Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.
To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.


Speaking and listening: The importance of stakeholder engagement in quality improvement in pediatric urology.
To improve health care, we as clinicians must work to change processes that make it easier to do our job well and reliably every day. Before improving a process, we must understand it and this often requires employing the expertise of others. Indeed, quality improvement work is often done in teams. The key is identifying and engaging the right stakeholders for each improvement initiative. The goal of this review is to provide health care professionals with the basis for how to do this. We describe four essential stakeholder steps that aid in the success of a quality improvement initiative. The steps of 1.) identifying and 2.) categorizing stakeholders involve spending the time to think about who the necessary stakeholders are and how to organize them. It is essential to consider stakeholders who are balanced for expertise, skills, experience, perspective, gender, race, and ethnicity. The process then moves on to 3.) analyzing stakeholders, which supports efforts that are focused on the stakeholder relationships that will most impact project success. The final step is 4.) stakeholder engagement. This represents a critical opportunity, not only upfront, but also to maintain a high level of stakeholder engagement throughout the quality improvement project. As the improvement work evolves, it is important to return to the earlier steps and reflect on the stakeholder group; the process is iterative. Devoting sufficient energy and time to these stakeholder steps will provide ample returns. This review should assist health care professionals in establishing an improvement team for each quality improvement initiative, which is foundational to initiating change efforts that better system performance, enhance the quality of care, and ensure patient safety.


Food and health considerations in Asia-Pacific regional security.
Recent dramatic increases in food prices in much of the world have caused much concern, and have even resulted in some public protests and riots. This is easy to understand given the large percentages of incomes that the poor devote to food purchases. Many commentators have predicted that food supplies in the Asia-Pacific region will become much more limited in the future as the result of population growth, the rapid growth of cities, new food demands by a growing middle class, the impacts of climate change, and the growth of a global food industry. But will these possible shortages of food result in pressures that will destabilise the security situation in the region? Recent work of the whole concept of security has resulted in some redefinition of the term to include issues of human security, but it could also be argued that severe strains on the human security situation could even result in increased instability in the more traditional kind of security regime. The extreme case of North Korea is used as an example of how this might happen. But we really do not know if such dangers are real ones for the region as a whole, and it is suggested that much more research is needed in this area. The whole concept of resilience has been used in some studies elsewhere and this may be useful starting point for new work in this area.


Laser beam diffraction at the edge of a film and application to thin film metrology.
The thickness change of a film is measured optically using self-interference of a single laser beam incident at the edge of the film. Theory suggests that when a half-plane phase shift is applied to a Gaussian laser beam, interference fringes appear in the near and far field, in which position varies with the amount of phase shift. By measuring fringe pattern displacement, we demonstrate detection of thickness changes in chitosan films induced by temperature rises of a few degrees centigrade. With a laser at 543 nm, the minimum detectable thickness change is 0.8 nm in ideal conditions (quarter wave films), corresponding with a phase shift of 0.02 rad, and the minimum detectable film thickness is ∼30 nm. Potential use for surface temperature measurements is discussed.


Economic analysis of esophageal stenting for management of malignant dysphagia.
Over half of patients diagnosed with esophageal cancer are unsuitable for curative resection. A significant proportion of these patients will subsequently require palliative stenting to alleviate dysphagia. There is growing consensus in the literature that the deployment of a Self-Expanding Metal Stent is the optimum stenting strategy; however, it remains unclear whether covered or uncovered metal stents are more cost-effective. In order to determine which type of prosthesis is more cost-effective, we compared the different stenting strategies in terms of 1-year stent-related mortality, health-related quality of life, and cost. A decision analytical model was constructed to compare the 1-year stent-related mortality, health-related quality of life, and cost between covered and uncovered stents. Probabilistic sensitivity analysis was performed to quantify the uncertainty associated with our results. Value of Information analysis was performed to assess the value of further research. In order to fully characterize the uncertainty associated with this decision, plastic stents were included in our analysis. Stent-related mortality was slightly lower following covered stent deployment compared with uncovered stent deployment (1.00% vs. 1.26%). Covered stents were more effective by 0.0013 Quality-Adjusted Life Years (Standard Deviation [SD] 0.0013 Quality-Adjusted Life Years). They were also less expensive by $729.58 (SD $390.63). Probabilistic sensitivity analysis suggested that these results were not sensitive to model parameter uncertainty. Plastic stents deployment was $2832.64 (SD $1182.72) more expensive than uncovered metal stent deployment. Value of Information analysis suggests that the maximum value of further research in the UK is $61,124.30. The results of this study represent strong evidence for the cost-effectiveness of covered compared with uncovered self-expanding metal stents for the palliation of patients with malignant dysphagia. The findings support previously published literature asserting the dominance of self-expanding metal stents over plastic stents. Value of Information analysis suggests that further research may not be cost-effective. These findings have significant implication for both current clinical practice and future clinical research.


Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer.
Breast cancer is the most common type of malignancy diagnosed in women. In the metastatic setting this disease is still uncurable. Taxanes represent an important class of antitumor agents which have proven to be fundamental in the treatment of advanced and early-stage breast cancer, but the clinical advances of taxanes have been limited by their highly hydrophobic molecular status. To overcome this poor water solubility, lipid-based solvents have been used as a vehicle, and new systemic formulations have been developed, mostly for paclitaxel, which are Cremophor-free and increase the circulation time of the drug. ABI-007 is a novel, albumin-bound, 130-nm particle formulation of paclitaxel, free from any kind of solvent. It has been demonstrated to be superior to an equitoxic dose of standard paclitaxel with a significantly lower incidence of toxicities in a large, international, randomized phase III trial. The availability of new drugs, such as Abraxane, in association with other traditional and non-traditional drugs (new antineoplastic agents and targeted molecules), will give the oncologist many different effective treatment options for patients in this setting.


Diagnostic and Treatment Challenges of Sighted Non-24-Hour Sleep-Wake Disorder.
To report the diagnostic and treatment challenges of sighted non-24-hour sleep-wake disorder (N24SWD). We report a series of seven sighted patients with N24SWD clinically evaluated by history and sleep diaries, and when available wrist actigraphy and salivary melatonin levels, and treated with timed melatonin and bright light therapy. Most patients had a history of a delayed sleep-wake pattern prior to developing N24SWD. The typical sleep-wake pattern of N24SWD was seen in the sleep diaries (and in actigraphy when available) in all patients with a daily delay in midpoint of sleep ranging 0.8 to 1.8 hours. Salivary dim light melatonin onset (DLMO) was evaluated in four patients but was missed in one. The estimated phase angle from DLMO to sleep onset ranged from 5.25 to 9 hours. All six patients who attempted timed melatonin and bright light therapy were able to entrain their sleep-wake schedules. Entrainment occurred at a late circadian phase, possibly related to the late timing of melatonin administration, though the patients often preferred late sleep times. Most did not continue treatment and continued to have a non-24-hour sleep-wake pattern. N24SWD is a chronic debilitating disorder that is often overlooked in sighted people and can be challenging to diagnose and treat. Tools to assess circadian pattern and timing can be effectively applied to aid the diagnosis. The progressive delay of the circadian rhythm poses a challenge for determining the most effective timing for melatonin and bright light therapies. Furthermore, once the circadian sleep-wake rhythm is entrained, long-term effectiveness is limited because of the behavioral and environmental structure that is required to maintain stable entrainment.


Fertility loss in senescing Arabidopsis ovules is controlled by the maternal sporophyte via a NAC transcription factor triad.
Flowers have a species-specific fertile period during which pollination and fertilization have to occur to initiate seed and fruit development. Unpollinated flowers remain receptive for mere hours in some species, and up to several weeks in others before flower senescence terminates fertility. As such, floral longevity is a key trait subject to both natural selection and plant breeding. Within the flower, the life span of the ovule containing the female gametophyte is decisive for fertilization and the initiation of seed development. Here, we show that unfertilized ovules in Arabidopsis thaliana undergo a senescence program that generates morphological and molecular hallmarks of canonical programmed cell death processes in the sporophytically derived ovule integuments. Transcriptome profiling of isolated aging ovules revealed substantial transcriptomic reprogramming during ovule senescence, and identified up-regulated transcription factors as candidate regulators of these processes. Combined mutation of three most-up-regulated NAC (NAM, ATAF1/2, and CUC2) transcription factors, NAP/ANAC029, SHYG/ANAC047, and ORE1/ANAC092, caused a substantial delay in ovule senescence and an extension of fertility in Arabidopsis ovules. These results suggest that timing of ovule senescence and duration of gametophyte receptivity are subject to genetic regulation controlled by the maternal sporophyte.


Really governing: what type of work should boards be doing?
Effectiveness is generally defined as "doing the right things." To be effective, boards of health systems and hospitals must have a clear, precise, and shared image of the type of work they should be doing to really govern their organizations. This article forwards a paradigm of board work--the five ultimate responsibilities and three core roles of governance. The paradigm is then employed to discuss the division of responsibilities and roles among boards and their standing committees, and superordinate and subordinate boards in tiered governance situations typical of many multifacility and integrated health care delivery systems.


Sonographic imaging of the glycogen stage of the fetal choroid plexus.
At 8-22 weeks gestation, the lateral ventricular choroid plexus swells with glycogen deposits, which are thought to be an important source of anaerobic energy for a relatively hypovascular stage of brain development. Sonographic images during this phase demonstrate enlarged and echogenic ventricles, accounting for up to 80%-90% of the cerebral axial dimension in the earliest gestations studied. This increased echogenicity may be due to these glycogen stores. Because a rapid but sonographically definable decrease in the relative size of these structures occurs, routine imaging for the presence and character of the choroid plexus might prove to be a useful parameter in fetal examination.


