Still wary of the Web? The evolution of state emergency management agency Web sites 2008-2017.
A 2008 content analysis of state emergency management agency Web sites showed that they tended to be internally focused and needed to be more citizen-focused and journalist friendly. The study was replicated in 2017. Because of changes in technology and agency missions, the content richness indicators were expanded. The study shows an increased acceptance of Internet and social communication. However, it also shows that the full potential of social media in emergency communication has not been reached.


Higher 25-Hydroxyvitamin D Levels Are Associated With Lower Proteinuria in Kidney Transplant Recipients.
Proteinuria is associated with decreased graft and patient survival after kidney transplantation. Increasing evidence shows that vitamin D has antiproteinuric and renoprotective effects. The aim of our study was to assess the influence of 25-hydroxyvitamin D levels on proteinuria after kidney transplantation. Between May 1, 2012, and November 30, 2012, we tested 395 kidney transplant recipients for 25-hydroxyvitamin D levels during their regular visits to our transplant center together with routine blood sampling and proteinuria testing. Patients within 12 months of transplant, who had undergone parathyroidectomy, had unstable graft function, had concomitant intake of calcineurin inhibitors and mammalian target of rapamycin inhibitors were not included in the study. Subjects with advanced liver disease, or receiving vitamin D supplementation were also excluded. All laboratory, clinical, and therapeutic factors for proteinuria were taken into consideration. Statistical analyses included descriptive statistics and univariate and multivariate log-log regression with backward selection (SPSS version 22.0; SPSS Inc., Chicago, IL, USA), with significance at P < .05. Determination of total 25-hydroxyvitamin D levels was performed by a validated liquid chromatography-tandem mass spectrometry method. Our study group included 230 patients (148 men, 82 women). Positive association was established between proteinuria and history of diabetes mellitus, rejection episode 12 months within testing for 25-hydroxyvitamin D levels, and use of mammalian target of rapamycin inhibitors (P < .05). Significant negative relations were detected for patient age, graft function, and 25-hydroxyvitamin D concentrations (P < .05). Our study established that better vitamin D status is associated with lower proteinuria. However, further research is needed to clarify the possible renoprotective properties of vitamin D.


Skin reactions to hydroxyzine.
Sensitivity to histamine H1-antagonists has mainly been observed with phenothiazine and ethylenediamine, and is very rare with hydroxyzine. We report 3 cases of sensitization to hydroxyzine, which was prescribed to treat urticaria and atopic dermatitis. A generalized maculopapular eruption appeared shortly after taking the drug. Patch tests with Atarax tablet were positive +3, and +2 or +3 with different dilutions of hydroxyzine. Patch tests with ethylenediamine, piperazine and other antihistamines were negative; therefore, there is no cross-allergy. We believe these rapid systemic reactions to hydroxyzine after the initial dose may have been due to prior systemic sensitivity to this drug, which cannot be used topically. Allergy to antihistamines must be considered when cutaneous lesions worsen on such therapy.


Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression.
Intensification in the frequency of diabetes and the associated vascular complications has been a root cause of blindness and visual impairment worldwide. One such vascular complication which has been the prominent cause of blindness; retinal vasculature, neuronal and glial abnormalities is diabetic retinopathy (DR), a chronic complicated outcome of Type 1 and Type 2 diabetes. It has also become clear that "genetic" variations in population alone can't explain the development and progression of diabetes and its complications including DR. DR experiences engagement of foremost mediators of diabetes such as hyperglycemia, oxidant stress, and inflammatory factors that lead to the dysregulation of "epigenetic" mechanisms involving histone acetylation and histone and DNA methylation, chromatin remodeling and expression of a complex set of stress-regulated and disease-associated genes. In addition, both elevated glucose concentration and insulin resistance leave a robust effect on epigenetic reprogramming of the endothelial cells too, since endothelium associated with the eye aids in maintaining the vascular homeostasis. Furthermore, several studies conducted on the disease suggest that the modifications of the epigenome might be the fundamental mechanism(s) for the proposed metabolic memory' resulting into prolonged gene expression for inflammation and cellular dysfunction even after attaining the glycemic control in diabetics. Henceforth, the present review focuses on the aspects of genetic and epigenetic alterations in genes such as vascular endothelial growth factor and aldose reductase considered being associated with DR. In addition, we discuss briefly the role of the thioredoxin-interacting protein TXNIP, which is strongly induced by high glucose and diabetes, in cellular oxidative stress and mitochondrial dysfunction potentially leading to chromatin remodeling and ocular complications of diabetes. The identification of disease-associated genes and their epigenetic regulations will lead to potential new drugs and gene therapies as well as personalized medicine to prevent or slow down the progression of DR.


Induction of long-term potentiation at perforant path dentate synapses does not affect place learning or memory.
In two experiments the authors failed to detect an effect of inducing bilateral, long-lasting synaptic potentiation at perforant path dentate synapses on spatial learning by rats in the Morris place navigation task. Daily sessions of high-frequency stimulation of perforant path axons produced large increases to an asymptotic level in population spike and field excitatory postsynaptic potential recorded in ipsilateral dentate gyrus. Place learning proceeded normally 24 hours after the last of 14 high-frequency stimulation sessions in rats that had previously mastered the procedural aspects of place navigation (Experiment 1) and in rats that were naive (Experiment 2).


Evaluation of RECIST in chemotherapy-treated lung cancer: the Pharmacogenoscan Study.
Response Evaluation Criteria in Solid Tumors (RECIST) are widely used to assess the effect of chemotherapy in patients with cancer. We hypothesised that the change in unidimensional tumour size handled as a continuous variable was more reliable than RECIST in predicting overall survival (OS). The prospective Pharmacogenoscan study enrolled consecutive patients with non-small-cell lung cancer (NSCLC) at any stage seen between 2005 and 2010 at six hospitals in France, given chemotherapy. After exclusion of patients without RECIST or continuous-scale tumour size data and of those with early death, 464 patients were left for the survival analyses. Cox models were built to assess relationships between RECIST 1.1 categories or change in continuous-scale tumour size and OS. The best model was defined as the model minimising the Akaike Information Criterion (AIC). OS was 14.2 months (IQR, 7.3-28.9 months). According to RECIST 1.1, 146 (31%) patients had a partial or complete response, 245 (53%) stable disease, and 73 (16%) disease progression. RECIST 1.1 predicted better OS than continuous-scale tumour in early (<6 months) predicted survival analyses (p = 0.03) but the accuracy of the two response evaluation methods was similar in late (≥6 months) predicted survival analyses (p = 0.15). In this large observational study, change in continuous-scale tumour size did not perform better than RECIST 1.1 in predicting survival of patients given chemotherapy to treat NSCLC. NCT00222404.


Community structure and distribution of benthic cyanobacteria in Antarctic lacustrine microbial mats.
The terrestrial Antarctic Realm has recently been divided into 16 Antarctic Conservation Biogeographic Regions (ACBRs) based on environmental properties and the distribution of biota. Despite their prominent role in the primary production and nutrient cycling in Antarctic lakes, cyanobacteria were only poorly represented in the biological dataset used to delineate these ACBRs. Here, we provide a first high-throughput sequencing insight into the spatial distribution of benthic cyanobacterial communities in Antarctic lakes located in four distinct, geographically distant ACBRs and covering a range of limnological conditions. Cyanobacterial community structure differed between saline and freshwater lakes. No clear bioregionalization was observed, as clusters of community similarity encompassed lakes from distinct ACBRs. Most phylotypes (77.0%) were related to cyanobacterial lineages (defined at ≥99.0% 16S rRNA gene sequence similarity) restricted to the cold biosphere, including lineages potentially endemic to Antarctica (55.4%). The latter were generally rare and restricted to a small number of lakes, while more ubiquitous phylotypes were generally abundant and present in different ACBRs. These results point to a widespread distribution of some cosmopolitan cyanobacterial phylotypes across the different Antarctic ice-free regions, but also suggest the existence of dispersal barriers both within and between Antarctica and the other continents.


Diet and lifestyle in managing postmenopausal obesity.
The majority of adults are becoming increasingly overweight and one of the sub-populations in which this prevalence is growing most rapidly is postmenopausal women. It is as yet unclear whether the menopausal transition itself leads to weight gain, but it is known that the physiological withdrawal of estrogen brings about changes in fat distribution that increase the risk for the metabolic syndrome, diabetes and cardiovascular disease. The treatment of postmenopausal obesity is very simple logically, but incredibly difficult - eat less and exercise more. Recent studies suggest that being active and fit is more important than losing weight; hence, a major recommendation is to exercise regularly, for at least 30 min on at least 5 days of the week, while maintaining a healthy balanced diet. Unfortunately, there are no 'magic bullets' (drugs) that may provide long-term treatment, and all diets work irrespective of their composition as long as people comply to them. There is no substitute for a sensible lifestyle.


Large area laser scanning optical resolution photoacoustic microscopy using a fibre optic sensor.
A laser scanning optical resolution photoacoustic microscopy (LS OR-PAM) system based on a stationary fibre optic sensor is described. The sensor comprises an optically resonant interferometric polymer cavity formed on the tip of a rounded single mode optical fibre. It provides low noise equivalent pressure (NEP = 68.7 Pa over a 20 MHz measurement bandwidth), a broad bandwidth that extends to 80 MHz and a near omnidirectional response. The latter is a significant advantage, as it allows large areas (>1cm2) to be imaged without the need for translational mechanical scanning offering the potential for fast image acquisition. The system provides a lateral resolution of 8 µm, an axial resolution of 21 µm, and a field of view up to 10 mm × 10 mm. To demonstrate the system, in vivo 3D structural images of the microvasculature of a mouse ear were obtained, showing single capillaries overlaying larger vessels as well as functional images revealing blood oxygen saturation.


Normal voice processing after posterior superior temporal sulcus lesion.
The right posterior superior temporal sulcus (pSTS) shows a strong response to voices, but the cognitive processes generating this response are unclear. One possibility is that this activity reflects basic voice processing. However, several fMRI and magnetoencephalography findings suggest instead that pSTS serves as an integrative hub that combines voice and face information. Here we investigate whether right pSTS contributes to basic voice processing by testing Faith, a patient whose right pSTS was resected, with eight behavioral tasks assessing voice identity perception and recognition, voice sex perception, and voice expression perception. Faith performed normally on all the tasks. Her normal performance indicates right pSTS is not necessary for intact voice recognition and suggests that pSTS activations to voices reflect higher-level processes.


