Multimodality imaging of small bowel neoplasms.
Although the small intestine accounts for over 90% of the surface area of the alimentary tract, tumors of the small intestine represent less than 5% of all gastrointestinal tract neoplasms. Common small bowel tumors typically are well evaluated with cross-sectional imaging modalities such as CT and MR, but accurate identification and differentiation can be challenging. Differentiating normal bowel from abnormal tumor depends on imaging modality and the particular technique. While endoscopic evaluation is typically more sensitive for the detection of intraluminal tumors that can be reached, CT and MR, as well as select nuclear medicine studies, remain superior for evaluating extraluminal neoplasms. Understanding the imaging characteristics of typical benign and malignant small bowel tumors is critical, because of overlapping features and associated secondary complications.


Assessing the effects of agricultural intensification on natural habitats and biodiversity in Southern Amazonia.
The ongoing trend toward agricultural intensification in Southern Amazonia makes it essential to explore the future impacts of this development on the extent of natural habitats and biodiversity. This type of analysis requires information on future pathways of land-use and land-cover change (LULCC) under different socio-economic conditions and policy settings. For this purpose, the spatially explicit land-use change model LandSHIFT was applied to calculate a set of high-resolution land-use change scenarios for the Brazilian states Para and Mato Grosso. The period of the analysis were the years 2010-2030. The resulting land-use maps were combined with maps depicting vertebrate species diversity in order to examine the impact of natural habitat loss on species ranges as well as the overall LULCC-induced effect on vertebrate diversity as expressed by the Biodiversity Intactness Index (BII). The results of this study indicate a general decrease in biodiversity intactness in all investigated scenarios. However, agricultural intensification combined with diversified environmental protection policies show least impact of LULCC on vertebrate species richness and conservation of natural habitats compared to scenarios with low agricultural intensification or scenarios with less effective conservation policies.


Changes in human amniotic fluid lecithin/sphingomyelin ratio and dipalmitoyl lecithin associated with maternal betamethasone therapy.
In an effort to understand the biochemical changes responsible for the decreased incidence of neonatal RDS observed in premature infants delivered after maternal glucocorticoid therapy we have compared quantitative changes in L/S ratio and qualitative changes in dipalmitoyl lecithin in serial amniotic fluid samples from 20 pregnant women treated with betamethasone and 11 patients who had repeated amniocentesis at similar gestational age but did not receive glucocorticoids. Initial L/S ratio values were not significantly different between treated (1.24 +/- 0.24 [S.D.]) and control (1.09 +/- 0.29 [S.D.]) groups but the values obtained within 1 week after therapy (1.49 +/- 0.21 [S.D.]) were significantly higher (t=3.8; p less than 0.01) than those obtained after a similar period in the untreated group (1.24+/- 0.29 [S.D.]). However, only one of the treated patients reached a mature L/S ratio (2.0 or more). Simultaneously, 10 of 17 treated patients exhibited increases in the amount of dipalmitoyl lecithin within the first week after treatment, wheras no change was detected in serial samples from six control patients (p = 0.016). These results indicate that qualitative changes in amniotic fluid lecithin composition are a part of the fetal response to glucocorticoids which may be responsible for the decreased incidence of RDS observed after treatment.


[Assessment of run-off in pollution of bodies of water with diphyllobothriiidae eggs by hydrometeorologic indicators].
Use of some hydrometheorological characteristics for assessing quantitative parameters of surface run-off in water reservoirs' areas is suggested. Conclusions concerning the potential threat of anthropogenic water pollution are drawn on the basis of above-mentioned indicators.


A comparison of two invasive strategies in patients with non-ST elevation acute coronary syndromes: results of the Early or Late Intervention in unStable Angina (ELISA) pilot study. 2b/3a upstream therapy and acute coronary syndromes.
Only few studies specifically addressed the effect of timing of angiography and/or pre-treatment with a glycoprotein 2b/3a receptor blocker in patients with non-ST elevation acute coronary syndromes (ACS) who undergo invasive treatment. In a 2-year period, 220 patients with non-ST elevation ACS, were randomized to early angiography without tirofiban pre-treatment (Early strategy) or to delayed angiography after 24-48h pre-treatment with tirofiban (Late strategy). The first 48h after admission, CKmb levels were measured and enzymatic infarct size (LDHQ(48)) was assessed by the area under the LDH release curve. When PCI was performed beyond 48h, CKmb was measured 6 and 12h afterwards. Median time to angiography was 6 (Early) and 50 (Late) hours. PCI was performed in 130 patients (59%). In these patients, a patent (TIMI 2 or 3 flow) culprit vessel was more often present in the Late group compared to the Early group (66% vs 82% p=0.05). In patients with an elevated CKmb (n=96, 44%), LDHQ(48)was significantly lower in patients who underwent angiography after pre-treatment with tirofiban (629+/-503U/L (Early) vs 432+/-441U/L (Late), p=0.02). No difference in clinical outcome between the groups was observed at 30 days follow-up. This pilot study showed that a strategy of delayed angiography with concomitant pre-treatment with tirofiban is associated with improved angiographic outcomes and less initial enzyme release, compared to a strategy of immediate angiography without 2b/3a inhibitor pre-treatment. The use of an end point parameter, which assess total enzyme release over a given period of time, might be of special value in patients with non-ST elevation ACS, who undergo very early invasive treatment.


[Occipital blindness in juvenile, spongiform glio-neuronal dystrophy (author's transl)].
A 17-year-old patient with spongiform glioneuronal dystrophy is described. Symptoms of a severe infection at the onset of this disease give an insight on the unknown etiology. Occipital visual disturbances were the main signs in this case. 5 years after the onset of the disease death occured. The pathological-anatomical findings were: necrosis of ganglion cells in the visual cortex, severe loss of Purkinje- and granular cells of the cerebellum with spongy changes and cavities in the occipital lobe. Slight loss of ganglion cells was to be seen in the striata area, thalamus, dentate nucleus, and in the inferior olive. In addition, there was a demyelinisation of the posterior funiculi.


Small-molecule inhibitors of ubiquitin-specific protease 7 enhance type-I interferon antiviral efficacy by destabilizing SOCS1.
Type-I interferons (IFN-I) are used as common antiviral drugs for a range of viral diseases in clinic. However, the antiviral efficacy of IFN-I is largely restricted by negative regulators of IFN-I signaling in cells. Therefore, identification of intracellular inhibitors of IFN-I signaling is important for developing novel targets to improve IFN-I antiviral therapy. In this study, we report that the deubiquitinase ubiquitin-specific protease 7 (USP7) negatively regulates IFN-I-mediated antiviral activity. USP7 physically interacts with suppressor of cytokine signaling 1 (SOCS1) and enhances SOCS1 protein stability by deubiquitination effects, which in turn restricts IFN-I-induced activation of Janus kinase-signal transducer and activator of transcription 1 signaling. Interestingly, viral infection up-regulates USP7 and therefore facilitates viral immune evasion. Importantly, the USP7 small-molecule inhibitors P5091 and P22077 inhibit SOCS1 expression and enhance IFN-I antiviral efficacy. Our findings identify a novel regulator of IFN-I antiviral activity and reveal that USP7 inhibitors could be potential enhancement agents for improving IFN-I antiviral therapy.


Characterization of human soft-tissue sarcoma xenografts for use in secondary drug screening.
We have established ten transplantable human soft-tissue sarcoma (STS) xenografts grown as subcutaneous tumours in the nude mouse. Nine xenografts originated from patients that needed chemotherapy in the course of their disease. The xenografts were tested for their sensitivity to maximum tolerated doses of five anti-cancer agents. Growth of treated tumours was expressed as a percentage of control tumour growth and a growth inhibition > 75% was measured for doxorubicin in 20% of the STS xenografts, for cyclophosphamide in 30%, for ifosfamide in 20%, for vincristine in 20%, whereas etoposide was not effective in the STS xenografts. In three out of ten STS xenografts MDR1 mRNA was detectable, but this was not related to the resistance against doxorubicin, vincristine or etoposide. Topoisomerase IIalpha mRNA expression levels did not reflect sensitivity to doxorubicin or etoposide. In all STS tissues, however, these levels were lower than topoisomerase IIalpha mRNA in a drug-sensitive human ovarian cancer xenograft. Glutathione concentrations and the activities of glutathione S-transferase, glutathione peroxidase and glutathione reductase were not related to resistance against the alkylating agents or doxorubicin. Of interest, in all STS tissues, glutathione S-transferase pi was the predominant isoenzyme present. In conclusion, chemosensitivity of the STS xenografts reflects clinical response rates in phase II trials on the same compounds in adult STS patients. Relatively low levels of topoisomerase IIalpha mRNA may partly account for intrinsic resistance against, for example, doxorubicin. Additional factors must contribute to moderate responsiveness to alkylating agents.


Effects of zinc supplementation in the prevention of respiratory tract infections and diarrheal disease in Colombian children: A 12-month randomised controlled trial.
Among the preventive strategies for lowering the incidence of upper respiratory tract infections (URTI) and acute diarrhoea episodes, two of the most common diseases in children, zinc supplementation has received special interest. However, there is a need for additional studies that determine the preventive effects of different doses of zinc on URTI and diarrhoeal disease episodes in children. In a randomised, triple-blind clinical trial, we evaluated the efficacy of 12 months of daily zinc supplementation in the incidence of URTI and acute diarrhoea in a population of healthy children aged between 6 and 12 months living in Bogota, Colombia. The outcomes analysed were incidence of URTI, acute diarrhoeal disease episodes, and side effects of the interventions. Between 2010 and 2013, a total of 355 children underwent randomisation, with 174 assigned to the zinc supplementation group and 181 to the control group. In the multivariate analyses, having been randomised to the non-supplemented control group (IRR 1.73, 95% CI 1.52-1.97, p<0.001), and nursery attendance (IRR 1.41, 95% CI 1.07-1.87, p=0.016) were independently linked to the number of URTI. Likewise, having been randomised to the non-supplemented group (IRR 1.43, 95% CI 1.20-1.71, p<0.001), and lower socioeconomic status (IRR 1.86, 95% CI 1.11-3.13, p=0.018) were independently associated to the number of diarrhoeal disease episodes. Daily supplementation of 5mg of zinc during 12 months significantly decreased the incidence of URTI and diarrhoeal disease episodes in a healthy population of children aged between 6 and 12 months.


Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development.
Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research.


Gambogic acid suppresses nasopharyngeal carcinoma via rewiring molecular network of cancer malignancy and immunosurveillance.
Nasopharyngeal carcinoma (NPC) is a malignant tumor highly prevalent in Southeast Asia. The distant metastasis and disease recurrence are still unsolved clinical problems. In recent years, traditional Chinese medicine (TCM) monomers have become significantly attractive due to their advantages. Using high throughput drug sensitivity screening, we identified gambogic acid (GA) as a common TCM monomer displaying multiple anti-NPC effects. GA could effectively inhibit the proliferation of low differentiated cells and highly metastatic cells in NPC via inducing apoptosis and G2/M cell cycle arrest. In addition, GA obviously repressed the abilities of cell clone, migration, invasion, angiogenesis and represented satisfied synergistic effects combined with chemotherapy. Importantly, we found the elevated immune checkpoint CD47 stimulated after chemotherapy was dramatically impaired by GA treatment. Mechanically, the network pharmacology analyses unraveled that the oncogenic signaling pathways including STATs were rewired by GA treatment. Taken together, our study reveals a molecular basis and provides a rationale for GA application as the treatment regime in NPC therapy in future.


Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases.
Synovial sarcomas are rare tumours occasionally arising in the pleural cavity, a site where their histological characteristics may be mistaken for those of malignant mesothelioma. We examined three cases of primary pleural synovial sarcoma in order to look for clinicopathological features that may help in distinguishing them from both mesotheliomas and other sarcomas that may arise in the pleura. All three patients were male, aged 42, 28 and 42, respectively, and had no known exposure to asbestos. One biphasic tumour contained neutral mucin in focal epithelial elements that also stained positively for BerEP4 and AUA1. All three tumours showed focal positivity for either keratin or EMA in the sarcomatous elements, and they also stained positively for bcl-2 protein and MIC2 gene product (CD99). Our results emphasize the importance of being aware of synovial sarcoma as a possible primary pleural malignancy, especially in a young patient with a localized mass. In addition, the presence of bcl-2 protein perhaps represents a useful marker in distinguishing synovial sarcoma, especially monophasic variants, from mesothelioma within a panel of antibodies.


A Retrospective Review of 193 Cases of Severe Eosinophilia in the Northeast United States.
This retrospective review evaluated the causes of severe eosinophilia (≥5000 eosinophils/L). Higher eosinophilia levels are more likely to cause tissue damage and may reflect disease severity. We reviewed 193 cases of patients seen at Beth Israel Deaconess Medical Center in Boston, Massachusetts, and at the University of Vermont Medical Center in Burlington, Vermont, between January 2015 to May 2020 who had a peak absolute eosinophil count of at least 5000/μL. Thirty-nine percent of cases were attributable to a hematologic or oncologic cause. These cases had the highest mean peak absolute eosinophil count at 11,698/μL. Twenty percent of cases were secondary to drug reactions, of which 90% took place in an inpatient setting. Three percent of cases were from helminthic infection, the majority of which were in returning travelers. In our region of study, hematologic and oncologic cases are important causes of severe eosinophilia, drug reactions are a common etiology in the inpatient setting, and infections are a rare cause.


Directed attention after unilateral frontal excisions in humans.
We investigated the ability of patients with frontal-lobe lesions to benefit from advance information in a simple reaction-time task. The task involved pressing a button in response to the appearance of a peripheral target (visual angle of 11.5 degrees). A cue, presented in the centre of the screen, preceded the target onset by either a short (average 500 ms) or a long (average 3000 ms) interval. In half of the trials, the cue was an arrow indicating the location, in the left or right hemifield, of the upcoming target; in the other half, the cue was an uninformative plus sign. In addition to patients with unilateral excisions of frontal cortex, we tested patients with anterior temporal-lobe excisions and normal controls. The frontal-lobe group was mildly impaired with respect to the temporal-lobe group in using advance spatial cues to speed response to the visual target. While the size of the cueing effect changed across the range of cue-target intervals tested, there was no variation across intervals in the size of the impairment exhibited by the frontal-lobe group. The site and the volume of the lesions were determined on the basis of magnetic resonance image (MRI) scans in 10 of the 17 patients in the frontal group. There was no correlation between lesion volume and benefit score in these patients.


Role of core needle biopsy and ultrasonographic finding in management of indeterminate thyroid nodules.
Thyroid fine-needle aspiration (FNA) is used as a screening test of choice for evaluation of thyroid nodules. However, approximately 15% to 25% of the cases are classified as indeterminate, posing dilemmas in decision-making. This study was designed to compare the diagnostic performances of second FNA and core needle biopsy of indeterminate nodules by initial FNA. From February 2005 through June 2009, 258 patients who completed scheduled follow-ups were enrolled and the follow-up results were analyzed. Nondiagnostic results were obtained in 41.8% of the second FNA group and in 1.7% of the core needle biopsy group (p < .001; chi-square). The nodules that show borderline features in preoperative ultrasonography had a malignancy rate of 18.3% and could be identified successfully with core needle biopsy. Core needle biopsy is a better method for evaluating indeterminate nodules by initial FNA than second FNA, especially in patients with ultrasonographic findings of a borderline nodule.


Relaxation of Mytilus catch muscle by 8-bromo-cyclic GMP and related compounds.
Relaxation of catch tension by 8-bromo-cyclic GMP in the ABRM of Mytilus was blocked in the presence of mersalyl and was markedly reduced after treatment of the muscle with alpha-methyldopa. In the muscle depolarized by 540 mM KCl + 5 mM EGTA solution, 8-bromo-cyclic GMP could not relax Ca-contracture. Hexylamine and phenylethylamine, which are assumed to relax the catch acting on relaxing nerve terminals, could not relax the contracture either. Serotonin and dopamine, which are known to relax the catch acting directly on the muscle fibre membrane, could relax it. In the muscle depolarized by 250 mM KCl + 5 mM EGTA solution, all of the cyclic nucleotides tested (cyclic AMP, cyclic GMP and their analogues), serotonin and dopamine relaxed Ca-contracture, but hexylamine and phenylethylamine did not relax the contracture. The possibilities of the involvement of cyclic GMP in the presynaptic and postsynaptic relaxing mechanisms in the ABRM are discussed.


Between challenges and support: Preceptors run clinical nursing training amidst unprecedented crisis.
This study aimed to address challenges facing nurse preceptors related to multifaceted educational roles, academic and institutional support during the COVID-19 pandemic in the Kingdom of Bahrain. Clinical nurse preceptors have faced great challenges since the influx of the COVID-19 pandemic. At this unprecedented time, they are overwhelmed with additional responsibilities to follow the COVID-19 precautionary measures alongside their usual educational role. So, they require careful preparation and massive institutional support. A descriptive study was conducted in different clinical settings in the Kingdom of Bahrain. A sample of 125 clinical nurse preceptors who participated in the students' training for at least one full clinical rotation during the COVID-19 pandemic responded to two questionnaires regarding the clinical nurse preceptor role, preparedness, and institutional support provided to them during the COVID-19 crisis. It is revealed that 40.8%, 51.0%, and 53.0% of the preceptors faced major challenges regarding the teacher, facilitator, and feedback provider/evaluator roles during the COVID-19 pandemic. Moreover, 71.2% of the preceptors were incredibly overwhelmed with additional instructions related to COVID-19 precautions alongside covering course learning objectives for the students. However, most of them did not perceive challenges concerning both academic and institutional support. The clinical nurse preceptors declared they received adequate pedogeological preparation, academic and institutional support throughout the COVID-19 pandemic. They also encountered moderate and minor challenges while mentoring nursing students during such a critical era.


Antibiotic-loaded acrylic bone cements: an in vitro study on the release mechanism and its efficacy.
An in vitro study was carried out in order to investigate the antibiotic release mechanism and the antibacterial properties of commercially (Palacos® R+G and Palacos® LV+G) and manually (Palacos® R+GM and Palacos® LV+GM) blended gentamicin-loaded bone cements. Samples were characterized by means of scanning electron microscopy (SEM) and compression strength was evaluated. The antibiotic release was investigated by dipping sample in simulated body fluid (SBF) and periodically analyzing the solution by means of high pressure liquid chromatography (HPLC). Different antibacterial tests were performed to investigate the possible influence of blending technique on antibacterial properties. Only some differences were observed between gentamicin manually added and commercial ones, in the release curves, while the antibacterial effect and the mechanical properties seem to not feel the blending technique.


Properties of cells projecting rostrally from the superficial layers of the cats superior colliculus.
Cells projecting rostrally from the cat's superior colliculus were identified by antidromic activation from the posterior thalamus. These cells occurred principally in the stratum griseum superficiale and stratum opticum, although some were also encountered in deeper laminae. The rostrally projecting neurons of the superficial laminae formed a heterogeneous group with respect to axonal conduction velocity, receptive field dimensions and special response properties, such as directional and velocity sensitivity. No correlation was detected between receptive field size and estimated axonal conduction velocity in these units. Cells with the smallest receptive fields, were rarely excited antidromically from the thalamus.


