Antisynthetase syndrome sine myositis presenting as severe acute respiratory failure.
A female in her late 40s presented to the emergency department during the COVID-19 pandemic with shortness of breath, fever and productive cough following a recent diagnosis of bilateral non-massive pulmonary emboli. She had elevated inflammatory markers and her chest X-ray revealed bilateral infiltrates. Her SARS-CoV-2 PCR was negative, and she was treated for community-acquired pneumonia. However, despite treatment she rapidly deteriorated and developed severe respiratory failure, requiring mechanical ventilation.On further investigation, she tested positive for anti-Jo-1 antibodies and a diagnosis of antisynthetase syndrome sine myositis was made. This led to successful treatment with high dose corticosteroids and intravenous immunoglobulin.This case highlights an uncommon presentation of a rare condition, as well as the benefits of working in a multidisciplinary team on the intensive care unit.


Epigenetic mechanisms in gastric cancer.
Cancer is considered one of the major health issues worldwide, and gastric cancer accounted for 8% of total cases and 10% of total deaths in 2008. Gastric cancer is considered an age-related disease, and the total number of newly diagnosed cases has been increasing as a result of the higher life expectancy. Therefore, the basic mechanisms underlying gastric tumorigenesis is worth investigation. This review provides an overview of the epigenetic mechanisms, such as DNA methylation, histone modifications, chromatin remodeling complex and miRNA, involved in gastric cancer. As the studies in gastric cancer continue, the mapping of an epigenome code is not far for this disease. In conclusion, an epigenetic therapy might appear in the not too distant future.


Natural language processing for automated annotation of medication mentions in primary care visit conversations.
The objective of this study is to build and evaluate a natural language processing approach to identify medication mentions in primary care visit conversations between patients and physicians. Eight clinicians contributed to a data set of 85 clinic visit transcripts, and 10 transcripts were randomly selected from this data set as a development set. Our approach utilizes Apache cTAKES and Unified Medical Language System controlled vocabulary to generate a list of medication candidates in the transcribed text and then performs multiple customized filters to exclude common false positives from this list while including some additional common mentions of the supplements and immunizations. Sixty-five transcripts with 1121 medication mentions were randomly selected as an evaluation set. Our proposed method achieved an F-score of 85.0% for identifying the medication mentions in the test set, significantly outperforming existing medication information extraction systems for medical records with F-scores ranging from 42.9% to 68.9% on the same test set. Our medication information extraction approach for primary care visit conversations showed promising results, extracting about 27% more medication mentions from our evaluation set while eliminating many false positives in comparison to existing baseline systems. We made our approach publicly available on the web as an open-source software. Integration of our annotation system with clinical recording applications has the potential to improve patients' understanding and recall of key information from their clinic visits, and, in turn, to positively impact health outcomes.


Occupational exposure to radon for underground tourist routes in Poland: Doses to lung and the risk of developing lung cancer.
Radon concentrations for 31 Polish underground tourist routes were analyzed. The equivalent dose to the lung, the effective dose and the relative risk were calculated for employees of the analyzed routes on the grounds of information on radon concentrations, work time, etc. The relative risk for lung cancers was calculated using the Biological Effects of Ionizing Radiation (BEIR) VI Committee model. Equivalent doses to the lungs of workers were determined using the coefficients calculated by the Kendall and Smith. The conversion coefficient proposed by the International Atomic Energy Agency (IAEA) in the report No. 33 was used for estimating the effective doses. In 13 routes, the effective dose was found to be above 1 mSv/year, and in 3 routes, it exceeded 6 mSv/year. For 5 routes, the equivalent dose to lungs was higher than 100 mSv/year, and in 1 case it was as high as 490 mSv/year. In 22.6% of underground workplaces the risk of developing lung cancer among employees was about 2 times higher than that for the general population, and for 1 tourist route it was about 5 times higher. The geometric mean of the relative risk of lung cancer for all workers of underground tourist routes was 1.73 (95% confidence interval (CI): 1.6-1.87). Routes were divided into: caves, mines, post-military underground constructions and urban underground constructions. The difference between levels of the relative risk of developing lung cancer for all types of underground tourist routes was not found to be significant. If we include the professional group of the employees of underground tourist routes into the group of occupational exposure, the number of persons who are included in the Category A due to occupational exposure may increase by about 3/4. The professional group of the employees of underground tourist routes should be monitored for their exposure to radon. Int J Occup Med Environ Health 2017;30(5):687-694.


The effect of benzoyl peroxide on acne.
A double-blind study of two commonly used (5%) benzoyl peroxide-containing preparations showed that they were equally effective in the treatment of acne. With these treatments there was a reduction in P. acnes, Micrococcaceae and surface-free fatty acids. These data support the continued use of benzoyl peroxide preparations in the treatment of acne.


Feasibility of screening young children in day care centers--a preliminary investigation.
A preliminary investigation of a method of providing health screening in day care centers was conducted. Ninety-four children, birth to 6 years, attending two day care centers were screened for health and developmental problems. A nurse trained day care staff to conduct the screenings, supervised their activities, rescreened children with questionable results, and conducted an interrater reliability study as well as referral and followup activities. The nurse also did assessments of environmental characteristics of the programs, their policies, procedures, and activities and assessed staff and parent information needs concerning child development, health practices, and health needs of children. Thirty-nine problems were identified in 33 children. Followups of 29 problems were completed, and 16 of these were verified. The 29 problems resulted in a total of 35 visits to primary health care providers. Among parents of children with verified problems, only three had been aware of the problem. The overreferral rate was 47 percent. Interrater percentages of agreement on most screenings were more than 80 percent. The findings suggested that the screenings were feasible with specific modifications. The screening activities were acceptable to parents, their physicians, and center staff. Centers were responsive to staff and parent needs identified in the screening process but not to recommendations for change within the environment and in operating procedures, partly because of fiscal implications. Screenings were adequate to identify a number of health problems prevalent in children under 6, and interrater reliabilities were acceptable.


Endotoxin-stimulated monocytes release multiple forms of IL-1 beta, including a proIL-1 beta form whose detection is affected by export.
The processing and release of 31-kDa proIL-1 beta to the mature 17-kDa form of IL-1 beta are still poorly understood. To help elucidate the mechanisms involved in IL-1 beta processing and release, we measured IL-1 beta forms released from endotoxin-stimulated monocytes by immunoprecipitation of [35S]methionine-labeled protein, by Western blots, and by our recently developed ELISA specific for proIL-1 beta. Our studies demonstrate that in addition to the 17-kDa mature IL-1 beta, IL-1 beta is also released as 31-, 28-, and 3-kDa molecules. The 31-kDa-released form of proIL-1 beta represented 20-40% of the total released IL-1 beta, as measured by SDS-PAGE with densitometry. This released proIL-1 beta was susceptible to ICE processing; however, this proIL-1 beta was not detectable by either a mature or proIL-1 beta-specific ELISA, suggesting that release induces a conformational change. The ELISA inability to detect proIL-1 beta was not due to inadequate sensitivity or subsequent degradation in the ELISA. Furthermore, while immunoaffinity-purified cytosolic proIL-1 beta could complex the type II IL-1R, released proIL-1 beta did not. Finally, the absence of a band shift in nondenaturing gel electrophoresis excluded proIL-1 beta binding to another protein. These findings imply that IL-1 beta is exported from monocytes as 3-, 17-, 28-, and 31-kDa forms and that the released 31-kDa form differs from cytosolic proIL-1 beta.


Management of Benign and Malignant Pancreatic Duct Strictures.
The diagnosis and management of pancreatic strictures, whether malignant or benign, remain challenging. The last 2 decades have seen dramatic progress in terms of both advanced imaging and endoscopic therapy. While plastic stents remain the cornerstone of the treatment of benign strictures, the advent of fully covered metal stents has initiated a new wave of interest in calibrating the pancreatic duct with fewer sessions. In malignant disease, palliation remains the priority and further data are necessary before offering systematic pancreatic stenting.


Carotid intima-media thickness is not associated with homocysteine and vitamin D levels in obstructive sleep apnea.
Obstructive sleep apnea syndrome (OSA) is associated with increased vascular morbidity. Accelerated atherosclerosis might be one of the most important mechanisms linking OSA with the development of vascular disorders. Homocysteine (HCY) and vitamin D has been associated with atherogenesis. The aim of this study was to assess a possible association between the levels of HCY and vitamin D and the carotid intima-media thickness (cIMT), which is a known marker for subclinical atherosclerosis in patients with OSA. We prospectively enrolled 110 patients with the history of snoring, who underwent standard overnight polysomnography. Clinical characteristics of the population were recorded on admission and blood samples were obtained in the fasting condition following morning. Extracranial cIMT measurements were performed according to the standardized scanning protocol. A significant correlation was found between cIMT and apnea-hypopnea index (r = .276, p = .006), age (r = .486, p < .001), diabetes mellitus (r = .377, p < .001), coronary artery disease (r = .274, p = .006) and history of stroke (r = .251, p = .012). We failed to find any significant correlation between cIMT and the levels of HCY (r = .036, p = .724) or vitamin D (r = .027, p = .800). In conclusion, our data suggest that the association of cIMT with the severity of OSA can be influenced by multiple metabolic consequences of OSA including traditional and non-traditional risk factors. HCY and vitamin D do not seem to play a superior role in this process.


Comparison of colony and stool blots for detection of enteropathogens by DNA probes.
DNA probes that identify genes coding for heat-labile type I (LT-I) and heat-stable type 1 (ST-I) enterotoxins, enteropathogenic Escherichia coli adherence factor (EAF), and Shigella-like invasiveness (INV) are used to evaluate the sensitivity and specificity of stool blots in comparison with the sensitivity and specificity of colony blots in detecting enteropathogens. The sensitivities of the probes in stool blots are 91.7% for the LT-I probe, 76.9% for the ST-I probes, 78.9% for the EAF probe, and 45.5% for the INV probe. The specificity of all probes is higher than 95%. In general, the stool blot method identifies as many if not more LT-I-, ST-I-, and EAF-producing E. coli infections than the colony blots.


[Maxillary metastasis revealing a prostate cancer].
A 57 year-old-man presented with a maxillary tumor which proved to be an adenocarcinoma. The prostate was hard and PSA were high. Biopsy confirmed the diagnosis of metastatic prostatic adenocarcinoma. Evolution was fatal despite a medico-surgical treatment. Facial bone metastases are rare comparatively to the high metastatic incidence in the rest of the skeleton.


