Autoimmune serology testing in clinical practice: An updated roadmap for the diagnosis of autoimmune hepatitis.
Diagnosis of autoimmune hepatitis (AIH) is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the disease. The clinical spectrum of AIH varies from completely asymptomatic to acute-severe or even rarely fulminant hepatic failure, while everybody can be affected irrespective of age, gender, and ethnicity. The old revised and the newer simplified diagnostic scores have been established by the International Autoimmune Hepatitis Group (IAIHG) in 1999 and 2008, respectively, which are based on several clinical, laboratory and histological parameters. Additionally, a thorough differential diagnosis from other diseases mimicking AIH is absolutely indicated. In this context, autoantibodies detection in patients with suspected AIH is mandatory -even though not pathognomonic- not only for AIH diagnosis but furthermore, for AIH classification (AIH-type 1 and AIH-type 2). Although autoimmune serology can be supportive of AIH diagnosis in ≥95% of cases if testing has been performed according to the IAIHG guidelines, this is not the case under real-life circumstances in routine clinical laboratories. Clinicians should be careful both for the importance of the required testing and how to interpret the results and therefore, they should communicate and discuss with the laboratory personnel to achieve the maximum benefit for the patient. Herein, a detailed and updated review of the diagnostic work-up for AIH diagnosis under real-life conditions is given to minimize the underestimation and misdiagnosis of AIH which can result in progression of the disease and unfavourable outcomes.


International dermatology: the many faces and challenges of the specialty in the global village.
The technical advances of the last century changed the understanding of the science of cutaneous physiology and pathology and the role of the dermatologist. The major challenges the international dermatologic community faces today are the lack of a common, logical, and accepted language within the specialty; long-accepted but questionable policies to advance academic careers; and the marginalization of dermatology. Methods for communicating and circulating data and ideas also have changed radically. The distribution of knowledge and essential/practical tools in different regions of the world is inequitable, and developing countries must cope with the challenges of high-impact skin diseases.


The effectiveness of adjuncts or alternatives to the use of orthodontic retainers in preserving posttreatment outcomes: A systematic review.
The objective of this study was to systematically evaluate the efficacy of adjuncts or alternatives to mechanical retention in preserving postorthodontic treatment outcomes. Electronic databases, unpublished literature, and ongoing trials were searched until July 22, 2022 (PROSPERO CRD42021291165). Randomized and nonrandomized controlled trials investigating the efficacy of adjuncts and alternatives to conventional orthodontic retainers were included. Stability, periodontal effects, cost-effectiveness, and patient-reported outcomes were to be evaluated. The Cochrane Risk of Bias Tool and Risk of Bias In Nonrandomized Studies of Interventions (ROBINS-I) were used for risk of bias assessment. The certainty of the evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation system. Exploratory sensitivity analysis was undertaken to calculate the weighted treatment effects of the intervention. A total of 5128 records were screened. Seven trials fulfilled the inclusion criteria, of which 5 were randomized controlled trials. Five trials were judged to be at high risk of bias, with 2 studies of unclear risk of bias. Heterogeneity between the limited number of included studies precluded the conduct of meta-analysis. Circumferential supracrestal fibrotomy resulted in less increase in the mandibular Little's Irregularity Index (mean difference, -2.30 mm; 95% confidence interval, -2.86 to -1.74). The overall level of evidence was of very low quality. Adjuncts and alternatives to mechanical retention have promise, but based on the existing evidence, the reliance on mechanical retention cannot be reduced. There is weak evidence supporting circumferential supracrestal fibrotomy to improve stability outcomes. Further high-quality prospective research focusing on the predictability and acceptability of these approaches is needed.