Medical Marijuana for Minors May Be Considered Child Abuse.
The Food and Drug Administration categorizes marijuana (cannabis) as a Schedule I drug, meaning that it has no currently accepted medical use, a high potential for abuse, and no good data on safety. Other Schedule I drugs are heroin, lysergic acid diethylamide, peyote, methaqualone, and 3,4-methylenedioxymethamphetamine ("ecstasy"). The authors of some studies have shown that marijuana can reduce nausea and vomiting from chemotherapy, can improve food intake in patients with HIV, can reduce neuropathic pain, and may slow the growth of cancer cells. In many states, marijuana use is illegal. No state has approved its use for children. What, then, should doctors do if they become aware that parents are using marijuana to treat medical conditions in their children? What if the children have adverse reactions to the marijuana? In this Ethics Rounds, we present such a case and ask experts in child protection and child abuse to discuss the appropriate response.


Overexpression of BHLHE41, correlated with DNA hypomethylation in 3'UTR region, promotes the growth of human clear cell renal cell carcinoma.
Basic helix‑loop‑helix family member e41 (BHLHE41) serves an important role in regulating cell differentiation, circadian rhythms and the response to hypoxia. However, the roles of BHLHE41 in clear cell renal cell carcinoma (ccRCC) remain unclear. The aim of the present study was to analyze the expression of BHLHE41 in ccRCC and investigate the effect of downregulated BHLHE41 on the growth and migration of ccRCC cells. The expression of BHLHE41 in ccRCC was demonstrated to be significantly increased in gene expression microarray datasets and RNA sequencing data. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis demonstrated that BHLHE41 expression in fresh ccRCC tissues was increased, compared with than their adjacent non‑tumorous controls. BHLHE41 knockdown significantly reduced cell proliferation and migration of A498 and CAKI‑1 cells. For the investigation of the molecules mediated by BHLHE41, immunoblotting analyses revealed that phosphorylation of p70S6K and protein levels of E‑cadherin were reduced. Additionally, a lower frequency methylation was determined in the BHLHE41 3'‑untranslated region through The Cancer Genome Atlas dataset analysis for the first time. These observations demonstrated that BHLHE41 could be a biomarker and an oncogene for ccRCC.


Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice.
Several lines of evidence suggest that the convulsant actions of caffeine are mediated through benzodiazepine receptors. A pharmacogenetic approach has been used to further explore the relationship of these receptors to caffeine-induced seizures. The susceptibility of two inbred strains of mice (CBA and SWR) to the convulsant actions of picrotoxinin, strychnine, Ro 5-4864 and DMCM was examined. Previous studies have demonstrated these two strains differ in their susceptibilities to the convulsant action of caffeine. While no differences were observed between these two strains in susceptibility to tonic seizures induced by picrotoxinin, RO 5-4864 or strychnine, SWR mice were significantly less sensitive to tonic seizures induced by DMCM compared to CBA mice (CD50 values in CBA and SWR mice were 6 and 12 mg/kg IP). Both clonazepam and the benzodiazepine receptor antagonist, Ro 15-1788, significantly blocked caffeine-induced seizures. Further, when subconvulsant doses of caffeine and DMCM were combined, a synergistic action was observed. Taken together, these findings support the hypothesis that the convulsant actions of caffeine result from an action at benzodiazepine receptors, and that the hyporesponsiveness of the SWR strain to both caffeine- and DMCM-induced seizures could result from an inherited abnormality in these sites.


Permanent planar iodine-125 implants: the dosimetric effect of geometric parameters for idealized source configurations.
To provide dosimetric information about permanent planar (125)I implants in a manner that is useful to the brachytherapist in the operative setting. Reference planar permanent implants were simulated for a variety of areas with sources placed uniformly on a 1-cm grid. Implants having variable source spacing and curvature were simulated and compared with the reference implants. Dosimetric measures were calculated at 0.5 and 1.0 cm from the implant plane. A method for calculating dosimetric statistics for permanent implants ranging from 5 x 5 cm to 13 x 13 cm is presented. A formula to predict the reference source strength needed to achieve a desired dosimetric quantity is also presented. The effect of adjusting strand spacing to compensate for source activity is presented and is shown to be an effective means to adjust implants to use source strengths other than the reference strength. The effect of implant curvature compared with flat implants on dosimetric statistics is presented as a function of radius of curvature. The results presented in this work may be used to provide information about dose delivered from planar permanent implants.


Factors associated with breath test refusals in drunken driving arrests.
Jurisdictions with per se breath alcohol legislation rely heavily on breath test evidence in prosecuting drunk driving cases. Depending on other legal considerations, where subjects refuse the breath test, prosecution may be more difficult. The objective was to identify factors significantly associated with the risk of test refusal. This knowledge would be relevant for improving the compliance rate. A retrospective observational study evaluated drunken driving arrest records (n = 38,687) within Washington State during 2003 where breath tests were requested under implied consent legislation. The association was determined between the risk of test refusal and several categorical variables including: arresting agency, gender, race, age, accident involvement, repeat offense, pre-arrest breath test, driver's license and all possible two-way interactions. The association was quantified by odds ratios (OR) and 95% confidence intervals (CI) using a logistic regression model. The overall refusal rate was 19.7%. The single main effect variable associated with the greatest reduction in risk of refusal was the performance of a pre-arrest breath test (OR = 0.31, 95% CI 0.30-0.33). No single main effect variables showed significant association with an increased risk of refusal. Several two-way interactions, however, were significant. Other possible predictor variables, not included in the analysis, are also discussed. An arrested subject's decision to refuse the breath test is clearly a multivariate issue. Knowledge of these results should help in developing a jurisdictionally specific breath test compliance model by identifying the legal, demographic and procedural factors contributing most significantly to breath test refusal rates.


Biomarkers for clinical and incipient tuberculosis: performance in a TB-endemic country.
Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB. Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects. These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB.


Same-day booking: success in a Canadian family practice.
Patients in a family practice had to wait 6 weeks for an appointment. To improve patient care by facilitating access to timely appointments. An FP from Halifax, NS, implemented advanced access in her practice. Advanced access is a same-day booking system, which has been shown to reduce or eliminate patient backlogs without the addition of resources. Theoretically, it can be put into effect in any practice with a stable backlog (which indicates that supply and demand are well matched). The first step to implement the advanced access system was to clear the existing appointment backlog. During a 6-week "boot camp" period, all prebooked patients and patients who called requesting same-day appointments were seen (between 50 and 60 patients per day). Same-day appointment rules apply to almost all patients. Staff begin accepting calls at 8:00 AM, and patients request the most convenient time available. Baseline and postimplementation data are not available, as this was not a formal research study. Nevertheless, this FP from Halifax who implemented advanced access experienced the following in her practice: elimination of patient backlog, fewer no-shows, patients' happiness with the system, increase in physician and staff morale, and stability in physician income. Formal feasibility studies and research evaluating patient outcomes, cost effectiveness, and physician and patient satisfaction in a variety of practice settings would help Canadian FPs decide if same-day booking could be successfully implemented in their practices.


Effects of time-compression on feature and frequency discrimination in aged listeners.
This study measured the ability of 16 aged listeners, normal for their age (age range, 63 to 84 yr.) to discriminate phonemic contrasts in sentential stimuli (Subtest 13 of the Carrow-Auditory Visual Abilities Test) presented at 50% time-compression rate. A series of linear regression analyses were performed in which each independent variable was regressed against the continuous variable of age. Over-all performance on the time-compressed task significantly decreased as a function of age. Also discrimination of place of articulation and mid- to high-frequency contrasts was significantly and negatively related to age. In general, such findings suggest that the course of aging continuously imposes degrading effects on speech-processing that are related to discrimination of place feature contrasts.


Memory of Chirality in Flow Electrochemistry: Fast Optimisation with DoE and Online 2D-HPLC.
Amino acid derivatives undergo non-Kolbe electrolysis to afford enantiomerically enriched α-alkoxyamino derivatives through intermediate chiral carbenium ions. The products contain N,O-acetals which are important structural motifs found in bioactive natural products. The reaction is performed in a continuous flow electrochemical reactor coupled to a 2D-HPLC for immediate online analysis. This allowed a fast screening of temperature, electrode material, current, flow-rate and concentration in a DoE approach. The combination with online HPLC demonstrates that also stereoselective reactions can benefit from a hugely accelerated optimisation by combining flow electrochemistry with multidimensional analysis.


Neoadjuvant Chemotherapy Creates Surgery Opportunities For Inoperable Locally Advanced Breast Cancer.
Neoadjuvant chemotherapy (NAC), the systematic chemotherapy given to patients with locally advanced and inoperable breast caner, has been proven to be of great clinical values. Many scientific reports confirmed NAC could effectively eliminate sub-clinical disseminated lesions of tumor, and improve long-term and disease-free survival rate of patients with locally advanced breast cancer (LABC); however, up to now, LABC is still a serious clinical issue given improved screening and early diagnosis. This study, with main focus on inoperable LABC, investigated the values of NAC in converting inoperable LABC into operable status and assessed the prognosis. Sixty-one patients with inoperable LABC were initially treated with neoadjuvant chemotherapy; their local conditions were improved to operable status. Radical surgery was exerted on 49 patients. Original chemotherapy was performed after surgery, followed by local radiotherapy. And endocrine therapy was optional according to the hormone receptor status. The quality of life for most patients with skin diabrosis was obviously improved because their local conditions were under control. For all recruited cases, the survival duration and life quality were significantly improved in patients who finished both NAC and surgery compared to those who did not. Further more, this study demonstrates improved prognostic consequences.