Conserved role of brain-derived neurotrophic factor in Val66Met: target-selective reinforcement of GABAergic synapses.
Brain-derived neurotrophic factor has been implicated in higher cognitive functions, and several neurological and psychiatric disorders. Recently, a variant brain-derived neurotrophic factor (BDNFMet), having a substitution referred to as Val66Met, was reported as a product of a bdnf allele with a common single nucleotide polymorphism. It has been reported that BDNFMet is impaired in its potential for activity-dependent release. We sparsely transfected cultured hippocampal neurons with BDNFMet or wild-type BDNFVal cDNAs and examined the amount of GABA-synthetic enzyme glutamic acid decarboxylase 65 (GAD65) in the adjacent region, probably in the GABAergic synapses. BDNFMet transfection increased the GAD65 level to the same extent as transfection with BDNFVal. Our findings suggest that the activity-independent secretion of brain-derived neurotrophic factor may be sufficient to induce inhibitory regulation.


Adenoid cystic carcinoma of the external auditory canal. A case report with diagnosis by fine needle aspiration.
Although the cytologic findings of adenoid cystic carcinoma have been reported frequently, fine needle aspiration diagnosis of adenoid cystic carcinoma of the external auditory canal has not been reported before in the English-language literature. A 70-year-old female presented with a mass occluding the external auditory canal. Fine needle aspiration cytology was performed. The smears showed hyaline globules surrounded by tumor cells. The tumor cells had uniform, round, hyperchromatic nuclei, visible nucleoli and little cytoplasm. Based on these cytomorphologic features, diagnosis of adenoid cystic carcinoma was rendered and then confirmed by histopathologic examination. This is the first cytologic report of adenoid cystic carcinoma of the external auditory canal, a rare site for this tumor.


Children exposed to intimate partner violence: influences of parenting, family distress, and siblings.
The aim of this study was to investigate associations between maternal stress, parenting behavior, and sibling adjustment in relation to child trauma symptoms in families with and without a history of intimate partner violence (IPV). Maternal report was used to measure maternal stress and child trauma symptoms, whereas parenting behavior was assessed through an observational measure. Participants consisted of mothers with 2 school-age siblings recruited from the community. Results indicated that violent families reported higher levels of maternal stress and sibling trauma symptoms than nonviolent families, although no differences were found in parenting behavior. Sibling trauma symptoms and negative maternal behavior toward a sibling were strong predictors of trauma symptoms in younger siblings exposed to IPV but only modest predictors for older siblings. Moderator analyses showed that in IPV-affected families, the trauma symptoms of older siblings were related to the trauma symptoms of younger siblings when maternal stress was high.


Mung bean lipoxygenase in the production of a C6-aldehyde. Natural green-note flavor generation via biotransformation.
Mung bean was investigated as a novel source of lipoxygenase in the natural production of the green-note aroma compound hexanal. Lipoxygenase extracted from mung bean catalyzed the oxidative reaction of linoleic acid, after which the intermediate hydroperoxide compound was split via green bell pepper hydroperoxide lyase to produce hexanal. In comparison to soybean lipoxygenase, mung bean lipoxygenase was found to be a good substitute as it produced 15.4 mM (76% yield) hexanal while soybean gave 60% yield. The mung bean pH profile comprised a wide peak (optimum pH 6.5) representing lipoxygenase-2 and lipoxygenase-3 isozymes, whereas two narrower peaks representing lipoxygenase-1 and lipoxygenase-2/3 isozymes were observed for soybean (optimum pH 10). Extraction at pH 4.5 was preferred, at which specific lipoxygenase activity was also the highest.


Giant intracanalicular fibroadenoma. With report of five cases.
Five cases of giant intracanalicular fibroadenoma ("cystosarcoma phylloides") were observed at one hospital in a period of three years. In a search of the literature, additional reports of breast tumors of this kind, not included in previous reviews, were noted. As there is record of 229 cases, it would appear that this rapidly growing benign tumor should be kept in mind in the diagnosis of masses in the breast. If removal is incomplete, there may be recurrence. Simple mastectomy is the treatment of choice. Radical mastectomy should be avoided.


Successful artificial reefs depend on getting the context right due to complex socio-bio-economic interactions.
Artificial reefs (ARs) are one of the most popular means of supporting marine ecosystem conservation and coastal fisheries, particularly in developing countries. However, ARs generate complex socio-bio-economic interactions that require careful evaluation. This is particularly the case for ARs outside no-take zones, where fish might be subject to enhanced exploitation due to easier catchability. Here, we conducted an interdisciplinary study on how ARs impact fish and fishing yields, combining mathematical and sociological approaches. Both approaches converge to confirm that fishery yields decline when ARs are exploited as if they were open access areas. This situation typically occurs in areas with weak governance and/or high levels of illegal fishing activity, both of which are common in many developing countries. To avoid these adverse effects and their associated ecological consequences, we recommend prioritizing the onset of a long-term surveillance system against illegal fishing activities, and adapting design and location of the ARs based on both and local and academic knowledge, before the deployment of ARs.


[Diagnostic clue and genomic analysis of LDH-M subunit deficiency].
Lactate dehydrogenase (LDH) M(A) subunit deficiency was first discovered by urinary discoloration and a discrepancy of laboratory data. Since then, five other families with this disorder have been reported in the Japanese population. The response of pyruvate concentration after forearm ischemic work is specific for LDH-M subunit deficiency. During strenuous exercise ATP production is significantly impaired and muscle tissue is damaged. A genetic study revealed a deletion of 20 base-pairs in exon 6 of the LDH-M gene in four families that were homozygous and one family that was heterozygous for LDH-M subunit deficiency. This mutation results in a frame-shift translation and premature termination. In addition to this mutation, we found a nonsense mutation at codon 328 in exon 7 in an individual heterozygous for LDH-M subunit deficiency, and a deletion of 3 base-pairs, TGT at codon 127 in exon 3 in a proposita who was homozygous and in her parents who were heterozygous for LDH-M subunit deficiency in the fifth family. Therefore, molecular heterogeneities were revealed in genetic mutations of LDH-M subunit deficiency.


Obesity and sexual abuse in American Indians and Alaska Natives.
Mainstream American culture frequently minimizes the prevalence and significance of sexual abuse. Unfortunately, this denial of extensive victimization of women is also present in many underserved populations. In June 2007, Amnesty International released its report on sexual abuse in indigenous women, which states that, "One in three Native American or Alaska Native women will be raped at some point in their lives. Most do not seek justice because they know they will be met with inaction or indifference." This report highlighted an infrequently discussed issue namely, very high levels of sexual abuse in Native American and Alaska Native women. The relationship between sexual abuse and obesity has been delineated in several studies; overall about one quarter to one half of women with high levels of obesity have been sexually abused and it has been postulated that weight-gain serves as an adaptive response for many survivors of sexual abuse. It is also well known in Native American and Alaskan Native women that there is a high prevalence of obesity (about 40% greater than the population average) and that this obesity is associated with a many-fold greater risk of diabetes and increased risks of hypertension, cancer and cardiovascular disease. The link between the concomitantly high rates of sexual abuse and obesity in this population may or may not be partial causality but the issue is nonetheless important. If approaches are to succeed in reversing the trend of increasing levels of obesity in Native American and Alaskan Native women, the high prevalence of sexual abuse will need to be specifically and comprehensively addressed.


Ivabradine: A Potential Therapeutic for Children With Refractory SVT.
Background: In April 2015, ivabradine was approved by the Food and Drug Administration for the treatment of patients with coronary artery disease and heart failure (HF). The use of this medication has been linked with improved clinical outcomes and reduced rates of hospitalization in patients with symptomatic HF and a baseline heart rate of 70 bpm and above. Nonetheless, little is known about the use of ivabradine in pediatric patients with supraventricular tachycardia (SVT). This use is not well-studied and is only endorsed by a few case reports and case series. Aim: This study discusses the off-label utilization of ivabradine in pediatric patients with SVT, and highlights its efficacy in treating treatment-resistant (refractory) SVT. Methods: We conducted a retrospective single-center observational study involving pediatric patients with SVT treated at our center between January 2016 and October 2020. We identified the total number of patients with SVT, and the number of patients with refractory SVT treated with Ivabradine. Similarly, we performed a thorough review of the databases of PubMed, Medline and Google Scholar to compare the clinical course of our patients to those described in the literature. Results: Between January 2016 and October 2020, 79 pediatric patients with SVT were seen and treated at our center. A treatment-resistant SVT was noted only in three patients (4%). Ivabradine was used in these patients as a single or combined therapy. The rest (96%) were successfully treated with conventional anti-arrhythmics such as β-blockers, flecainide, and other approved medications. In the ivabradine group, successful reversal to sinus rhythm was achieved in two of the three patients (66%), one patient was treated with a combination therapy of amiodarone and ivabradine, and the other patient was treated only with ivabradine. Conclusion: Overall, promissory results are associated with the use of ivabradine in pediatric patients with refractory SVT. Ivabradine appears to be a safe and well-tolerated medication that can induce adequate suppression of SVT, complete reversal to sinus rhythm, and effective enhancement of left ventricular function.


COVID-19-induced transaminitis and hyperbilirubinemia: Presentation and outcomes.
The risk of liver injury in patients with coronavirus disease 2019 (COVID-19) infection is quite evident. Furthermore, liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines. This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury, such as chronic liver disease, to elucidate COVID-19-induced liver function abnormalities and their severity, pathophysiology, clinical manifestations, and clinical and laboratory outcomes. We also discuss the effect of vaccination against COVID-19 to better understand host factors, such as age, gender, and race, on the incidence and severity of liver dysfunction at initial presentation and during the illness. Finally, we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.


Syringoacanthoma. Acanthotic lesion of the acrosyringium.
An acanthotic and papillomatous cutaneous lesion with a seborrheic verruca (keratosis)-like clinical appearance that, under light microscope examination, shows intermingling of sweat ductal and epidermal cells is described. Other lesions related to the distal end of the eccrine sweat duct have been recorded before, but these lesions, named syringoacanthoma herein, have not been described previously, to my knowledge. Twenty-one cases of syringoacanthoma , 12 benign and nine malignant, are reviewed and their relationship with similar lesions is discussed.