Prenatal hypoxia programs changes in β-adrenergic signaling and postnatal cardiac contractile dysfunction.
Prenatal hypoxia leads to an increased risk of adult cardiovascular disease. We have previously demonstrated a programming effect of prenatal hypoxia on the cardiac β-adrenergic (βAR) response. The aim of this study was to determine 1) whether the decrease in βAR sensitivity in prenatally hypoxic 5-wk old chicken hearts is linked to changes in β1AR/β2ARs, Gαi expression and cAMP accumulation and 2) whether prenatal hypoxia has an effect on heart function in vivo. We incubated eggs in normoxia (N, 21% O2) or hypoxia from day 0 (H, 14% O2) and raised the posthatchlings to 5 wk of age. Cardiac β1AR/β2ARs were assessed through competitive binding of [(3)H]CGP-12177 with specific β1AR or β2AR blockers. Gαs and Gαi proteins were assessed by Western blot and cAMP accumulation by ELISA. Echocardiograms were recorded in anesthetized birds to evaluate diastolic/systolic diameter and heart rate and tissue sections were stained for collagen. We found an increase in relative heart mass, β1ARs, and Gαs in prenatally hypoxic hearts. cAMP levels after isoproterenol stimulation and collagen content was not changed in H compared with N, but in vivo echocardiograms showed systolic contractile dysfunction. The changes in βAR and G protein subtypes may be indicative of an early compensatory stage in the progression of cardiac dysfunction, further supported by the cardiac hypertrophy and systolic contractile dysfunction. We suggest that it is not the changes in the proximal part of the βAR system that causes the decreased cardiac contractility, but Ca(2+) handling mechanisms further downstream in the βAR signaling cascade.


Characterization of messenger RNA from the cerebral cortex of control and Alzheimer-afflicted brain.
A detailed comparative study of RNA transcripts isolated from the neocortex of control and Alzheimer postmortem brains was made to determine whether morphological changes in the chromatin of Alzheimer neurons and glia, which we reported earlier, are accompanied by changes in the products of transcription. A number of parameters were determined including the yields of total and mRNA per gram of tissue, the relative proportions of polyadenylated [poly(A)+] mRNA in the total RNA, the size distribution of the transcripts and the length of their poly(A) tails, and the nature of their in vitro translation products. The levels of endogenous RNase activity were also measured. The effect of the agonal process on the transcript complement was examined by Northern blotting of a cloned human heat-shock cDNA to total human brain RNA. Our results reveal that the yields of total RNA, unadenylated mRNA, and poly(A) tail lengths from Alzheimer neocortex samples do not differ significantly from those of control and non-Alzheimer dementia neocortex. On the other hand we find a significant reduction in the levels and proportion of poly(A)+ mRNA in the Alzheimer samples as compared to control brain samples. Quantitative rather than qualitative differences were observed in the in vitro translation products when programmed with control and Alzheimer mRNA. No differences were found in the levels of RNase activity between control and Alzheimer samples. Heat-shock mRNA transcripts were detected in brain samples from patients in whom fever was associated with death. The direct correlation of reduced poly(A)+ mRNA and chromatin condensation in Alzheimer neocortex suggests a cause-and-effect relationship. Whether all transcribed genes are affected or only a specific subset has yet to be determined.


Peptide-Binding Groove Contraction Linked to the Lack of T Cell Response: Using Complex Structure and Energy To Identify Neoantigens.
Using personalized peptide vaccines (PPVs) to target tumor-specific nonself-antigens (neoantigens) is a promising approach to cancer treatment. However, the development of PPVs is hindered by the challenge of identifying tumor-specific neoantigens, in part because current in silico methods for identifying such neoantigens have limited effectiveness. In this article, we report the results of molecular dynamics simulations of 12 oligopeptides bound with an HLA, revealing a previously unrecognized association between the inability of an oligopeptide to elicit a T cell response and the contraction of the peptide-binding groove upon binding of the oligopeptide to the HLA. Our conformational analysis showed that this association was due to incompatibility at the interface between the contracted groove and its αβ-T cell Ag receptor. This structural demonstration that having the capability to bind HLA does not guarantee immunogenicity prompted us to develop an atom-based method (SEFF12MC) to predict immunogenicity through using the structure and energy of a peptide·HLA complex to assess the propensity of the complex for further complexation with its TCR. In predicting the immunogenicities of the 12 oligopeptides, SEFF12MC achieved a 100% success rate, compared with success rates of 25-50% for 11 publicly available residue-based methods including NetMHC-4.0. Although further validation and refinements of SEFF12MC are required, our results suggest a need to develop in silico methods that assess peptide characteristics beyond their capability to form stable binary complexes with HLAs to help remove hurdles in using the patient tumor DNA information to develop PPVs for personalized cancer immunotherapy.


Inguinal Herniation Containing Bladder, Causing Contralateral Allograft Hydroureteronephrosis-A Case Report and Literature Review.
We report the first documented case of an inguinal hernia containing bladder, resulting in contralateral allograft hydroureteronephrosis. A 39-year-old male patient presented with allograft dysfunction, a contralateral inguinoscrotal hernia, and marked hydroureteronephrosis on ultrasound (US). Percutaneous nephrostogram and a retrograde cystogram suggested bladder herniation with incorporation of the contralateral ureteroneocystostomy into the hernia. Paraperitoneal bladder herniation was confirmed at surgery and hernioplasty was performed. Six-week follow-up revealed normal renal function with no sign of hernia recurrence. Despite occurring rarely, transplant ureter or bladder herniation should be considered in the differential diagnosis of hydroureteronephrosis. This case illustrates that the contralateral position of hernia to allograft does not necessarily preclude the hernia as the source of ureteric obstruction.


Sorafenib inhibits 5-fluorouracil-resistant gastric cancer cell growth.
Sorafenib is a multi-kinase inhibitor used in the treatment of various cancers. This study investigated the inhibitory effect of sorafenib on xenograft models of gastric cancer cells and 5-fluorouracil (5-FU)-resistant cells. The half-maximal inhibitory concentration (IC50) of sorafenib in NCI-N87 cells was determined. Xenograft models were established using BALB/c nude mice and were divided into four groups treated with vehicle, sorafenib (20 mg kg-1 day-1), 5-FU (50 mg kg-1 week-1), or a combination of sorafenib (20 mg kg-1 day-1) plus 5-FU (50 mg kg-1 week-1). 5-FU-resistant NCI-N87 cells were established by repeated exposure to 5-FU. Sorafenib inhibited NCI-N87 cell growth in a concentration-dependent manner with a mean IC50 of 16.345 ± 5.391 μM. Phosphorylation levels of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase in these cells decreased in a dose-dependent manner after exposure to sorafenib. Sorafenib induced the activation of caspase-3, and its combination with 5-FU more effectively inhibited the growth of xenograft tumors than either sorafenib or 5-FU alone (p < 0.05). Sorafenib markedly inhibited 5-FU-resistant NCI-N87 cell growth as well as sphere formation in both parental and 5-FU-resistant NCI-N87 cells. The sorafenib and 5-FU combination exhibited enhanced antitumor effects in a gastric cancer xenograft model and inhibited 5-FU-resistant cell proliferation and sphere formation. These findings suggest that sorafenib is useful in overcoming gastric cancer resistance to conventional chemotherapy.


Comparison of the Expression of Hepatic Genes by Human Wharton's Jelly Mesenchymal Stem Cells Cultured in 2D and 3D Collagen Culture Systems.
Human Wharton's jelly mesenchymal stem cells (HWJMSCs) express liver-specific markers such as albumin, alpha-fetoprotein, cytokeratin-19, cytokeratin-18, and glucose-6-phosphatase. Therefore, they can be considered as a good source for cell replacement therapy for liver diseases. This study aimed to evaluate the effects of various culture systems on the hepatocyte-specific gene expression pattern of naïve HWJMSCs. HWJMSCs were characterized as MSCs by detecting the surface CD markers and capability to differentiate toward osteoblast and adipocyte. HWJMSCs were cultured in 2D collagen films and 3D collagen scaffolds for 21 days and were compared to control cultures. Real time RT-PCR was used to evaluate the expression of liver-specific genes. The HWJMSCs which were grown on non-coated culture plates expressed cytokeratin-18 and -19, alpha-fetoprotein, albumin, glucose-6-phosphatase, and claudin. The expression of the hepatic nuclear factor 4 (HNF4) was very low. The cells showed a significant increase in caludin expression when they cultured in 3D collagen scaffolds compared to the conventional monolayer culture and 2D collagen scaffold. Various culture systems did not influence on hepatocyte specific marker expression by HWJMSCs, except for claudin. The expression of claudin showed that 3D collagen scaffold provided the extracellular matrix for induction of the cells to interconnect with each other.


Alport Syndrome and Femtosecond Laser-assisted Cataract Surgery.
We report the surgical management of a patient with bilateral anterior lenticonus due to Alport syndrome using femtosecond laser-assisted cataract surgery (FLACS) and the Optiwave Refractive Analysis (ORA) system. A 38-year-old man with Alport syndrome presented to our department with visual loss due to anterior lenticonus in both eyes. Adjustments during bilateral FLACS were performed with the software's calipers to manually delineate the anterior capsulotomy. Multifocal toric intraocular lenses (IOLs) were selected and placed in the posterior chamber with the aid of intraoperative aberrometry. The intended postoperative positioning parameters for the IOL as well as the planned visual acuity and refraction were achieved. The implementation of FLACS and intraoperative wavefront aberrometry is a safe and useful surgical approach for the management of cataract in challenging cases such as patients with anterior lenticonus due to Alport syndrome.