Sulfur transformations during two-stage anaerobic digestion and intermediate thermal hydrolysis.
The formation of hydrogen sulfide (H2S) during anaerobic digestion (AD) imposes constraints on the valorisation of biogas. So far, inorganic sulfur compounds -mainly sulfate - have been considered as the main contributors to H2S formation, while the contribution of organic sulfur compounds is mostly neglected. This study investigates the fate of organic and inorganic sulfur compounds during two-stage anaerobic digestion with intermediate thermal hydrolysis for treatment of primary and secondary sludge in a WWTP treating domestic wastewater. The results of a seven-week monitoring campaign showed an overall decrease of organic sulfur compounds in both stages of anaerobic digestion. Further fractionation of organic sulfur revealed a high conversion of the particulate organic fraction during the first digestion stage and of the soluble organic fraction during the second digestion stage. The decrease of soluble organic sulfur during the second digestion stage was attributed to the solubilisation and hydrolysis of sulfur-containing organic compounds during thermal hydrolysis. In both digestion stages, more organic sulfur was taken up than particulate inorganic sulfur (metal sulfide) was produced, indicating the formation of other reduced sulfur forms (e.g. H2S). Further batch experiments confirmed the role of organic sulfur uptake in the formation of H2S during anaerobic digestion as sulfate reduction only partly explained the total sulfide formed (H2S in biogas and precipitated FeS). Overall, the conversion of organic sulfur was demonstrated to play a major role in H2S formation (and thus the biogas quality), especially in case of thermal hydrolysis pretreatment.


Long-term mortality in very old patients with cancer admitted to intensive care unit: A retrospective cohort study.
Long-term outcomes of older patients referred to intensive care unit (ICU) are of paramount importance for care planning and counseling of patients and relatives. We performed a retrospective study with patients aged ≥80 years admitted to ICU from 2011 to 2017 in a cancer center. We performed two Cox proportional hazard regressions. In the first, we tested whether type of cancer (solid locoregional, solid metastatic or hematologic), Eastern Cooperative Oncology Group Performance Status (ECOG PS), and comorbidities [Charlson Comorbidity Index - CCI]) were associated with one-year mortality in all patients. In the second, we assessed whether delirium, use of vasopressors, mechanical ventilation, renal replacement therapy, and forgoing life-sustaining therapies were associated with one-year mortality in survivors to hospital discharge. Of 763 patients included, 482 (62.3%) patients died at one year. Metastatic cancer was significantly associated with one-year mortality (HR = 1.97; CI 95%, 1.16-3.36), but hematologic cancer, CCI and ECOG PS were not. Among patients who survived to hospital discharge, delirium, use of vasopressors, mechanical ventilation, renal replacement therapy and decisions to forgo life-sustaining therapies in ICU were not associated with one-year mortality. Metastatic disease at ICU admission was associated with one-year mortality in patients aged ≥80 years. Delirium, use of vasopressors, mechanical ventilation and renal replacement therapy and decisions to forgo life-sustaining therapies in ICU were not associated with one-year mortality among the patients discharged from hospital.


Influence of virtual height exposure on postural reactions to support surface translations.
As fear of falling is related to the increased likelihood of falls, it is important to understand the effects of threat-related factors (fear, anxiety and confidence) on dynamic postural reactions. Previous studies designed to examine threat effects on dynamic postural reactions have methodological limitations and lack a comprehensive analysis of simultaneous kinetic, kinematic and electromyographical recordings. The current study addressed these limitations by examining postural reactions of 26 healthy young adults to unpredictable anterior-posterior support-surface translations (acceleration=0.6m/s(2), constant velocity=0.25m/s, total displacement=0.75m) while standing on a narrow virtual surface at Low (0.4cm) and High (3.2m) virtual heights. Standing at virtual height increased fear and anxiety, and decreased confidence. Prior to perturbations, threat led to increased tonic muscle activity in tibialis anterior, resulting in a higher co-contraction index between lower leg muscles. For backward perturbations, muscle activity in the lower leg and arm, and center of pressure peak displacements, were earlier and larger when standing at virtual height. In addition, arm flexion significantly increased while leg, trunk and center of mass displacements remained unchanged across heights. When controlling for leaning, threat-related factors can influence the neuro-mechanical responses to an unpredictable perturbation, causing specific characteristics of postural reactions to be facilitated in young adults when their balance is threatened.


[Analysis of uric acid stone formation through the marking of layers].
Administration at predetermined intervals of a dye which becomes incorporated into uric acid calculi offers information concerning the formation and growth of the calculi, as well as about the effect or failure of the therapy applied.


Safety of an Enhanced Recovery Pathway for Patients Undergoing Open Hepatic Resection.
Enhanced recovery pathways (ERP) have not been widely implemented for hepatic surgery. The aim of this study was to evaluate the safety of an ERP for patients undergoing open hepatic resection. A single-surgeon, retrospective observational cohort study was performed comparing the clinical outcomes of patients undergoing open hepatic resection treated before and after implementation of an ERP. Morbidity, mortality, and length of hospital stay (LOS) were compared between pre-ERP and ERP groups. 126 patients (pre-ERP n = 73, ERP n = 53) were identified for the study. Patient characteristics and operative details were similar between groups. Overall complication rate was similar between pre-ERP and ERP groups (37% vs. 28%, p = 0.343). Before and after pathway implementation, the median LOS was similar, 5 (IQR 4-7) vs. 5 (IQR 4-6) days, p = 0.708. After adjusting for age, type of liver resection, and ASA, the ERP group had no increased risk of major complication (OR 0.38, 95% CI 0.14-1.02, p = 0.055) or LOS greater than 5 days (OR 1.21, 95% CI 0.56-2.62, p = 0.627). Routine use of a multimodal ERP is safe and is not associated with increased postoperative morbidity after open hepatic resection.


Preparation, characterization and functional properties of flax seed protein isolate.
Flaxseed protein isolate (FPI) was extracted from flaxseeds, and its amino acid composition and functional properties (solubility, thermal stability, emulsifying properties and electrostatic charge density, water holding and fat absorption capacities) were determined. The highest purity of FPI (90.6%) was achieved by extraction at 60°C. FPI had a low lysine to arginine ratio of 0.25, which is desired in heart-healthy foods and infant formulas. The denaturation temperature of FPI was 105°C. FPI had the highest emulsion activity index (375.51 m(2)/g), highest emulsion stability index (179.5 h) and zeta potential (-67.4 mV) when compared to those of other commonly used proteins, such as sodium caseinate (SC), whey protein isolate (WPI), gelatin (Gel) and soy protein isolate (SPI). The average emulsion droplet size of emulsions stabilized by these proteins was in the order SC<FPI<WPI<Gel<SPI. Water holding and fat absorption capacities of FPI were similar to those of the above mentioned proteins.


Small GTPases in mechanosensitive regulation of endothelial barrier.
Alterations in vascular permeability are defining feature of diverse processes including atherosclerosis, inflammation, ischemia/reperfusion injury, and ventilator-induced lung injury. Clinical observations and experimental studies support an essential role of mechanical forces in pathophysiologic regulation of lung barrier. Accumulating data demonstrate that decreased levels of blood flow and increased cyclic stretch of lung tissues associated with lung mechanical ventilation at high tidal volumes increase vascular permeability, activate inflammatory cytokine production, alveolar flooding, leukocyte infiltration, and hypoxemia, and increase morbidity and mortality. Potential synergism between pathologic mechanical stimulation and inflammatory molecules resulting in vascular leak and lung injury becomes increasingly recognized. This review will discuss a role of Rho family of small GTPases in the mechanochemical regulation of pulmonary endothelial permeability associated with ventilator induced lung injury.


Novel in vitro methods for simultaneous screening of two antagonistic bacteria against multiple fungal phytopathogens in a single agar plate.
Two novel and rapid in vitro agar plate methods for simultaneous screening of two bacterial isolates for antagonism against multiple fungal phytopathogens in a single agar plate are described. In the modified plus streak method (MPS), in a 10 cm diameter PDA agar plate, two different bacterial isolates were screened against four fungal pathogens. The second method used 20 cm diameter PDA agar plate surface and was termed as the parallel multiple streak (PMS) method. Here, two bacterial isolates were screened for antagonism against ten fungal phytopathogens on a single agar plate surface. Our new methods are rapid and more economical, and could reduce the number of agar plates and the medium required for in vitro screening by several fold, compared to that used in the conventional dual culture plate assay.


Comparison of the sex hormones' serum level in women with recurrent aphthous stomatitis and healthy population: a cross-sectional study.
In this study, we aimed to evaluate the sex hormonal serum level in patients with recurrent aphthous stomatitis and compare them with healthy participants. This cross-sectional study was done on patients with recurrent aphthous stomatitis who had referred to Shiraz Dental Faculty, Oral and Maxillofacial Medicine Department during 2018-2019. The non -menopause women with recurrence of at least 3 lesions per year were enrolled in this study. The mean serum level of FSH, LH, PRL (prolactin), testosterone, DHT (Dihydrotestosterone), DHEA-S (Dehydroepiandrosterone sulfate), estradiol and progesterone of 30 participants in each group of case and control were measured and compared. The data were analyzed by SPSS version 18 and independent T-test, Mann-Whitney U test, Spearman's correlation coefficient test, Chi-square test and Fisher's test. The mean serum level of DHEA-S in patients with recurrent aphthous stomatitis (RAS) was significantly lower than the control group (p value = 0.02). In addition to DHEA-S, the mean serum level of testosterone was lower in the evaluation group although this difference was not significant (p value = 0.057). Considering the effect of age on the mean serum level of sex hormones, our results revealed that only DHEA-S mean serum level was decreased by increasing the age of participants in patients with RAS (p value = 0.018). The number of participants with abnormal range of testosterone (p value < 0.0001) and progesterone (p value = 0.037) serum level was significantly more in patients with RAS. The frequency of RAS in a year did not show a significant relationship with the serum level of the evaluated hormones. The patients with RAS had a lower serum level of DHEA-S. The mean serum level of testosterone and progesterone was significantly abnormal in RAS patients.