Effect of temperature, food availability, and estradiol injection on gametogenesis and gender in the pearl oyster Pinctada margaritifera.
The black-lip pearl oyster Pinctada margaritifera is a protandrous hermaphrodite species. Its economic value has led to the development of controlled hatchery reproduction techniques, although many aspects remain to be optimized. In order to understand reproductive mechanisms and their controlling factors, two independent experiments were designed to test hypotheses of gametogenesis and sex ratio control by environmental and hormonal factors. In one, pearl oysters were exposed under controlled conditions at different combinations of temperature (24 and 28°C) and food level (10,000 and 40,000 cells mL(-1) ); whereas in the other, pearl oysters were conditioned under natural conditions into the lagoon and subjected to successive 17β-estradiol injections (100 μg per injection). Gametogenesis and sex ratio were assessed by histology for each treatment. In parallel, mRNA expressions of nine marker genes of the sexual pathway (pmarg-foxl2, pmarg-c43476, pmarg-c45042, pmarg-c19309, pmarg-c54338, pmarg-vit6, pmarg-zglp1, pmarg-dmrt, and pmarg-fem1-like) were investigated. Maximum maturation was observed in the treatment combining the highest temperature (28°C) and the highest microalgae concentration (40,000 cells mL(-1) ), where the female sex tended to be maintained. Injection of 17β-estradiol induced a significant increase of undetermined stage proportion 2 weeks after the final injection. These results suggest that gametogenesis and gender in adult pearl oysters can be controlled by environmental factors and estrogens. While there were no significant effects on relative gene expression, the 3-gene-pair expression ratio model of the sexual pathway of P. margaritifera, suggest a probable dominance of genetic sex determinism without excluding a mixed sex determination mode (genetic + environmental). J. Exp. Zool. 325A:13-24, 2016. © 2015 Wiley Periodicals, Inc.


[Effect of obstructive sleep apnea on sleep architecture of acute ischemic stroke patients].
Objective: To investigate the effect of obstructive sleep apnea (OSA) on sleep architecture in acute ischemic stroke (AIS) patients. Methods: Seventy AIS patients with polysomnography examination from June 2014 to April 2016 were included in the Second Affiliated Hospital of Soochow University. Twenty-seven healthy controls during the same period were chosen as control group. According to apnea-hypopnea index (AHI), AIS patients were divided into AIS group (AHI<5/h) and AIS+ OSA group (AHI≥5/h). Their general conditions, Neurological function defect (national institutes of health stroke scale, NIHSS) on admission and at discharge and self-care ability (modified Rankin Scale, mRS) at discharge and 3 months later (mRS score <2 reflected good prognosis, and mRS score≥2 reflected unfavorable prognosis) were collected. Results: Fifty-two patients (74.3%) had OSA in total seventy AIS patients. Total sleep time (TST) was significantly shorter and sleep efficiency (SE) was lower in AIS group than the control group (P=0.007, 0.008, respectively). AIS+ OSA group had longer non-rapid eye movement (NREM)1 than control group [24.9(21.3) vs 14.3(10.6), P=0.044]. Compared with AIS group, AIS+ OSA group had shorter NREM3 [13.0(13.2) vs 19.6(12.8), P=0.039]. There was no significant difference between the infarct location of AIS group and AIS+ OSA group. However, AIS+ OSA group had higher mRS score observed at 3 months through follow-up visit than AIS group (P=0.027). Spearman correlation analysis showed a positive correlation between unfavorable prognosis of stroke at 3 months and atrial fibrillation, the oxygen desaturation index (ODI), percentage of oxygen saturation <90% of total recording time (TS90%), AHI, the longest time of apnea and hypopnea, respiratory related microarousal and NIHSS, while a negative correlation between unfavorable prognosis of stroke and NREM3, lowest nocturnal oxygen saturation (L-SaO(2)). On Logistic analysis, the unfavorable prognosis was independently predicted by AHI and NIHSS. Conclusions: Sleep architecture of cerebral infarction patients are disturbed with its characteristic of shorter total sleep time and lower sleep efficiency. Cerebral infarction patients with OSA have longer NREM1 and shorter NREM3.


Microfabricated filters for microfluidic analytical systems.
Solvent and reagent filters were micromachined into quartz wafers using deep reactive ion etching to create a network of intersecting 1.5 x 10 microns channels. When placed at the bottom of reservoirs with a side exit, this channel network behaved as a lateral percolation filter composed of an array of cubelike structures one layer deep. Flow through these filters was driven by electroosmotic flow (EOF). Silanol groups at the walls of channels in the network provided the requisite charge to trigger EOF when voltage was applied laterally to the filter. Adsorption of cationic proteins in this silanol-rich matrix was controlled by the application of a polyacrylamide coating prepared by bonding N-hydroxysuccinimide (NHS)-activated poly(acrylic acid) to (gamma-aminopropyl)silane-derivatized filters. Subsequent reaction of residual NHS groups in the coating with 2-(2-aminoethoxy)ethanol provided channels of low charge density and adsorptivity. These lateral percolation filters were shown to be efficacious in filtering solvents containing a variety of particulate materials, ranging from dust to cells.


Comparison of the Papanicolaou and Feulgen staining methods for DNA quantification by image analysis.
The possibility of using archival cytology material to study the evolution of neoplastic disease with regard to DNA content abnormalities was investigated. The accuracy of measuring the integrity optical density (OD) of nuclei that correlates to DNA amounts of those nuclei, on slides stained by the Papanicolaou method, was assessed and compared with a standard Feulgen method. Our data on rat liver nuclei peritoneal washings from patients with ovarian cystadenofibromas and ovarian cystadenocarcinomas suggested that analysis of cytological material using the Papanicolaou method is not reliable and that destaining the slides followed by Feulgen staining provides an optimal and reliable method of DNA quantification.


Hydrodynamic interactions of filaments polymerizing against obstacles.
Polymerization and depolymerization of cytoskeletal filaments against cellular structures can generate forces that are key to many cellular processes, such as cell motility and chromosomes movements during cell division. Motions generated by these forces induce global cytoplasmic flows and couple the dynamics of the polymerizing filaments and other bodies immersed in the fluid through their long-range hydrodynamic interactions (HIs). Previous theoretical and computational studies have largely ignored HIs. We use three dimensional discrete simulations to study the relationship between polymerization forces and their resulting flows and HIs. As a model system, we choose a filament that is polymerizing against an obstacle, and is embedded in a cylindrical array of parallel filaments of the same length. We consider three distinct mechanical scenarios for the filaments within the array: (a) all of the filaments are polymerizing with the same velocity; (b) they are all fixed in space, and (c) they are freely suspended. We show that each of these conditions produce their unique cytoplasmic flows and each result in differentiable polymerization forces and velocities. We also study the effect of buckling of filaments on polymerization forces and velocities and discuss the effect of HIs on the onset of buckling transition. Finally, we show that HIs result in the bundling of the buckled filaments within the array.


Effects of dihydroergotoxine methane sulphonate (Redergine) on sleep in cats deprived of paradoxical sleep.
Dihydroergotoxine methane sulphonate (DHET 1.0 mg/kg i.p.) was administered to cats deprived of paradoxical sleep (PS) for 72 h and 23 h of recovery sleep were recorded. During the first 12 h of recovery sleep slow-wave sleep (SWS) was significantly increased. There were no significant changes in the amounts of wakefulness (W), PS and several sleep indices. Analysis of the entire 23 h of recording period revealed no significant changes in any of the parameters studied. The results suggest that DHET has SWS enhancing property in the condition where "pressure" for PS was increased.


Bystander responses induced by low LET radiation.
Radiation-induced bystander responses are observed when cells respond to their neighbours being irradiated. Considerable evidence is now available regarding the importance of these responses in cell and tissue models. Most studies have utilized two approaches where either a media-transferable factor has been assessed or cells have been exposed to low fluences of charged particles, where only a few percent are exposed. The development of microbeams has allowed nontargeted responses such as bystander effects to be more carefully analysed. As well as charged particle microbeams, X-ray microprobes have been developed, and several groups are also developing electron microbeams. Using the Gray Cancer Institute soft X-ray microprobe, it has been possible to follow the response of individual cells to targeted low doses of carbon-characteristic soft X-rays. Studies in human fibroblasts have shown evidence of a significant radiation quality-dependent bystander effect, measured as chromosomal damage in the form of micronuclei which is radiation quality dependent. Other studies show that even under conditions when only a single cell is targeted with soft X-rays, significant bystander-mediated cell killing is observed. The observation of bystander responses with low LET radiation suggests that these may be important in understanding radiation risk from background levels of radiation, where cells observe only single electron track traversals. Also, the indirect evidence for these responses in vivo indicates that they may have a role to play in current radiotherapy approaches and future novel strategies involving modulating nontargeted responses.


RBP7 Regulated by EBF1 Affects Th2 Cells and the Oocyte Meiosis Pathway in Bone Metastases of Bladder Urothelial Carcinoma.
Bladder urothelial carcinoma (BLCA) is a malignancy with a high incidence worldwide. One-third of patients may experience aggressive progression later on, and 70% of patients who have undergone surgical intervention will still suffer from metastasis. RNA sequencing profiles of BLCA samples were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression and univariate Cox regression analyses were performed to identify prognosis-related differentially expressed immune genes (DEIGs). Subsequently, a proportional hazards model of DEIGs was then constructed by univariate regression analysis. Differential expression and correlation analyses, CIBERSORT, Single Sample Gene Set Enrichment Analysis (ssGSEA), GSVA were conducted on transcription factors (TFs), immune cells/pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The regulation network was then constructed. Eventually, ATAC-seq, ChIP-seq, scRNA-seq, and multiple online databases were employed for further validation. A proportional hazards model of 31 DEIGs was constructed and risk score was calculated and proven to be a independent prognostic factor. Then 5 immune genes were characterized to be significantly correlated with bone metastasis, stage and TF expression simultaneously. 4 TFs were identified to be significantly correlated with prognosis and RBP7 expression. 5 immune cells/pathways were revealed to be significantly correlated with RBP7 expression. Only 1 KEGG pathway was identified to be significant in Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) analyses. The regulatory relationship was then constructed, in which the correlation between EBF1 and RBP7 (R = 0.677, p < 0.001), Th2 cells and RBP7 (R = 0.23, p < 0.001), the oocyte meiosis pathway and RBP7 (R = 0.14, p = 0.042) were the most statistically significant. The results were further confirmed by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), Chromatin Immunoprecipitation sequencing (ChIP-seq), single-cell RNA sequencing (scRNA-seq), and multiple online databases validation. This study revealed that the EBF1-RBP7 regulatory relationship had potential importance in the bone metastasis in BLCA through Th2 cells and the oocyte meiosis pathway.