[Correlation between the changes of fibrinogen and the treatment effect of all-frequency sudden deafness].
Objective: To analyze the correlation between the changes of fibrinogen and the treatment effect of all-frequency sudden deafness, and to explore the individualized treatment strategy for the use of Batroxobin. Methods: Patients with all-frequency sudden deafness who were admitted to Department of Otorhinolaryngology, People's Hospital of Peking University, from January 2010 to September 2016 were selected. All patients were given standard treatment and regular use of Batroxobin. Value of fibrinogen on D1 (before treatment) / D3 / D7 (±1) and D14 (±2) were recorded, at the same time, the correlation between the changes of fibrinogen and prognosis of all-frequency sudden deafness by the audiograms of onset and after-treatment of all patients were analyzed. Independent t-test was used to analyze normal distributed measurement data and chi square linear trend test was used to analyze the curative effect of different fibrinogen groups. Results: A total of 148 patients were included, the outcomes were worst when the patient's fibrinogen was below 2 g/L or above 4 g/L before treatment, ineffective rate were both 50%. The fibrinogen was lowest when the treatment came to the third day. Normally, the patient's prognosis was best when this value waved between 0.7 and 0.9 g/L, with a total effective rate between 73.9% and 83.3%. The fibrinogen value of the 7th day was a good indicator of the outcome, and Fib7 value was significant lower in patients of effective group than ineffective ones ((1.25±0.37)g/L vs (1.38±0.35) g/L, t=-0.27, P=0.04). Patients found a best recovery when Fib7 was below 1 g/L, and the higher the Fib7 value, the higher the inefficiency (χ(2)=7.55, P=0.01). Batroxobin showed safety during the treatment and found no complications. Conclusion: The change of fibrinogen in the process of all-frequency sudden deafness is closely related to the curative effect.


Ergonomics in schools.
This Special Issue on Ergonomics in Schools is dedicated to the memory of my co-guest editor Cheryl Bennett who sadly and unexpectedly passed away peacefully on 2 July 2007 - only 10 days before this editorial was completed. Cheryl was inspirational in her vigorous championing of this new area of ergonomics activity, most prominently and to great effect through her foundation chairmanship of the International Ergonomics Association (IEA) Technical Committee on Ergonomics for Children in Educational Environments (ECEE) (see www.iea.cc).


Student-Led Training Day Increases Student Confidence in Women's Primary Care Skills.
Medical students are often apprehensive in approaching basic women's health concepts, including wellness exams, reproductive health concerns, and patient counseling. This study evaluates a novel student-developed and student-run Women's Health Training Day (WHTD) as a means of cultivating medical student confidence in women's primary care early in medical training. Sixty-six first-year medical students participated in WHTD, a voluntary 6-hour weekend day of interactive workshops. Students were divided into groups of six to eight students that rotated together through five workshops focused on the breast exam, pelvic exam, microscopy, family planning, and patient interviews. Before participating in WHTD, students completed surveys indicating their confidence in performing skills related to women's health on a 5-point Likert scale. Students completed an identical survey after participating in all of the WHTD workshops. Changes in pre- and post-training day confidence scores were assessed. Students reported increased confidence in all of the composite sessions that were assessed. The specific skillsets demonstrating the greatest increases in student confidence were speculum handling during pelvic examinations, detecting abnormal breast masses, and recognizing the clinical presentations of common sexually transmitted infections. All but one of the evaluated skills, using a microscope, demonstrated a significant increase in student confidence. These results indicate that the student-implemented and student-run Women's Health Training Day increases student confidence in women's primary care skills. Further studies are needed to determine whether this perceived increase in confidence is associated with increased objective knowledge pertaining to primary care and women's health.


[Description and life history of Tetrameres (Tetrameres) cardinalis sp. n (author's transl)].
A new species of Spirurid Nematode Tetrameres (Tetrameres) cardinalis n. sp. parasite of a Cardinal: Richmondia cardinalis is described. This Tetrameres shows primitive cephalic structures, 33 to 43 pairs of somatic spines in male, spicules of unequal length: left 365-440, right 65-350 mu, mature eggs with tufts of polar filaments. The life-cycle of this Spirurid has been obtained experimentally with the grass-hopper Locusta migratoria as an intermediate host. Its larval development is characterized by the quickness of organogenesis, the stability of cephalic structures from third stage to adult stage, the small size (800 mu) of infective larva, the localization of larva in the insect fat tissue.


Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy.
Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the alpha-particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycarbonic anhydride of diethylenetriaminepentaacetic acid. The physical properties of 212Bi are appropriate for radioimmunotherapy in that it has a short half-life, deposits its high energy over a short distance, and can be obtained in large quantities from a radium generator. Antibody specific activities of 1-40 microCi/microgram (1 Ci = 37 GBq) were achieved. Specificity of the 212Bi-labeled anti-Tac was demonstrated for the IL-2 receptor-positive adult T-cell leukemia line HUT-102B2 by protein synthesis inhibition and clonogenic assays. Activity levels of 0.5 microCi or the equivalent of 12 rad/ml of alpha radiation targeted by anti-Tac eliminated greater than 98% the proliferative capabilities of HUT-102B2 cells with more modest effects on IL-2 receptor-negative cell lines. Specific cytotoxicity was blocked by excess unlabeled anti-Tac but not by human IgG. In addition, an irrelevant control monoclonal antibody of the same isotype labeled with 212Bi was unable to target alpha radiation to cell lines. Therefore, 212Bi-labeled anti-Tac is a potentially effective and specific immunocytotoxic reagent for the elimination of IL-2 receptor-positive cells. These experiments thus provide the scientific basis for use of alpha-particle-emitting radionuclides in immunotherapy.


The intracranial vasculature of canines represents a model for neurovascular ischemia and training residents and fellows in endovascular neurosurgery.
We describe use of a canine model to evaluate physiological effects and neuroprotective strategies in the setting of cerebral ischemia and endovascular neurosurgery training. We performed transfemoral digital subtraction cerebral and cervical angiography on eight anesthetized dogs. Angiographic images of cerebral arteries were obtained following cannulation of the femoral artery. Cerebral ischemia models were made after angiography. The canine cerebral vasculature exhibited extensive tortuosity of the carotid and vertebral arteries. Conversely, the bilateral anterior spinal arteries were easily catheterized using microcatheters and microguidewires. The basilar artery and its branches were facilely cannulable. Circle of Willis continuity sans hypoplasia or aplasia of its constitutive segments was appreciated in all animals. The middle cerebral arteries could be easily accessed via the posterior communicating arteries. We generated an empirically evaluable therapeutically interventional experimental animal model of cerebral ischemia by occluding the middle cerebral artery using small coils for a duration between 15 and 60 min. Unique amenability of the canine intracranial vasculature to selective and microcatheter cannulation renders experimentally induced cerebral, cerebellar, and brainstem via occlusion of the supratentorial and infratentorial arteries a simple matter. The neural vasculature irrigating the canine cerebrum, brainstem, and cerebellum may consequently prove useful in helping young and nascent endovascular neurosurgeons in developing and refining their skills of microcatheter navigation and manipulation and deployment of therapeutic devices to achieve effective occlusion of aneurysms, arteriovenous malformations, arteriovenous fistulas, and neoplasms of the intracranial cavity.


Antidepressants. Current concepts of mode of action.
Two approaches have been followed in attempting to elucidate the mechanisms of action of antidepressants. The first involves studies on the chronic effects of antidepressants and ECT on neurotransmitter receptor function in the rat brain. Such studies suggest that antidepressants decrease alpha 2 and beta-adrenoceptor function, increase alpha 1 receptor function, reduce 5-HT1A and dopamine autoreceptor function and increase GABA B function; changes also occur in 5-HT2 receptor function with antidepressants decreasing while ECT increases the activity of these receptors. The second approach involves studying platelets, lymphocytes and amine metabolites in the body fluids of depressed patients before and following effective treatment. Results of these studies suggest that while alpha-adrenoreceptors are largely unchanged, beta-receptors are increased and 5-HT2 receptors decreased in the depressed patient but normalise following effective treatment irrespective of the type of treatment. Such findings emphasize the importance of receptor adaptations in evaluating the mode of action of antidepressant treatments.


Structural re-arrangement and peroxidase activation of cytochrome c by anionic analogues of vitamin E, tocopherol succinate and tocopherol phosphate.
Cytochrome c is a multifunctional hemoprotein in the mitochondrial intermembrane space whereby its participation in electron shuttling between respiratory complexes III and IV is alternative to its role in apoptosis as a peroxidase activated by interaction with cardiolipin (CL), and resulting in selective CL peroxidation. The switch from electron transfer to peroxidase function requires partial unfolding of the protein upon binding of CL, whose specific features combine negative charges of the two phosphate groups with four hydrophobic fatty acid residues. Assuming that other endogenous small molecule ligands with a hydrophobic chain and a negatively charged functionality may activate cytochrome c into a peroxidase, we investigated two hydrophobic anionic analogues of vitamin E, α-tocopherol succinate (α-TOS) and α-tocopherol phosphate (α-TOP), as potential inducers of peroxidase activity of cytochrome c. NMR studies and computational modeling indicate that they interact with cytochrome c at similar sites previously proposed for CL. Absorption spectroscopy showed that both analogues effectively disrupt the Fe-S(Met(80)) bond associated with unfolding of cytochrome c. We found that α-TOS and α-TOP stimulate peroxidase activity of cytochrome c. Enhanced peroxidase activity was also observed in isolated rat liver mitochondria incubated with α-TOS and tBOOH. A mitochondria-targeted derivative of TOS, triphenylphosphonium-TOS (mito-VES), was more efficient in inducing H2O2-dependent apoptosis in mouse embryonic cytochrome c(+/+) cells than in cytochrome c(-/-) cells. Essential for execution of the apoptotic program peroxidase activation of cytochrome c by α-TOS may contribute to its known anti-cancer pharmacological activity.