[Glycine in the treatment of trigeminal neuralgia].
As many as 98 patients suffering from trigeminal neuralgia were given myeglynol (glycine) in a dose of 110 mg/kg a day for 4-5 weeks. A noticeable effect manifesting in the counteracting painful paroxysms was attained in more than 86% of cases. The drug was administered alone at the disease onset. The treatment effect of myeglynol may be related to its capacity to decrease to normal the high concentration of formaldehyde in the blood serum of patients suffering from trigeminal neuralgia.


Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma.
Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposi's sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients, but efforts to develop superior therapeutic approaches have been impeded by lack of animal models that accurately mimic human disease. To address this issue, we developed a direct xenograft model, UM-PEL-1, by transferring freshly isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth to avoid the changes in KSHV gene expression evident in cultured cells. We used this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. The proapoptotic effects of bortezomib are not mediated by inhibition of the prosurvival NF-kappaB pathway or by induction of a terminal unfolded protein response. Transcriptome analysis by genomic arrays revealed that bortezomib down-regulated cell-cycle progression, DNA replication, and Myc-target genes. Furthermore, we demonstrate that in vivo treatment with either bortezomib or doxorubicin induces KSHV lytic reactivation. These reactivations were temporally distinct, and this difference may help elucidate the therapeutic window for use of antivirals concurrently with chemotherapy. Our findings show that this direct xenograft model can be used for testing novel PEL therapeutic strategies and also can provide a rational basis for evaluation of bortezomib in clinical trials.


Evaluation of the pharmacological profile of ramosetron, a novel therapeutic agent for irritable bowel syndrome.
We examined the pharmacological profile of ramosetron, a 5-HT(3)-receptor antagonist for irritable bowel syndrome with diarrhea, comparing it with those of other 5-HT(3)-receptor antagonists, alosetron and cilansetron, and the anti-diarrheal agent loperamide. Ramosetron showed high affinity for cloned human and rat 5-HT(3) receptors, with K(i) values of 0.091 +/- 0.014 and 0.22 +/- 0.051 nmol/L, respectively, while its affinities for other receptors, transporters, ion channels, and enzymes were negligible. Dissociation of ramosetron from the human 5-HT(3) receptor was extremely slow (t(1/2) = 560 min), while alosetron (t(1/2) = 180 min) and cilansetron (t(1/2) = 88 min) dissociated relatively rapidly. Ramosetron competitively inhibited 5-HT-induced contraction of isolated guinea-pig colon, with pA(2) values of 8.6 (8.5 - 9.0). Ramosetron given orally also dose-dependently inhibited the von Bezold-Jarisch reflex in rats, with an ED(50) value of 1.2 (0.93 - 1.6) microg/kg. In addition, oral ramosetron dose-dependently inhibited restraint stress-induced defecation in rats, with an ED(50) value of 0.62 (0.17 - 1.2) microg/kg. In all of these experiments, the potencies of ramosetron were greater than those of alosetron, cilansetron, or loperamide. These results indicate that ramosetron is a highly potent and selective 5-HT(3)-receptor antagonist, with beneficial effects against stress-induced abnormal defecation in rats.


Blockade of antimicrobial proteins S100A8 and S100A9 inhibits phagocyte migration to the alveoli in streptococcal pneumonia.
We investigated the roles of the potent, chemotactic antimicrobial proteins S100A8, S100A9, and S100A8/A9 in leukocyte migration in a model of streptococcal pneumonia. We first observed differential secretion of S100A8, S100A9, and S100A8/A9 that preceded neutrophil recruitment. This is partially explained by the expression of S100A8 and S100A9 proteins by pneumocytes in the early phase of Streptococcus pneumoniae infection. Pretreatment of mice with anti-S100A8 and anti-S100A9 Abs, alone or in combination had no effect on bacterial load or mice survival, but caused neutrophil and macrophage recruitment to the alveoli to diminish by 70 and 80%, respectively, without modifying leukocyte blood count, transendothelial migration or neutrophil sequestration in the lung vasculature. These decreases were also associated with a 68% increase of phagocyte accumulation in lung tissue and increased expression of the chemokines CXCL1, CXCL2, and CCL2 in lung tissues and bronchoalveolar lavages. These results show that S100A8 and S100A9 play an important role in leukocyte migration and strongly suggest their involvement in the transepithelial migration of macrophages and neutrophils. They also indicate the importance of antimicrobial proteins, as opposed to classical chemotactic factors such as chemokines, in regulating innate immune responses in the lung.


Consumer and staff perspectives of the implementation frequency and value of recovery and wellbeing oriented practices.
Despite advances in our understanding of what mental health systems and services can do to enhance recovery and wellbeing outcomes for people seeking support, there is limited evidence demonstrating that this body of work has translated successfully into mental health service practice. The Collaborative Recovery Model (CRM) is a practice framework that has been designed to support application of recovery and wellbeing oriented principles and practices within mental health service delivery. The aims of this study were to assess consumer and staff perceptions of implementation frequency during service engagement and the value of this approach for assisting recovery within a setting where the CRM approach had been adopted. The setting was a large Australian community managed mental health organisation. The study involved a cross-sectional analysis of consumer (n = 116) and staff practitioner (n = 62) perspectives. A series of paired sample t-tests assessed for differences between consumer and staff perceptions of the: (i) importance of key practice elements for assisting recovery, and the (ii) frequency that key practice elements are utilised during engagement sessions. Spearman's r correlational analysis explored associations between importance, frequency and helpfulness of sessions. Key practice elements of the model were applied during service interactions at a high level and perceived by the majority of consumers and staff participants as being important or very important for assisting recovery. Significant moderate correlations were found between the extent that practice elements were valued and the level at which they were applied. Higher levels of implementation of CRM practices were associated with higher ratings of perceived session helpfulness. The strongest association was between 'encouragement to set tasks to complete between support visits' and perceived helpfulness. Consumer and staff responses revealed that the key practice elements of the CRM were frequently implemented during service engagement interactions and were seen as valuable for assisting recovery. The level of agreement between raters suggests firstly, that the key practice elements were apparent and able to be rated as occurring, and secondly that the CRM approach is seen as responsive to consumer needs. The results have implications for translating recovery and wellbeing oriented knowledge into mental health service practice.


Internet addiction detection rate among college students in the People's Republic of China: a meta-analysis.
With the development of economy and technology, the Internet is becoming more and more popular. Internet addiction has gradually become a serious issue in public health worldwide. The number of Internet users in China has reached 731 million, with an estimated 24 million adolescents determined as having Internet addiction. In this meta-analysis, we attempted to estimate the prevalence of Internet addiction among College Students in the People's Republic of China in order to improve the mental health level of college students and provide evidence for the prevention of Internet addiction. Eligible articles about the prevalence of Internet addiction among college students in China published between 2006 and 2017 were retrieved from online Chinese periodicals, the full-text databases of Wan Fang, VIP, and the Chinese National Knowledge Infrastructure, as well as PubMed. Stata 11.0 was used to perform the analyses. A total of 26 papers were included in the analyses. The overall sample size was 38,245, with 4573 diagnosed with Internet addiction. The pooled detection rate of Internet addiction was 11% (95% confidence interval [CI] 9-13%) among college students in China. The detection rate was higher in male students (16%) than female students (8%). The Internet addiction detection rate was 11% (95% CI 8-14%) in southern areas, 11% (95% CI 7-14%) in northern areas, 13% (95% CI 8-18%) in eastern areas and 9% (95% CI 8-11%) in the mid-western areas. According to different scales, the Internet addiction detection rate was 11% (95% CI 8-15%) using the Young scale and 9% (95% CI 6-11%) using the Chen scale respectively. Cumulative meta analysis showed that the detection rate had a slight upward trend and gradually stabilized in the last 3 years. The pooled Internet addiction detection rate of Chinese college students in out study was 11%, which is higher than in some other countries and strongly demonstrates a worrisome situation. Effective measures should be taken to prevent further Internet addiction and improve the current situation.


Location of the maltosyl isothiocyanate binding site on the human erythrocyte glucose transporter.
The covalent affinity probe maltosyl isothiocyanate (MITC) has been used previously to identify the glucose transporter of human erythrocytes as a component of band 3. By use of limited proteolysis, the site on the Mr 100 000 protein to which MITC attaches has been localized to a 17 000-dalton region near the center of the polypeptide chain which is intimately associated with the membrane. The erythrocyte anion transporter, which is probably homologous to the glucose carrier, has a corresponding segment which is known to bind the covalent affinity label 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid [Ramjeesingh, M., Gaarn, A., & Rothstein, A. (1980) Biochim. Biophys. Acta 559, 127-139]. These results suggest that, in addition to having structural features in common, the two carrier proteins may be quite similar with regard to functional organization.


Permanently open stomata of aquatic angiosperms display modified cellulose crystallinity patterns.
Most floating aquatic plants have stomata on their upper leaf surfaces, and usually their stomata are permanently open. We previously identified 3 distinct crystallinity patterns in stomatal cell walls, with angiosperm kidney-shaped stomata having the highest crystallinity in the polar end walls as well as the adjacent polar regions of the guard cells. A numerical bio-mechanical model suggested that the high crystallinity areas are localized to regions where the highest stress is imposed. Here, stomatal cell wall crystallinity was examined in 4 floating plants from 2 different taxa: basal angiosperms from the ANITA grade and monocots. It appears that the non-functional stomata of floating plants display reduced crystallinity in the polar regions as compared with high crystallinity of the ventral (inner) walls. Thus their guard cells are both less flexible and less stress resistant. Our findings suggest that the pattern of cellulose crystallinity in stomata of floating plants from different families was altered as a consequence of similar evolutionary pressures.