[A model for the embryological instruction of the branchial arteries].
It is difficult to teach students about the embryological transformation of the branchial arteries. In mammals, six pairs of branchial arteries develop, but all are not present at the same embryological stage. The first, second, fifth and a part of right sixth branchial artery disappear early in embryological development. The remaining third, fourth and sixth branchial arteries mainly constitute the arterial system of the breast. The aorta and pulmonary trunk are derived from the truncus arteriosus. Because of the complexity of this developmental process, we have devised a user-friendly model in order to assist with educational presentations. In this model, the shrinkage of a vessel has been represented by inserting a wire inside of the hose representing the artery. Degenerated or disappearing parts of the vessel are removable by using hooks and Velcro tape. Branchial arteries, truncus arteriosus, aortic sac and dorsal arteries are represented by different colors. The descent of the heart is represented by the relational change between larynx and heart. Additionally we represented the vagus nerve and recurrent laryngeal nerve by using strings. The right vagus nerve can move dorsally and the left ventrally by rotating the digestive tract. The right recurrent laryngeal nerve can move superiorly to hook around the right subclavian artery, and left recurrent laryngeal nerve can hook around the ductus arteriosus formed by the left sixth branchial artery.


Desferoxamine and ethyl-3,4-dihydroxybenzoate protect myocardium by activating NOS and generating mitochondrial ROS.
Protection from a prolyl hydroxylase domain-containing enzyme (PHD) inhibitor, desferoxamine (DFO), was recently reported to be dependent on production of reactive oxygen species (ROS). Ischemic preconditioning triggers the protected state by stimulating nitric oxide (NO) production to open mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels, generating ROS required for protection. We tested whether DFO and a second PHD inhibitor, ethyl-3,4-dihydroxybenzoate (EDHB), might have similar mechanisms. EDHB and DFO increased ROS generation by 50-75% (P < 0.001) in isolated rabbit cardiomyocytes. This increase after EDHB exposure was blocked by N(omega)-nitro-L-arginine methyl ester (L-NAME), an NO synthase (NOS) inhibitor; ODQ, a guanylyl cyclase antagonist; and Rp-8-bromoguanosine-3',5'-cyclic monophosphorothioate Rp isomer, a PKG blocker, thus implicating the NO pathway in EDHB's signaling. Glibenclamide, a nonselective K(ATP) channel blocker, or 5-hydroxydecanoate, a selective mitoK(ATP) channel antagonist, also prevented EDHB's ROS production, as did blockade of mitochondrial electron transport with myxothiazol. NOS is activated by Akt. However, neither wortmannin, an inhibitor of phosphatidylinositol-3-kinase, nor Akt inhibitor blocked EDHB-induced ROS generation, indicating that EDHB initiates signaling downstream of Akt. DFO also increased ROS production, and this effect was blocked by ODQ, 5-hydroxydecanoate, and N-(2-mercaptopropionyl)glycine, an ROS scavenger. DFO increased cardiomyocyte production of nitrite, a metabolite of NO, and this effect was blocked by an inhibitor of NOS. DFO also spared ischemic myocardium in intact hearts. This infarct-sparing effect was blocked by ODQ, L-NAME, and N-(2-mercaptopropionyl)glycine. Hence, DFO and EDHB stimulate NO-dependent activation of PKG to open mitoK(ATP) channels and produce ROS, which act as second messengers to trigger entrance into the preconditioned state.


Charging and interaction of individual impurities in a monolayer organic crystal.
We use a scanning tunneling microscope to study the charging of Ag-doping centers in a monolayer of C(60) molecules supported on a thin Al(2)O(3) film grown on the NiAl(110) surface. Differential conductance spectroscopy shows that charging affects the conduction through C(60) molecules located around the doping centers. This effect is used to observe the electrostatic interaction of a pair of centers. Charging of one doping center affects the energy levels of the other, an analogue of the field-effect action.


Revealing Crystallization-Induced Blue-Shift Emission of a Di-Boron Complex by Enhanced Photoluminescence and Electrochemiluminescence.
Elucidating the effects of crystallization-induced blue-shift emission of a newly synthesized di-boron complex (DBC) by enhanced photoluminescence (PL) and electrochemiluminescence (ECL) in the annihilation pathway was realized for the first time. The 57 nm blue-shift and great enhancement in the crystalline lattice relative to the DBC solution were attributed to the restriction of intramolecular rotation (RIR) and confirmed by PL imaging, X-ray diffraction, as well as DFT calculations. It was discovered that ECL at crystalline film/solution interfaces can be further enhanced by means of both co-reactant route and RIR. The RIR contributions with co-reactant increased ECL up to 5 times more. Very interestingly, the co-reactant system was found to give off a red-shifted light emission. Mechanistic studies reveal that a difference between location of the ECL in the co-reactant route and that in the annihilation pathway leads to an alternative emission wavelength.


Bimodal benefit for cochlear implant listeners with different grades of hearing loss in the opposite ear.
To determine speech perception in quiet and noise of adult cochlear implant listeners retaining a hearing aid contralaterally. Second, to investigate the influence of contralateral hearing thresholds and speech perception on bimodal hearing. Sentence recognition with hearing aid alone, cochlear implant alone and bimodally at 6 months after cochlear implantation were assessed in 148 postlingually deafened adults. Data were analyzed for bimodal summation using measures of speech perception in quiet and in noise. Most of the subjects showed improved sentence recognition in quiet and in noise in the bimodal condition compared to the hearing aid-only or cochlear implant-only mode. The large variability of bimodal benefit in quiet can be partially explained by the degree of pure tone loss. Also, subjects with better hearing on the acoustic side experience significant benefit from the additional electrical input. Bimodal summation shows different characteristics in quiet and noise. Bimodal benefit in quiet depends on hearing thresholds at higher frequencies as well as in the lower- and middle-frequency ranges. For the bimodal benefit in noise, no correlation with hearing threshold in any frequency range was found.


A pervasive role of ubiquitin conjugation in activation and termination of IkappaB kinase pathways.
The nuclear factor (NF)-kappaB pathway is a paradigm for gene expression control by ubiquitin-mediated protein degradation. In stimulated cells, phosphorylation by the IkappaB kinase (IKK) complex primes NF-kappaB-inhibiting IkappaB molecules for lysine (Lys)-48-linked polyubiquitination and subsequent destruction by the 26S proteasome. However, recent studies indicate that the ubiquitin (Ub) system controls NF-kappaB pathways at many levels. Ub ligases are activated by different upstream signalling pathways, and they function as central regulators of IKK and c-Jun amino-terminal kinase activation. The assembly of Lys 63 polyUb chains provides docking surfaces for the recruitment of IKK-activating complexes, a reaction that is counteracted by deubiquitinating enzymes. Furthermore, Ub conjugation targets upstream signalling mediators as well as nuclear NF-kappaB for post-inductive degradation to limit the duration of signalling.


Observation of stable Néel skyrmions in cobalt/palladium multilayers with Lorentz transmission electron microscopy.
Néel skyrmions are of high interest due to their potential applications in a variety of spintronic devices, currently accessible in ultrathin heavy metal/ferromagnetic bilayers and multilayers with a strong Dzyaloshinskii-Moriya interaction. Here we report on the direct imaging of chiral spin structures including skyrmions in an exchange-coupled cobalt/palladium multilayer at room temperature with Lorentz transmission electron microscopy, a high-resolution technique previously suggested to exhibit no Néel skyrmion contrast. Phase retrieval methods allow us to map the internal spin structure of the skyrmion core, identifying a 25 nm central region of uniform magnetization followed by a larger region characterized by rotation from in- to out-of-plane. The formation and resolution of the internal spin structure of room temperature skyrmions without a stabilizing out-of-plane field in thick magnetic multilayers opens up a new set of tools and materials to study the physics and device applications associated with chiral ordering and skyrmions.


Short wavelength automated perimetry, frequency doubling technology perimetry, and pattern electroretinography for prediction of progressive glaucomatous standard visual field defects.
To evaluate the clinical use of a test battery of short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), and pattern electroretinography (PERG) in predicting progressive glaucomatous visual field defects on standard automated perimetry (SAP). A prospective, longitudinal, observational case series. One hundred and fifty-two patients with primary open-angle glaucoma (POAG) with bilateral glaucomatous visual field defects on SAP were followed at 6-month intervals over a period of 30 months. Short wavelength automated perimetry, FDT, and PERG results were compared between POAG eyes with and without progressive field loss on SAP. These two groups were used to evaluate whether PERG, SWAP, and/or FDT is predictive of future progression of field loss on SAP. Using the criteria of progressive field loss on SAP defined by the Collaborative Normal Tension Glaucoma Study, 54 eyes (study group) of 54 POAG patients showed progressive defects, whereas 84 eyes (control group) of 84 POAG patients showed no progression. Only 11.1% (6 of 54) of the eyes with a progression of field loss on SAP showed no increase of deficits on the three functional tests before progression. Short wavelength automated perimetry detected early progressive defects on SAP in 43 of the 54 eyes (79.6%). Of these 54 POAG eyes, FDT showed progressive deficits in 40 eyes (74.1%), whereas PERG amplitude P1N2 showed progressive deficits in 35 eyes (64.8%) before progression of field loss on SAP. A test battery consisting of SWAP and PERG P1N2-amplitude was able to detect 88.9% of eyes before a prediction of field loss on SAP. When comparing the results of the two functional tests, SWAP and FDT in the 84 eyes without progression of field loss on SAP between baseline and at 30 months, SWAP and FDT showed progressive deficits in 34.5% and 35.7%, respectively. All three tests (SWAP, FDT, and PERG) have been successful in detecting glaucoma eyes with a future progression of standard visual field defects. A test battery of SWAP and PERG P1N2-amplitude improved the power to predict these progressive defects on SAP. It remains to be seen whether the long-term follow-up in POAG eyes will improve the false-positive rate of SWAP and FDT.