Bioelectrical impedance analysis versus physician adjustment in acute kidney injury patients to reduce intradialytic hypotension: A randomized controlled trial.
Volume overload and intradialytic hypotension (IDH) are significant complications that can increase the mortality rate in hemodialysis patients.Bioelectrical impedance analysis (BIA) has been used to estimate the optimum weight in chronic hemodialysis patients to prevent intradialytic hypotension. However, data regarding BIA for evaluating hydration in acute kidney injury patients is scarce. We reported the case series of 9 patients who used BIA in comparison with physician adjustment to prevent intradialytic hypotension in patients with acute kidney injury who received renal replacement therapy. We randomized 9 patients with acute kidney injury (AKI) and volume overload who underwent 45 sessions of acute hemodialysis at Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand between October 2017 and February 2018 to BIA and physician -adjusted group. Volume overload was defined as a BIA value of more than>0.4. In the physician-adjusted group (control), the estimates for physical examination and fluid balance were recorded. The primary outcome was an intradialytic hypotensive episode.The secondary outcome was hemodialysis-related adverse events and other clinical outcomes. This work is fully compliant with CONSORT criteria (detailed in the supplemental file). Among 9 patients (55.6% male, median age 65.56 years),the main underlying diseases were hypertension and diabetes mellitus. The main cause of AKI was sepsis. After randomization of overall of 45 sessions in 9 patients with AKI, the intradialytic hypotension event rate in the BIA group was significantly lower than that in the control group (5 events vs 12 events; P = 0.042). There were no differences in the rates of hemodialysis-related adverse events and other clinical outcomes between the two groups. The use of bioelectrical impedance analysis-guided ultrafiltration in patients with acute kidney injury requiring renal replacement therapy can help reduce intradialytic hypotension.


A chaperone-assisted high yield system for the production of HLA-DR4 tetramers in insect cells.
MHC tetramers have become essential tools for the analysis of antigen specific responses of CD8+ and CD4+ T cells. However, the use of MHC class II tetramers is hampered by the relatively low yields of most current expression systems. We have devised an insect cell/baculovirus expression system in which yields of 50-70 mg of recombinant HLA-DR4 molecules, with or without covalently linked peptide, per liter of insect cell supernatant, are routinely obtained. These yields are rendered possible by an optimized design and use of DRalpha and DRbeta expression cassettes and by co-expression of a housekeeping chaperone of the endoplasmic reticulum, calreticulin, which, due to its co-secretion, increases secretion of HLA-DR molecules two- to threefold. A tetramer produced in the system specifically was shown to stain an HLA-DR4 restricted T cell line obtained from a healthy donor by in vitro priming, but which recognizes a type I diabetes autoantigen. Co-expression of chaperones may represent a general strategy for enhancing yields of recombinant proteins expressed in insect cells and facilitate production of MHC class II tetramers in the future.


LncRNA ELF3-AS1 is involved in the regulation of oral squamous cell carcinoma cell proliferation by reprogramming glucose metabolism.
The present study aims to investigate the role of ELF3-AS1 in oral squamous cell carcinoma (OSCC). A total of 112 patients with OSCC were admitted in Guangdong Provincial Stomatological Hospital from March 2016 to March 2019. RT-qPCR, cells and transient transfections, cell proliferation rate measurements and Western blots were carried out to analyze the samples. In the present study, we showed that ELF3-AS1 and glucose transporter 1 (GLUT1) were both upregulated in OSCC tissues, and those two factors were positively correlated. In OSCC cells, ELF3-AS1 overexpression resulted in upregulation, while ELF3-AS1 siRNA silencing caused downregulated expression of GLUT1 and glucose uptake. ELF3-AS1 and GLUT1 overexpression resulted in increased rate of OSCC cells, while ELF3-AS1 and GLUT1 siRNA silencing resulted in decreased proliferation rate of OSCC cells. In addition, GLUT1 siRNA silencing attenuated the effects of ELF3-AS1 overexpression. Therefore, ELF3-AS1 promotes the proliferation of OSCC cells by reprogramming glucose metabolism.