[The exploration of aerobic power and energy expenditure of Chinese rugby players].
To explore aerobic power and energy expenditure of high level rugby players in China, which provide experimental basis for accurate training and nutritional strategy in match-play. Eighteen master rugby players were selected as research subjects. The parameters such as VO2max, lactic aicd threshold (LT) and modify conconi test were measured respectively. The differences of energy were compared between the forward and the defender. The data were analyzed by independent sample t test. The VO2max(42.05±3.69 ml/min ·kg-1) of rugby players was poorer. The VO2max of the forward was 38.83±3.52 (ml/min ·kg-1), and that of the defender was 47.31±3.17 (ml/min ·kg-1),and there was significant difference between the forwards and the defenders (P<0.05). The LT of the defenders was obviously higher than that of the forwards. Modifier conconi test had a high correlation (r = 0.772) with VO2max. The average energy consumption in the first half of the game was about(276.94±18.08)kcals, the second half was(225.58±22.86)kcals, and the second half was less than the first half (P<0.05). The aerobic power is different between the forwards and the defenders. The power of aerobic of Chinese players is weaker than that of the foreign rugby players.


A comparison of four clustering methods for brain expression microarray data.
DNA microarrays, which determine the expression levels of tens of thousands of genes from a sample, are an important research tool. However, the volume of data they produce can be an obstacle to interpretation of the results. Clustering the genes on the basis of similarity of their expression profiles can simplify the data, and potentially provides an important source of biological inference, but these methods have not been tested systematically on datasets from complex human tissues. In this paper, four clustering methods, CRC, k-means, ISA and memISA, are used upon three brain expression datasets. The results are compared on speed, gene coverage and GO enrichment. The effects of combining the clusters produced by each method are also assessed. k-means outperforms the other methods, with 100% gene coverage and GO enrichments only slightly exceeded by memISA and ISA. Those two methods produce greater GO enrichments on the datasets used, but at the cost of much lower gene coverage, fewer clusters produced, and speed. The clusters they find are largely different to those produced by k-means. Combining clusters produced by k-means and memISA or ISA leads to increased GO enrichment and number of clusters produced (compared to k-means alone), without negatively impacting gene coverage. memISA can also find potentially disease-related clusters. In two independent dorsolateral prefrontal cortex datasets, it finds three overlapping clusters that are either enriched for genes associated with schizophrenia, genes differentially expressed in schizophrenia, or both. Two of these clusters are enriched for genes of the MAP kinase pathway, suggesting a possible role for this pathway in the aetiology of schizophrenia. Considered alone, k-means clustering is the most effective of the four methods on typical microarray brain expression datasets. However, memISA and ISA can add extra high-quality clusters to the set produced by k-means, so combining these three methods is the method of choice.


Personality disorders over time: implications for psychotherapy.
Personality disorders have an early onset, and are associated with dysfunction over the course of adult life. Antisocial and borderline personality disorders tend to remit with age, but other categories do not usually show improvement. The chronicity of personality disorders is both a challenge and a frame for treatment planning. Psychotherapy for these patients can focus on rehabilitation and the development of social niches that match their personality profiles.


CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody.
There is a need for in vivo diagnostic imaging probes that can noninvasively measure tumor-infiltrating CD8+ leukocytes. Such imaging probes could be used to predict early response to cancer immunotherapy, help select effective single or combination immunotherapies, and facilitate the development of new immunotherapies or immunotherapy combinations. This study was designed to optimize conditions for performing CD8 PET imaging with 89Zr-Df-IAB22M2C and determine whether CD8 PET imaging could provide a safe and effective noninvasive method of visualizing the whole-body biodistribution of CD8+ leukocytes. Methods: We conducted a phase 1 first-in-humans PET imaging study using an anti-CD8 radiolabeled minibody, 89Zr-Df-IAB22M2C, to detect whole-body and tumor CD8+ leukocyte distribution in patients with metastatic solid tumors. Patients received 111 MBq of 89Zr-Df-IAB22M2C followed by serial PET scanning over 5-7 d. A 2-stage design included a dose-escalation phase and a dose-expansion phase. Biodistribution, radiation dosimetry, and semiquantitative evaluation of 89Zr-Df-IAB22M2C uptake were performed in all patients. Results: Fifteen subjects with metastatic melanoma, non-small cell lung cancer, and hepatocellular carcinoma were enrolled. No drug-related adverse events or abnormal laboratory results were noted except for a transient increase in antidrug antibodies in 1 subject. 89Zr-Df-IAB22M2C accumulated in tumors and CD8-rich tissues (e.g., spleen, bone marrow, nodes), with maximum uptake at 24-48 h after injection and low background activity in CD8-poor tissues (e.g., muscle and lung). Radiotracer uptake in tumors was noted in 10 of 15 subjects, including 7 of 8 subjects on immunotherapy, 1 of 2 subjects on targeted therapy, and 2 of 5 treatment-naïve subjects. In 3 patients with advanced melanoma or hepatocellular carcinoma on immunotherapy, posttreatment CD8 PET/CT scans demonstrated increased 89Zr-Df-IAB22M2C uptake in tumor lesions, which correlated with response. Conclusion: CD8 PET imaging with 89Zr-Df-IAB22M2C is safe and has the potential to visualize the whole-body biodistribution of CD8+ leukocytes in tumors and reference tissues, and may predict early response to immunotherapy.


Proatlantal intersegmental arteries of external carotid artery origin associated with Galen's vein malformation.
Carotid basilar anastomoses can occasionally persist beyond the embryonic period. These anomalies are most often incidentally detected in adulthood, during workups for unrelated pathologies. Persistence of the proatlantal intersegmental arteries is a rare form of primitive carotid-basilar anastomoses. Bilateral proatlantal inter- segmental arteries are an extremely rare occurrence, of which only 3 cases have been reported in the literature. An analysis of vascular anomalies associated with Galen's vein malformations revealed 3 children in whom persistence of type II proatlantal arteries was seen. These included one child in whom proatlantal arteries were persistent bilaterally. We report the clinical and angiographic findings and discuss the embryologic and therapeutic implications of this unique association.


Successful placement of the Essure device after a failed procedure using the Adiana system for hysteroscopic sterilisation.
This case report describes a successful hysteroscopic sterilisation using the Essure Permanent Birth Control device (Conceptus Inc., Mountain View, California, United States) after a failed procedure of the Adiana Permanent Contraception system (Hologic, Inc., Bedford, Maryland, United States). The delivery catheter of the Adiana system was able to be inserted into the left fallopian tube without difficulty and per manufacturer specifications. However, the position detection array was unable to sense four-quadrant tissue contact. The same issue occurred at the contralateral tube. Using the Essure system, the coils were able to be placed in both ostia easily and adequately. In patients in whom the Adiana system fails to occlude the fallopian tubes due to procedural, anatomic or device-related factors, the Essure procedure may be an efficient alternative.


Hemodynamics in sepsis: its relationship to pulmonary complication.
Serial clinical observations and hemodynamic measurements were made on seventeen patients with sepsis and ten control cases. Control patients were slightly hypovolemic immediately after operation. In the eleven high flow patients, that is, those with the initial cardiac index higher than 3.0 liters/min/m(2), we observed characteristic hemodynamics with lowered vascular resistance, higher cardiac output and hypotension. The anomalous vascular resistance began to return to normal approximately 48 hr after operation. In three cases pulmonary complication developed at this time and therefore pulmonary artery pressure and/or pulmonary wedge pressure exceeded the normal range. In these cases treatment was aimed at lowering the pulmonary pressure. Pulmonary complication was improved when these pressures returned within normal range. In the seven low flow patients, that is, those with cardiac index lower than 2.9 liters/min/m(2), we observed decreased cardiac index with increased systemic and pulmonary vascular resistance. In these cases pulmonary complication appeared to develop by increased permeability of the pulmonary capillary wall. Elevated pulmonary artery pressure might accelerate the progress of the complication. Monitoring and controlling pulmonary artery pressure and pulmonary wedge pressure were effective in prevention and treatment of pulmonary complication in this group.


Retrospective evaluation of an integrated molecular-epidemiological approach to cyclosporiasis outbreak investigations - United States, 2021.
Cyclosporiasis results from an infection of the small intestine by Cyclospora parasites after ingestion of contaminated food or water, often leading to gastrointestinal distress. Recent developments in temporally linking genetically related Cyclospora isolates demonstrated effectiveness in supporting epidemiological investigations. We used 'temporal-genetic clusters' (TGCs) to investigate reported cyclosporiasis cases in the United States during the 2021 peak-period (1 May - 31 August 2021). Our approach split 655 genotyped isolates into 55 genetic clusters and 31 TGCs. We linked two large multi-state epidemiological clusters (Epidemiologic Cluster 1 [n = 136 cases, 54 genotyped] and Epidemiologic Cluster 2 [n = 42 cases, 15 genotyped]) to consumption of lettuce varieties; however, product traceback did not identify a specific product for either cluster due to the lack of detailed product information. To evaluate the utility of TGCs, we performed a retrospective case study comparing investigation outcomes of outbreaks first detected using epidemiological methods with those of the same outbreaks had TGCs been used to first detect them. Our study results indicate that adjustments to routine epidemiological approaches could link additional cases to epidemiological clusters of cyclosporiasis. Overall, we show that CDC's integrated genotyping and epidemiological investigations provide valuable insights into cyclosporiasis outbreaks in the United States.


Dopaminergic resistant prolactinomas in the peripubertal population.
We report two children with macroadenomas and hyperprolactinemia resistant to medical therapy using dopamine agonists, who experienced secondary pituitary dysfunction. Both required surgical debulking, and one has received growth hormone treatment with no increase in tumor size.


Single lung transplantation involving a donor with documented pulmonary sarcoidosis.
We report the case of a 32-year-old female patient with primary pulmonary hypertension who received a lung transplant from a donor who, unbeknownst to the medical staff, had pulmonary sarcoidosis diagnosed by lung biopsy 16 months earlier. After 16 months of follow-up, our patient did not show any histologic, radiologic, or clinical evidence of pulmonary sarcoidosis involving the transplanted lung. We reviewed the transplant experience involving donors or recipients with known sarcoidosis, and the available data suggest that normal organs transplanted into recipients with preexisting sarcoidosis are likely to develop sarcoid granulomas, whereas organs from donors with known sarcoidosis given to a "normal" recipient do not appear to develop significant or progressive disease. Although the available data in this regard are limited, we do believe that, on the basis of current information, sarcoidosis cannot be considered a priori to be an absolute contraindication to organ donation.