Improving health services in India: a different perspective.
Two papers in this volume focus on public finance and decentralization as central to resolving India's systemic public health crisis. However, some states and districts have achieved success despite serious financial and administrative deficits; this suggests that factors such as political commitment, community participation, human resource management, women's empowerment, and governance may be as or more important. The success of the National Rural Health Mission will depend on state and local institutional capacity, including strong partnerships with civil society organizations and private-sector actors. Increased resources and decentralization will not be sufficient by themselves.


Network Visualization Analysis on MicroRNAs in Infectious Diseases Research Area.
The discovery of microRNAs (miRNAs) has revealed a new level in gene expression post-transcriptional control. Several studies have been published to date looking at the relationship between miRNAs and viral (swine flu, HIV, and hepatitis B) or bacterial infections. We conducted a bibliometric evaluation of the existing literature on miRNAs in the infectious disease research area. The major purpose of this study was to investigate the significance of publications and identify research developments and clusters using bibliometric methods. Data was obtained from the Web of Science (WoS) database. The titles, document types, publication years, authors, affiliations, keywords, publishing journals, abstracts of each document, and citations within the WoS database were saved as TXT files and retrieved into Microsoft Office Excel 2019. Data for this investigation was obtained from the WoS database on 10 April 2022. The WoS database's Results Analysis and Citation Report were used to analyze the number of publications from various viewpoints, such as years, journals, and authors. To visualize country collaboration networks and keywords we used the VOSviewer software version 1.6.18 for Microsoft Windows. We found 623 documents of which 251 (40.3%) were articles. All the publications were published in English. The first document was published in 2007, and the maximum number of documents was published in 2021. The number of documents has been increasing since 2019. China dominated the scientific production with 398 (63.9%) publications. The top five leading scientifically productive countries on this topic also included the USA (n = 100; 16.1%), Japan (n = 24; 3.9%), Germany (n = 20; 3.2%), and Italy (n = 17; 2.7%). The documents originating from China were cited 5705 times (an average of 14.3/document). The documents originating from the USA were cited 2190 times (an average of 21.9/document). Since 2019, the number of studies on miRNA in infectious illnesses has steadily increased. China and the USA have made tremendous contributions to this field's study. We discovered several deregulated miRNAs, including miR-122, miR-133a, miR-146, miR-155, and miR-370, were described in the context of sepsis and infection using bibliometric methods. Understanding these crucial factors, as well as how research is performed and directed, might lead to a new perspective in the creation of new strategies to manage variable infections in the coming years.


Preoperative computed tomography or intraoperative epiaortic ultrasound for the diagnosis of atherosclerosis of the ascending aorta?
Extensive atherosclerotic disease, usually first diagnosed intraoperatively, is the most important risk factor for postoperative stroke after cardiac surgery. The aim of this study was to investigate if preoperative computed tomography (CT) is comparable with intraoperative epiaortic ultrasound to diagnose severe atherosclerosis in the ascending aorta. The study included 20 consecutive patients who underwent elective coronary artery bypass surgery. Preoperative CT evaluation of the ascending aorta was compared with intraoperative epiaortic ultrasound findings. The ascending aorta was divided into 12 segments per patient, giving 240 segments to compare. Epiaortic ultrasound detected atherosclerosis in 16.7% +/- 2.4% of the segments, a rate significantly higher than with CT ( P < or =.03). There was a low reliability between the 2 methods, indicated by kappa coefficients of 0.45 or lower. The CT method is inferior to epiaortic ultrasound, today's gold standard, in diagnosing the extent and location of atherosclerosis of the ascending aorta. Other methods, possibly magnetic resonance imaging, should be considered.


[Ca2+]i regulates trafficking of Cav1.3 (alpha1D Ca2+ channel) in insulin-secreting cells.
Chronic exposure of pancreatic beta-cells to high concentrations of glucose impairs the insulin secretory response to further glucose stimulation. This phenomenon is referred to as glucose desensitization. It has been shown that glucose desensitization is associated with abnormal elevation of beta-cell basal intracellular free Ca2+ concentration ([Ca2+]i). We have investigated the relationship between the basal intracellular free Ca2+ and the L-type (Cav1.3) Ca2+ channel translocation in insulin-secreting cells. Glucose stimulation or membrane depolarization induced a nifedipine-sensitive Ca2+ influx, which was attenuated when the basal [Ca2+]i was elevated. Using voltage-clamp techniques, we found that changing [Ca2+]i could regulate the amplitude of the Ca2+ current. This effect was attenuated by drugs that interfere with the cytoskeleton. Immunofluorescent labeling of Cav1.3 showed an increase in the cytoplasmic distribution of the channels under high [Ca2+]i conditions by deconvolution microscopy. The [Ca2+]i-dependent translocation of Cav1.3 channel was also demonstrated by Western blot analysis of biotinylation/NeutrAvidin-bead-eluted surface proteins in cells preincubated at various [Ca2+]i. These results suggest that Cav1.3 channel trafficking is involved in glucose desensitization of pancreatic beta-cells.


A Volunteer Basketball Clinic for Children with Disabilities: Professional Development Impact on Student-Athletes and Physical Therapy Students.
The purpose of this study was to assess the change in perceptions of student-athletes, physical therapy students, and parents of children who helped to facilitate an athletic skills camp for children with disabilities. Participants experienced 3 hours of basketball activity yearly. Data were collected for 3 consecutive years from a total of 51 parents, 15 student-athletes, and 22 physical therapy students. Pre- and post-survey data were evaluated by two independent researchers. Common themes were developed for all participant groups and cross-group comparisons were evaluated. Findings indicated a synergistic benefit for student-athletes and physical therapy students derived from their impact and children with disabilities. Perceptual changes in students included a decrease in fear in working with disabled children, an appreciation for the value of having fun, and increased growth in civic identity and desire to volunteer.


The immunomodulating effect of a new polyamine (the MAP-1987) administered with chloroquine in plasmodia infected mice.
The biological activity of a new synthetic polypeptide, the MAP-1987 was proved in the rodent malaria system. The administration of 4 micrograms/kg of MAP-1987 prevents the haemolysis of the Plasmodium berghei infected erythrocytes but not the Plasmodium vinckei infected ones. The MAP-1987 given alone changes neither the survival time of the infected mice nor the rate of parasitaemia. The chloroquine given alone increases the survival time of the mice infected with P. berghei under the standardized experimental condition but later the animals die with a low rate of parasitaemia. Chloroquine administered together with MAP-1987 definitely cures the P. berghei infected animals. This activity is unique and specific and it does not apply to P. vinckei infection.


Pleistocene climatic oscillations rather than recent human disturbance influence genetic diversity in one of the world's highest treeline species.
Biological responses to climatic change usually leave imprints on the genetic diversity and structure of plants. Information on the current genetic diversity and structure of dominant tree species has facilitated our general understanding of phylogeographical patterns. Using amplified fragment length polymorphism (AFLPs), we compared genetic diversity and structure of 384 adults of P. tarapacana with those of 384 seedlings across 32 forest sites spanning a latitudinal gradient of 600 km occurring between 4100 m and 5000 m a.s.l. in Polylepis tarapacana (Rosaceae), one of the world's highest treeline species endemic to the central Andes. Moderate to high levels of genetic diversity and low genetic differentiation were detected in both adults and seedlings, with levels of genetic diversity and differentiation being almost identical. Four slightly genetically divergent clusters were identified that accorded to differing geographical regions. Genetic diversity decreased from south to north and with increasing precipitation for adults and seedlings, but there was no relationship to elevation. Our study shows that, unlike the case for other Andean treeline species, recent human activities have not affected the genetic structure of P. tarapacana, possibly because its inhospitable habitat is unsuitable for agriculture. The current genetic pattern of P. tarapacana points to a historically more widespread distribution at lower altitudes, which allowed considerable gene flow possibly during the glacial periods of the Pleistocene epoch, and also suggests that the northern Argentinean Andes may have served as a refugium for historical populations.


Upconversion luminescence properties of Er(3+)-Bi3+ codoped CaSnO3 nanocrystals with perovskite structure.
New phosphor nanocrystals of ASnO3:Er3+ (A = Ca, Sr, and Ba) and CaSnO3:Er(3+)-Bi3+ were prepared by a hydrothermal method. Their structures were examined by X-ray diffraction and Raman spectroscopy. Upconversion luminescence properties of the Er3+ ions in these host materials were investigated upon excitation at 980 nm. Green emission bands of Er3+ around 528 and 545 nm were more favorable in CaSnO3 than in SrSnO3 and BaSnO3. This was interpreted in terms of a crystal structural distortion and configuration coordinate model. The investigation of the upconversion luminescence of Er(3+)-Bi3+codoped CaSnO3 nanocrystals indicates that Bi3+ ions could largely sensitize the emission of Er3+ ions which was attributed to the efficient energy transfer from Bi3+ to Er3+ ions and the modification of the local symmetry of Er3+ ions. The results show that the CaSnO3:Er(3+)-Bi3+ nanocrystals have potential application for fabricating visible upconversion devices.


A simple synthetic liquid medium for development of yeast and mycelial form of pathogenic species of Candida.
Thirty two known strains of Candida species were used for evaluation of glucose, serine, ornithine, methionine, GSOM medium and its comparison with Lee's medium for the production of yeast and mycelial phase at different temperatures and on prolonged incubation. No mycelial form was observed when various Candida species in GSOM and Lee's medium were incubated at 25 degrees C up to 72 hours. Percentage of mycelial forming cells of Candida species were more in GSOM medium than Lee's medium in 48 hours at 37 degrees C. Among various species of Candida, albicans and C. parapsilosis showed maximum mycelium formation. GSOM medium can be used for growing Candida species particularly C. albicans in mycelial phase.


Quantitative noninvasive electrophysiological evaluation of the activity of the cutaneous division of the sympathetic nervous system.
The functional status of the cutaneous division of the orthosympathetic nervous system was indirectly and non-invasively assessed by monitoring the skin electrical relative resistance variations (SERV). The advantages of our recording system of second generation were (1) simultaneous recording on two or four channels of the evoked electrodermal response to psychic or to sensorial stimulus; (2) self-balancing system which allows the recording of the relative variation of the electric parameter, i.e. its variation with time; (3) precise determination of the amplitude (omega/s, mu F/s) of the evoked response; (4) reference of the latency time (LT) of the evoked response to the length of the anatomical pathway of the signal giving the autonomic conduction velocity (ACV). Decrease in diabetic autonomic neuropathy of both spontaneous and evoked electrodermal activities suggested their relationship with cutaneous sympathetic activity.