Augmentation of Circulating Follicular Helper T Cells and Their Impact on Autoreactive B Cells in Myasthenia Gravis.
Myasthenia gravis (MG) is a chronic humoral immunity-mediated autoimmune disorder of the neuromuscular junction characterized by muscle weakness. Follicular helper T (Tfh) cells may be the key Th cell subset that promotes MG development, as their major function is helping B cell activation and Ab production. Aberrance of thymus-derived Tfh cells might be implicated in autoimmune diseases including MG; just how circulating Tfh cells, especially those from patients with a normal thymus, contribute to MG pathogenesis remains to be uncovered. In this article, we characterize a population of circulating CD4(+)CXCR5(+)PD-1(+) Tfh cells in ocular and generalized MG patients without thymic abnormalities and demonstrate that the circulating Tfh cells are significantly enriched in generalized MG patients but not in ocular MG patients compared with healthy subjects, whereas a proportion of follicular regulatory T cells decreased in MG patients. In addition, the frequency of plasma cells and B cells was higher and the serum levels of IL-6/IL-21 were also elevated in these MG patients. The activated Tfh1 and Tfh17 in Tfh cells are the major source for IL-21 production in MG patients. A strong correlation between Tfh cells and the plasma cell frequency and anti-acetylcholine receptor Ab titers was evident in generalized MG patients. In particular, we found that Tfh cells derived from MG patients promoted B cells to produce Abs in an IL-21 signaling-dependent manner. Collectively, our results suggest that circulating Tfh cells may act on autoreactive B cells and thus contribute to the development of MG in patients without thymic abnormalities.


From operational diagnostic to dimensional-continuum concepts of psychotic and non-psychotic illness: Embracing catatonia across psychopathology and intrinsic movement disorder in neural network dysfunction.
Psychiatry is currently negotiating several challenges that are typified by (but are not unique to) schizophrenia: do periodic refinements in operational diagnostic algorithms (a) resolve intricacies and subtleties within and between psychotic and non-psychotic disorders that are authentic and impactful, or (b) constitute arbitrary and porous boundaries that should be complemented, or even replaced, by dimensional-continuum concepts of abnormality and dysfunction. Critically, these issues relate not only to apparent boundaries between diagnoses but also to those between 'health' and 'illness'. This article considers catatonia within evolving dimensional-continuum approaches to the description of impairment and dysfunction among psychotic and non-psychotic disorders. It begins by considering the definition and assessment of catatonia vis-à-vis other disorders, followed by its long-standing conjunction with schizophrenia, relationship with antipsychotic drug treatment, transdiagnostic perspectives and relationships, and pathobiological processes. These appear to involve dysfunction across elements in overlapping neural networks that result in a confluence of psychopathology and intrinsic hypo- and hyperkinetic motor dysfunction. It has been argued that while current diagnostic approaches can have utility in defining groups of cases that are closely related, contemporary evidence indicates categorical diagnoses to be arbitrary divisions of what is essentially a continuous landscape. Psychotic and non-psychotic diagnoses, including catatonia, may reflect arbitrary areas around points of intersection between orthogonal dimensions of psychopathology and intrinsic movement disorder in a poly-dimensional space that characterises this continuous landscape of mental health and dysfunction.


The estrogen receptor fusion system in mouse models: a reversible switch.
Reversible regulatory mouse models have significantly contributed to our understanding of normal tissue and cancer biology, providing the opportunity to temporally control initiation, progression, and evolution of physiological and pathological events. The tamoxifen inducible system, one of the best-characterized "reversible switch" models, has a number of beneficial features. In this system, the hormone-binding domain of the mammalian estrogen receptor is used as a heterologous regulatory domain. Upon ligand binding, the receptor is released from its inhibitory complex and the fusion protein becomes functional. We summarize the advantages and drawbacks of the system, describe several mouse models that rely on it, and discuss potential improvements that could render it even more useful and versatile.


Mechanisms for stable, robust, and adaptive development of orientation maps in the primary visual cortex.
Development of orientation maps in ferret and cat primary visual cortex (V1) has been shown to be stable, in that the earliest measurable maps are similar in form to the eventual adult map, robust, in that similar maps develop in both dark rearing and in a variety of normal visual environments, and yet adaptive, in that the final map pattern reflects the statistics of the specific visual environment. How can these three properties be reconciled? Using mechanistic models of the development of neural connectivity in V1, we show for the first time that realistic stable, robust, and adaptive map development can be achieved by including two low-level mechanisms originally motivated from single-neuron results. Specifically, contrast-gain control in the retinal ganglion cells and the lateral geniculate nucleus reduces variation in the presynaptic drive due to differences in input patterns, while homeostatic plasticity of V1 neuron excitability reduces the postsynaptic variability in firing rates. Together these two mechanisms, thought to be applicable across sensory systems in general, lead to biological maps that develop stably and robustly, yet adapt to the visual environment. The modeling results suggest that topographic map stability is a natural outcome of low-level processes of adaptation and normalization. The resulting model is more realistic, simpler, and far more robust, and is thus a good starting point for future studies of cortical map development.


Microsatellites reveal divergence in population genetic diversity, and structure of osyris lanceolata (santalaceae) in Uganda and Kenya.
Osyris lanceolata (Hochst. & Steud.) (Santalaceae) is a multipurpose plant highly valued culturally and economically in Africa. However, O. lanceolata populations have rapidly dwindled in East Africa due to overexploitation and this is believed to cause further consequences on the species' genetic diversity and structure within the region. Information regarding a species' genetic diversity and structure is necessary for conservation but this is currently lacking for O. lanceolata in Uganda and Kenya. Lack of adequate scientific data hinders conservation efforts hence threatening the species survival and livelihoods. This study investigated patterns in genetic diversity and structure of O. lanceolata in Uganda and Kenya. Ten polymorphic microsatellite loci were used to genotype 210 individuals: 96 from Ugandan and 114 from Kenyan populations. All populations were highly polymorphic (80-100% polymorphism). A genetic differentiation was found between Kenyan and Ugandan populations. The highest genetic differentiation was among individuals and the least among populations. The Kenyan populations showed higher genetic diversity than Ugandan populations. The Ugandan populations showed more marker deviations from Hardy-Weinberg equilibrium and inbreeding coefficient. Two populations showed evidence of going through a recent bottleneck. There was significant genetic differentiation and structuring at higher K values into larger clusters and observed admixture between populations. The populations were significantly isolated by altitude as opposed to distance and climatic variables. Main barriers were associated with altitude differences. The data supports the idea of long-distance gene-flow between high altitude populations in both countries. The divergence in genetic structure suggests unrecognised taxonomic units within O. lanceolata which are characteristic to lower altitudes and higher altitudes including most Kenyan populations with divergent evolutionary patterns. Geographical barriers and environmental gradients could have influenced this genetic divergence, and such patterns may escalate the species microevolutionary processes into full allopatric speciation. Further investigations into the species' genetic admixture and emerging taxonomic units are necessary to guide conservation strategies in the region.


A chemical dataset for evaluation of alternative approaches to skin-sensitization testing.
Allergic contact dermatitis resulting from skin sensitization is a common occupational and environmental health problem. In recent years, the local lymph node assay (LLNA) has emerged as a practical option for assessing the skin-sensitization potential of chemicals. In addition to accurate identification of skin sensitizers, the LLNA can also provide a reliable measure of relative sensitization potency, information that is pivotal in successful management of human health risks. However, even with the significant animal welfare benefits provided by the LLNA, there is interest still in the development of non-animal test methods for skin sensitization. Here, we provide a dataset of chemicals that have been tested in the LLNA and the activity of which correspond with what is known of their potential to cause skin sensitization in humans. It is anticipated that this will be of value to other investigators in the evaluation and calibration of novel approaches to skin-sensitization testing. The materials that comprise this dataset encompass both the chemical and biological diversity of known chemical allergens and provide also examples of negative controls. It is hoped that this dataset will accelerate the development, evaluation and eventual validation of new approaches to skin-sensitization testing.


Influence of ceramide on lipid domain stability studied with small-angle neutron scattering: The role of acyl chain length and unsaturation.
Ceramides and diacylglycerols are groups of lipids capable of nucleating and stabilizing ordered lipid domains, structures that have been implicated in a range of biological processes. Previous studies have used fluorescence reporter molecules to explore the influence of ceramide acyl chain structure on sphingolipid-rich ordered phases. Here, we use small-angle neutron scattering (SANS) to examine the ability of ceramides and diacylglycerols to promote lipid domain formation in the well-characterized domain-forming mixture DPPC/DOPC/cholesterol. SANS is a powerful, probe-free technique for interrogating membrane heterogeneity, as it is differentially sensitive to hydrogen's stable isotopes protium and deuterium. Specifically, neutron contrast is generated through selective deuteration of lipid species, thus enabling the detection of nanoscopic domains enriched in deuterated saturated lipids dispersed in a matrix of protiated unsaturated lipids. Using large unilamellar vesicles, we found that upon replacing 10 mol% DPPC with either C16:0 or C18:0 ceramide, or 16:0 diacylglycerol (dag), lipid domains persisted to higher temperatures. However, when DPPC was replaced with short chain (C6:0 or C12:0) or very long chain (C24:0) ceramides, or ceramides with unsaturated acyl chains of any length (C6:1(3), C6:1(5), C18:1, and C24:1), as well as C18:1-dag, lipid domains were destabilized, melting at lower temperatures than those in the DPPC/DOPC/cholesterol system. These results show how ceramide acyl chain length and unsaturation influence lipid domains and have implications for how cell membranes might modify their function through the generation of different ceramide species.