The Pharma Summit 2010: competing in the future healthcare system.
The Pharma Summit 2010, held in London, included topics covering the future changes and developments that are expected in the pharmaceutical industry. This conference report highlights selected presentations on various visions for the future of the pharma industry, the expected revolution in healthcare, changes with patients driving healthcare innovation, the future of healthcare technology, and the outlook for the global economy and emerging markets in the pharma industry.


Psychotherapy with HIV-positive gay men: a psychodynamic perspective.
This paper examines psychotherapy with HIV-positive gay men from a psychodynamic perspective. Adjustment to being HIV-positive is conceptualized as an ongoing process of confrontation with loss and uncertainty. Interventions offered to HIV-positive gay men range from counseling, indicated in response to an "uncomplicated" adjustment process; to dynamically oriented psychotherapy, indicated when the functioning of the self has been thrown off balance by HIV illness. The client's process of accepting his HIV illness is shaped and colored by the degree to, and manner in, which he has accepted being gay and integrated this into his identity. Sexuality is a core theme in psychotherapy with this population. It often plays a prominent role in the past unresolved conflicts (feelings about having become HIV-infected) as well as present concerns (feelings about living with HIV illness) which the client has come to therapy to address. The process of addressing the meanings being HIV-positive holds for the client in therapy can promote acceptance of the illness and cohesiveness of the self. Cultural and subcultural differences in how life stress is experienced must also be taken into account by the therapist in order to fully appreciate the client's concerns.


Muscle fiber type compartmentalization and expression of an immature myosin isoform in the sternocleidomastoid muscle of rabbits and primates.
The sternocleidomastoid muscle is located in the neck and is both a neck rotator and flexor. Cervical dystonia, a focal dystonia disorder, is characterized by forceful involuntary contraction of a group of neck muscles, usually including the sternocleidomastoid. Little is known about the fiber type composition, fiber type compartmentalization and innervation patterns in this muscle in rabbit and primates. Sternocleidomastoid muscles from rabbit and monkey were analyzed for muscle fiber type composition and number, muscle fiber cross-sectional area and patterns of innervation. The sternocleidomastoid muscle was composed of two distinct regions, or compartments, with different fiber type compositions: an outer or superficial region composed of mostly type 2 myofibers and an inner deep region composed of both type 2 and type 1 myofibers. Neonatal myosin heavy chain isoform was detected in approximately 25% of the myofibers in both regions of the muscle. Neuromuscular junctions were located in seven endplate bands approximately 1-3 cm apart throughout the length of the muscle. There is clear evidence of anatomical subdivisions within this muscle. Not only is there variation in fiber type composition between superficial and deep regions of the muscle, but unlike most other mature skeletal muscles, it continues to express neonatal myosin heavy chain isoform in the adult. The motor program for neck movements is extremely complex, and the histological complexity plays a role in allowing for a continuum of movements of the head and neck, from maintenance of posture to rapid head movements.


Calculation of power and sample size with bounded outcome scores.
The two-sample Wilcoxon rank sum test is the most popular non-parametric test for the comparison of two samples when the underlying distributions are not normal. Although the underlying distributions need not be known in detail to calculate the null distribution of the test statistic, parametric assumptions are often made to determine the power of the test or the sample size. We encountered difficulties with this approach in the planning of a recent clinical trial in stroke patients. It is shown that, for power and sample size estimation, it can be dangerous to apply the classical formulae routinely, especially with outcome scores having a U-shaped or a J-shaped distribution. As an example we have taken the Barthel index, a quality-of-life outcome measure in stroke patients. Further, we have investigated alternative methods by means of Monte Carlo simulation. The distributional characteristics of the estimated powers were compared. Our findings suggest more appropriate computer software is necessary for the calculation of power and sample size when efficacy is measured by a non-parametric method.


Effect of vacancies on the mechanical properties of phosphorene nanotubes.
Using density functional tight-binding method, we studied the mechanical properties, deformation and failure of armchair (AC) and zigzag (ZZ) phosphorene nanotubes (PNTs) with monovacancies and divacancies subjected to uniaxial tensile strain. We found that divacancies in AC PNTs and monovacancies in ZZ PNTs possess the lowest vacancy formation energy, which decreases with the tube diameter in AC PNTs and increases in ZZ PNTs. The Young's modulus is reduced, while the radial and thickness Poisson's ratios are increased by hosted vacancies. In defective AC PNTs, deformation involves fracture of the intra-pucker bonds and formation of the new inter-pucker bonds at a critical strain, and the most stretched bonds around the vacancy rupture first, triggering a sequence of the structural transformations terminated by the ultimate failure. The critical strain of AC PNTs is reduced significantly by hosted vacancies, whereas their effect on the critical stress is relatively weaker. Defective ZZ PNTs fail in a brittle-like manner once the most stretched bonds around a vacancy rupture, and vacancies are able to significantly reduce the failure strain but only moderately reduce the failure stress of ZZ PNTs. The understandings revealed here on the mechanical properties and the deformation and failure mechanisms of PNTs provide useful guidelines for their design and fabrication as building blocks in nanodevices.


Methodological approaches to the study of carbohydrate surface receptore on macrophages and tumor cells.
Ultracytochemical visualization of specific carbohydrate receptors by means of lectins can provide valuable topological information about the functional status of cell surfaces in normal and transformed cells. In addition to the concanavalin A (Con A) rection and precoupling of lectin--peroxidase (PO) a new method is suggested using precoupling of the marker enzyme (PO) with an appropriated glycoprotein (glycopeptide) containing a lectin-specific carbohydrate. Furthermore, quantitative estimations of Con A reaction by means of automatic umage analysis are performed on peritoneal macrophages which point out a cluster formation, but give no hints for a loss of glycocalyx during the preparation process contrary to tumor cells.


Investigating energy-based pool structure selection in the structure ensemble modeling with experimental distance constraints: The example from a multidomain protein Pub1.
The structural variations of multidomain proteins with flexible parts mediate many biological processes, and a structure ensemble can be determined by selecting a weighted combination of representative structures from a simulated structure pool, producing the best fit to experimental constraints such as interatomic distance. In this study, a hybrid structure-based and physics-based atomistic force field with an efficient sampling strategy is adopted to simulate a model di-domain protein against experimental paramagnetic relaxation enhancement (PRE) data that correspond to distance constraints. The molecular dynamics simulations produce a wide range of conformations depicted on a protein energy landscape. Subsequently, a conformational ensemble recovered with low-energy structures and the minimum-size restraint is identified in good agreement with experimental PRE rates, and the result is also supported by chemical shift perturbations and small-angle X-ray scattering data. It is illustrated that the regularizations of energy and ensemble-size prevent an arbitrary interpretation of protein conformations. Moreover, energy is found to serve as a critical control to refine the structure pool and prevent data overfitting, because the absence of energy regularization exposes ensemble construction to the noise from high-energy structures and causes a more ambiguous representation of protein conformations. Finally, we perform structure-ensemble optimizations with a topology-based structure pool, to enhance the understanding on the ensemble results from different sources of pool candidates.


National Service Framework for Older People: promoting health.
In March 2001, the National Service Framework (NSF) for Older People set out standards for the care and treatment of the over 60s in England. In Wales, a strategy for older people is expected in 2002. The eight standards of the NSF for Older People include strategies to reduce falls, strokes and poor mental health among older people as well as improving general and intermediate care. The final standard "Promoting health and active life in older age" is an overarching theme. As well as strategies to promote health in older people, the NSF requires service providers to develop long-term strategies to promote health throughout life in order to prevent chronic illness. This should include the prevention and treatment of osteoporosis. In promoting positive role models, the NSF for Older People is reflecting social trends in tackling ambivalence about ageing. Key themes of the standard include empowerment and improving quality of life for older people. Patient-centred care and the appointment of older people's champions are possible routes towards this aim. Although there is evidence of some patient-focused models of health promotion, a review of the literature suggests that these are limited.


NMR-based structural modeling of graphite oxide using multidimensional 13C solid-state NMR and ab initio chemical shift calculations.
Chemically modified graphenes and other graphite-based materials have attracted growing interest for their unique potential as lightweight electronic and structural nanomaterials. It is an important challenge to construct structural models of noncrystalline graphite-based materials on the basis of NMR or other spectroscopic data. To address this challenge, a solid-state NMR (SSNMR)-based structural modeling approach is presented on graphite oxide (GO), which is a prominent precursor and interesting benchmark system of modified graphene. An experimental 2D (13)C double-quantum/single-quantum correlation SSNMR spectrum of (13)C-labeled GO was compared with spectra simulated for different structural models using ab initio geometry optimization and chemical shift calculations. The results show that the spectral features of the GO sample are best reproduced by a geometry-optimized structural model that is based on the Lerf-Klinowski model (Lerf, A. et al. Phys. Chem. B 1998, 102, 4477); this model is composed of interconnected sp(2), 1,2-epoxide, and COH carbons. This study also convincingly excludes the possibility of other previously proposed models, including the highly oxidized structures involving 1,3-epoxide carbons (Szabo, I. et al. Chem. Mater. 2006, 18, 2740). (13)C chemical shift anisotropy (CSA) patterns measured by a 2D (13)C CSA/isotropic shift correlation SSNMR were well reproduced by the chemical shift tensor obtained by the ab initio calculation for the former model. The approach presented here is likely to be applicable to other chemically modified graphenes and graphite-based systems.


Selective Reductive Elimination at Alkyl Palladium(IV) by Dissociative Ligand Ionization: Catalytic C(sp3 )-H Amination to Azetidines.
A palladium(II)-catalyzed γ-C-H amination of cyclic alkyl amines to deliver highly substituted azetidines is reported. The use of a benziodoxole tosylate oxidant in combination with AgOAc was found to be crucial for controlling a selective reductive elimination pathway to the azetidines. The process is tolerant of a range of functional groups, including structural features derived from chiral α-amino alcohols, and leads to the diastereoselective formation of enantiopure azetidines.


Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia.
Pharmacological management of acute leukemia remains a challenge. A seashell protein Haishengsu (HSS) has been found to exert anticancer activities in recent in vitro studies. The aim of this study was to determine whether the addition of HSS to the conventional chemotherapies would increase chemosensitivity and improves quality of life in patients with acute leukemia. Two hundred and forty-eight patients with acute leukemia were enrolled in a double-blind, and placebo-controlled study. In addition to conventional chemotherapy, 142 patients received HSS and 106 received placebo. In an in vitro study, the expression of P-gp was evaluated by flow cytometry in a drug-resistant leukemia cell line (K562/ADM cells). Sorcin was examined by Western blot. The complete remission rates in the HSS treatment group were all higher than in the placebo group with non-relapsing leukemia and relapsed leukemia (p<0.05). Less patients in the HSS group experienced gastrointestinal side effects from chemotherapy, whereas more patients had increased food take and an increase in Karnofsky performance status (KPS) score (p<0.01). In vitro, the expression of P-gp and sorcin in the HSS treated cells were lower than in the control group cells (p<0.01). When added to conventional chemotherapy, HSS improves the complete remission rates and quality of life in patients with acute leukemia. The in vitro findings indicate that suppression of P-gp and sorcin genes in leukemia cells may be involved in the beneficial effects of HSS.


Predicting the stage shift as a result of breast cancer screening in low- and middle-income countries: a proof of concept.
To provide proof of concept for a simple model to estimate the stage shift as a result of breast cancer screening in low- and middle-income countries (LMICs). Stage shift is an essential early detection indicator and an important proxy for the performance and possible further impact of screening programmes. Our model could help LIMCs to choose appropriate control strategies. We assessed our model concept in three steps. First, we calculated the proportional performance rates (i.e. index number Z) based on 16 screening rounds of the Nijmegen Screening Program (384,884 screened women). Second, we used linear regression to assess the association between Z and the amount of stage shift observed in the programme. Third, we hypothesized how Z could be used to estimate the stage shift as a result of breast cancer screening in LMICs. Stage shifts can be estimated by the proportional performance rates (Zs) using linear regression. Zs calculated for each screening round are highly associated with the observed stage shifts in the Nijmegen Screening Program (Pearson's R: 0.798, R square: 0.637). Our model can predict the stage shifts in the Nijmegen Screening Program, and could be applied to settings with different characteristics, although it should not be straightforwardly used to estimate the impact on mortality. Further research should investigate the extrapolation of our model to other settings. As stage shift is an essential screening performance indicator, our model could provide important information on the performance of breast cancer screening programmes that LMICs consider implementing.


Depressor effect of chymase inhibitor in mice with high salt-induced moderate hypertension.
The aim of the present study was to determine whether long-term high salt intake in the drinking water induces hypertension in wild-type (WT) mice and whether a chymase inhibitor or other antihypertensive drugs could reverse the increase of blood pressure. Eight-week-old male WT mice were supplied with drinking water containing 2% salt for 12 wk (high-salt group) or high-salt drinking water plus an oral chymase inhibitor (TPC-806) at four different doses (25, 50, 75, or 100 mg/kg), captopril (75 mg/kg), losartan (100 mg/kg), hydrochlorothiazide (3 mg/kg), eplerenone (200 mg/kg), or amlodipine (6 mg/kg). Control groups were given normal water with or without the chymase inhibitor. Blood pressure and heart rate gradually showed a significant increase in the high-salt group, whereas a dose-dependent depressor effect of the chymase inhibitor was observed. There was also partial improvement of hypertension in the losartan- and eplerenone-treated groups but not in the captopril-, hydrochlorothiazide-, and amlodipine-treated groups. A high salt load significantly increased chymase-dependent ANG II-forming activity in the alimentary tract. In addition, the relative contribution of chymase to ANG II formation, but not actual average activity, showed a significant increase in skin and skeletal muscle, whereas angiotensin-converting enzyme-dependent ANG II-forming activity and its relative contribution were reduced by high salt intake. Plasma and urinary renin-angiotensin system components were significantly increased in the high-salt group but were significantly suppressed in the chymase inhibitor-treated group. In conclusion, 2% salt water drinking for 12 wk caused moderate hypertension and activated the renin-angiotensin system in WT mice. A chymase inhibitor suppressed both the elevation of blood pressure and heart rate, indicating a definite involvement of chymase in salt-sensitive hypertension.


Ipratropium bromide in the management of chronic obstructive pulmonary disease: effect on health service expenditures.
Chronic obstructive pulmonary disease (COPD), which is estimated to affect 32 million Americans, is the fifth leading cause of death in the United States. This retrospective study was designed to discern the economic utility of initial pharmacotherapy with various individual drugs in the management of COPD, as well as subsequent costs incurred as disease progression necessitated combination therapy. Data for this analysis were derived from the computer archive of a network-model health maintenance organization. During the first 6 months post-diagnosis for COPD, results indicated a significant (P < or = 0.05) increase in expenditures for physicians, hospital care, and total health service utilization for patients prescribed theophylline, a corticosteroid (triamcinolone or beclomethasone) delivered via a metered-dose inhaler, or albuterol delivered via a metered-dose inhaler as initial monotherapy compared with patients prescribed ipratropium bromide (IB) delivered via a metered-dose inhaler. Patients receiving initial pharmacotherapy with ipratropium bromide and subsequently adding albuterol used significantly less health care services (P < or = 0.05) during the first 15 months post-diagnosis for COPD than did patients prescribed all other combination therapies we evaluated.


Effects of processing on structural, mechanical and biological properties of collagen-based substrates for regenerative medicine.
The aim of this work was to investigate the structural features of type I collagen isoforms and collagen-based films at atomic and molecular scales, in order to evaluate whether and to what extent different protocols of slurry synthesis may change the protein structure and the final properties of the developed scaffolds. Wide Angle X-ray Scattering data on raw materials demonstrated the preferential orientation of collagen molecules in equine tendon-derived collagens, while randomly oriented molecules were found in bovine skin collagens, together with a lower crystalline degree, analyzed by the assessment of FWHM (Full Width at Half Maximum), and a certain degree of salt contamination. WAXS and FT-IR (Fourier Transform Infrared) analyses on bovine collagen-based films, showed that mechanical homogenization of slurry in acidic solution was the treatment ensuring a high content of super-organization of collagen into triple helices and a high crystalline domain into the material. In vitro tests on rat Schwannoma cells showed that Schwann cell differentiation into myelinating cells was dependent on the specific collagen film being used, and was found to be stimulated in case of homogenization-treated samples. Finally DHT/EDC crosslinking treatment was shown to affect mechanical stiffness of films depending on collagen source and processing conditions.


Synthesis, structure, and reactivity of an anionic Zr-oxo relevant to CO2 reduction by a Zr/Co heterobimetallic complex.
Oxidative addition of CO2 to the reduced Zr/Co complex (THF)Zr(MesNP(i)Pr2)3Co (1) followed by one-electron reduction leads to formation of an unusual terminal Zr-oxo anion [2][Na(THF)3] in low yield. To facilitate further study of this compound, an alternative high-yielding synthetic route has been devised. First, 1 is treated with CO to form (THF)Zr(MesNP(i)Pr2)3Co(CO) (3); then, addition of H2O to 3 leads to the Zr-hydroxide complex (HO)Zr(MesNP(i)Pr2)3Co(CO) (4). Deprotonation of 4 with Li(N(SiMe3)2) leads to the anionic Zr-oxo species [2][Li(THF)3] or [2][Li(12-c-4)] in the absence or presence of 12-crown-4, respectively. The coordination sphere of the Li(+) countercation is shown to lead to interesting structural differences between these two species. The anionic oxo fragment in complex [2][Li(12-c-4)] reacts with electrophiles such as MeOTf and Me3SiOTf to generate (MeO)Zr(MesNP(i)Pr2)3Co(CO) (5) and (Me3SiO)Zr(MesNP(i)Pr2)3Co(CO) (6), respectively, and addition of acetic anhydride generates (AcO)Zr(MesNP(i)Pr2)3Co(CO) (7). Complex [2][Li(12-c-4)] is also shown to bind CO2 to form a monoanionic Zr-carbonate, [(12-crown-4)Li][(κ(2)-CO3)Zr(MesNP(i)Pr2)3Co(CO)] ([8][Li(12-c-4)]). A more stable version of this compound [8][K(18-c-6)] is formed when a K(+) counteranion and 18-crown-6 are used. Binding of CO2 to [2][Li(12-c-4)] is shown to be reversible using isotopic labeling studies. In an effort to address methods by which these CO2-derived products could be turned over in a catalytic cycle, it is shown that the Zr-OMe bond in 5 can be cleaved using H(+) and the CO ligand can be released from Co under photolytic conditions in the presence of I2.


[Reducing fear in preschool children receiving intravenous injections].
Our pediatric medical ward administers an average of 80 intravenous injections to preschool children. We found that 91.1% exhibit behavior indicative of fear and anxiety. Over three-quarters (77.8%) of this number suffer severe fear and actively resist receiving injections. Such behavior places a greater than normal burden on human and material resources and often gives family members negative impressions that lower their trust in the healthcare service while raising nurse-patient tensions. Using observation and interviews, we found primary factors in injection fear to be: Past negative experiences, lack of adequate prior communication, measures taken to preemptively control child resistance, and default cognitive behavioral strategies from nursing staff. This project worked to develop a strategy to reduce cases of severe injection fear in preschool children from 77.8% to 38.9% and achieve a capacity improvement target for members of 50%. Our team identified several potential strategy solutions from research papers and books between August 1st, 2009 and April 30th, 2010. Our proposed method included therapeutic games, self-selection of injection position, and cognitive behavioral strategies to divert attention. Other measures were also specified as standard operating procedures for administering pediatric intravenous injections. We applied the strategy on 45 preschool children and identified a post-injection "severe fear" level of 37.8%. This project was designed to reduce fear in children to make them more accepting of vaccinations and to enhance children's positive treatment experience in order to raise nursing care quality.


Survey of nurse perceptions regarding the utilization of bedside computers.
In December 1993, Intermountain Health Care (IHC) placed a moratorium on the installation of bedside computers in the acute care setting unless information could be obtained to justify resumption of these installations. A survey was developed and administered to nurses at two IHC hospitals. The survey results indicate that acute care nurses value bedside computers and believe that IHC should install them at other facilities. In addition, the acute care nurses estimate that they are using the bedside computers over 75% of the time during the day shift to document vital signs/measurements and intake/output quantities. Based on the results of this survey, IHC has decided to continue installing bedside computers in the acute care setting.


