. Spontaneous bleeding was thought to be related to his initiation of apixaban 1 week previously. The patient made an excellent recovery and was transitioned back to oral anticoagulation.


When Does Organic Chemistry Follow Nature's Lead and "Make the Switch"?
The case is made for transitioning organic chemistry from a developed discipline that remains highly dependent upon organic solvents to one that will be sustainable, based on water as the reaction medium. Processes in hand that today achieve the same bond constructions characteristic of traditional organic synthesis, but can be accomplished under environmentally responsible conditions, are discussed as representative of the potential that lies ahead.


[The effect of leukotrienes B4, C4, 12-hydroxyeicosatetraenoic acid and of the threo- and erythro-epimers of hepoxilin B3 on the plasticity of the neuronal cholinoreceptors in the snail].
Effects of several acyclic eicosanoids (which are formed from arachidonic acid under the action of 5- and 12-lipoxygenases) on desensitization of somatic cholinoreceptors of Helix lucorum RPa3 and LPa3 neurons were studied by means of two-electrode voltage clamp technique. The substances under study were: leukotrienes B4, C4, 12(S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoic acid (12-HETE), threo- and erythro-epimers of hepoxilin B3. Cholinoreceptor plasticity was evaluated by a degree of depression of inward current, induced by rhythmical local ACh applications on the soma with intervals 55-180 sec. Leukotrienes B4 and C4 intensified cholinoreceptor plasticity. Inhibitor of inositol-1,4,5-trisphosphate-dependent (IP3-d) mobilization of deposited Ca2+, TMB-8, prevented the effect of leukotriene C4. 12-HETE, threo- and erythro-epimers of hepoxilin B3 did not change plasticity. A conclusion is made that cholinoreceptor plasticity is controlled by leukotrienes B4 and C4. One of the regulatory pathways includes IP3-d Ca-mobilization. Eicosanoids from 12-lipoxygenase pathway (12-HETE, threo- and erythro-epimers of hepoxilin B3) do not participate in this intracellular regulatory mechanism.


Parametric polar maps of regional myocardial beta-adrenoceptor density.
Quantification of myocardial beta-adrenoceptor density (Bmax) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of Bmax. Dynamic PET with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[11C]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimaz ole-2)-on hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean Bmax of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate Bmax(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in Bmax(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of Bmax obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating Bmax. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (Bmax(PMF1/2/3)) were compared with Bmax(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated Bmax outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. The differences between the two methods of calculating Bmax were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. When using PET for the quantification of beta-adrenoceptor density, the regional variation in Bmax can be reliably assessed using the parametric polar map approach.


Transdifferentiation of pancreatic α-cells into insulin-secreting cells: From experimental models to underlying mechanisms.
Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are currently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.


Interplay between the structure and dynamics in liquid and undercooled boron: an ab initio molecular dynamics simulation study.
In the present work, the structural and dynamic properties of liquid and undercooled boron are investigated by means of ab initio molecular dynamics simulation. Our results show that both liquid and undercooled states present a well pronounced short-range order (SRO) mainly due to the formation of inverted umbrella structural units. Moreover, we observe the development of a medium-range order (MRO) in the undercooling regime related to the increase of inverted umbrella structural units and of their interconnection as the temperature decreases. We also evidence that this MRO leads to a partial crystallization in the β-rhombohedral crystal below T = 1900 K. Finally, we discuss the role played by the SRO and MRO in the nearly Arrhenius evolution of the diffusion and the non-Arrhenius temperature dependence of the shear viscosity, in agreement with the experiment.


An integrated view of gene expression and solute profiles of Arabidopsis tumors: a genome-wide approach.
Transformation of plant cells with T-DNA of virulent agrobacteria is one of the most extreme triggers of developmental changes in higher plants. For rapid growth and development of resulting tumors, specific changes in the gene expression profile and metabolic adaptations are required. Increased transport and metabolic fluxes are critical preconditions for growth and tumor development. A functional genomics approach, using the Affymetrix whole genome microarray (approximately 22,800 genes), was applied to measure changes in gene expression. The solute pattern of Arabidopsis thaliana tumors and uninfected plant tissues was compared with the respective gene expression profile. Increased levels of anions, sugars, and amino acids were correlated with changes in the gene expression of specific enzymes and solute transporters. The expression profile of genes pivotal for energy metabolism, such as those involved in photosynthesis, mitochondrial electron transport, and fermentation, suggested that tumors produce C and N compounds heterotrophically and gain energy mainly anaerobically. Thus, understanding of gene-to-metabolite networks in plant tumors promotes the identification of mechanisms that control tumor development.