Assumed equity: early observations from the first hospital disparities collaborative.
Disparities in healthcare represent a failure in the equity domain of quality. Although disparities have been well documented, little has been written about how hospitals might use improved data collection and quality improvement techniques to eliminate disparities. This article describes early findings from the planning phase of the first hospital-based disparities collaborative. The authors also discuss the changes in policy and practice that may speed hospitals in placing disparities and equity on their quality agendas.


Assessment of the relation between land use and carbon emission in Eindhoven, the Netherlands.
The impact of the urban morphology on greenhouse gas emission is one of the key issues on global climate change. Since the urban form is directly related to the spatial distribution of urban land use, it is necessary to investigate the relation between carbon emission and different land use categories. In this paper, the city of Eindhoven (230,000 inhabitants) was used as a case study. According to the main road network, the entire city is divided into 6754 irregular patterns. Agglomerative cluster analysis was conducted to classify the patterns into 14 valid land use categories based on their land use function and land cover composition namely: agriculture, transport, retail trade, green space (with 3 sub-categories), residential (with 7 sub-categories), and others. The random forest algorithm was applied to select the significant features and to measure the relation between land use and carbon emission. The results have shown the importance of various landscape metrics on the carbon emission in each land use category. The most significant landscape metric is selected to describe the impact of spatial attributes on carbon emission. The outcomes show the carbon emission distribution of each land use category in the city. The retail trade and residential land use categories contribute a large proportion of carbon emission, terrace houses produce more carbon emission than other residential building categories. The combination of mid-rise buildings and low-rise buildings has a higher probability to produce more carbon emission. The assessment results can provide important support for the low carbon city spatial planning.


Towards the virtual human patient. Quantitative Systems Pharmacology in Alzheimer's disease.
Development of successful therapeutic interventions in Central Nervous Systems (CNS) disorders is a daunting challenge with a low success rate. Probable reasons include the lack of translation from preclinical animal models, the individual variability of many pathological processes converging upon the same clinical phenotype, the pharmacodynamical interaction of various comedications and last but not least the complexity of the human brain. This paper argues for a re-engineering of the pharmaceutical CNS Research & Development strategy using ideas focused on advanced computer modeling and simulation from adjacent engineering-based industries. We provide examples that such a Quantitative Systems Pharmacology approach based on computer simulation of biological processes and that combines the best of preclinical research with actual clinical outcomes can enhance translation to the clinical situation. We will expand upon (1) the need to go from Big Data to Smart Data and develop predictive and quantitative algorithms that are actionable for the pharma industry, (2) using this platform as a "knowledge machine" that captures community-wide expertise in an active hypothesis-testing approach, (3) learning from failed clinical trials and (4) the need to go beyond simple linear hypotheses and embrace complex non-linear hypotheses. We will propose a strategy for applying these concepts to the substantial individual variability of AD patient subgroups and the treatment of neuropsychiatric problems in AD. Quantitative Systems Pharmacology is a new 'humanized' tool for supporting drug discovery and development in general and CNS disorders in particular.


Unilateral pulmonary hypertension as a result of chronic high flow to one lung.
The patient presented is a 27-month-old male with complex congenital heart disease consisting of severe left ventricular outflow tract obstruction and ventricular septal defect who had undergone a pulmonary trunk-to-aorta graft and a pulmonary artery banding procedure as a neonate. Sometime after this repair, but at least 15 months prior to presentation to this institution for placement of an aortic homograft, the pulmonary trunk band apparently slipped and migrated over the right pulmonary artery, severely limiting blood flow to the right lung and increasing flow to the left. Severe pulmonary hypertension developed, with a main pulmonary artery pressure of 94/53 mm Hg. We present clinical and radiographic evidence that the resulting chronic high blood flow and pressure in the left lung ultimately resulted in hypoperfusion of that lung, presumably secondary to chronic vascular changes with greatly increased vascular resistance. Upon surgical repair and removal of the constrictive band from the previously banded right PA, blood flow was increased to the low resistance right lung causing right-sided unilateral pulmonary edema, ventilation/perfusion mismatching, and severe hypoxemia. Perfusion studies documented that less than 10% of blood was directed to the left lung, with greater than 90% to the right. Perfusion studies 9 months postoperatively continued to demonstrate minimal blood flow to the left lung. Discussion focuses on the effects of mechanical forces and the interaction with hypoxia in causing pulmonary vascular remodeling.


CREB4, a transmembrane bZip transcription factor and potential new substrate for regulation and cleavage by S1P.
Regulated intramembrane proteolysis of the factors SREBP and ATF6 represents a central control mechanism in sterol homeostasis and stress response within the endoplasmic reticulum. Here, we compare localization of ATF6-related bZip factors CREB4, CREB-H, Luman, and OASIS. These factors contain the defining features of a bZip domain, a predicted transmembrane domain and an adjacent cleavage site for the Golgi protease S1P, with conserved features which indicate that it represents a specific subclass of S1P sites. Each factor localizes to the endoplasmic reticulum (ER), but a population of CREB4 was also observed in the Golgi. Deletion of the transmembrane domain in CREB4 resulted in efficient nuclear accumulation. An N-terminal variant of CREB4 containing the BZIp domain potently activated expression from a target gene containing ATF6 binding sites and from the promoter for the ER chaperone GRP78/BIP. CREB4 was cleaved in a site-specific manner in response to brefeldin A disruption of the Golgi or by coexpression with S1P but only after deletion or substitution of its C-terminal lumenal domain. Thus, S1P cleavage of CREB4 may be suppressed by a determinant in the C-terminal region. Dithiothreitol induced more complete transport of CREB4 to the Golgi, but not cleavage. Together, the data identify at least one additional bZip factor whose localization responds to ER stress, and we propose a model based on these results that indicates additional levels of control of this novel class of transcription factors.


Clinical Translation of [68Ga]Ga-NOTA-anti-MMR-sdAb for PET/CT Imaging of Protumorigenic Macrophages.
Macrophage mannose receptor (MMR, CD206) expressing tumor-associated macrophages (TAM) are protumorigenic and was reported to negatively impact therapy responsiveness and is associated with higher chances of tumor relapse following multiple treatment regimens in preclinical tumor models. Since the distribution of immune cells within the tumor is often heterogeneous, sampling "errors" using tissue biopsies will occur. In order to overcome this limitation, we propose positron emission tomography (PET)/X-ray computed tomography (CT) imaging using 68Ga-labeled anti-MMR single-domain antibody fragment (sdAb) to assess the presence of these protumorigenic TAM. Cross-reactive anti-MMR-sdAb was produced according to good manufacturing practice (GMP) and conjugated to p-SCN-Bn-NOTA bifunctional chelator for 68Ga-labeling. Biodistribution and PET/CT studies were performed in wild-type and MMR-deficient 3LL-R tumor-bearing mice. Biodistribution data obtained in mice were extrapolated to calculate radiation dose estimates for the human adult using OLINDA software. A 7-day repeated dose toxicity study for NOTA-anti-MMR-sdAb was performed in healthy mice up to a dose of 1.68 mg/kg. [68Ga]Ga-NOTA-anti-MMR-sdAb was obtained with 76 ± 2 % radiochemical yield, 99 ± 1 % radiochemical purity, and apparent molar activity of 57 ± 11 GBq/μmol. In vivo biodistribution analysis showed fast clearance via the kidneys and retention in MMR-expressing organs and tumor, with tumor-to-blood and tumor-to-muscle ratios of 6.80 ± 0.62 and 5.47 ± 1.82, respectively. The calculated effective dose was 0.027 mSv/MBq and 0.034 mSv/MBq for male and female, respectively, which means that a proposed dose of 185 MBq in humans would yield a radiation dose of 5.0 and 6.3 mSv to male and female patients, respectively. In the toxicity study, no adverse effects were observed. Preclinical validation of [68Ga]Ga-NOTA-anti-MMR-sdAb showed high specific uptake of this tracer in MMR-expressing TAM and organs, with no observed toxicity. [68Ga]Ga-NOTA-anti-MMR-sdAb is ready for a phase I clinical trial.


Can the MRI signal of aggressive fibromatosis be used to predict its behavior?
Aggressive fibromatosis is an invasive non-metastasizing soft-tissue tumor. Until recently, the standard treatment combined surgery and radiation therapy, but new studies reported that conservative strategies with or without medical treatment could be the best management. The aim of this study was to analyze and correlate the size and MR imaging signal features of aggressive fibromatosis with its behavior in order to choose the best treatment. Between March 1985 and December 2005, 27 patients with at least 2 consecutive MRI examinations and no surgery or radiation therapy in between were recorded. There were 9 men and 18 women, and median age was 31 years. They underwent 107 MRI examinations of 47 lesions, 29 of which were medically treated, while the remaining 18 did not receive any drug administration. The size and signal changes of each lesion were studied over time on T2- and/or T1-weighted sequences after injection of contrast medium. RECIST criteria were used for size: only a 30% decrease or a 20% increase in the size of the main dimension was considered significant. We classified the appearance of the signal into six categories in order of increasing intensity and then we established the related variations over time. The size of 79% of the lesions in the treated group and 82% in the untreated group remained stable. The initial signal of stable lesions or those exhibiting an increase in size was most frequently high. There was a high rate of signal stability over time, whatever the initial signal and size changes. Changes in size were not correlated with the initial MR signal. A decrease in size associated with a decreased signal was observed in three cases exclusively in the treated group. Fibromatoses are a group of soft-tissue tumors with variable characteristics on MRI, but it is not possible to predict their behavior based on the MRI signal.