Reply to "Comment on 'Harvesting information to control nonequilibrium states of active matter' ".
We stress that the limitations on one of the results of our paper [R. Goerlich et al., Phys. Rev. E 106, 054617 (2022)2470-004510.1103/PhysRevE.106.054617], which are mentioned in the preceding Comment [A. Bérut, preceding Comment, Phys. Rev. E 107, 056601 (2023)10.1103/PhysRevE.107.056601], were actually already acknowledged and discussed in the original publication. Although the observed relationship between the released heat and the spectral entropy of the correlated noise is not universal (but limited to one-parameter Lorentzian spectra), the existence of such a clear relationship is a solid experimental finding. It not only gives a convincing explanation for the surprising thermodynamics observed in the transitions between nonequilibrium steady states, but also provides new tools for the analysis of nontrivial baths. In addition, by using different measures of the correlated noise information content, it may be possible to generalize these results to non-Lorentzian spectra.


Measurements of venous oxygen saturation in the superior sagittal sinus using conventional 3D multiple gradient-echo MRI: Effects of flow velocity and acceleration.
This work investigates the effects of flow acceleration in the superior sagittal sinus on slice-dependent variations in venous oxygen saturation (SvO2 ) estimations using susceptibility-based MR oximetry. Three-dimensional multiple gradient-echo images, with first-order flow compensation along the anterior-posterior readout direction for the first echo, were acquired twice from 15 healthy volunteers. For all slices, phases within the superior sagittal sinus were fitted using linear regression across four TEs to obtain the Pearson's correlation coefficients (PCCs), the largest of which corresponded to minimum acceleration influence. SvO2 derived from odd echoes on this slice was used to assess interscan difference, and compared with the central 15th slice for slice-dependent difference, both using Bland-Altman analysis. Within-scan interslice SvO2 consistency was examined versus PCC. Multislice-averaged SvO2 values were then computed from slices with PCCs above a certain threshold. Slice-dependent difference in SvO2 varied from -16.2% to 21.5% at two SDs, in agreement with a recent report, and about twice larger than interscan differences for the automatically selected slice (-7.5% to 10.3%) and for the central 15th slice (-8.0% to 8.8%). For slices with PCCs higher than -0.98, interslice SvO2 deviations were all found to be less than 5.0%. Multislice-averaged SvO2 with PCCs higher than -0.98 further reduced interscan difference to -4.7% to 8.2%. Slice-dependent variations in SvO2 may partly be explained by the effects of flow acceleration. Our method may enable conventional 3D multiple gradient echo to be used for SvO2 estimations in the presence of pulsatile flow.


Experimental inoculation of Neospora caninum in pregnant water buffalo.
The aim of this study was to characterize the pathogenesis of Neospora caninum in experimentally inoculated pregnant water buffalo (Bubalus bubalis). Twelve Mediterranean female water buffaloes ranging in age from 4 to 14 years old and seronegative to N. caninum by indirect fluorescent antibody test (IFAT) were involved. Ten females were intravenously inoculated with 10(8) tachyzoites of NC-1 strain at 70 (n=3) or 90 (n=7) days of pregnancy (dp). Two control animals were inoculated with placebo at 70 and 90 dp, respectively. Serum samples were obtained weekly following inoculation to the end of the experiment. Three animals inoculated at 70 dp were slaughtered at 28 days post inoculation (dpi), three animals inoculated at 90 dp were slaughtered at 28 dpi and the remaining four animals inoculated at 90 dp were slaughtered at 42 dpi. Fetal fluids from cavities and tissue samples were recovered for IFAT and histopathology, immunohistochemistry and PCR, respectively. Genomic DNA from fetal tissues was used for parasite DNA detection and microsatellite genotyping in order to confirm the NC-1 specific-infection. Dams developed specific antibodies one week after the inoculation and serological titers did not decrease significantly to the end of the experiment. No abortions were recorded during the experimental time; however, one fetus from a dam inoculated at 70 dp was not viable at necropsy. Specific antibodies were detected in only two fetuses from dams inoculated at 90 dp that were slaughtered at 42 dpi. No macroscopic changes in the placentas and organs of viable fetuses were observed. Nonsuppurative placentitis was a common microscopic observation in Neospora-inoculated specimens. Microscopic fetal lesions included nonsuppurative peribronchiolar interstitial pneumonia, epicarditis and myocarditis, interstitial nephritis, myositis and periportal hepatitis. Positive IHC results were obtained in two fetuses from dams inoculated at 70 dp and slaughtered at 28 dpi. N. caninum DNA was detected in placentas and fetuses from all inoculated animals. The pattern of amplified microsatellites from placental and fetal tissues resembled the NC-1 strain. Water buffaloes, like cattle, are susceptible to experimental inoculation with N. caninum at early pregnancy.