[Dynamic scintigraphy of the liver using 131I-rose bengal and the bile acid content of the blood following gastrectomy for cancer].
Liver function was studied in 84 patients with operable stomach cancer prior to and at varying times after gastrectomy using dynamic scintigraphy with 131I-rose bengal and determination by a radioimmunoassay of bile acids in the peripheral blood. A group of patients without signs of focal lesion of the liver and a history of its diseases was examined. It was shown that disorders of hepatocytic function took place before the operation. After gastrectomy the disorders were accompanied by considerable retardation of the basal secretion of bile into the intestine. At the same time an increase in the concentration of bile acids in the peripheral blood above the discriminant level of healthy persons, i.e. over 0.5 mg/l was observed. Disorders of liver function were of long duration and persistent over 1 year after gastrectomy.


Direct and indirect effects of parents' education on reading achievement among third graders in Sweden.
Cultural capital in families and especially, the educational level of parents, has during the last decades been found to be the most important dimension of socio-economic influence on school performance. How the transmission of cultural capital over generations is concretized is however not yet fully investigated. The aim is to unfold the influence of home background and more specifically, to reveal some important mediating factors between the educational levels of parents and the reading achievement levels of children. Data comes from the Swedish participation in Progress in International Reading Literacy Study 2001 conducted by the The International Association for the Evaluation of Educational Achievement and comprises some 10,000 students in grade 3. The effects of parents' education on reading achievement are estimated with structural equation modelling. The results reveal that the total effect of parents' education is substantial and that almost half of this effect is mediated through other variables, i.e. the number of books at home, early literacy activities, and emergent literacy abilities at the time for school start. The article thus identifies some of the mechanisms through which parents' education exert an influence on children's literacy development. Cultural reproduction starts in the very early childhood, in informal settings where reading aloud is an important activity. The knowledge of written language that children have at the time for school-start influences further reading acquisition.


Model for particle migration in bidisperse suspensions by use of effective temperature.
A model for the particle migration in a bidisperse flowing suspension is proposed and compared to experimental data. A mixture formulation, describing the suspension velocity and pressure and the concentrations of two solid fractions is derived from a multi-fluid model. In the multi-fluid model the liquid phase and both dispersed phases are interpenetrating phases. The closure relations are based on a mean field approach extending closure relations of a monodisperse suspension. The model is used to predict segregation based on particle size in channel flow where the particles are subjected to Brownian motion and shear-induced migration. The comparison of the model results with experimental data shows that particle migration is predicted well by the given formulation.


Molecular property prediction by semantic-invariant contrastive learning.
Contrastive learning has been widely used as pretext tasks for self-supervised pre-trained molecular representation learning models in AI-aided drug design and discovery. However, existing methods that generate molecular views by noise-adding operations for contrastive learning may face the semantic inconsistency problem, which leads to false positive pairs and consequently poor prediction performance. To address this problem, in this article, we first propose a semantic-invariant view generation method by properly breaking molecular graphs into fragment pairs. Then, we develop a Fragment-based Semantic-Invariant Contrastive Learning (FraSICL) model based on this view generation method for molecular property prediction. The FraSICL model consists of two branches to generate representations of views for contrastive learning, meanwhile a multi-view fusion and an auxiliary similarity loss are introduced to make better use of the information contained in different fragment-pair views. Extensive experiments on various benchmark datasets show that with the least number of pre-training samples, FraSICL can achieve state-of-the-art performance, compared with major existing counterpart models. The code is publicly available at https://github.com/ZiqiaoZhang/FraSICL.


Cri du chat syndrome and congenital heart disease: a review of previously reported cases and presentation of an additional 21 cases from the Pediatric Cardiac Care Consortium.
To analyze the cases submitted to the Pediatric Cardiac Care Consortium (PCCC) database from 1982 to 2002 to determine the frequency and distribution of congenital heart disease (CHD) found in this population, to review the literature for previously published accounts of CHD in this population, and to review current genotype-phenotype associations for cri du chat (CDC) syndrome with CHD. We performed a retrospective review of the 98422 CHD cases submitted to the PCCC between 1982 and 2002, to find patients who had a noncardiac diagnosis of CDC syndrome. A total of 21 patients (15 female and 6 male patients) were identified. Although some patients had multiple cardiac anomalies, they were categorized according to primary diagnoses on the basis of the most hemodynamically significant component. The patient groups were ventricular septal defect (n = 6), patent ductus arteriosus (n = 6), tetralogy of Fallot (n = 5), pulmonary valve atresia with ventricular septal defect (n = 2), pulmonary valve stenosis (n = 1), and double-outlet right ventricle (n = 1). Eighteen of the 21 patients underwent surgical repair of their defects. There was 1 late operative death. To determine whether the observed frequency of these cardiac defects among patients with CDC syndrome was comparable to that of the general population of patients with CHD, data for all cases submitted to the PCCC from 1982 to 2002 were used. Use of these numbers to determine expected frequencies for these defects showed significantly greater proportions of patients with these specific lesions among the patients with CDC syndrome. Currently there is no clear understanding of the genomic cause of the prevalence of these defects in the population with CDC syndrome, although CHD has been noted among patients with other deletion syndromes.


Atrial receptors and renal function.
The hypothesis that receptors in the heart or pulmonary vasculature initiate a reflex that influences urine flow was derived from experiments designed to evaluate the effect of mechanical ventilation on renal function. These experiments indicated that urine flow usually decreases during positive-pressure breathing and usually increases during negative-pressure breathing. It was surmised that impulses from certain cardiopulmonary receptors affect the secretion of ADH, which in turn influences urine flow. A subsequent investigation appeared to localize the pertinent receptors to the left atrium, but the results of this particular investigation were influenced by several complication factors that have not been widely appreciated. The apparent localization of volume-regulating recpetors to the left atrium and the accumulating evidence that atrial receptors do respond to changes in atrial pressure or atrial volume triggered a myriad of further studies on the function of left receptors. Nearly all these studies employed indirect techniques that produced changes in systemic and pulmonary hemodynamics in addition to changes in left atrial pressure. Nevertheless, it often was assumed that if changes in left pressure were produced, any concomitant changes in circulating ADH or in urine flow were attributable to a reflex elicited from atrial receptors. Mush of the data obtained were interpreted as being compatible with the elft atrial volume-receptor hypothesis, but very liggle of the data pertained to left atrial receptors specifically.


Estrogenic induction of ornithine decarboxylase in vivo and in vitro.
Injection of estrogens (17beta-estradiol or diethylstilbestrol) into immature chicks results in a marked (30- to 50-fold) increase in the ornithine decarboxylase activity of oviductal homogenates within a 4-hour period. Similar stimulations were obtained when estrogen was injected into hypophysectomized or castrated rats and the uterus was examined for decarboxylase activity. An elevation of decarboxylase activity was obtained in vitro when oviducts from immature chicks were incubated in the presence of estrogen. These data indicate a direct action of estrogen on oviduct tissue to promote a rapid increase in the activity of a specific enzyme and represent the first example of a completely in vitro enzyme response to estrogen.


Lateral mobility of reconstituted Sendai virus envelope glycoproteins on human erythrocytes: correlation with cell-cell fusion.
We have recently employed fluorescence photobleaching recovery (FPR) to demonstrate that the envelope glycoproteins of Sendai virions become laterally mobile on the surface of human erythrocytes following fusion [Henis, Y. I., Gutman, O., & Loyter, A. (1985) Exp. Cell Res. 160, 514-526]. In order to investigate whether this lateral mobilization is involved in the mechanism of virally mediated cell-cell fusion, or is merely a result of viral envelope-cell fusion, we have now performed FPR studies on erythrocytes fused with reconstituted Sendai virus envelopes (RSVE). These RSVE, which were prepared by solubilization of Sendai virions with Triton X-100 followed by removal of the detergent through adsorption to SM-2 Bio-beads, fused with human erythrocytes as efficiently as native virions but induced cell-cell fusion to a much lower degree. The fraction of the viral envelope glycoproteins that became laterally mobile in the erythrocyte membrane following fusion was markedly lower in the case of RSVE than in the case of native virions. The lower cell-cell fusion activity of the RSVE does not appear to be due to inactivation of the viral fusion protein, since the envelope-cell fusion and hemolytic activities of the RSVE were similar to those of native virions. Moreover, fusion with RSVE or with native virions resulted in the incorporation of rather similar amounts of viral glycoproteins into the cell membrane. Since the reduced fraction of laterally mobile viral glycoproteins correlates with the lower cell-cell fusion activity of the RSVE.(ABSTRACT TRUNCATED AT 250 WORDS)


Dengue vaccines: implications for dengue control.
Dengue, the most common arbovirus, is an increasingly significant cause of morbidity worldwide. After decades of research, an approved tetravalent dengue vaccine is finally available. Models constructed using recently available vaccine efficacy data allow for a data-driven discussion of the potential impact of dengue vaccine deployment on global control. Phase 3 efficacy trials demonstrated that the approved dengue vaccine, chimeric yellow fever-dengue-tetravalent dengue vaccine, has an efficacy of 60% against dengue illness of any severity. However, among dengue unexposed recipients, vaccination offers limited efficacy and may increase dengue severity. The WHO consequently recommends dengue vaccination for populations in which 70% of intended recipients are dengue seropositive. Models predict that routine childhood dengue vaccine may reduce dengue burden, but over time, population-level impact may be limited. Additional vaccine candidates in late-stage development may not suffer from the same limitations as chimeric yellow fever-dengue-tetravalent dengue vaccine. The efficacy and safety profile of the recently approved dengue vaccine is favorable only in previously dengue exposed recipients, which limits its potential for global control. Future work must evaluate the approved vaccine's long-term durability, efficacy of other late phase vaccine candidates, and potential for vector control efforts to work synergistically with vaccine deployment.