Searching for new strategies against polymicrobial biofilm infections: guanylated polymethacrylates kill mixed fungal/bacterial biofilms.
Biofilm-related human infections have high mortality rates due to drug resistance. Cohabitation of diverse microbes in polymicrobial biofilms is common and these infections present additional challenges for treatment compared with monomicrobial biofilms. Here, we address this therapeutic gap by assessing the potential of a new class of antimicrobial agents, guanylated polymethacrylates, in the treatment of polymicrobial biofilms built by two prominent human pathogens, the fungus Candida albicans and the bacterium Staphylococcus aureus. We used imaging and quantitative methods to test the antibiofilm efficacy of guanylated polymethacrylates, a new class of drugs that structurally mimic antimicrobial peptides. We further compared guanylated polymethacrylates with first-line antistaphylococcal and anti-Candida agents used as combinatorial therapy against polymicrobial biofilms. Guanylated polymethacrylates were highly effective as a sole agent, killing both C. albicans and S. aureus when applied to established polymicrobial biofilms. Furthermore, they outperformed multiple combinations of current antimicrobial drugs, with one of the tested compounds killing 99.98% of S. aureus and 82.2% of C. albicans at a concentration of 128 mg/L. The extracellular biofilm matrix provided protection, increasing the MIC of the polymethacrylates by 2-4-fold when added to planktonic assays. Using the C. albicans bgl2ΔΔ mutant, we implicate matrix polysaccharide β-1,3 glucan in the mechanism of protection. Data for two structurally distinct polymers suggest that this mechanism could be minimized through chemical optimization of the polymer structure. Finally, we demonstrate that a potential application for these polymers is in antimicrobial lock therapy. Guanylated polymethacrylates are a promising lead for the development of an effective monotherapy against C. albicans/S. aureus polymicrobial biofilms.


Engineering of lactic acid bacteria for delivery of therapeutic proteins and peptides.
Lactic acid bacteria (LAB) have a long-term history of use in food industry and are becoming attractive for use in therapy on account of their safety, intrinsic beneficial health effects, and considerable biotechnological potential. The established systems for engineering are combined with novel approaches, such as CRISPR-Cas, to enable the use of LAB as vectors for delivery of various therapeutic molecules. The latter are either secreted or surface displayed and can be used for the treatment or prevention of numerous conditions: inflammatory bowel diseases, infections, autoimmune diseases, and even cancer. This review presents some recent data on engineering of LAB, with the emphasis on the most commonly used genera Lactococcus and Lactobacillus. Their use for the delivery of therapeutic proteins is discussed, while a special focus is given to the delivery of therapeutic peptides. Therapeutically relevant improvements of engineered LAB, such as containment systems, ability to visualize bacteria, or target specific host cells are also addressed. Future engineering of LAB for therapy will adopt the capabilities of synthetic biology, with first examples already emerging.


The performance of different classification criteria for systemic lupus erythematosus in a real-world rheumatology department.
New classification criteria have been proposed to improve classification of systemic lupus erythematosus (SLE). We aimed to evaluate their performance by determining their sensitivity, specificity and accuracy in a real-world rheumatology department. SLE patients who were enrolled in the Australian Lupus Registry and Biobank were included and compared with controls recruited from other rheumatology clinics. Clinical and immunological features were reviewed, according to ACR 1997, SLICC 2012, EULAR/ACR 2019, or Systemic Lupus Erythematosus Risk Probability Index (SLERPI). Performance of each set of criteria was evaluated for the overall cohort and in a subgroup of patients with early SLE. The study included 394 SLE and 123 control patients with other rheumatological conditions. Sensitivity was highest using SLICC 2012 or SLERPI 2020 criteria. Specificity was highest using ACR 1997 criteria. The SLICC 2012 criteria had the highest overall accuracy at 94.4% (95% CI: 91.7, 97.1%). In the subgroup analysis of SLE patients with early disease, SLICC 2012 performed similarly well. The sensitivity and specificity of each set of classification criteria vary slightly, with SLICC 2012 and SLERPI 2020 having the highest sensitivities and the ACR 1997 criteria having the highest specificity in our patient cohort. All classification criteria serve as good instructional aids for clinicians to understand SLE manifestations. For the Australian Lupus Registry and Biobank, we will continue to use the ACR 1997 and/or SLICC 2012 as entry to the observational cohort.


Combining explicitly correlated R12 and Gaussian geminal electronic structure theories.
Explicitly correlated R12 methods using a single short-range correlation factor (also known as F12 methods) have dramatically smaller basis set errors compared to the standard wave function counterparts, even when used with small basis sets. Correlations on several length scales, however, may not be described efficiently with one correlation factor. Here the authors explore a more general MP2-R12 method in which each electron pair uses a set of (contracted) Gaussian-type geminals (GTGs) with fixed exponents, whose coefficients are optimized linearly. The following features distinguish the current method from related explicitly correlated approaches published in the literature: (1) only two-electron integrals are needed, (2) the only approximations are the resolution of the identity and the generalized Brillouin condition, (3) only linear parameters are optimized, and (4) an arbitrary number of (non-)contracted GTGs can appear. The present method using only three GTGs and a double-zeta quality basis computed valence correlation energies for a set of 20 small molecules only 2.2% removed from the basis set limit. The average basis set error reduces to 1.2% using a near-complete set of seven GTGs with the double-zeta basis set. The conventional MP2 energies computed with much larger quadruple, quintuple, and sextuple basis sets all had larger average errors: 4.6%, 2.4%, and 1.5%, respectively. The new method compares well to the published MP2-R12 method using a single Slater-type geminal (STG) correlation factor. For example, the average basis set error in the absolute MP2-R12 energy obtained with the exp(-r12) correlation factor is 1.7%. Correlation contribution to atomization energies evaluated with the present method and with the STG-based method only required a double-zeta basis set to exceed the precision of the conventional sextuple-zeta result. The new method is shown to always be numerically stable if linear dependencies are removed from the two-particle basis and the zeroth-order Hamiltonian matrix is made positive definite.


Prion strain- and species-dependent effects of antiprion molecules in primary neuronal cultures.
Transmissible spongiform encephalopathies (TSE) arise as a consequence of infection of the central nervous system by prions and are incurable. To date, most antiprion compounds identified by in vitro screening failed to exhibit therapeutic activity in animals, thus calling for new assays that could more accurately predict their in vivo potency. Primary nerve cell cultures are routinely used to assess neurotoxicity of chemical compounds. Here, we report that prion strains from different species can propagate in primary neuronal cultures derived from transgenic mouse lines overexpressing ovine, murine, hamster, or human prion protein. Using this newly developed cell system, the activity of three generic compounds known to cure prion-infected cell lines was evaluated. We show that the antiprion activity observed in neuronal cultures is species or strain dependent and recapitulates to some extent the activity reported in vivo in rodent models. Therefore, infected primary neuronal cultures may be a relevant system in which to investigate the efficacy and mode of action of antiprion drugs, including toward human transmissible spongiform encephalopathy agents.


Accuracy of a pregnancy-associated glycoprotein ELISA to determine pregnancy status of lactating dairy cows twenty-seven days after timed artificial insemination.
To determine the accuracy of a pregnancy-associated glycoprotein (PAG) ELISA in identifying pregnancy status 27 d after timed artificial insemination (TAI), blood samples were collected from lactating Holstein cows (n = 1,079) 27 d after their first, second, and third postpartum TAI services. Pregnancy diagnosis by transrectal ultrasonography (TU) was performed immediately after blood sample collection, and pregnancy outcomes by TU served as a standard to test the accuracy of the PAG ELISA. Pregnancy outcomes based on the PAG ELISA and TU that agreed were considered correct, whereas the pregnancy status of cows in which pregnancy outcomes between PAG and TU disagreed were reassessed by TU 5 d later. The accuracy of pregnancy diagnosis was less than expected when using TU 27 d after TAI (93.7 to 97.8%), especially when pregnancy outcomes were based on visualization of chorioallantoic fluid and a corpus luteum but when an embryo was not visualized. The accuracy of PAG ELISA outcomes 27 d after TAI was 93.7, 95.4, and 96.2% for first, second, and third postpartum TAI services, respectively. Statistical agreement (kappa) between TU and the PAG ELISA 27 d after TAI was 0.87 to 0.90. Pregnancy outcomes based on the PAG ELISA had a high negative predictive value, indicating that the probability of incorrectly administering PGF(2alpha) to pregnant cows would be low if this test were implemented on a commercial dairy.


Bottom-Up Synthesis of Helical Plasmonic Nanorods and Their Application in Generating Circularly Polarized Luminescence.
Chiral growth and chirality transfer associated with plasmonic nanostructures have rejuvenated the field of chirality. As the precise regioselective growth of inorganic crystals into chiral shapes at the nanoscale is extremely challenging, "bottom-up" synthesis of intrinsically chiral nanoparticles with structural stability is obviously attractive and important. With the thiolated bimolecular cosurfactants, we demonstrated a chemical strategy for the synthesis of intrinsically helical plasmonic nanorods (HPNRs) with strong and tailorable plasmonic circular dichroism (PCD) responses, deriving from the zwitterionic interactions between the -NH3+ and -COO- groups of the cysteine molecules (Cys). The influence of structural parameters of HPNRs on PCD responses was analyzed systematically by theoretical simulations. Among the different structural parameters, the pitch depth was found to have the greatest impact on the PCD signals, in agreement with the experimental results. Moreover, the obtained HPNRs with the strong, tunable, and stable chiroptical properties were found to be able to induce circularly polarized luminescence of achiral luminophores. Due to the generality of this effect, this chiral plasmonic nanostructure may have great potential for use in the fields of chiral sensors, chiral catalysis, and displays.


Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons.
Chronic olfactory inflammation (COI) in conditions such as chronic rhinosinusitis significantly impairs the functional and anatomical components of the olfactory system. COI induced by intranasal administration of lipopolysaccharide (LPS) results in atrophy, gliosis, and pro-inflammatory cytokine production in the olfactory bulb (OB). Although chronic rhinosinusitis patients have smaller OBs, the consequences of olfactory inflammation on OB neurons are largely unknown. In this study, we investigated the neurological consequences of COI on OB projection neurons, mitral cells (MCs) and tufted cells (TCs). To induce COI, we performed unilateral intranasal administration of LPS to mice for 4 and 10 weeks. Effects of COI on the OB were examined using RNA-sequencing approaches and immunohistochemical analyses. We found that repeated LPS administration upregulated immune-related biological pathways in the OB after 4 weeks. We also determined that the length of TC lateral dendrites in the OB significantly decreased after 10 weeks of COI. The axon initial segment of TCs decreased in number and in length after 10 weeks of COI. The lateral dendrites and axon initial segments of MCs, however, were largely unaffected. In addition, dendritic arborization and AIS reconstruction both took place following a 10-week recovery period. Our findings suggest that olfactory inflammation specifically affects TCs and their integrated circuitry, whereas MCs are potentially protected from this condition. This data demonstrates unique characteristics of the OBs ability to undergo neuroplastic changes in response to stress.