An examination of the role of chiasma frequency in the genetic system of marsupials.
Chiasma frequencies have been collected from males of 33 species of marsupial, varying widely with respect to size, reproduction and development. Correlation analyses show that species with lower levels of recombination are smaller, have larger litters and develop more quickly. Two indices of recombination level were considered: Darlington's Recombination Index, and the Excess Chiasma frequency (chiasmata above one per bivalent). The EC is in general more strongly correlated than RI with aspects of life history. It is suggested that EC levels have evolved due to the effects of EC on recombination, but that chromosome number has evolved independently.


Effects of the sequence and size of non-polar residues on self-assembly of amphiphilic peptides.
Peptides with alternating hydrophobic and polar amino acids have been shown to form stable beta-sheet secondary structures and self-assemble into hydrogel-like matrices in the presence of physiological salt concentrations. We hypothesized that the sequence and steric size differences of non-polar residues can affect the balance of peptide intermolecular forces in solution that drive self-assembly. To test this hypothesis, we designed a library of artificial amphiphilic peptides based on the sequence (FEFEFKFK)2 by substituting combinations of the non-polar residues glycine, alanine, valine, leucine and isoleucine for phenylalanine. Peptide structure and self-assembly were characterized using scanning electron microscopy, the Thioflavin T assay, transmission electron microscopy, X-ray fiber diffraction and circular dichroism spectroscopy. The sequence and steric size of non-polar residues are shown to cause variations in peptide secondary structures and create significant differences in the matrix morphology of self-assembled peptides.


In-toto non-destructive assay methodology for the elimination of metallic waste from particle accelerators after melting.
Melting of metallic waste reduces the waste volume, allows more accurate radiological characterization, and minimizes handling at the waste production site. This paper proposes a new non-destructive assay methodology to radiologically characterize low- and intermediate-level (LILW) waste before melting. A non-destructive assay technique is developed and qualified using geometry optimization technique and sample analysis after melting. Additionally, we present an operational methodology to predict the activity values of the major gamma emitters based on the average dose rate measurements.


Solid phase microextraction and gas chromatography with ion trap detector (GC-ITD) analysis of amitraz residues in beeswax after hydrolysis to 2,4-dimethylaniline.
An analytical method for the determination of amitraz residues in beeswax after hydrolysis to 2,4-dimethylaniline is reported. It consists of wax extraction with an acid buffer solution, head space solid phase microextraction and GC-ITD analysis. The limit of determination is 1 ng g(-1). Wax samples from beekepers and commercial foundations were analysed, content of residues varied from <1 to 20.5 ng g(-1).