Carbachol-induced EEG 'theta' activity in hippocampal brain slices.
Application of the cholinergic agonist carbachol (50 microM) produced theta-like rhythmical waveforms, recorded in the stratum moleculare of the dentate gyrus. Atropine sulfate (50 microM) antagonized the carbachol-induced theta-like activity, consistent with this action of atropine in vivo. These results provide the first direct evidence that hippocampal neurons are capable of producing synchronized slow-wave activity when isolated from pulsed rhythmic inputs of the medial septum and other brain regions.


MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors.
MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation.


Theoretical study of the hydration effects on alkylamine and alkanolamine clusters and the atmospheric implication.
Amines are important atmospheric nucleation precursors in polluted areas. However, specific roles of various amines in enhancing the stability of pre-nucleation clusters are poorly understood. Herein, different roles of trimethylamine (TMA) and monoethanolamine (MEA) in the formation of sulfuric acid (SA)-based pre-nucleation clusters were investigated. The hydration effects of up to four water (W) molecules on the interaction of the acid-base pairs of (TMA)(SA) and (MEA)(SA) were computationally investigated at the M06-2X/6-311++G (3df, 3pd) level of theory. Results show that the formation thermodynamics of key intermediate clusters are different with amines. Besides, MEA-enhanced formation of pre-nucleation clusters plays an important role in environments with high humidity while TMA may be the dominant nucleation precursors in dry conditions. The concentration of dominant MEA-containing pre-nucleation cluster is at least three orders of magnitude higher than that of TMA and dimethylamine near emission sources at conditions of T = 298.15 K and RH = 60%, indicating that alkanolamine may play an important role in atmospheric nucleation. Furthermore, the hydration of MEA is easier than that of alkylamines. Our results put forward the need to distinguish the performance of different types of amine under specific conditions to better model the new particle formation events in highly polluted areas. Besides, this study indicates that alkanolamines such as MEA are important participator in new particle formation.


Treatment patterns, risk for hospitalization and mortality in older patients with triple negative breast cancer.
To study the treatment patterns, potential risk factors for hospitalization within one year from diagnosis, and causes of death in older patients with triple negative breast cancer (TNBC). We performed a registry-based cohort study using the BCBaSe database which links cases of breast cancer from three Swedish healthcare regions with socioeconomic factors, hospitalizations and causes of death. Women ≥70 years old with non-metastatic TNBC, between 1/12007 and 31/122012 were included (n = 413). In total, 168 patients (40.7%) received chemotherapy after surgery and 123 patients (30.0%) in the whole cohort had at least one hospitalization within one year from diagnosis. The risk of hospitalization overall was increased in the group receiving chemotherapy (Odds Ratio 2.35, 95% Confidence Intervall: 1.30-4.26) mainly due to toxicities. Cumulative incidence of breast cancer mortality was comparable among different age groups (70-74 vs. 75-79 vs. ≥ 80 years old) whereas non-breast cancer mortality was higher in patients ≥80 years old. Stage at diagnosis and comorbidities were independently associated with both breast cancer-specific- and overall mortality whereas age was only associated with overall mortality. The use of chemotherapy in older patients with TNBC was associated with age, tumor stage, and comorbidities. Chemotherapy use was also associated with increased risk for hospitalization within one year from diagnosis. Although the impact of chemotherapy on mortality was analyzed in a multivariate manner showing neither increased or decreased mortality, no firm conclusion can be drawn due to unmeasured confounders.


Temperature dependent local atomic displacements in ammonia intercalated iron selenide superconductor.
Recently, ammonia-thermal reaction has been used for molecular intercalation in layered FeSe, resulting a new Lix(NH3)yFe2Se2 superconductor with Tc ~ 45 K. Here, we have used temperature dependent extended x-ray absorption fine structure (EXAFS) to investigate local atomic displacements in single crystals of this new superconductor. Using polarized EXAFS at Fe K-edge we have obtained direct information on the local Fe-Se and Fe-Fe bondlengths and corresponding mean square relative displacements (MSRD). We find that the Se-height in the intercalated system is lower than the one in the binary FeSe, suggesting compressed FeSe4 tetrahedron in the title system. Incidentally, there is hardly any effect of the intercalation on the bondlengths characteristics, revealed by the Einstein temperatures, that are similar to those found in the binary FeSe. Therefore, the molecular intercalation induces an effective compression and decouples the FeSe slabs. Furthermore, the results reveal an anomalous change in the atomic correlations across Tc, appearing as a clear decrease in the MSRD, indicating hardening of the local lattice mode. Similar response of the local lattice has been found in other families of superconductors, e.g., A15-type and cuprates superconductors. This observation suggests that local atomic correlations should have some direct correlation with the superconductivity.


Optimal conditions to induce rat adrenal medullary changes, such as pheochromocytoma, by nicotine.
Nicotine-induced adrenal medullary hypertrophy in rats has been suggested to be a model for pheochromocytoma. Study conditions for proving such an assertion, however, have not been optimized. Studies on strain difference, dose dependency, and the time course of catecholamine metabolism in response to nicotine treatment were conducted. Under the putative optimal experimental conditions, metabolic and histologic changes in the adrenal medulla were investigated. Male Wistar rats treated with a maximum dose of 4 mg/kg per day of nicotine for 9 weeks, including a 2-week lead-in period, developed highly consistent changes in the adrenal medulla. Concerning metabolic indices, the norepinephrine content of the adrenal and the urinary excretion of epinephrine and metanephrine were significantly elevated. Hyperplastic and hyperactive states of the adrenal medulla were also indicated by a morphometric analysis on electron microscopic figures. These showed an enlarged cytoplasmic area, the development of a rough-surfaced endoplasmic reticulum, and an increased number and density of intracellular catecholamine granules. The metabolic changes were found to reverse 3 weeks after the cessation of nicotine administration. These results provide better-defined experimental conditions for an animal model of pheochromocytoma.


Intense, reversible aggregation of intramembrane particles in non-haemolyzed human erythrocytes. A freeze-fracture study.
Acridine orange, a strongly cationic, membrane-penetrating dye, caused intense aggregation of intramembrane particles in non-haemolyzed human erythrocytes at 5 mM concentration. Simultaneously with the particle aggregation, large, empty, intramembrane particle-free or particle-depleted vesicles were detached from the red cells. Washing the erythrocytes after Acridine orange treatment resulted in complete disaggregation of the intramembrane particles. Less cationic acridine dyes (9-aminoacridine, 5-aminoacridine and Quinacrine) caused much less conspicuous alterations. Rivanol (ethacrine lactate), on the one hand, caused intramembrane particle aggregation in human red cells as well as ribosome aggregation in rabbit reticulocytes when it was dissolved in lactate-buffered sucrose. On the other, Rivanol dissolved in phosphate-buffered saline failed to induce these alterations. Neuraminidase treatment had no effect on the intensity of Acridine orange-induced particle aggregation, but impeded disaggregation. Our results indicate that, in contrast to previous observations, intense and reversible clustering of intramembrane particles is certainly possible in non-haemolyzed erythrocytes. The intramembrane particle aggregation may be due primarily to perturbation of the inner red cell surface by strongly cationic dyes and the presence of sialic acid residues on the outer red cell surface seems to be essential for the reversibility of the process.


Substance P-immunoreactive and serotonin-containing neurones in the ventral brainstem of the cat.
Substance P-like immunoreactive cell bodies have been described in the cat brainstem after local injections of colchicine. Substance P-containing neurons were found in the nucleus raphe pallidus, the nucleus raphe obscurus and at the caudal end of the nucleus raphe magnus. Two groups of substance P-positive (+) cells were also found in the ventrolateral medulla. Small substance P+ cells were present in a narrow band immediately ventral to the facial nucleus, and a second group of small and medium sized neurones was found in a strip ventrolateral to the rostral half of the inferior olive. Some of these cells lay in close proximity to the ventral surface of the brain. Double labelling studies indicated that within the raphe nuclei many substance P+ neurones also contained serotonin, while within ventrolateral areas of the medulla, the most rostral cell group stained only for substance P and the more caudal nucleus for both substance P and serotonin.


A doxorubicin delivery system: Samarium/mesoporous bioactive glass/alginate composite microspheres.
Samarium (Sm) incorporated mesoporous bioactive glasses (MBG) microspheres have been prepared using the method of alginate cross-linking with Ca(2+) ions. The in vitro bioactivities of Sm/MBG/alginate microspheres were studied by immersing in simulated body fluid (SBF) for various periods. The results indicated that the Sm/MBG/alginate microspheres have a faster apatite formation rate on the surface. To investigate their delivery properties further, doxorubicin (DOX) was selected as a model drug. The results showed that the Sm/MBG/alginate microspheres exhibit sustained DOX delivery, and their release mechanism is controlled by Fickian diffusion according the Higuchi model. In addition, the delivery of DOX from Sm/MBG/alginate microspheres can be dominated by changing the doping concentration of Sm and the values of pH microenvironment. These all revealed that this material is a promising candidate for the therapy of bone cancer.


High-performance affinity beads for identifying drug receptors.
We have developed a method using novel latex beads for rapid identification of drug receptors using affinity purification. Composed of a glycidylmethacrylate (GMA) and styrene copolymer core with a GMA polymer surface, the beads minimize nonspecific protein binding and maximize purification efficiency. We demonstrated their performance by efficiently purifying FK506-binding protein using FK506-conjugated beads, and found that the amount of material needed was significantly reduced compared with previous methods. Using the latex beads, we identified a redox-related factor, Ref-1, as a target protein of an anti-NF-kappaB drug, E3330, demonstrating the existence of a new class of receptors of anti-NF-kappaB drugs. Our results suggest that the latex beads could provide a tool for the identification and analysis of drug receptors and should therefore be useful in drug development.