Esophageal cancer after distal gastrectomy.
The effect of gastrectomy on the subsequent development of esophageal cancer was investigated. Duodenogastroesophageal reflux is thought to be common in patients after distal gastrectomy, but whether this contributes to the development of esophageal cancer in such patients is controversial. We retrospectively evaluated 153 patients who underwent subtotal esophagectomy for thoracic esophageal cancer between January 2002 and July 2005. They were divided into two groups, according to whether or not they had previously undergone a gastrectomy: group 1, comprising 14 patients who had undergone gastrectomy and group 2, comprising 139 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer (10.5 +/- 4.2 years) than in those who had undergone gastrectomy for a peptic ulcer (28.9 +/- 3.0 years). The interval was also somehow shorter in the patients for whom anastomosis had been performed by Billroth I (21.3 +/- 5.6 years) compared with Billroth II (29.7 +/- 3.2 years), although the difference did not reach its statistical significance (P = 0.11). Moreover, the proportion of lower third tumors in patients after gastrectomy was significantly higher compared with that of the patients with intact stomach. These findings suggest that a history of gastrectomy is associated with more lower-third squamous cell esophageal carcinoma.


Use of cryopreserved cell aliquots in the high-throughput screening of small interfering RNA libraries.
Screening small interfering RNA (siRNA) libraries holds the potential to elucidate gene function as well as discover new targets for the therapeutic treatment of disease. Since the inception of siRNA as a discovery tool, there have been progressive improvements in siRNA design algorithms, the transfection reagents used to deliver them, and the assay formats used to monitor phenotypic changes. These changes have helped to improve the quality of the data emerging from siRNA screens. One variable that introduces inconsistency into high-throughput screening (HTS) of siRNA libraries is the state of the cells used in the assays. Multiple factors can contribute to differences in transfection efficiency as well as the basic cell biology, which can lead to differences in the genes identified in siRNA screens. The authors have developed a system using frozen cell aliquots to use in siRNA HTS, so that a major source of variability introduced into cell-based screens can be standardized. In addition, by transiently transfecting plasmids into cell lines and then freezing these cells down to use in siRNA transfection experiments, they have used this same technology to create new cell lines. This process of using aliquots of frozen cells is logistically advantageous in an HTS setting, as it reduces the time spent maintaining cell lines, as well as reducing possible downtime in screening due to lack of cells or poor cell health.


Predictors of trust in low-income, minority neighborhoods in Texas.
Given the importance of trust to population health, it is also important to understand individual and neighborhood predictors of trust among residents of low-income and minority communities. In this paper, we investigate predictors of trust among residents of 98 low-income and minority neighborhoods in Texas. Census data and survey data on 1,966 residents provided information on individual and neighborhood characteristics. Predictors of trust were modeled using multi-level probit models. We found that linguistic heterogeneities, but not racial/ethnic diversity nor income inequality, were associated with general trust. More detailed analyses indicated that people tend to trust people in the neighborhood more than those who belong to the same racial/ethnic group. Interventions in diverse communities should focus on increasing social integration among residents in order to reach higher levels of trust, contributing to positive health outcomes.


Migratory dermal dendritic cells act as rapid sensors of protozoan parasites.
Dendritic cells (DC), including those of the skin, act as sentinels for intruding microorganisms. In the epidermis, DC (termed Langerhans cells, LC) are sessile and screen their microenvironment through occasional movements of their dendrites. The spatio-temporal orchestration of antigen encounter by dermal DC (DDC) is not known. Since these cells are thought to be instrumental in the initiation of immune responses during infection, we investigated their behavior directly within their natural microenvironment using intravital two-photon microscopy. Surprisingly, we found that, under homeostatic conditions, DDC were highly motile, continuously crawling through the interstitial space in a Galpha(i) protein-coupled receptor-dependent manner. However, within minutes after intradermal delivery of the protozoan parasite Leishmania major, DDC became immobile and incorporated multiple parasites into cytosolic vacuoles. Parasite uptake occurred through the extension of long, highly dynamic pseudopods capable of tracking and engulfing parasites. This was then followed by rapid dendrite retraction towards the cell body. DDC were proficient at discriminating between parasites and inert particles, and parasite uptake was independent of the presence of neutrophils. Together, our study has visualized the dynamics and microenvironmental context of parasite encounter by an innate immune cell subset during the initiation of the immune response. Our results uncover a unique migratory tissue surveillance program of DDC that ensures the rapid detection of pathogens.


Attachment of human endothelial cells to polyester vascular grafts: pre-coating with adhesive protein assemblies and resistance to short-term shear stress.
Cardiovascular prosthetic bypass grafts do not endothelialize spontaneously in humans, and so they pose a thrombotic risk. Seeding with cells improves their performance, particularly in small-caliber applications. Knitted tubular polyethylene-terephthalate (PET) vascular prostheses (6 mm) with commercial type I collagen (PET/Co) were modified in the lumen by the adsorption of laminin (LM), by coating with a fibrin network (Fb) or a combination of Fb and fibronectin (Fb/FN). Primary human saphenous vein endothelial cells were seeded (1.50 × 10(5)/cm2), cultured for 72 h and exposed to laminar shear stress 15 dyn/cm(2) for 40 and 120 min. The control static grafts were excluded from shearing. The cell adherence after 4 h on PET/Co, PET/Co +LM, PET/Co +Fb and PET/Co +Fb/FN was 22%, 30%, 19% and 27% of seeding, respectively. Compared to the static grafts, the cell density on PET/Co and PET/Co +LM dropped to 61% and 50%, respectively, after 120 min of flow. The cells on PET/Co +Fb and PET/Co +Fb/FN did not show any detachment during 2 h of shear stress. Pre-coating the clinically-used PET/Co vascular prosthesis with LM or Fb/FN adhesive protein assemblies promotes the adherence of endothelium. Cell retention under flow is improved particularly on fibrin-containing (Fb and Fb/FN) surfaces.


Effect of dietary carbohydrates on glucagon and insulin receptors in genetically obese female Zucker rats.
Obese Zucker rats are hyperlipemic and mildly hyperglycemic. Because insulin and glucagon are involved in lipid and carbohydrate metabolism and they act via their receptors, we investigated the role of insulin and glucagon receptors in obese and lean female Zucker rats. Because dietary sucrose is more lipogenic than starch, we also studied the effect of dietary carbohydrates on the receptors. Significant phenotypic effect (obese greater than lean) was observed on plasma levels of glucose, triglyceride and insulin. Binding of insulin and glucagon to liver plasma membranes was significantly lower in obese rats than in lean rats. Lower insulin binding was due to a lower number of receptors as well as a lower affinity, whereas the lower glucagon binding was due only to a lower receptor number. Insulin binding in lean rats but not in obese rats was lower in sucrose-fed than in starch-fed rats. Diet had no effect on glucagon binding. We propose that in obese Zucker rats, in addition to hyperinsulinemia, impaired glucagon activity as manifested by decreased glucagon binding to target tissues may be an important contributor to the hyperlipemia and obesity.


[Koro syndrome--clinical and cultural aspects].
Koro syndrome is a triad which includes a deep-seated fear that the penis will shrink, disappear into the abdomen, and that death will follow. The patient experiences profound anxiety and performs preventive manoeuvres, such as pulling his penis outward. The disorder is considered culture-related, and is endemic in South-East Asia and China, where it occurs in epidemic and sporadic forms. Sporadic cases appear in the western hemisphere, often in association with an underlying psychiatric or organic disorder, usually of the central nervous system. 6 cases of koro have been published from Israel.


A highly pathogenic porcine reproductive and respiratory syndrome virus candidate vaccine based on Japanese encephalitis virus replicon system.
In the swine industry, porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease which causes heavy economic losses worldwide. Effective prevention and disease control is an important issue. In this study, we described the construction of a Japanese encephalitis virus (JEV) DNA-based replicon with a cytomegalovirus (CMV) promoter based on the genome of Japanese encephalitis live vaccine virus SA14-14-2, which is capable of offering a potentially novel way to develop and produce vaccines against a major pathogen of global health. This JEV DNA-based replicon contains a large deletion in the structural genes (C-prM-E). A PRRSV GP5/M was inserted into the deletion position of JEV DNA-based replicons to develop a chimeric replicon vaccine candidate for PRRSV. The results showed that BALB/c mice models with the replicon vaccines pJEV-REP-G-2A-M-IRES and pJEV-REP-G-2A-M stimulated antibody responses and induced a cellular immune response. Analysis of ELSA data showed that vaccination with the replicon vaccine expressing GP5/M induced a better antibodies response than traditional DNA vaccines. Therefore, the results suggested that this ectopic expression system based on JEV DNA-based replicons may represent a useful molecular platform for various biological applications, and the JEV DNA-based replicons expressing GP5/M can be further developed into a novel, safe vaccine candidate for PRRS.


DNA-dependent RNA polymerase subunits encoded within the vaccinia virus genome.
Antiserum to a multisubunit DNA-dependent RNA polymerase from vaccinia virions was prepared to carry out genetic studies. This antiserum selectively inhibited the activity of the viral polymerase but had no effect on calf thymus RNA polymerase II. The specificity of the antiserum was further demonstrated by immunoprecipitation of RNA polymerase subunits from dissociated virus particles. The presence in vaccinia virus-infected cells of mRNA that encodes the polymerase subunits was determined by in vitro translation. Immunoprecipitable polypeptides with Mrs of about 135,000, 128,000, 36,000, 34,000, 31,000, 23,000, 21,000, 20,000, and 17,000 were made when early mRNA was added to reticulocyte extracts. The subunits were encoded within the vaccinia virus genome, as demonstrated by translation of early mRNA that hybridized to vaccinia virus DNA. The locations of the subunit genes were determined initially by hybridization of RNA to a series of overlapping 40-kilobase-pair DNA fragments that were cloned in a cosmid vector. Further mapping was achieved with cloned HindIII restriction fragments. Results of these studies indicated that RNA polymerase subunit genes are transcribed early in infection and are distributed within the highly conserved central portion of the poxvirus genome in HindIII fragments E, J, H, D, and A.