Function of the diabetic retina after panretinal argon laser coagulation.
Panretinal photocoagulation has been demonstrated to have a beneficial effect on the natural history of diabetic retinopathy. However, it is associated with detectable loss of retinal function. To determine the best coagulation technique we conducted a prospective study in 32 eyes of 16 patients. We investigated retinal function in relation to spot size and scatter density after panretinal laser coagulation. One eye was treated with approximately 400 comparatively large laser spots (0.6-0.8 mm diameter), whereas the fellow eye was coagulated with approximately 1500 small spots (0.2-0.4 mm diameter), so that the total coagulated area was almost the same in both eyes. Subjective parameters (visual acuity, perimetry, dark adaptation, photostress), as well as objective functions (electroretinogram, ERG; electro-oculogram, EOG), were studied preoperatively and then postoperatively over a time span of 6 months. Pronounced impairment of retinal function was detected, which recovered after 3 months on the average. When the pairs of eyes were compared, persistent visual field scotomas as detected by computerized static perimetry, occurred less frequently in eyes subjected to small coagulation spots, although this tendency was not statistically significant.


Role of obesity and adiposity in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Obesity may have a marked impact on both the development and progression of the syndrome. A high proportion of women with PCOS are obese. Regardless of the degree of obesity, women with PCOS are more likely to have central (abdominal) distribution of body fat, which is associated with insulin resistance and hyperandrogenaemia. PCOS is not only a reproductive disorder, but is also associated with significant increase in metabolic aberrations and cardiovascular risk factors. It has been shown that weight loss improves the metabolic and reproductive abnormalities that characterise the syndrome.


Diltiazem and progression of myocardial ischemic damage during coronary artery occlusion and reperfusion in porcine hearts.
This study was designed to investigate whether a cardioprotective intervention could delay the completion of necrosis so that subsequent reperfusion would be more useful. Thirty-six pigs were randomly allocated to treatment with diltiazem (15 micrograms/kg per min) or saline solution and to a 60 or 120 minute coronary occlusion period followed by reperfusion. The treatment was begun 15 minutes before coronary occlusion and terminated 75 minutes after reperfusion. Twenty-four hours after the procedure, the heart was sliced and incubated in triphenyltetrazolium chloride. The infarct area and the maximal transmural area of extension of the infarct were calculated by planimetry. The total number of red blood cells in a transmural section was also counted. In the pigs with a 60 minute coronary occlusion, diltiazem (compared with saline solution) significantly reduced infarct size from 9.7 +/- 1.5% of left ventricular mass to 5.9 +/- 0.6% (p less than 0.05) and the percent transmural extension from 0.72 +/- 0.05 to 0.61 +/- 0.05% (p less than 0.05). Red blood cell extravasation in the infarcted area was reduced from 161,934 +/- 59,905 to 78,525 +/- 46,484 cells/mm3 (p less than 0.05) with diltiazem and the percent transmural extension of the hemorrhagic necrosis from 70 +/- 10 to 36 +/- 15% (p less than 0.05). No such differences were observed in the 120 minute coronary occlusion groups. Mean red blood cell counts and the extent of hemorrhagic necrosis did not correlate with either infarct size or transmural extension.(ABSTRACT TRUNCATED AT 250 WORDS)


Controversies and Trends in United Kingdom Bunion Surgery.
Current practice and controversies in UK bunion surgery are discussed. Patients tend to be offered a distally based metatarsal osteotomy, such as a chevron or scarf osteotomy, for mild to moderate symptomatic bunions. Greater deformities are managed with a more extreme scarf, supplemented with a proximal phalangeal osteotomy. A proximal fusion in the form of the Lapidus-type procedure is still reserved for the most severe, hypermobile, or arthritic cases. Minimally invasive techniques for bunions have failed to disseminate into common UK practice. The trends in the United Kingdom regarding litigation, venous thromboembolism, and osteodesis for bunion surgery are also discussed.