Aspiration pneumonia. Strategies for early recognition and prevention.
Aspiration is the result of dysfunction during the oral, pharyngeal, or esophageal stage of deglutition. Depending on the type of aspirate, the resultant lung injury may include chemical or bacterial inflammation or obstruction of the airways. Tools for evaluation include roentgenography, upper GI tract studies, bronchoscopy, and esophageal pH studies. Medical management is primarily supportive. Because aspiration pneumonia has a high morbidity rate, prevention involving early recognition and modification of predisposing factors whenever possible is critical for improving outcomes.


Use of carbon dioxide in enhanced oil recovery.
Large volumes of oil will remain in U.S. oil reservoirs when standard recovery methods have been completed. Supercritical carbon dioxide can be used to recover part of that remaining oil. If carbon dioxide is dense enough, it extracts hydrocarbons from the oil to make a mixture miscible with crude oil. Such a mixture can recover 95 percent of the oil in controlled laboratory flow settings. Heterogeneity of reservoir rocks and the low viscosity of carbon dioxide reduce the fraction of oil recovered in projects to lower but still significant levels. With the construction of three pipelines to carry naturally occurring carbon dioxide from Colorado and New Mexico to Permian basin oil fields, large-scale implementation of enhanced oil recovery by carbon dioxide flooding is now beginning.


New treatment options for alcoholic hepatitis.
The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using "Omics" platforms, newer options for patients with alcoholic hepatitis are expected soon.


Biochemical and functional characterization of H(+)-K(+)-ATPase in distal amphibian nephron.
Because proton secretion and K+ reabsorption in the late distal tubule of amphibians are active, we evaluated whether these processes could be mediated by an H(+)-K(+)-ATPase similar to the gastric H(+)-K+ pump and to the K(+)-ATPase previously described in the terminal segments of the mammalian nephron. K(+)-stimulated ATPase activity was detected in microdissected segments of frog and Necturus nephron: its activity was high in the late distal and collecting tubules, whereas it was undetectable in the proximal convoluted tubule and early distal tubule. In frog collecting tubule, K(+)-ATPase had a high affinity for K+ (Km approximately 0.30 mM), was inhibited by vanadate, omeprazole, and the imidazopyridine Sch 28080, and was insensitive to ouabain. Furthermore, in vivo administration of Sch 28080 to anesthetized Necturus induced a significant rise of the steadystate intratubular pH in the late distal tubule, demonstrating that this drug inhibited tubular fluid acidification. It is suggested that K(+)-ATPase present in the terminal segments of amphibian nephron is similar to the gastric H(+)-K+ pump and is involved in urinary acidification.


Effective synthesis of magnetic porous molecularly imprinted polymers for efficient and selective extraction of cinnamic acid from apple juices.
An effective strategy was proposed to prepare novel magnetic porous molecularly imprinted polymers (MPMIPs) for highly selective extraction of cinnamic acid (CMA) from complex matrices. Characterization and various parameters affecting adsorption and desorption behaviors were investigated. Results revealed adsorption behavior between CMA and MPMIPs followed Freundlich equation adsorption isotherm with a maximum adsorption capacity at 4.35mg/g and pseudo-second-order reaction kinetics with equilibrium time at 60min. Subsequently, MPMIPs were successfully used to selectively extract CMA from apple juice with a relatively satisfactory recovery (92.7-101.4%). Coupling with high-performance liquid chromatography and ultraviolet detection (HPLC-UV), the limit of detection (LOD) for CMA was 0.006µg/mL, and the linear range (0.02-10μg/mL) was wide with correlation coefficient at 0.9995. Finally, the contents of CMA in two kinds of apple juices were determined as 0.132 and 0.120μg/mL. Results indicated the superiority of MPMIPs in the selective extraction field.


Paced glottic closure for controlling aspiration pneumonia in patients with neurologic deficits of various causes.
We undertook to determine whether paced vocal fold adduction can check aspiration in patients with various neurologic conditions. Five patients with fluoroscopically documented aspiration and repeated pneumonias were enrolled. Two previously reported patients with hemispheric stroke were compared to 3 additional subjects with brain stem-basal ganglia and cerebellar stroke, cerebral palsy, and multiple sclerosis. A modified Vocare stimulator was implanted subcutaneously and linked to the ipsilateral recurrent laryngeal nerve via perineural electrodes. Vocal fold adduction and glottic closure were effected with pulse trains (42 Hz; 1.2 mA; 188 to 560 micros) and recorded with Enhanced Image J. Fluoroscopy results with and without stimulation were assessed by 2 independent blinded reviewers. Pneumonia rates were compared before, during, and after the 6- to 12-month enrollment periods. There was statistically significant vocal fold adduction (p < 0.05) for all patients, further verified with bolus arrest (p < 0.05 for thin liquids, thick liquids, and puree depending on the speech-language pathologist). Pneumonia was prevented in 4 of the 5 patients during enrollment. In the fifth patient, who had brain stem-basal ganglia and cerebellar stroke, we were unable to completely seal the glottis and open the cricopharyngeus enough to handle his secretions. Vocal fold pacing for aspiration pneumonia from a variety of neurologic insults appears to be appropriate as long as the glottis can be sealed. It is not sufficient when the cricopharyngeus must be independently opened.


Fertility exposure analysis: A new method for assessing the contribution of proximate determinants to fertility differentials.
Summary Several recent papers have dealt with the problem of assessing the impact of the proximate determinants on fertility. All these approaches rely on combining a series of separately estimated aggregate level indicators. This paper proposes an approach which uses individual-level data and thus permits regression analyses as well as analyses for sub-groups. In the course of development it became clear that there are several deficiencies and inconsistencies in the measurement and formation of indices proposed elsewhere, which are overcome. We illustrate our approach with data from the Dominican Republic. The approach used involves attributing exposure to one or more of several states, including pregnancy, lactational and non-lactational components of post-partum amenorrhoea, absence of sexual relations and contraception. Key elements are efficacies of contraception and components of post-partum infecundity and the treatment of overlaps through an explicit hierarchy. We treat both unconditional (or additive) and conditional analyses. Intriguing findings on the age-specific pattern of fertility control emerge. Major advantages of regression analysis, such as simultaneous treatment of several variables and estimation of sampling variation are stressed.


Epidemiology and grade 2 disability of leprosy among migrant and resident patients in Guangdong: an unignorable continued transmission of leprosy.
Leprosy remains a major public health concern worldwide and one of the leading causes of disability. New cases of leprosy with grade 2 disability (G2D) often reflect delayed detection due to the limited capacity of the health system to recognize leprosy early. This study aimed to describe the epidemiology and G2D of leprosy among migrant and resident patients with leprosy in Guangdong province, China. Data on newly diagnosed cases of leprosy were collected from the leprosy management information system in China. Descriptive statistical analysis was used to describe the status of G2D. Joinpoint regression model and logistic regression were performed to analyze the temporal trends and influencing factors for G2D. The G2D rate among migrant, resident, and total patients with leprosy was 17.5%, 18.7%, and 18.4%, respectively. The total G2D rate increased significantly from 18.0% in 2001 to 25.7% in 2021 (average annual per cent change: 2.5%). Multivariate analysis revealed that factors that negatively influence G2D between migrant and resident patients included delayed discovery time (migrants: OR = 2.57; residents: OR = 4.99) and nerve damage when diagnosed (migrants: OR = 9.40; residents: OR = 21.28). Our findings indicate that the targeted intervention measures implemented by our health system are urgently needed to improve the current situation, such as programs to promote early detection, strengthen awareness and skills of healthcare workers, and rehabilitation for disabled patients to improve their quality of life.


Bacterial glutaminase in treatment of acute leukaemia.
A glutaminase-asparaginase enzyme from Achromobacter sp has antitumour activity in vitro and in animals. Glutaminase was administered in doses of 3500-20 000 IU/m2 body surface area/day to six patients with acute lymphoblastic leukaemia (ALL) and three patients with acute myeloid leukaemia (AML). The enzyme had a blood half life of 80 minutes but depletion of blood glutamine persisted for 12 hours after single doses. Seven patients, including four (two with AML and two with ALL) resistant to asparaginase, received repeated doses of glutaminase. Antileukaemic effects were observed in all seven; one elderly patient developed metabolic acidosis. Study of this new antileukaemic agent in patients with acute leukaemia at an earlier stage of their disease is now justified.


Administration of the Short Musculoskeletal Function Assessment: impact on office routine and physician-patient interaction.
Outcome instrument use is becoming widespread. They must fit smoothly into the office flow and show the physician and patient value. Five practices incorporated the Short Musculoskeletal Functional Assessment (SMFA) into their office. Existing staff scored the SMFA. At the conclusion of the visit, the patient and physician assessed the impact of the SMFA on their interaction. Five hundred ten patients completed the SMFA. Physicians believed the verbal interaction had some effect with their patients 44% of the time. Physicians reported the SMFA had some effect on their management decisions 36% of the time. Physicians reported that the total score was helpful 43% of the time and the category scores were helpful 65% of the time. On completing the SMFA, patients reported no effect on their physician interaction 74% of the time and 88% believed it was worthwhile to complete. This validated musculoskeletal questionnaire adds value to the physician-patient interaction in approximately 30%-40% of encounters.


Energy requirements of spasticity.
Direct measurement of energy expended by spasticity in children with severe spastic quadriparesis is difficult. Insertion of an intrathecal baclofen pump in a 13-year-old boy with severe spasticity and profound mental retardation resulted in an estimated 30 to 40% decrease in his spasticity. As he had been on a carefully calculated ketogenic diet and fed by gastrostomy, his precise caloric intake was known. Decrease in spasticity, on the same caloric intake, led to marked weight gain. Reduction of 100 calories intake resulted in new weight stability. It was possible therefore, to estimate indirectly energy used by his spasticity. This 100 calories, representing 34% of calories above his resting energy requirement, corresponded to an independently estimated 30 to 40% of caloric expenditure of his spasticity. It was concluded that when calculation of calories is critical, energy utilization by spasticity must be taken into consideration.