TREM-1 Inhibition Restores Impaired Autophagy Activity and Reduces Colitis in Mice.
Triggering receptor expressed on myeloid cells-1 [TREM-1] is known to amplify inflammation in several diseases. Autophagy and endoplasmic reticulum [ER] stress, which activate the unfolded protein response [UPR], are closely linked and defects in these pathways contribute to the pathogenesis of inflammatory bowel disease [IBD]. Both autophagy and UPR are deeply involved in host-microbiota interactions for the clearance of intracellular pathogens, thus contributing to dysbiosis. We investigated whether inhibition of TREM-1 would prevent aberrant inflammation by modulating autophagy and ER stress and preventing dysbiosis. An experimental mouse model of colitis was established by dextran sulphate sodium treatment. TREM-1 was inhibited, either pharmacologically by LR12 peptide or genetically with Trem-1 knock-out [KO] mice. Colon tissues and faecal pellets of control and colitic mice were used. Levels of macroautophagy, chaperone-mediated autophagy [CMA], and UPR proteins were evaluated by western blotting. The composition of the intestinal microbiota was assessed by MiSeq sequencing in both LR12-treated and KO animals. We confirmed that inhibition of TREM-1 attenuates the severity of colitis clinically, endoscopically and histologically. We observed an increase in macroautophagy [ATG1/ULK-1, ATG13, ATG5, ATG16L1, and MAP1LC3-I/II] and in CMA [HSPA8 and HSP90AA1], whereas there was a decrease in the UPR [PERK, IRE-1α, and ATF-6α] protein expression levels in TREM-1 inhibited colitic mice. TREM-1 inhibition prevented dysbiosis. TREM-1 may represent a novel drug target for the treatment of IBD, by modulating autophagy activity and ER stress.


Construction of composite slides.
This article describes a method for constructing composite slides without destroying the original slide. A conventional slide projector, rear-projector screen, modified 35 mm camera, and slide-duplicating film are required for this technique.


Changes in public bike usage after the COVID-19 outbreak: A survey of Seoul public bike sharing users.
When the COVID-19 pandemic swept across the world, people tended to seek more individualized and viable transportation modes, such as a bicycle. In this study, we examined the factors influencing changes in public bike sharing (PBS) in Seoul, to assess this trend post-pandemic. We conducted an online survey of 1,590 Seoul PBS users between July 30 and August 7, 2020. Using a difference-in-differences analysis, we found that participants who were affected by the pandemic used PBS 44.6 h more than unaffected individuals throughout the year. In addition, we used a multinomial logistic regression analysis to identify the factors affecting changes in PBS usage. In this analysis, the discrete dependent variables of increased, unchanged, and decreased were considered, representing the changes in PBS usage after the COVID-19 outbreak. Results revealed that PBS usage increased among female participants during weekday trips such as commuting to work and when there were perceived health benefits of using PBS. Conversely, PBS usage tended to decrease when the weekday trip purpose was for leisure or working out. Our findings offer insight into PBS user behaviors within the context of the COVID-19 pandemic and present policy implications to revitalize PBS usage.


CT-guided cervical nerve root injections: comparing the immediate post-injection anesthetic-related effects of the transforaminal injection with a new indirect technique.
To describe an "indirect" cervical nerve root injection technique with a dorsal approach that should carry less inherent risk than the "direct" cervical transforaminal injection approach, and to compare the immediate post-injection results of the two procedures. The indirect and direct cervical nerve root injection procedures are described in detail. Fifty-three consecutive patients receiving the indirect nerve root injections during 2009-2010 were age- and gender-matched to 53 patients who underwent direct transforaminal nerve root injections performed in 2006. Pain level data were collected immediately before and 20-30 min after each procedure. The percentages of pain change in the two groups were compared using the unpaired Student's t test. Fifty-two men (mean age 49) and 54 women (mean age 55) were included. The mean percentage of pain reduction for patients receiving indirect nerve root injections was 38.4% and for those undergoing the direct nerve root injections approach it was 43.2%. This was not significantly different (P = 0.455). No immediate or late adverse effects were reported after either injection procedure. The indirect cervical nerve root injection procedure is a potentially safer alternative to direct cervical transforaminal nerve root injections. The short-term pain reduction is similar using the two injection methods.


Flour and starch characteristics of soft wheat cultivars and their effect on cookie quality.
Studies on Argentinian soft wheat cultivars are scarce, although the flours obtained from these wheats are the most suitable for cookie making. This work studies the behavior of the flours obtained from 44 adapted soft wheat lines harvested in two consecutive years for cookie making, focusing on starch properties. Starch granule size distribution, and thermal and pasting properties of flour samples were studied. Large variations in flour and starch characteristics were found between all experimental lines, indicating a wide variability among wheat genotypes and a noticeable effect of crop year conditions. Starch granule size distribution showed the typical bimodal distribution observed for wheat. Flours with higher proportion of large A-type granules were associated with lower damaged starch (DS). As expected, the lower the DS content, the lower the solvent retention capacity, gelatinization temperature and enthalpy, with a positive impact on cookie diameter. Flours from soft wheat genotypes with higher proportion of large A-type granules were associated with lower DS content and reduced water absorption capacity. Both genotype and environment exert an effect on soft wheat flour characteristics.


Petrologic Characteristics of the Lunar Surface.
Petrologic analysis of the lunar surface is critical for determining lunar formation and evolution. Here, we report the first global petrologic map that includes the five most important lunar lithological units: the Ferroan Anorthositic (FAN) Unit, the Magnesian Suite (MS) Unit, the Alkali Suite (AS) Unit, the KREEP Basalt (KB) Unit and the Mare Basalt (MB) Unit. Based on the petrologic map and focusing on four long-debated and important issues related to lunar formation and evolution, we draw the following conclusions from the new insights into the global distribution of the five petrologic units: (1) there may be no petrogenetic relationship between MS rocks and KB; (2) there may be no petrogenetic link between MS and AS rocks; (3) the exposure of the KREEP component on the lunar surface is likely not a result of MB volcanism but is instead mainly associated with the combined action of plutonic intrusion, KREEP volcanism and celestial collision; (4) the impact size of the South Pole-Aitken basin is constrained, i.e., the basin has been excavated through the whole crust to exhume a vast majority of lower-crustal material and a very limited mantle components to the lunar surface.


Retinal vessels change in primary angle-closure glaucoma: the Handan Eye Study.
Glaucoma is the second leading cause of blindness worldwide. To examine the relationship between angle closure and the retinal vessel diameter in Chinese adults, we conducted Handan Eye Study (HES), a large population-based cross-sectional study, which enrolled 6830 participants >30 year-old living in 13 randomly selected villages of Yongnian County. After adjusting for age, gender, spherical equivalent (SE), diabetes, and hypertension, the mean central retinal artery equivalent (CRAE, μm) was 127.1 ± 7.0 and 145.6 ± 4.4 in primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG), respectively; narrower than that in normal control (156.1 ± 0.4), primary angle-closure suspect (PACS) (156.3 ± 1.1) or primary angle closure (PAC) (156.0 ± 3.4) (P = 0.001). The mean central retinal vein equivalent (CRVE, μm) was 229.0 ± 5.9 and 215.8 ± 9.5 in POAG and PACG, respectively; narrower than that in normal control (238.3 ± 0.5), PACS (241.2 ± 1.4) or PAC (242.2 ± 4.6) (P = 0.001). There was no significant difference in the mean CRAE or CRVE between PACG and POAG. Compared to the normal control (0.66), the mean arterio-venous ratio (AVR) was smaller in POAG (0.64) and PACG (0.59), whereas larger in PACS (0.65) and PAC (0.67) (P = 0.003). To conclude, PACG and POAG individuals have narrower retinal arteries and veins.


Pregnancy outcome in women working as dentists, dental assistants or dental technicians.
Pregnancy outcome in women with work in dentistry was studied using various central health registries. A total of 8157 infants born of dentists, dental assistants, or dental technicians in 1976 or 1982-1986 in Sweden were studied with respect to perinatal survival, low birthweight, and malformations and compared with all births. The only deviating finding was that of a significantly low perinatal death rate. Specifically, no increase in a risk for spina bifida was seen and the upper 95% confidence limit for the risk ratio was 2.1. A study was also made of hospitalized spontaneous abortions in women with these occupations in the years 1980-1981. No significant deviations from expected values were found. In a small study of only 78 such pregnancies in 1964-1965, no increase in spontaneous abortion rate was seen. Only one infant was malformed (anencephaly): both its parents worked as dental technicians. None of the mothers of 220 infants with a neural tube defect born in 1965-1967 in Sweden was a dentist. We find no indications that this occupation represents a significant reproduction hazard at the present time in Sweden.


Restoration and analysis of standing-up in complete paraplegia utilizing functional electrical stimulation.
Restoration of stand-up motion in patients with complete paraplegia utilizing multichannel functional electrical stimulation, and analysis of the restored motion. Nonrandomized control trial. General community, a referral center, institutional practice, and ambulatory care: Twelve volunteer samples were used for the collection of normal data. Two complete paraplegics received treatment for the restoration of stand-up motion. The electromyogram, joint angle, and floor reaction force were investigated during standing-up with arms crossed in front of the chest, and hands-assisted standing-up using parallel bars. The maximum knee joint torque during standing-up without hands-assists was calculated using a three-segment link model. Standing-up motion in complete paraplegics was restored, and then analyzed using the three-dimensional floor reaction force and the hip, knee, and ankle angles. Main muscles used to stand up were the quadriceps, tibialis anterior, and paraspinal muscles. Hands-assists reduced the muscle activity and the vertical floor reaction force. Peak muscle activity was less during hands-assisted standing-up, except for the rectus femoris and the iliopsoas muscle. The maximum knee joint torque during standing-up was 1.6Nm/kg for both knees. Two complete paraplegics were able to stand up smoothly from a wheelchair based on stimulation data obtained from normal subjects. The characteristic pattern during standing-up was knee flexion preceding extension. Stand-up motion was restored utilizing electromyogram data and knee joint torque data from normal subjects.