The Polish Interventional Cardiology TAVI Survey (PICTS): adoption and practice of transcatheter aortic valve implantation in Poland.
Few studies have assessed the development of transcatheter aortic valve implantation (TAVI) in Poland since its introduction in 2008, and data on current TAVI activity or practice are missing. To assess the dynamics of TAVI adoption in Poland and to detect differences among Polish centres in TAVI practice and decision-making. The Polish Interventional Cardiology TAVI Survey (PICTS) was approved by the Polish Association of Cardiovascular Interventions and presented to all 21 national TAVI centres. Between 2008 and 2015 the cumulative number of TAVI performed in Poland was 2189. The annual number of TAVI rose from 8 in 2008 to 670 in 2015 (0.21 to 17.4 implants per million inhabitants, respectively). The median TAVI experience per centre was 80 procedures (95% CI: 38.1-154.6). In 2015 the TAVI penetration rate reached 5.12% of the estimated eligible Polish population. Inoperable and high-risk patients are treated with TAVI in all centres, with 52% of Heart Teams also qualifying medium-risk patients. The rate of transfemoral implantations increased to 83.2% of all procedures in 2015, while transapical implantations decreased to 12%. The frequency of subclavian, direct aortic or transcarotid routes in 2015 was below 3% each. The PICTS survey observed a positive but slow rate of adoption of TAVI in Poland. When compared to Western European countries, our findings highlight a significant treatment gap in high or prohibitive surgical risk patients with severe aortic stenosis. Remarkable variations in TAVI practices among Polish TAVI centres warrant publication of joint national guidelines and recommendations.


Utilization of board gaming for conceptual models of nursing.
Gaming can be an effective teaching strategy for reinforcing and motivating students to learn. Development of the game discussed in this article is not intended to replace classroom instruction. Instead, it is intended to augment course content. Board gaming can make learning a pleasant experience. It provides students and educators an opportunity to interact in an informal atmosphere and provides enjoyment, while at the same time may promote learning. Therefore, educators should consider further development of games for use with students in nursing education.


Structural characterisation of neutrophil glycans by ultra sensitive mass spectrometric glycomics methodology.
Neutrophils are the most abundant white blood cells in humans and play a vital role in several aspects of the immune response. Numerous reports have implicated neutrophil glycosylation as an important factor in mediating these interactions. We report here the application of high sensitivity glycomics methodologies, including matrix assisted laser desorption ionisation (MALDI-TOF) and MALDI-TOF/TOF analyses, to the structural analysis of N- and O-linked carbohydrates released from two samples of neutrophils, prepared by two separate and geographically remote laboratories. The data produced demonstrates that the cells display a diverse range of sialylated and fucosylated complex glycans, with a high level of similarity between the two preparations.


Rapid response to dexamethasone intravitreal implant in diabetic macular edema.
To evaluate the early effects of dexamethasone (DEX) intravitreal implants in patients with diabetic macular edema (DME). This was a prospective, single-arm, interventional clinical series. Eighteen patients (18 eyes) with chronic/recalcitrant or naive DME were included. Patients underwent single DEX intravitreal implant. Clinical assessments, including ophthalmologic examination, central retinal thickness (CRT) measurement by spectral-domain optical coherence tomography (SD-OCT) scan, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were carried out at baseline, 1-3 hours, and then 3, 7, and 30 days after treatment. The main outcome was change in CRT on SD-OCT, while secondary outcome measures included visual acuity (VA) and changes in IOP following implant. Mean CRT significantly decreased from 565 ± 171 µm at baseline to 310 ± 89 µm at end of follow-up (p<0.001), with reduction becoming evident 1-3 hours after injection. Mean BCVA also significantly improved 7 days and 30 days after treatment up to 0.14 logMAR (p<0.05). All patients had a controlled IOP after the injection with only 1/18 eyes having a transient increase in IOP during follow-up. This is the first study showing very early effects of DEX implants on CRT reduction and VA improvement in DME.