Interventions to support shared decision making for hypertension: A systematic review of controlled studies.
Hypertension (high blood pressure) is a common long-term health condition. Patient involvement in treating and monitoring hypertension is essential. Control of hypertension improves population cardiovascular outcomes. However, for an individual, potential benefits and harms of treatment are finely balanced. Shared decision making has the potential to align decisions with the preferences and values of patients. Determine the effectiveness of interventions to support shared decision making in hypertension. Searches in MEDLINE, EMBASE, CINAHL, Web of Science and PsycINFO up to 30 September 2017. Controlled studies evaluating the effects of shared decision-making interventions for adults with hypertension compared with any comparator in any setting and reporting any outcome measures. Six studies (five randomized controlled trials) in European primary care were included. Main intervention components were as follows: training for health-care professionals, decision aids, patient coaching and a patient leaflet. Four studies, none at low risk of bias, reported a measure of shared decision making; the intervention increased shared decision making in one study. Four studies reported blood pressure between 6 months and 3 years after the intervention; there was no difference in blood pressure between intervention and control groups in any study. Lack of comparability between studies prevented meta-analysis. Despite widespread calls for shared decision making to be embedded in health care, there is little evidence to inform shared decision making for hypertension, one of the most common conditions managed in primary care.


Determination of the thiol redox state of organisms: new oxidative stress indicators.
This study describes a new methodology by which the concentrations of non-protein (NP) thiols glutathione (GSH), cysteine (CSH), N-acetylcysteine (AcCSH), and protein (P) thiols (PSH), as well as the contribution of these components to symmetric and mixed disulfides (NPSSR, NPSSC, NPSSCAc, PSSR, PSSC, PSSCAc, PSSP) can reliably be measured. The methodology consists of a strict sequence of methods which are applied to every sample. Free thiols at any given state of the procedure are measured by Ellman's assay, the CSH fraction is measured by its unique response in the ninhydrin assay, AcCSH is selectively measured with ninhydrin after enzymatic deacylation, proteins are separated from non-protein thiols/disulfides by precipitation with trichloroacetic or perchloric acid, disulfides are reduced into free thiols with borohydride, mixed disulfides between a protein and a non-protein component are measured by extracting the non-protein thiol from the protein pellet after borohydride treatment, and protein thiols/disulfides are measured after resolubilization of the protein pellet. When this method was applied to animal and fungal tissue, new molecular indicators of the thiol redox state of living cells were identified. The findings of the present study clearly show that the new parameters are very sensitive indicators of redox state, while at the same time the traditional parameters GSH and GSSG often remain constant even upon dramatic changes in the overall redox state of biological tissue. Therefore, unbiased assessment of the redox state also requires explicit measurement of its most sensitive thiol indicators.


Perceptions about using mindfulness therapy: a lung cancer focus group study.
Patients with lung cancer are in need of effective strategies to modify symptom burden and improve health-related quality of life (HRQOL). One promising approach to symptom management is an 8-week mindfulness-based intervention, which incorporates meditation, breathing, and gentle yoga exercises. It requires few resources to implement, but has not been adequately tested with lung cancer patients. The purpose of this study was to obtain lung cancer patient perceptions of a mindfulness-based intervention. Eleven lung cancer patients participated in audio-taped focus group sessions led by the investigator. Discussion questions probed patient perceptions of mindfulness in terms of symptom management, including benefits and barriers to this therapy and ways the intervention may need to be adapted to accommodate them. Three primary themes from the qualitative analysis include (1) awareness and interest, (2) perceived barriers and benefits, and (3) recommended adaptations. Specific perceptions included the importance of targeting key symptoms such as dyspnea, worry, and insomnia, whereas recommendations pointed out the need for a shorter duration than the standard 8-week protocol and a home-based approach for greater accessibility. The design of mindfulness-based intervention protocols must consider unique characteristics of this vulnerable group, such as targeting specific symptoms, reducing the 8-week protocol, and a home-based offering. Nurses are integral to optimizing HRQOL and independent functioning for lung cancer patients. As lung cancer survivorship is extended, it becomes increasingly imperative that a range of supportive resources is available for patients to manage symptoms and improve HRQOL.