Morphologic Classification Is an Important Prognostic Factor in Patients with Newly Diagnosed Multiple Myeloma Treated with Bortezomib or Lenalidomide.
The morphological classification of multiple myeloma (MM) has long been known to have an impact on its clinical course. We retrospectively analyzed 30 cases of newly diagnosed MM initially treated with bortezomib or lenalidomide between November 2014 and November 2018. The morphological bone marrow types were assessed on the basis of the Greipp classification. The patients' median age was 74.5 years (range, 49-88), and the male-to-female ratio was 0.67. The International Staging System stages were as follows: stages I, II, and III accounted for 3.3%, 46.7%, and 50.0% of patients, respectively. The M-proteins were IgG (n=21) and non-IgG (n=9). The median progression free survival (PFS) was not reached. The proportion of plasma, immature, and plasmablastic cells in the bone marrow was significantly affected by PFS. When scored with 1 point each, PFS could be stratified into three groups. All patients who had ≥5% of immature cells had a complex karyotype. This study shows that the visual morphological classification of plasma cells is an important prognostic factor even when bortezomib or lenalidomide is used as induction therapy. Further research is expected to reveal the optimal treatment strategy for immature and plasmablastic MM.


Pyrethroid Pesticide Metabolite in Urine and Microelements in Hair of Children Affected by Autism Spectrum Disorders: A Preliminary Investigation.
The number of children affected by Autism Spectrum Disorders (ASD) is dramatically increasing as well as the studies aimed at understanding the risk factors associated with the development of ASD. Since the etiology of ASD is partly genetic and partly environmental, factors (i.e., heavy metals, pesticides) as well as lifestyle seem to have a key role in the development of the disease. ASD and Control (CTR) children, aged 5-12 years, were compared. Gas chromatography coupled with trap mass detector was used to measure the level of 3-PBA, the main pyrethroid metabolite in urine in a group of ASD patients, while optical emission spectrometry analysis was employed to estimate the level of metals and microelements in hair in a different group of ASD children. The presence of 3-PBA in urine seems to be independent of age in ASD children, while a positive correlation between 3-PBA and age was observed in the control group of the same age range. Urine concentration of 3-BPA in ASD children had higher values than in the control group, which were marginally significant (p = 0.054). Mg results were significantly decreased in ASD with respect to controls, while V, S, Zn, and Ca/Mg were marginally increased, without reaching statistical significance. Results of Principal Component (PC) analysis of metals and microelements in hair were not associated with either age or health status. In conclusion, 3-PBA in urine and Mg in hair were changed in ASD children relative to control ones.


Stem cell-mediated functionalization of titanium implants.
Prosthetic implants are used daily to treat edentulous people and to restore mobility in patients affected by skeletal defects. Titanium (Ti) is the material of choice in prosthetics, because it can form a stable bond with the surrounding bone following implantation-a process known as osseointegration. Yet, full integration of prosthetic implants takes time, and fails in clinical situations characterized by limited bone quantity and/or compromised regenerative capacity, and in at-risk patients. Intense research efforts are thus made to develop new implants that are cost-effective, safe, and suited to every patient in each clinical situation. In this study, we tested the possibility to functionalize Ti implants using stem cells. Human induced pluripotent stem cell-derived mesenchymal progenitor (iPSC-MP) cells were cultured on Ti model disks for 2 weeks in osteogenic conditions. Samples were then treated using four different decellularization methods to wash off the cells and expose the matrix. The functionalized disks were finally sterilized and seeded with fresh human iPSC-MP cells to study the effect of stem cell-mediated surface functionalization on cell behavior. The results show that different decellularization methods produce diverse surface modifications, and that these modifications promote proliferation of human iPSC-MP cells, affect the expression of genes involved in development and differentiation, and stimulate the release of alkaline phosphatase. Cell-mediated functionalization represents an attractive strategy to modify the surface of prosthetic implants with cues of biological relevance, and opens unprecedented possibilities for development of new devices with enhanced therapeutic potential.


Simulating soil organic carbon stock as affected by land cover change and climate change, Hyrcanian forests (northern Iran).
Soil organic carbon (SOC) contains a considerable portion of the world's terrestrial carbon stock, and is affected by changes in land cover and climate. SOC modeling is a useful approach to assess the impact of land use, land use change and climate change on carbon (C) sequestration. This study aimed to: (i) test the performance of RothC model using data measured from different land covers in Hyrcanian forests (northern Iran); and (ii) predict changes in SOC under different climate change scenarios that may occur in the future. The following land covers were considered: Quercus castaneifolia (QC), Acer velutinum (AV), Alnus subcordata (AS), Cupressus sempervirens (CS) plantations and a natural forest (NF). For assessment of future climate change projections the Fifth Assessment IPCC report was used. These projections were generated with nine Global Climate Models (GCMs), for two Representative Concentration Pathways (RCPs) leading to very low and high greenhouse gases concentration levels (RCP 2.6 and RCP 8.5 respectively), and for four 20year-periods up to 2099 (2030s, 2050s, 2070s and 2090s). Simulated values of SOC correlated well with measured data (R2=0.64 to 0.91) indicating a good efficiency of the RothC model. Our results showed an overall decrease in SOC stocks by 2099 under all land covers and climate change scenarios, but the extent of the decrease varied with the climate models, the emissions scenarios, time periods and land covers. Acer velutinum plantation was the most sensitive land cover to future climate change (range of decrease 8.34-21.83tCha-1). Results suggest that modeling techniques can be effectively applied for evaluating SOC stocks, allowing the identification of current patterns in the soil and the prediction of future conditions.


Repair of wounded monolayers of cultured bovine aortic endothelial cells is inhibited by calcium spirulan, a novel sulfated polysaccharide isolated from Spirulina platensis.
Calcium spirulan (Ca-SP) is a novel sulfated polysaccharide isolated from a blue-green alga Spirulina platensis. Ca-SP inhibits thrombin by activation of heparin cofactor II. Therefore, it could serve as an origin of anti-atherogenic medicines. Since maintenance of vascular endothelial cell monolayers is important for prevention of vascular lesions such as atherosclerosis, the effect of Ca-SP at 20 microg/ml or less on the repair of wounded bovine aortic endothelial cell monolayers in culture was investigated in the present study. When the monolayers were wounded and cultured in the presence of Ca-SP, the polysaccharide inhibited the appearance of the cells in the wounded area. The inhibition was also observed even when the repair was promoted by excess basic fibroblast growth factor, which is one of the autocrine growth factors that are involved in the endothelial cell monolayer maintenance. On the other hand, Ca-SP inhibited the cell growth and the incorporation of [3H]thymidine into the acid-insoluble fraction of proliferating endothelial cells, suggesting that Ca-SP inhibits endothelial cell proliferation. From these results, it is concluded that Ca-SP may retard the repair process of damaged vascular endothelium through inhibition of vascular endothelial cell proliferation by induction of a lower ability to respond to stimulation by endogenous basic fibroblast growth factor.


Large-Scale Membrane Permeability Prediction of Cyclic Peptides Crossing a Lipid Bilayer Based on Enhanced Sampling Molecular Dynamics Simulations.
Membrane permeability is a significant obstacle facing the development of cyclic peptide drugs. However, membrane permeation mechanisms are poorly understood. To investigate common features of permeable (and nonpermeable) designs, it is necessary to reproduce the membrane permeation process of cyclic peptides through the lipid bilayer. We simulated the membrane permeation process of 100 six-residue cyclic peptides across the lipid bilayer based on steered molecular dynamics (MD) and replica-exchange umbrella sampling simulations and predicted membrane permeability using the inhomogeneous solubility-diffusion model and a modified version of it. Furthermore, we confirmed the effectiveness of this protocol by predicting the membrane permeability of 56 eight-residue cyclic peptides with diverse chemical structures, including some confidential designs from a pharmaceutical company. As a result, a reasonable correlation between experimentally assessed and calculated membrane permeability of cyclic peptides was observed for the peptide libraries, except for strongly hydrophobic peptides. Our analysis of the MD trajectory demonstrated that most peptides were stabilized in the boundary region between bulk water and membrane and that for most peptides, the process of crossing the center of the membrane is the main obstacle to membrane permeation. The height of this barrier is well correlated with the electrostatic interaction between the peptide and the surrounding media. The structural and energetic features of the representative peptide at each vertical position within the membrane were also analyzed, revealing that peptides permeate the membrane by changing their orientation and conformation according to the surrounding environment.


Return of the old guard: a case of tetanus in an unvaccinated patient.
A 78-year-old woman with no known medical history presented with severe neck pain that began 4 days prior to admission located in the paraspinal cervical region radiating to the shoulders, legs and back. She had associated stiffness of her neck and progression of pain to her jaw and throat with progression to generalised body spasms with lower extremity stiffness and weakness that limited her ability to walk. She quickly developed dysphagia and odynophagia with subsequent generalised spasms and profound hypoxic respiratory failure requiring nasotracheal intubation. The presumptive diagnosis of tetanus was made and she was given tetanus toxoid immune globulin and Tdap vaccine. She was managed in the intensive care unit and after a week of admission, required a tracheostomy and gastrostomy tube placement. She required a prolonged hospitalisation stay of 21 days before being transferred to a long-term vent facility.