Analysis of differences between coomassie blue stain and silver stain procedures in polyacrylamide gels: conditions for the detection of calmodulin and troponin C.
It is reported that the conditions used in some silver stain procedures can fail to detect calmodulin, troponin C, and other proteins with similar physical properties. Conditions are described that allow the reproducible detection of these proteins. Two phenomena are described: (1) lack of protein staining when treatment with glutaraldehyde is omitted from the protocol, and (2) loss of small proteins from the gel matrix during prolonged washing procedures. These data directly demonstrate that the use of some silver staining protocols can result in misleading data in biological studies and provide an explanation for at least one class of proteins of how silver staining and Coomassie blue staining of gels can give different results.


Denoised encoder-based residual U-net for precise teeth image segmentation and damage prediction on panoramic radiographs.
This research focuses on performing teeth segmentation with panoramic radiograph images using a denoised encoder-based residual U-Net model, which enhances segmentation techniques and has the capacity to adapt to predictions with different and new data in the dataset, making the proposed model more robust and assisting in the accurate identification of damages in individual teeth. The effective segmentation starts with pre-processing the Tufts dataset to resize images to avoid computational complexities. Subsequently, the prediction of the defect in teeth is performed with the denoised encoder block in the residual U-Net model, in which a modified identity block is provided in the encoder section for finer segmentation on specific regions in images, and features are identified optimally. The denoised block aids in handling noisy ground truth images effectively. Proposed module achieved greater values of mean dice and mean IoU with 98.90075 and 98.74147 CONCLUSIONS: Proposed AI enabled model permitted a precise approach to segment the teeth on Tuffs dental dataset in spite of the existence of densed dental filling and the kind of tooth. The proposed model is pivotal for improved dental diagnostics, offering precise identification of dental anomalies. This could revolutionize clinical dental settings by facilitating more accurate treatments and safer examination processes with lower radiation exposure, thus enhancing overall patient care.


Long-term follow-up of a randomized controlled trial comparing acceptance and commitment therapy and standard cognitive behavior therapy for anxiety and depression.
The present study represents one of the first comparisons of the long-term effectiveness of traditional cognitive behavior therapy (i.e., Beckian cognitive therapy; CT) and acceptance and commitment therapy (ACT). One hundred thirty-two anxious or depressed outpatients were randomly assigned to receive either CT or ACT, and were assessed at posttreatment (n=90) and at 1.5-year (n=91) follow-up. As previously reported, the two treatments were equivalently effective at posttreatment according to measures of depression, anxiety, overall (social/occupational/symptom-related) functioning, and quality of life. However, current results suggest that treatment gains were better maintained at follow-up in the CT condition. Clinical significance analyses revealed that, at follow-up, one-third more CT patients were in the clinically normative range in terms of depressive symptoms and more than twice as many CT patients were in the normative range in terms of functioning levels. The possible long-term advantage of CT relative to ACT in this population is discussed.


X-linked adult form of spinal muscular atrophy.
Neurological and endocrinological studies were carried out in 8 of 12 male patients with X-linked spinal muscular atrophy. In six investigated cases, gynaecomastia was discovered. First muscle symptoms started between 21 and 44 years of age, at which time the patients observed disturbances in their sexual life. In three cases decreased fertility and in two cases sterility was reported. Diagnostic testicular biopsy showed pronounced involutional changes of the Leydig cells. The plasma testosterone level was decreased, while the levels of luteinizing hormone and prolactine were normal, and the follicle stimulating hormone was at a high normal level. The dexamethasone/human chorionic gonadotrophin test revealed a pronounced decrease in the functional reserve of the Leydig cells. It is suggested that all these anomalies are connected with an increased ratio of oestrogen to androgen level.


Synthesis and characterization of green rust-deposited MoS2 composites for adsorptive removal of EDTA-chelated Ni(II) in wastewater.
Ethylenediamminetetraacetatonickel(II) (EDTA-Ni(II)) has emerged as a significant soil and groundwater contaminant due to the increasing agricultural and industrial activities, posing environmental challenges. This study focuses on addressing the reactivity of green rust (GR), which can be hindered by oxidation with oxygen, limiting its effectiveness in remediation processes. To overcome this limitation and enhance the adsorptive capacities, the combination of sulfate green rust (SO4-GR) with various Fe(II)/Fe(III) ratios with a high-surface-area adsorbent, MoS2, resulting in the formation of binary composites of green rust-deposited MoS2 (MSGs) were explored. The aim was to improve the removal efficiency of EDTA-Ni(II) from contaminated wastewater. To characterize the MSGs, a comprehensive analysis using XRD, SEM, TEM, FTIR, and X-ray absorption spectroscopy was performed. The surface areas of the MSGs were smaller than that of MoS2 but larger than that of the SO4-GRs, indicating a promising composite material. XANES spectra analysis revealed that both MSGs and SO4-GRs exhibited a mixture of ferrous and ferric ions, as evident from their spectral positioning between FeO and Fe2O3. The optimal pH for efficient removal of EDTA-Ni(II) was 3, which resulted in removal efficiencies of 45.6%, 47.3%, 46.0%, and 46.2% for MSG 1, MSG 2, MSG 3, and MSG 4 after 24 h, respectively. Reducing the initial concentration of EDTA-Ni(II) to 50 mg Ni(II)/L effectively doubled the removal efficiency. Notably, as EDTA-Ni(II) was removed, an increased leaching of iron was observed, leading to a total iron concentration exceeding 40 mg/L for the composites with higher Fe(II)/Fe(III) ratios. These findings underscore the potential of MSG as a promising material for degrading EDTA-Ni(II) in contaminated wastewater, offering a viable solution to mitigate the environmental impact of this emerging contaminant. This study contributes to the understanding of green rust reactivity and provides valuable insights for developing effective strategies to address the challenges associated with EDTA-Ni(II) contamination.


Assessment and analysis of outpatient medication errors related to pediatric prescriptions.
Medication errors are the errors that impact the efficacy and safety of the therapy. The impact of medication errors is higher for certain subjects, such as pediatrics, who require more attention. Hence, the current study aimed to investigate the types and frequency of outpatient medication errors of pediatric subjects related to different prescription types. A cross-sectional study was carried in several community pharmacies to record the medication errors found in outpatient pediatric prescriptions by gathering data from the outpatient prescriptions besides direct counseling with the subjects and their parents. Many medical resources (disease and drug-related) were used for checking the different aspects of medication errors. The data collection process included a preprepared sheet containing several items representing the medication errors in addition to a counseling session. Data were expressed as percentages and compared through the Chi-square test for results of handwritten and computerized prescriptions. 752 outpatient pediatric prescriptions were recruited in the study as they involve medication errors. Among the highest percentage of medication errors was the absence of essential data in the prescription, such as diagnosis, age, and weight. The duration of the therapy and contraindication for some of the prescribed medications were among the highest recorded errors. Among the critical errors were the drug interaction and drug duplication that directly affect the drug's efficacy and safety. There was a significant difference between computerized and handwritten prescriptions regarding the number of medication errors related to each type. Medication errors related to outpatient pediatric prescriptions vary from one to another prescription with predominant errors that influence the therapy's safety or efficacy. The role of patient counseling and prescription checking is critical for improving patient therapy.


Sialic acid content in mouse myeloma cells and derived B-cell hybridomas with different metastatic potentials.
In a previous work we have reported on the metastatic capacities of mouse myeloma cells (NSO) and of two hybridomas derived from them. The present study was designed to examine the sialic acid content of these cell types, their attachment to glass and their capping in the presence of wheat germ agglutinin (WGA). The results showed no significant differences in sialic acid content between NSO and Hybridoma A (Hy A) cells which are non and low metastatic, respectively, whereas Hybridoma B (Hy B), which is highly metastatic, contained 1.4-1.6-fold higher sialic acid compared to the other two cell types. NSO cells exhibited a high, Hy A a moderate and Hy B a negligible attachment to glass. Capping experiments showed a low response of NSO cells, a moderate response of Hy A and a high response of Hy B in the presence of WGA. The results are discussed with regard to the metastatic potential of these cell types taking into consideration the properties cell surface sialic acid is known to endow to cells, determining various aspects of their behaviour.


Can Molecular Biology Propose Reliable Biomarkers for Diagnosing Major Depression?
Modern medicine has provided considerable knowledge of the pathophysiology of mental disorders at the body, systemic, organ and neurochemical levels of the biological organization of the body. Modern clinical diagnostics of depression have some problems, that is why psychiatric society makes use of diagnostics and taxonomy of different types of depression by implemention of modern molecular biomarkers in diagnostic procedures. But up to now, there are no reliable biomarkers of major depressive disorder (MDD) and other types of depression. The purpose of this review is to find fundamentals in pathological mechanisms of depression, which could be a basis for development of molecular and genetic biomarkers, being the most feasible for clinical use. This review summarizes the published data using PubMed, Science Direct, Google Scholar and Scopus. In this review, we summarized and discussed findings in molecular biology, genetics, neuroplasticity, neurotransmitters, and neuroimaging that could increase our understanding of the biological foundations of depression and show new directions for the development of reliable biomarkers. We did not find any molecular and genetic biomarker approved for the clinic. But the Genome-Wide Association Study method promises some progress in the development of biomarkers based on SNP in the future. Epigenetic factors also are a promising target for biomarkers. We have found some differences in the etiology of different types of atypical and melancholic depression. This knowledge could be the basis for development of biomarkers for clinical practice in diagnosis, prognosis and selection of treatment. Depression is not a monoetiological disease. Many pathological mechanisms are involved in depression, thus up to now, there is no approved and reliable biomarker for diagnosis, prognosis and correction of treatment of depression. The structural and functional complexity of the brain, the lack of invasive technology, poor correlations between genetic and clinical manifestation of depression, imperfect psychiatric classification and taxonomy of subtypes of disease are the main causes of this situation. One of the possible ways to come over this situation can be to pay attention to the trigger mechanism of disease and its subtypes. Researchers and clinicians should focus their efforts on searching the trigger mechanism of depression and different types of it . HPA axis can be a candidate for such trigger in depression caused by stress, because it influences the main branches of disease: neuroinflammation, activity of biogenic amines, oxidative and nitrosative stress, epigenetic factors, metabolomics, etc. But before we shall find any trigger mechanism, we need to create complex biomarkers reflecting genetic, epigenetic, metabolomics and other pathological changes in different types of depression. Recently the most encouraging results have been obtained from genetics and neuroimaging. Continuing research in these areas should be forced by using computational, statistical and systems biology approaches, which can allow to obtain more knowledge about the neurobiology of depression. In order to obtain clinically useful tests, search for biomarkers should use appropriate research methodologies with increasing samples and identifying more homogeneous groups of depressed patients.