Functional and pharmacological characterization of two different ASIC1a/2a heteromers reveals their sensitivity to the spider toxin PcTx1.
Acid Sensing Ion Channels (ASICs) detect extracellular proton signals and are involved in synaptic transmission and pain sensation. ASIC subunits assemble into homo- and heteromeric channels composed of three subunits. Single molecule imaging revealed that heteromers composed of ASIC1a and ASIC2a, which are widely expressed in the central nervous system, have a flexible 2:1/1:2 stoichiometry. It was hitherto not possible, however, to functionally differentiate these two heteromers. To have a homogenous population of ASIC1a/2a heteromers with either 2:1 or 1:2 stoichiometry, we covalently linked subunits in the desired configuration and characterized their functional properties in Xenopus oocytes. We show that the two heteromers have slightly different proton affinity, with an additional ASIC1a subunit increasing apparent affinity. Moreover, we found that zinc, which potentiates ASIC2a-containing ASICs but not homomeric ASIC1a, potentiates both heteromers. Finally, we show that PcTx1, which binds at subunit-subunit interfaces of homomeric ASIC1a, inhibits both heteromers suggesting that ASIC2a can also contribute to a PcTx1 binding site. Using this functional fingerprint, we show that rat cortical neurons predominantly express the ASIC1a/2a heteromer with a 2:1 stoichiometry. Collectively, our results reveal the contribution of individual subunits to the functional properties of ASIC1a/2a heteromers.


Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria.
Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. In the experimental model of cerebral malaria (ECM) by Plasmodium berghei ANKA, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ECM. However, the dose and administration route used is associated with cardiovascular side effects such as hypotension and bradycardia in humans and mice, which could preclude its potential use as adjunctive treatment in HCM. In the present study, alternative delivery systems for nimodipine during late-stage ECM in association with artesunate were searched to define optimal protocols to achieve maximum efficacy in increasing survival in rescue therapy while causing the least cardiac side effects. The baseline electrocardiogram (ECG) and arterial pressure characteristics of uninfected control animals and of mice with ECM and its response upon rescue treatment with artesunate associated or not with nimodipine is also analysed. Nimodipine, given at 0.5 mg/kg/day via a slow and continuous delivery system by osmotic pumps, increases survival of mice with ECM when used as adjunctive treatment to artesunate. Mice with ECM showed hypotension and ECG changes, including bradycardia and increases in PR, QRS, QTc and ST interval duration. ECM mice also show increased QTc dispersion, heart rate variability (HRV), RMSSD, low frequency (LF) and high frequency (HF) bands of the power spectrum. Both sympathetic and parasympathetic inputs to the heart were increased, but there was a predominance of sympathetic tone as demonstrated by an increased LF/HF ratio. Nimodipine potentiated bradycardia when given by bolus injection, but not when via osmotic pumps. In addition, nimodipine shortened PR duration and improved HRV, RMSSD, LF and HF powers in mice with ECM. In addition, nimodipine did not increased hypotension or decreased the speed of arterial pressure recovery when used in rescue therapy with artesunate. These data show that slow and continuous delivery of lower doses of nimodipine improves survival of mice with ECM in rescue therapy with artesunate while showing a safer profile in terms of cardiovascular effects.


Direct and Indirect Effects of Behavioral Parent Training on Infant Language Production.
Given the strong association between early behavior problems and language impairment, we examined the effect of a brief home-based adaptation of Parent-child Interaction Therapy on infant language production. Sixty infants (55% male; mean age 13.47±1.31 months) were recruited at a large urban primary care clinic and were included if their scores exceeded the 75th percentile on a brief screener of early behavior problems. Families were randomly assigned to receive the home-based parenting intervention or standard pediatric primary care. The observed number of infant total (i.e., token) and different (i.e., type) utterances spoken during an observation of an infant-led play and a parent-report measure of infant externalizing behavior problems were examined at pre- and post-intervention and at 3- and 6-month follow-ups. Infants receiving the intervention demonstrated a significantly higher number of observed different and total utterances at the 6-month follow-up compared to infants in standard care. Furthermore, there was an indirect effect of the intervention on infant language production, such that the intervention led to decreases in infant externalizing behavior problems from pre- to post-intervention, which, in turn, led to increases in infant different utterances at the 3- and 6-month follow-ups and total utterances at the 6-month follow-up. Results provide initial evidence for the effect of this brief and home-based intervention on infant language production, including the indirect effect of the intervention on infant language through improvements in infant behavior, highlighting the importance of targeting behavior problems in early intervention.