[Pharmacokinetics and clinical evaluation of ceftriaxone in neonates].
A parenteral cephem antibiotic ceftriaxone (CTRX) was studied for its pharmacokinetic features and clinical efficacy and safety in various infections in neonates including premature infants at 11 institutions associated with Japan Perinatal Infection Research Group. The following results obtained are summarized as follows. 1. Following single intravenous bolus injections with 10 and 20 mg/kg of CTRX, serum levels of the drug at 30 minutes post-dose 36-42 micrograms/ml and 46-76 micrograms/ml, respectively, and those at 12 hours post-dose were 10-14 micrograms/ml and 13-21 micrograms/ml, respectively, in a total of 105 neonates. Serum levels detected were on very gentle descending curves. 2. Half-lives (T 1/2) of the drug in serum were significantly prolonged in 0-3 day age groups of both mature and premature infants: it was especially long in premature infants with age of 0-3 days; i.e., 17.1 hours. There was no difference in T 1/2 between the 4-7 day and 8-28 day age groups. 3. Urinary excretion rates were 20-30% in the first 6 hours post-dose and 30-40% in 12 hours post-dose, in 80 neonates examined. 4. Clinical efficacy: Clinical efficacies were evaluated in 112 of 168 enrolled excluding infants with 90 days of age or older, who were treated for prophylaxis and unevaluable cases. The safety was evaluated in 161 of the 168. (1) Demographic background of the 112 cases: The 112 cases were composed of 89 neonates with ages of 28 days or younger, 21 premature infants, 57 males and 55 females. The drug was given to 102 of the cases by intravenous bolus injection, with 81 cases administered twice a day and 97 cases receiving 10-50 mg/kg a day. (2) Efficacy rate in the 112 cases: In 60 cases for whom causative pathogens were identified the efficacy rate was 90.0% in total (excellent: 31/60; good: 23/60); efficacy rates of 87.5% were obtained in 8 cases with purulent meningitis and 90.9% in 11 with septicemia. In 52 with causative pathogen not identified, the efficacy rate was 96.2% in total (excellent: 21/52; good: 29/52). (3) Adverse reaction: Adverse reactions were noted in 14 of the 161 cases where the safety was evaluated (8.7%). These reactions included diarrhea in 11, vomiting in 2 and exanthema in 1. Abnormalities in laboratory test values were observed in 25 of the 152 cases (16.4%). They included eosinophilia in 14, elevated GOT in 4 and thrombocytosis in 3 etc.(ABSTRACT TRUNCATED AT 250 WORDS)


Partial eating disorders among adolescents: a review.
Many adolescents do not fulfill all the DSM-IV criteria's for anorexia nervosa and bulimia, but do nevertheless suffer from partial eating disorders (EDs). This review focuses on the definition, epidemiology and clinical aspects of these disorders. Search on Medline & PsycINFO, review of websites, screening of bibliographies of articles and book chapters. There is still no consensus on the definition of these disorders, which cover a wide range of severity. Affected adolescents often suffer from physical and psychological problems owing to co-morbidity or as a consequence of their eating patterns: chronic constipation, dyspeptic symptoms, nausea, abdominal pain, fatigue, headaches, hypotension, menstrual dysfunction as well as dysthymia, depressive and anxiety disorders, or substance misuse and abuse. In comparison with those who are unaffected, adolescents with partial ED are at higher risk of evolving into full ED. However, most of them evolve into spontaneous remission. Adolescents with partial ED engaged, over a period of several months, in potentially unhealthy weight-control practices, suffering from intense fear of gaining weight and a disturbed body weight/image should be offered therapeutic support. Future research should focus on the exact delineation of various subtypes of clinical presentations in partial ED and on evidence-based treatment and follow-up of these various situations.


Effect of Inosiplex on BHK cells "in vitro".
The effect of different Inosiplex doses in tissue culture was studied utilizing a cellular line derived from the Hamster Kidney (BHK). Inosiplex doses used were 0.1, 1, 10 and 100 mg/ml of Eagle basal medium adding 10 per cent of heat inactivated fetal calf serum. Increase in cellular growth that was statistically significant was observed in 10 and 100 microgram/ml Inosiplex doses. Also this substance was studied at same concentrations in other two cellular lines, one derived from loose connective tissue in mice (L-929) and the other from cervical carcinoma (HeLa). In the first, 10 and 100 microgram/ml doses produced growth inhibition while in the second no effect was observed.


A Simple Method for Purified Primary Culture of Enteric Glial Cells from Mouse Small Intestine.
Enteric glial cells (EGCs) have been recognized as an important cell type constituting the enteric nervous system. EGCs control intestinal function and homeostasis through interactions with enteric neurons, epithelial cells and immune cells. To clarify the roles of EGCs in intestinal function and homeostasis, especially through secretion of and response to physiologically active substances, purified EGCs in primary culture have great advantages as an experimental tool. However, contamination by other cell types, fibroblasts in particular, is problematic in conventional primary myenteric culture. Previous methods to purify primary EGCs take a long time (over one month), are expensive, and are labor intensive. In the present study, we sought to purify primary EGCs from mouse small intestine by a simpler method than previous ones. After trying various protocols, we have established a method combining serum-free treatment and scraping fibroblasts off with a pipette tip. With our method, a purity of more than 90% EGCs was achieved after 14-d primary culture. Thus, our method is useful for investigating the roles of EGCs in intestinal function and homeostasis in detail in vitro.


Inactivation of interleukin-6 in vitro by monoblastic U937 cell plasma membranes involves both protease and peptidyl-transferase activities.
Human promonocytic U937 cells have previously been shown to possess at their cell surface specific transmembrane serine proteases and N-terminal amino acid proteases as well as associated enzymes including elastase and cathepsin G. In this study, purified plasma membranes from U937 cells are reported to degrade the recombinant 21-kDa 125I-interleukin-6 (125I-IL-6) into 8-kDa products with loss of biological activity, as monitored by polyacrylamide gel electrophoresis and a cell-proliferation bioassay. Degradation of 125I-IL-6 by plasma membranes was completely prevented by the serine-protease inhibitor diisopropyl fluorophosphate, but was only partially impaired by alpha 1-protease inhibitor and antibody against cathepsin G. A similar incubation of 125I-IL-6 with cathepsin G purified from U937 cells caused hydrolysis of the cytokine into similar inactive 8-kDa fragments, whereas incubation with purified U937 cell elastase failed to degrade the peptide. These findings indicate that U937 cells hydrolyze IL-6 using cell-associated serine-protease activity and that cathepsin G partially participates in this degradation. Prolonged incubation of 8-kDa 125I-IL-6 fragments with purified U937 plasma membranes, led to a complete loss of IL-6 activity related to the transformation of the 8-kDa forms into a higher-molecular-mass complex (16 kDa). This complex was stable in SDS and 2-mercaptoethanol at 100 degrees C and was not dissociated by hydroxylamine treatment, indicating the formation of a covalent non-ester bond between the 8-kDa 125I-IL-6-derived peptide and an undetermined acceptor. An initial oxidative treatment of 125I-IL-6 partially prevented complex formation, suggesting the presence of one or more oxidizable methionine residues at the binding site of 8-kDa 125I-IL-6 peptide. The kinetics of complex formation (time dependence and plasma-membrane-concentration dependence), as well as its inhibition by a specific inhibitor of N-amino-peptidase activity, bestatin, suggest the participation of peptidyl-transferase activity in complex formation. Finally, a plasma-membrane fraction, corresponding to a molecular mass > or = 30 kDa, was able to convert the 8-kDa 125I-IL-6 forms into the 125I-labeled 16-kDa complex, suggesting that a > or = 30-kDa peptidyl-transferase enzyme catalyzes the reaction and provides the 125I-labeled 16-kDa peptide by dimerization of 8-kDa 125I-IL-6-derived intermediates. Further identification of the plasma-membrane-associated peptidyl transferase as a regulator of IL-6 proteolysis may be of physiological relevance for the control of IL-6 biological activity.


Class II members of the poly(A) binding protein family exhibit distinct functions during Arabidopsis growth and development.
The poly(A)-binding protein (PABP) binds to the poly(A) tail of eukaryotic cellular mRNAs and contributes to their stability and translational efficiency. In plants, PABP is expressed from an unusually large gene family grouped into 3 classes that expanded during the evolution of land plants. Subsequent to expansion of the family, members diverged in their primary sequence and in expression. Further expansion of the family and divergence of its members in the Brassicaceae demonstrate the continued dynamic evolution of PABP in plants. In this study, the function of the widely-expressed class II PABP family members was examined to determine how individual class II members contribute to plant growth and development. Of the 3 class II PABP members, PAB2 and PAB4 contribute most to vegetative growth and vegetative-to-floral transition whereas PAB2, and the recently-evolved third class II member, PAB8, contribute to inflorescence and silique growth. Interestingly, although class I and class III PABP members are expressed specifically in reproductive organs, class II PABP members are also necessary for fertility in that the combinatorial loss of PAB2 and either PAB4 or PAB8 expression resulted in reduced fertility. Although all 3 class II members are required for protein expression, PAB4 contributes most to the steady-state level of a reporter mRNA and to protein expression. These findings suggest that class II PABP members are partially overlapping in function but also involved in distinct aspects of plant growth and development.


Learning from Adversity?
Many two-component regulatory systems, including Escherichia coli PhoRB, are positively autoregulated, so stimuli result in an increase in the concentration of signaling proteins. When the quantity of signaling proteins depends on exposure history, how do past conditions affect future responses to stimuli? Hoffer et al. (J. Bacteriol. 183:4914-4917, 2001, https://doi.org/doi:10.1128/JB.183.16.4914-4917.2001) previously reported that E. coli bacteria "learn" from phosphate starvation and respond more rapidly to subsequent episodes of starvation. Gao et al. (J. Bacteriol. 199:e00390-17, 2017, https://doi.org/doi:10.1128/JB.00390-17) describe another aspect of hysteresis in the PhoRB regulon. Phosphate starvation also leads to a global decline in transcription, counteracting the effects of positive autoregulation and resulting in a similar net pho response (homeostasis), regardless of exposure history.


Nerve growth factor and mast cell distribution in the skin of patients with systemic sclerosis.
Nerve growth factor (NGF), a well-characterized neurotrophic factor, induces an increase in the number of mast cells (MCs) in the peripheral tissues of developing rats, as well as histamine release in fully differentiated MCs. Since MCs increase in the dermis of patients with early systemic sclerosis (SSc), we examined the distribution of NGF in the skin of patients affected by SSc. Immunohistochemical studies showed that NGF distribution was more intense in the dermis of patients with SSc than in the skin of controls. A possible correlation between MCs and NGF in disease activity is hypothesized.