Tumor necrosis factor-alpha (TNF-alpha) stimulates chemotactic response in mouse myogenic cells.
Migration of transplanted myogenic cells occurs during both embryogenesis and regeneration of skeletal muscles and is important for successful myoblast transplantation, but little is known about factors that promote chemotaxis of these cells. Tumor necrosis factor-alpha (TNF-alpha) is known to induce chemotactic effect on several cell types. In this study, we investigated its influence on the in vitro and in vivo motility of C2C12 and primary myoblasts. In the in vitro test performed in the blind-well Boyden chambers, we showed that TNF-alpha (50-400 U/ml) significantly enhanced the ability of myogenic cells to migrate. The dose-response curve for this factor was bell shaped, with maximum activity in the 200 U/ml range. In the in vivo test, intramuscular administration of TNF-alpha was performed by an Alzet pump connected to a perforated polyethylene microtube inserted in the tibialis anterior (TA) of CD1 mice. In these experiments, myoblasts were injected under the muscle epimysium. The recipient mice were immunosuppressed with FK506. Our results showed that, 5 days after myoblast transplantation, cells migrated further in the muscles infused with TNF-alpha than in the muscles not exposed to TNF-alpha. TNF-alpha not only has a chemotactic activity but may also modify cell migration via its action on matrix metalloproteinase (MMP) expression. The proteolytic activities of the MMPs secreted in the muscles were thus also assessed by gelatin zymography. The results showed an increased of MMP-2 and MMP-9 transcripts in the TNF-alpha-infused muscles injected with myogenic cells. Myoblast migration during transplantation may be enhanced by overlapping gradients of several effector molecules such as TNF-alpha, interferon-gamma (INF-gamma), and interleukins, released at the site of muscle injury. We propose that TNF-alpha may promote myoblast migration directly through chemotactic activity and indirectly by enhancing MMP activity at the site of muscle injury.


Effect of aminophylline on amphotericin B nephrotoxicity in the dog.
The polyene antibiotic, amphotericin B, causes an acute reduction in renal blood flow and glomerular filtration rate. The purpose of this study was to evaluate the hypothesis that the renal vascular response to amphotericin B can be blocked by aminophylline. Toward this end, the effect of aminophylline on the renal response to amphotericin B in sodium-depleted dogs was examined. In dogs not treated with aminophylline, amphotericin B (0.5 mg/kg infused i.v. over 20 min) significantly reduced renal blood flow and glomerular filtration by 49.9 +/- 12.6 ml/min (mean +/- S.E.M.) and 23.4 +/- 2.4 ml/min, respectively at 140 min after the amphotericin B infusion. In dogs treated with an intrarenal aminophylline infusion (5 mg/min), the renal blood flow and glomerular filtration rate response to amphotericin B did not differ from that of amphotericin B vehicle. We conclude that aminophylline inhibits the renal response to amphotericin B. The possible clinical relevance of these observations are discussed.


The Critical Power Model as a Potential Tool for Anti-doping.
Existing doping detection strategies rely on direct and indirect biochemical measurement methods focused on detecting banned substances, their metabolites, or biomarkers related to their use. However, the goal of doping is to improve performance, and yet evidence from performance data is not considered by these strategies. The emergence of portable sensors for measuring exercise intensities and of player tracking technologies may enable the widespread collection of performance data. How these data should be used for doping detection is an open question. Herein, we review the basis by which performance models could be used for doping detection, followed by critically reviewing the potential of the critical power (CP) model as a prototypical performance model that could be used in this regard. Performance models are mathematical representations of performance data specific to the athlete. Some models feature parameters with physiological interpretations, changes to which may provide clues regarding the specific doping method. The CP model is a simple model of the power-duration curve and features two physiologically interpretable parameters, CP and W'. We argue that the CP model could be useful for doping detection mainly based on the predictable sensitivities of its parameters to ergogenic aids and other performance-enhancing interventions. However, our argument is counterbalanced by the existence of important limitations and unresolved questions that need to be addressed before the model is used for doping detection. We conclude by providing a simple worked example showing how it could be used and propose recommendations for its implementation.


Strontium and Magnesium in Water and in Crassostrea Calcite.
Distribution of magnesium and strontium was determined between waters and calcites secreted by the oyster species Crassostrea virginica and C. rhizophorae in natural habitats at eight localities, from Maine to Puerto Rico. The concentration of strontium in the calcite shells increases with increasing temperature in the range 13 degrees to 25 degrees C, and also with increasing Sr(++)/Ca(++) molal ratio in the water. The concentration of magnesium in the shells increases irregularly with temperature, and it is apparently independent of the Mg(++)/Ca(++) ratio in the water. The greater variation with temperature in the distribution factor for magnesium may be related to genetic differences between semi-isolated populations.


Molybdenum carbide as a highly selective deoxygenation catalyst for converting furfural to 2-methylfuran.
Selectively cleaving the C=O bond outside the furan ring of furfural is crucial for converting this important biomass-derived molecule to value-added fuels such as 2-methylfuran. In this work, a combination of density functional theory (DFT) calculations, surface science studies, and reactor evaluation identified molybdenum carbide (Mo2 C) as a highly selective deoxygenation catalyst for converting furfural to 2-methylfuran. These results indicate the potential application of Mo2 C as an efficient catalyst for the selective deoxygenation of biomass-derived oxygenates including furanics and aromatics.


Arteriovenous malformation mimicking femoral osteolysis after total hip arthroplasty.
We encountered a case of apparent progressive femoral osteolysis around a well-fixed cementless implant in a young patient. At the time of revision arthroplasty, massive hemorrhaging occurred during exposure and attempted femoral component extraction. Urgent packing of the exposed endosteum with polymethyl methacrylate controlled the bone bleeding. Emergent angiography confirmed an arteriovenous malformation with extensive proximal diaphyseal involvement directly at the site of osteolysis. This arteriovenous malformation was treated successfully with selective arterial embolization and second-stage resection. In retrospect, the index arthroplasty operative note indicated an excessive amount of blood loss, and prerevision radiographs showed osteolysis with uncharacteristic vascular markings. The presence of an osteolytic lesion in total hip arthroplasty should not be assumed to be attributed to polyethylene granuloma, and any atypical radiographic features should prompt further preoperative investigations.


Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice.
Patients with congenital disorder of glycosylation (CDG), type Ib (MPI-CDG or CDG-Ib) have mutations in phosphomannose isomerase (MPI) that impair glycosylation and lead to stunted growth, liver dysfunction, coagulopathy, hypoglycemia, and intestinal abnormalities. Mannose supplements correct hypoglycosylation and most symptoms by providing mannose-6-P (Man-6-P) via hexokinase. We generated viable Mpi hypomorphic mice with residual enzymatic activity comparable to that of patients, but surprisingly, these mice appeared completely normal except for modest (~15%) embryonic lethality. To overcome this lethality, pregnant dams were provided 1-2% mannose in their drinking water. However, mannose further reduced litter size and survival to weaning by 40 and 66%, respectively. Moreover, ~50% of survivors developed eye defects beginning around midgestation. Mannose started at birth also led to eye defects but had no effect when started after eye development was complete. Man-6-P and related metabolites accumulated in the affected adult eye and in developing embryos and placentas. Our results demonstrate that disturbing mannose metabolic flux in mice, especially during embryonic development, induces a highly specific, unanticipated pathological state. It is unknown whether mannose is harmful to human fetuses during gestation; however, mothers who are at risk for having MPI-CDG children and who consume mannose during pregnancy hoping to benefit an affected fetus in utero should be cautious.


Shimia marina gen. nov., sp. nov., a novel bacterium of the Roseobacter clade isolated from biofilm in a coastal fish farm.
A rod-shaped marine bacterium, CL-TA03(T), isolated from a biofilm in a coastal fish farm in Tongyeong, Korea, was characterized for physiological and biochemical features, fatty acid profile and phylogenetic position based on 16S rRNA gene sequences. Analysis of the 16S rRNA gene sequence revealed a clear affiliation with the family Rhodobacteraceae. Phylogenetic analysis of the 16S rRNA gene sequence showed that the closest relatives of CL-TA03(T) were Thalassobius gelatinovorus and Thalassobius mediterraneus (95.6 % similarity). The sequence similarities between CL-TA03(T) and other type species of the Roseobacter lineage ranged from 92.4 to 95.4 %. Strain CL-TA03(T) is motile and grows on marine agar as colourless or beige colonies. The strain is able to grow optimally in the range of 3-5 % sea salts. It grows within a temperature range of 15-35 degrees C and at pH 6-10. The fatty acids are dominated by 18 : 1omega7c (64.1 %) and 11-methyl 18 : 1omega7c (10.6 %). The DNA G+C content is 57.2 mol%. According to physiological data, fatty acid composition and phylogenetic analysis of the 16S rRNA gene sequence, CL-TA03(T) is considered to represent a new genus in the family Rhodobacteraceae and the name Shimia marina gen. nov., sp. nov. is proposed. The type strain of Shimia marina is CL-TA03(T) (=KCCM 42117(T)=JCM 13038(T)).


[Somaticoautonomic functions of rabbits exposed to an ultrahigh-frequency electromagnetic field at acupuncture points].
The action of electromagnetic field of ultrahigh frequency with power from 1 to 1000 mwt and acupuncture on the functional state of rabbits under the tooth pulp irritation conditions has been investigated. The action on the points has been established to be accompanied by decrease of the rythm breathing irregularity and motion of animals jaws. The most effectiveness during the action of the field has been registered with power 1-20 mwt that corresponds to the effectiveness of acupuncture. However during the action of the field the frequency of breathing does not change while during acupuncture it increases. This fact points out the differences of the mechanism of normalized effect of these species influence on acupuncture points. The point of view concerning the invariable information action of fields upon the points and the system of points as constantly acting communication channel between an organism and the environment is under discussion.