Alleviation of aqueous nitrogen loss from paddy fields by growth and decomposition of duckweed (Lemna minor L.) after fertilization.
Runoff loss of nitrogen from paddy fields has received increasing attention in recent years. Duckweed is an aquatic plant frequently found in paddy fields. In this study, the effects of duckweed (Lemna minor L.) in floodwater on aqueous nitrogen losses from paddy fields were systematically investigated. Results demonstrated that the growth of duckweed decreased total nitrogen concentrations in floodwater and nitrogen runoff loss from paddy fields by 16.7%-18.3% and 11.2%-13.6%, respectively. Moreover, compared with NO3-, NH4+ was preferentially removed by duckweed. 15N isotope tracer experiments revealed that the growth and decomposition of duckweed acted as a "buffer" against the nitrogen variation in floodwater after fertilization. During the growth of duckweed, leaves were found to be the principal organ to assimilate NH4+ and release NO3- by using non-invasive micro-test technology. Duckweed degradation increased the content of hydrophobic acids and marine humic-like substances in floodwater, which promoted the migration of nitrogen from floodwater to soil. Redundancy analysis and structural equation models further illustrated that pH and temperature variation in floodwater caused by duckweed played a greater role in aqueous nitrogen loss reduction than the nitrogen accumulation in duckweed. This study suggested that the growth of duckweed in paddy fields was an effective supplementary method for controlling aqueous nitrogen loss during agricultural production.


Fractionation of rhodopsin and other components in the rod outer segment membrane by ammonium sulfate salting-out.
Purified bovine rod outer segment membrane was solubilized in a mixture of 1.5% cholic acid/20% saturated ammonium sulfate and 0.05 M phosphate buffer (pH 7.5). The solubilized rod outer segment membrane was fractionated with ammonium sulfate and 70--90% of rhodopsin (A278/A498= 1.6--1.9) was recovered in the fraction of 50 to 60% saturation with ammonium sulfate, giving a highly concentrated solution of purified rhodopsin (A1CM 498 = 83). By the method of ammonium sulfate salting-out, the solubilized rod outer segment membrane was divided into several fractions without a loss of components. The components in each fraction were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Rhodopsin and opsin amounted to 93% of the total protein in the membrane. Other proteins with molecular weights of 46 000, 52 000, 56 000, 70 000, 95 000, 105 000, 130 000 and 270 000 were also detected. Most of phospholipids in the rod outer segment membrane remained in the supernatant above 60% saturation with ammonium sulfate.


Longitudinal effects of U.S. students' reentry shock on psychological health after returning home during the COVID-19 global pandemic.
Guided by the stress process model (Pearlin, Mullan, Semple, & Skaff, 1990; Pearlin, 1999), the purpose of this longitudinal investigation was to examine the extent to which the stressor of premature forced reentry from studying abroad during the COVID-19 pandemic (e.g., reentry shock, reacculturative stress) was predictive of stress-related compromised mental health (i.e., perceived stress and loneliness) into the subsequent academic year. A total of 133 college students from different U.S. universities completed a short online questionnaire as soon as they came back from their study abroad experience (T1) and approximately six months after (T2), when they were resuming their Fall 2020 academic semester. Consistent with the stress process model, secondary stressors associated with reacculturation were predictive, concurrently and longitudinally, of mental health outcomes, especially loneliness, indicating that students who had the hardest time returning home unexpectedly were at the highest risk for worsened mental health over the following months. These findings reveal that reacculturation following unplanned termination of a study abroad experience is not an event as much as it is a process that unfolds over a period of months, as would be understood from the perspective of the stress process model.


Using Rapid Randomized Trials to Improve Health Care Systems.
Rapid randomized controlled trials have been surprisingly rare in health care quality improvement (QI) and systems interventions. Applying clinical trials methodology QI work brings two distinct fields together, applying the robustness of randomized controlled trials (RCTs) to the practical, operational learnings of the well-established QI field. Rapid trials also add a third element-speed-that enables health care systems to rapidly test multiple variations of an intervention in much the same way that A/B testing is done in the technology sector. When performed well, these rapid trials free researchers and health care systems from the requirement to be correct the first time (because it is low cost and quick to try something else) while offering a standard of evidence often absent in QI. Here we outline the historical underpinnings of this approach, provide guidance about how best to implement it, and describe lessons learned from running more than 20 randomized projects in the NYU Langone Health system.


Enabling Chemo-Immunotherapy with HIFU in Canine Cancer Patients.
High intensity focused ultrasound (HIFU) is a promising non-invasive technique for treating solid tumors using thermal and histotripsy-based mechanical ablation. However, its clinical significance in different tumor types is not fully understood. To assess its therapeutic efficacy and immunomodulatory properties, we compared HIFU thermal ablation and histotripsy ablation in dogs with spontaneous tumors. We also evaluated the ability of non-ablative HIFU-based mild hyperthermia (40-45 ºC) to improve Doxorubicin delivery and immunomodulation. Our results showed that HIFU thermal ablation induced tumor remission in the majority of treated patients over 60 days, while histotripsy achieved partial response to stable disease persistence. The adverse effects of thermal ablation were minor to moderate, while histotripsy exposures were relatively well-tolerated. Furthermore, we observed a correlation between HIFU-therapeutic response and serum anti-tumor cytokine profiles and the presence of functionally active cytotoxic immune cells in patients. Similarly, Doxorubicin-treated patients showed improved drug delivery, efficacy, and anti-tumor immune responses with HIFU hyperthermia. In conclusion, our study demonstrates that depending on the tumor type and treatment parameters, HIFU treatments can enable tumor growth control, immune activation, and chemotherapy in veterinary patient. These findings have significant clinical implications and highlight the potential of HIFU as a promising cancer treatment approach.


Profile analysis of organic micropollutants in the environment of a coal burning area, NW Greece.
The concentrations and profiles of dibenzo-p-dioxins, dibenzofurans, polychlorinated biphenyls and polynuclear aromatic compounds in various environmental matrices are presented in this study. The examined environmental matrices are total suspended particles, fly ash and soil collected in NW Greece, an area characterized by intensive coal burning for electrical power generation. Moreover, the occurrence of organic micropollutants in soot after an accidental fire was examined and the possible impact on the outdoor environment was evaluated. Results were statistically treated to obtain information on representative PCDD/F profiles in each matrix and to compare these profiles with the compositional patterns of possible sources from literature. Coal combustion, fly ash and vehicle exhausts appeared to be the most possible sources in local atmosphere.


Treatment of chronic Chagas' disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up.
Prescribing etiologic treatment for chronic Chagas' disease is highly controversial because of the difficulties involved in assessing its therapeutic efficacy--the low degree of parasitemia, the persistence of positive immunologic reactions, the lack of clinical findings to support each type of treatment, and the necessarily prolonged follow-up of the patient. An 8-year average follow-up was performed on 131 patients treated with benznidazole (5 mg/kg/day for 30 days) (TP) and 70 untreated patients (UTP) by serial electrocardiograms and analysis of the cardiomyopathic progress of the clinical groups, and by immunologic tests at both the beginning and end of the study. TPs presented less electrocardiographic changes during the follow-up period (4.2% vs 30%) and a lower frequency of deterioration in their clinical condition (2.1% vs 17%). The percentage of TPs who were serologically negative was 19.1% whereas 6% of the UTPs became serologically negative, a result that correlated with a lack of progress in the cardiomyopathy. Benznidazole treatment significantly decreased serologic titers, signifying parasitologic cure in two patients.


Pulse dosing versus continuous infusion of antibiotics. Pharmacokinetic-pharmacodynamic considerations.
The issue of whether it is better to administer antibiotics as an intermittent bolus dose or a continuous intravenous infusion has been debated for several decades. This paper reviews the extensive literature on the topic, considering both the pharmacokinetic and pharmacodynamic aspects of antibacterials as well as experimental results from studies conducted in vitro, in animals and in humans. It is evident from reviewing the literature that neither mode of administration is clearly superior to the other. The decision regarding the mode of administration must take into account the antibiotic being used, the bacteria, the patient and the infection, as well as the pharmacokinetics of the particular drug in the individual patient. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) are useful indicators of the relative in vitro effectiveness of antibiotics, but it is not clear what relevance these parameters have to the desired antibiotic concentrations in vivo. Furthermore, questions of serum vs tissue fluid concentrations, peak concentrations vs AUC, and free vs total concentration are all important issues to consider in assessing the optimal mode of administration. The importance of newer indices such as the post-antibiotic effect are now beginning to be recognised. A number of scientists are actively engaged in developing a system to identify the most appropriate mode of administration based upon the integration of an antibiotic's pharmacodynamics and pharmacokinetics. Within the next few years we anticipate that appropriate guidelines should have been developed to aid the optimisation of parenteral administration, at least for some antibiotics.