A strategy for in vivo screening of subtilisin E reaction specificity in E. coli periplasm.
We developed a protocol for efficient expression of the functional serine protease, subtilisin E, in Escherichia coli periplasm that permits direct in vivo measurement of the enzyme's catalytic activity. Activity assays and SDS-PAGE/Western blot analysis showed that the levels of expressed subtilisin varied and were correlated with both the culture conditions and the induction procedures. The highest level of subtilisin expression was achieved at 0.10-0.15% (w/v) of arabinose as inducer and a temperature of 20-22 degrees C, and was ca. eightfold higher as compared to the expression level at 30 degrees C. Cultivation of bacterial cells to a steady state of balanced growth before induction was required for uniform subtilisin expression in cell cultures growing in wells of microtiter plates. Amidase and esterase cell-based kinetic assays on microtiter plates were developed based on the direct measurement of subtilisin activity in vivo. Intact E. coli cells displaying wild-type, dimethylformamide-resistant, and temperature-resistant subtilisins were assayed on N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide and N-acetyl-Phe-p-nitrophenyl ester for their amidase and esterase activity, respectively. Additionally, the periplasmic fractions were isolated from the three E. coli strains expressing the respective subtilisins and tested for amidase activity. The amidase activity of the three subtilisins was ca. 15-fold higher than the esterolytic activity when measured in both the intact cells and in the periplasmic fractions. The strategy combining periplasmic expression of subtilisins with two cell-based kinetic assays permits rapid screening of subtilisin mutant libraries for desired activities.


Reduction of Bladder Capacity Under Anesthesia Following Multiple Recurrences and Repeated Surgeries of Hunner Lesions in Patients With Interstitial Cystitis.
To investigate the influence of multiple recurrences and repeated surgeries of Hunner lesions on bladder capacity under general anesthesia in patients with interstitial cystitis (IC). We retrospectively reviewed the clinical records of Hunner-type IC (HIC) patients who underwent transurethral fulguration or resection of Hunner lesions combined with hydrodistension by a single surgeon between 2011 and 2020. Recurrence was defined as reappearance of uncontrolled urinary symptoms in association with new Hunner lesions identified by cystoscopy. Recurrent Hunner lesions were then treated by transurethral surgeries. The recurrence-free rate, potential predictive factors of recurrence, and changes in bladder capacity under anesthesia were examined at each surgical procedure. A total of 92 surgeries were performed in 47 HIC patients, 23 (49%) of whom required multiple procedures (range, 1-5 times). The mean recurrence-free time after the first surgery was 21.7 months. The recurrence-free rate was 53% at 24 months, and decreased to 32% at 48 months. There were no significant differences in age, sex, bladder capacity under anesthesia at the first surgery, duration from symptom onset to the first surgery, O'Leary-Sant questionnaire including symptom and problem indexes, visual analogue scale pain score, and the number of comorbidities between the cases with or without recurrence. Bladder capacity under anesthesia was gradually decreased as the number of surgeries was increased, and bladder capacity at the fourth procedure was significantly decreased to 80% of the capacity at the first surgery. These results suggest that multiple recurrences and repeated surgeries of Hunner lesions result in a reduction of bladder capacity under anesthesia in HIC patients although no predictive factors for recurrence of Hunner lesions were detected.


Noninvasive imaging of protein-protein interactions in living animals.
Protein-protein interactions control transcription, cell division, and cell proliferation as well as mediate signal transduction, oncogenic transformation, and regulation of cell death. Although a variety of methods have been used to investigate protein interactions in vitro and in cultured cells, none can analyze these interactions in intact, living animals. To enable noninvasive molecular imaging of protein-protein interactions in vivo by positron-emission tomography and fluorescence imaging, we engineered a fusion reporter gene comprising a mutant herpes simplex virus 1 thymidine kinase and green fluorescent protein for readout of a tetracycline-inducible, two-hybrid system in vivo. By using micro-positron-emission tomography, interactions between p53 tumor suppressor and the large T antigen of simian virus 40 were visualized in tumor xenografts of HeLa cells stably transfected with the imaging constructs. Imaging protein-binding partners in vivo will enable functional proteomics in whole animals and provide a tool for screening compounds targeted to specific protein-protein interactions in living animals.


[A Case of Laparoscopic Uterine and Vaginal Resection for Local Recurrence after Abdominoperineal Resection for Anal Canal Cancer].
The patient was an 80s woman. She visited our hospital with chief complaint of melena, and further evaluation revealed anal canal cancer. We performed robot-assisted abdominoperineal resection(D3 lymphadenectomy)and lateral lymph node dissection. The pathological diagnosis was anal canal cancer, muc>por1>tub2, T3N1bM0, pStage Ⅲb. One year after the surgery, she had a mass in the soft tissue of perineum on CT scan and PET-CT showed abnormal accumulation, which was diagnosed as local recurrence. At the same time, she also had a mass with abnormal accumulation in ascending colon, and it was diagnosed as ascending colon cancer. In both cases, we judged radical resection was possible, and the policy of surgery was decided. First, laparoscopic ileocecal resection was performed. The local recurrence lesion became a mass, invading the soft tissue of the perineum, the posterior wall of the vagina, and the cervix. So, we performed laparoscopic excision of local recurrent region together with the uterus and the posterior wall of the vagina. Based on the result of pathological examination, the patient was diagnosed with ascending colon cancer(tub1, pT1bN1aM0, pStage Ⅲa), and recurrence of anal canal cancer. The postoperative course is good and there are no signs of recurrence for 6 months after the operation.


Picture this: photos improve wound management.
Harefield Hospital's clinical nurse specialist in surveillance Melissa Rochon introduced Photo at Discharge (PaD) to reduce the impact of surgical site infections (SSIs).


Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes.
Cellular reproduction defines life, yet our textbook-level understanding of cell division is limited to a small number of model organisms centered around humans. The horizon on cell division variants is expanded here by advancing insights on the fascinating cell division modes found in the Apicomplexa, a key group of protozoan parasites. The Apicomplexa display remarkable variation in offspring number, whether karyokinesis follows each S/M-phase or not, and whether daughter cells bud in the cytoplasm or bud from the cortex. We find that the terminology used to describe the various manifestations of asexual apicomplexan cell division emphasizes either the number of offspring or site of budding, which are not directly comparable features and has led to confusion in the literature. Division modes have been primarily studied in two human pathogenic Apicomplexa, malaria-causing Plasmodium spp. and Toxoplasma gondii, a major cause of opportunistic infections. Plasmodium spp. divide asexually by schizogony, producing multiple daughters per division round through a cortical budding process, though at several life-cycle nuclear amplifications stages, are not followed by karyokinesis. T. gondii divides by endodyogeny producing two internally budding daughters per division round. Here we add to this diversity in replication mechanisms by considering the cattle parasite Babesia bigemina and the pig parasite Cystoisospora suis. B. bigemina produces two daughters per division round by a "binary fission" mechanism whereas C. suis produces daughters through both endodyogeny and multiple internal budding known as endopolygeny. In addition, we provide new data from the causative agent of equine protozoal myeloencephalitis (EPM), Sarcocystis neurona, which also undergoes endopolygeny but differs from C. suis by maintaining a single multiploid nucleus. Overall, we operationally define two principally different division modes: internal budding found in cyst-forming Coccidia (comprising endodyogeny and two forms of endopolygeny) and external budding found in the other parasites studied (comprising the two forms of schizogony, binary fission and multiple fission). Progressive insights into the principles defining the molecular and cellular requirements for internal vs. external budding, as well as variations encountered in sexual stages are discussed. The evolutionary pressures and mechanisms underlying apicomplexan cell division diversification carries relevance across Eukaryota.


Fabrication and Characterization of In Situ Synthesized SiC/Al Composites by Combustion Synthesis and Hot Press Consolidation Method.
The in situ SiC/Al composites were fabricated in Al-Si-C systems with different Si/C mass ratios and holding time by the method of combustion synthesis and hot press consolidation. The influences of Si/C mass ratio and holding time on the phase constitution, microstructure, and hardness of the composites were investigated. The results indicate that the increase of Si/C mass ratio leads to more uniform size distribution of the SiC particles in the Al matrix. Moreover, by improving the Si/C mass ratio from 4 : 1 to 5 : 1, the maximum size of SiC particle was reduced from 4.1 μm to 2.0 μm. Meanwhile, the percentage of submicroparticles was increased from 22% to 63%, and the average hardness value of the composites was increased by 13%. In addition, when the holding time is set to be fifteen minutes, the Al4C3 phase did not exist in the composites because of its total reactions with Si atoms to form SiC particles, and the average hardness value was 73.8 HB.


The Association of Midday Napping With Hypertension Among Chinese Adults Older Than 45 Years: Cross-sectional Study.
Hypertension is one of the main public health issues around worldwide, and midday napping is a popular habit. The association between the two remains to be explored. The goal of the research was to explore the association of midday napping with hypertension. This study separately selected 11,439, 12,689, and 9464 Chinese respondents aged over 45 years from the China Health and Retirement Longitudinal Study 2011, 2015, and 2018 data sets. Binary logistic regression was used to explore the association of midday napping with hypertension, and the 3-step method was used to test the mediation effect of BMI. Among all respondents, the prevalence rates of hypertension were 24.6% (2818/11439) in 2011, 21.1% (2683/12689) in 2015, and 22.1% (2092/9464) in 2018. Midday napping was positively correlated with hypertension. In 2011 and 2015, napping 60 to 90 minutes had the greatest odds ratios [OR] (OR2011 1.705, OR2015 1.494). In 2018, the biggest OR came from the group napping 30 to 60 minutes (OR 1.223), and ORs of different napping durations decreased from 2011 to 2018. In addition, BMI had a partial mediation effect in 2015 and 2018. Midday napping is a potential risk factor for hypertension with BMI acting as a mediator. To prevent hypertension, avoiding prolonged duration of midday napping and taking action to maintain a normal BMI level are recommended.


Thermal tissue damage following laser and large loop conization of the cervix.
To compare thermal injury zones produced with laser and diathermy loop conization. Excisional cervical specimens (cones and cervices) were obtained from 40 consecutive women who underwent abdominal hysterectomy. The subjects were assigned to have either laser or diathermy loop conization (20 in each group). The duration of each procedure was recorded. Histopathologic measurements of thermal injury zones were performed in all specimens. The techniques produced cone specimens of similar depth. The mean depth of thermal injury produced with laser conization in cone specimens (mean +/- standard deviation 0.49 +/- 0.16 mm) and cervical craters (0.58 +/- 0.24 mm) was significantly greater (P < .001) than the corresponding depth in cone specimens (0.22 +/- 0.09 mm) and cervical craters (0.27 +/- 0.11 mm) obtained by diathermy loop excision. The mean time of the two procedures was also significantly different (P < .001); laser conization 11 +/- 4.5 minutes and loop conization 2 +/- 1.2 minutes. For routine conization, loop diathermy causes less thermal damage to the specimen and is a faster procedure than laser.