Forced expression of muscle specific kinase slows postsynaptic acetylcholine receptor loss in a mouse model of MuSK myasthenia gravis.
We investigated the influence of postsynaptic tyrosine kinase signaling in a mouse model of muscle-specific kinase (MuSK) myasthenia gravis (MG). Mice administered repeated daily injections of IgG from MuSK MG patients developed impaired neuromuscular transmission due to progressive loss of acetylcholine receptor (AChR) from the postsynaptic membrane of the neuromuscular junction. In this model, anti-MuSK-positive IgG caused a reduction in motor endplate immunolabeling for phosphorylated Src-Y418 and AChR β-subunit-Y390 before any detectable loss of MuSK or AChR from the endplate. Adeno-associated viral vector (rAAV) encoding MuSK fused to enhanced green fluorescent protein (MuSK-EGFP) was injected into the tibialis anterior muscle to increase MuSK synthesis. When mice were subsequently challenged with 11 daily injections of IgG from MuSK MG patients, endplates expressing MuSK-EGFP retained more MuSK and AChR than endplates of contralateral muscles administered empty vector. Recordings of compound muscle action potentials from myasthenic mice revealed less impairment of neuromuscular transmission in muscles that had been injected with rAAV-MuSK-EGFP than contralateral muscles (empty rAAV controls). In contrast to the effects of MuSK-EGFP, forced expression of rapsyn-EGFP provided no such protection to endplate AChR when mice were subsequently challenged with MuSK MG IgG. In summary, the immediate in vivo effect of MuSK autoantibodies was to suppress MuSK-dependent tyrosine phosphorylation of proteins in the postsynaptic membrane, while increased MuSK synthesis protected endplates against AChR loss. These results support the hypothesis that reduced MuSK kinase signaling initiates the progressive disassembly of the postsynaptic membrane scaffold in this mouse model of MuSK MG.


Using quantitative reconstitution to investigate multicomponent condensates.
Many biomolecular condensates are thought to form via liquid-liquid phase separation (LLPS) of multivalent macromolecules. For those that form through this mechanism, our understanding has benefitted significantly from biochemical reconstitutions of key components and activities. Reconstitutions of RNA-based condensates to date have mostly been based on relatively simple collections of molecules. However, proteomics and sequencing data indicate that natural RNA-based condensates are enriched in hundreds to thousands of different components, and genetic data suggest multiple interactions can contribute to condensate formation to varying degrees. In this Perspective, we describe recent progress in understanding RNA-based condensates through different levels of biochemical reconstitutions as a means to bridge the gap between simple in vitro reconstitution and cellular analyses. Complex reconstitutions provide insight into the formation, regulation, and functions of multicomponent condensates. We focus on two RNA-protein condensate case studies: stress granules and RNA processing bodies (P bodies), and examine the evidence for cooperative interactions among multiple components promoting LLPS. An important concept emerging from these studies is that composition and stoichiometry regulate biochemical activities within condensates. Based on the lessons learned from stress granules and P bodies, we discuss forward-looking approaches to understand the thermodynamic relationships between condensate components, with the goal of developing predictive models of composition and material properties, and their effects on biochemical activities. We anticipate that quantitative reconstitutions will facilitate understanding of the complex thermodynamics and functions of diverse RNA-protein condensates.


Highly turbulent solutions of the Lagrangian-averaged Navier-Stokes alpha model and their large-eddy-simulation potential.
We compute solutions of the Lagrangian-averaged Navier-Stokes alpha - (LANS alpha ) model for significantly higher Reynolds numbers (up to Re approximately 8300 ) than have previously been accomplished. This allows sufficient separation of scales to observe a Navier-Stokes inertial range followed by a second inertial range specific to the LANS alpha model. Both fully helical and nonhelical flows are examined, up to Reynolds numbers of approximately 1300. Analysis of the third-order structure function scaling supports the predicted l3 scaling; it corresponds to a k-1 scaling of the energy spectrum for scales smaller than alpha. The energy spectrum itself shows a different scaling, which goes as k1. This latter spectrum is consistent with the absence of stretching in the subfilter scales due to the Taylor frozen-in hypothesis employed as a closure in the derivation of the LANS alpha model. These two scalings are conjectured to coexist in different spatial portions of the flow. The l3 [E(k) approximately k-1] scaling is subdominant to k1 in the energy spectrum, but the l3 scaling is responsible for the direct energy cascade, as no cascade can result from motions with no internal degrees of freedom. We demonstrate verification of the prediction for the size of the LANS alpha attractor resulting from this scaling. From this, we give a methodology either for arriving at grid-independent solutions for the LANS alpha model, or for obtaining a formulation of the large eddy simulation optimal in the context of the alpha models. The fully converged grid-independent LANS alpha model may not be the best approximation to a direct numerical simulation of the Navier-Stokes equations, since the minimum error is a balance between truncation errors and the approximation error due to using the LANS alpha instead of the primitive equations. Furthermore, the small-scale behavior of the LANS alpha model contributes to a reduction of flux at constant energy, leading to a shallower energy spectrum for large alpha. These small-scale features, however, do not preclude the LANS alpha model from reproducing correctly the intermittency properties of the high-Reynolds-number flow.


Antifouling and antimicrobial biomaterials: an overview.
The use of implantable medical devices is a common and indispensable part of medical care for both diagnostic and therapeutic purposes. However, as side effect, the implant of medical devices quite often leads to the occurrence of difficult-to-treat infections, as a consequence of the colonization of their abiotic surfaces by biofilm-growing microorganisms increasingly resistant to antimicrobial therapies. A promising strategy to combat device-related infections is based on anti-infective biomaterials that either repel microbes, so they cannot attach to the device surfaces, or kill them in the surrounding areas. In general, such biomaterials are characterized by antifouling coatings, exhibiting low adhesion or even repellent properties towards microorganisms, or antimicrobial coatings, able to kill microbes approaching the surface. In this light, the present overview will address the development in the last two decades of antifouling and antimicrobial biomaterials designed to potentially limit the initial stages of microbial adhesion, as well as the microbial growth and biofilm formation on medical device surfaces.


Speech and music shape the listening brain: evidence for shared domain-general mechanisms.
Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This review summarizes a large body of behavioral and neuroscientific findings which suggest that the musical experience of trained musicians does modulate speech processing, and a sparser set of data, largely on pitch processing, which suggest in addition that linguistic experience, in particular learning a tone language, modulates music processing. Although research has focused mostly on music on speech effects, we argue that both directions of influence need to be studied, and conclude that the picture which thus emerges is one of mutual interaction across domains. In particular, it is not simply that experience with spoken language has some effects on music perception, and vice versa, but that because of shared domain-general subcortical and cortical networks, experiences in both domains influence behavior in both domains.


Effects of barriers on chemical and biological properties of two dual resin cements.
The aim of this study was to investigate the degree of conversion, monomer release, and cytotoxicity of two dual-cure resin cements (Cement-One and SmartCem2), light-cured across two indirect restorative materials in an attempt to simulate in vitro the clinical conditions. The results obtained show that the degree of conversion was influenced by both barriers, but the effect of the composite material was greater than that of the ceramic one. The amount of monomers released from the polymerized materials in the absence of barriers was significantly lower than that released in the presence of either the ceramic or the composite barrier. However, a higher amount of monomers was released in the presence of the ceramic barrier. All materials, in all the experimental conditions employed, induced slight cytotoxicity (5-10%) on human pulp cells. Our examinations showed that the two resin cements had similar chemical and biological properties. The decreased degree of conversion of the dual-curing self-adhesive composite showed that the light-curing component of these materials has an important role in the polymerization process. In clinical practice, it is therefore important to pay attention to the thickness of the material used for the reconstruction.


Spatial Profiles of Intratumoral PD-1+ Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma.
Functional interactions between immune cells and neoplastic cells in the tumor immune microenvironment have been actively pursued for both biomarker discovery for patient stratification, as well as therapeutic anti-cancer targets to improve clinical outcomes. Although accumulating evidence indicates that intratumoral infiltration of immune cells has prognostic significance, limited information is available on the spatial infiltration patterns of immune cells within intratumoral regions. This study aimed to understand the intratumoral heterogeneity and spatial distribution of immune cell infiltrates associated with cell phenotypes and prognosis in head and neck squamous cell carcinoma (HNSCC). A total of 88 specimens of oropharyngeal squamous cell carcinoma, categorized into discovery (n = 38) and validation cohorts (n = 51), were analyzed for immune contexture by multiplexed immunohistochemistry (IHC) and image cytometry-based quantification. Tissue segmentation was performed according to a mathematical morphological approach using neoplastic cell IHC images to dissect intratumoral regions into tumor cell nests versus intratumoral stroma. Tissue segmentation revealed heterogeneity in intratumoral T cells, varying from tumor cell nest-polarized to intratumoral stroma-polarized distributions. Leukocyte composition analysis revealed higher ratios of TH1/TH2 in tumor cell nests with higher percentages of helper T cells, B cells, and CD66b+ granulocytes within intratumoral stroma. A discovery and validation approach revealed a high density of programmed death receptor-1 (PD-1)+ helper T cells in tumor cell nests as a negative prognostic factor for short overall survival. CD163+ tumor-associated macrophages (TAM) provided the strongest correlation with PD-1+ helper T cells, and cases with a high density of PD-1+ helper T cells and CD163+ TAM had a significantly shorter overall survival than other cases. This study reveals the significance of analyzing intratumoral cell nests and reports that an immune microenvironment with a high density of PD-1+ helper T cells in tumoral cell nests is a poor prognostic factor for HNSCC.