Investigation of heavy metal (Cu, Pb, Cd, and Cr) stabilization in river sediment by nano-zero-valent iron/activated carbon composite.
Nano-zero-valent iron/activated carbon (nZVI/AC) composite was evaluated for its effectiveness in the stabilization of Cu, Pb, Cd, and Cr in dredged river sediment. Synthetic precipitation leaching procedure (SPLP) and toxicity characteristic leaching procedure (TCLP) were adopted to compare the effects of nZVI/AC dosage, particle size, time duration, and temperature on heavy metal leachability. The results show that leachability dropped considerably with the addition of nZVI/AC and powdered particles in the size of 0.075-0.18 mm was more effective in stabilization than granular ones. Stabilization effect was stable in long-term and robust against changes in temperature. Tessier sequential extraction revealed that heavy metals were associated with solid particle, inorganic or organic matters in sediment. The addition of nZVI/AC was able to convert relatively weakly bound heavy metals into more strongly bound species and thus reduce the bioavailability and toxicity. Also, the standard potential of heavy metals may decide the mechanism of stabilization process.


Abdominal aortic aneurysms. Ultrasonic measurement of the transverse diameter and its prognostic significance in the light of pathological observations.
The risk of rupture of an abdominal aortic aneurysm is related to size. Pathological observations suggest that there is usually an asymmetric formation of mural thrombus in the aneurysm sac and that rupture occurs more commonly through the lateral walls where there would be less. Ultrasonic estimation of the transverse diameter of an aneurysm offers a useful clinical method of monitoring size and likelihood of rupture.


Development of a sensitive and selective kojic acid sensor based on molecularly imprinted polymer modified electrode in the lab-on-valve system.
In this work, a kojic acid electrochemical sensor, based on a non-covalent molecularly imprinted polymer (MIP) modified electrode, had been fabricated in the lab-on-valve system. The sensitive layer was synthesized by cyclic voltammetry using o-phenylenediamine as the functional monomer and kojic acid as the template. The template molecules were then removed from the modified electrode surface by washing with NaOH solution. Differential pulse voltammetry method using ferricyanide as probe was applied as the analytical technique, after extraction of kojic acid on the electrode. Chemical and flow parameters associated with the extraction process were investigated. The response recorded with the imprinted sensor exhibited a response in a range of 0.01-0.2 μmol L(-1) with a detection limit of 3 nmol L(-1). The interference studies showed that the MIP modified electrode had excellent selectivity. Furthermore, the proposed MIP electrode exhibited good sensitivity and low sample/reagent consumption, and the sensor could be applied to the determination kojic acid in cosmetics samples.


Trends in Utilization and Safety of In-Hospital Coronary Artery Bypass Grafting During a Non-ST-Segment Elevation Myocardial Infarction.
Up to 10% of non-ST-segment elevation myocardial infarction (NSTEMI) patients require coronary artery bypass graft (CABG) surgery during their hospitalization. Contemporary, real-world, data regarding CABG utilization and safety in NSTEMI patients are lacking. Our objectives were to investigate the contemporary trends in utilization and outcomes of CABG in patients admitted for NSTEMI. Using the 2003 to 2015 National Inpatient Sample data, we identified hospitalizations for NSTEMI, during which a CABG was performed. Patients' sociodemographic and clinical characteristics, incidence of surgical complications, length of stay, and mortality were analyzed. Multivariate analyses were performed to identify predictors of in-hospital complications and mortality. An estimated total of 440,371 CABG surgeries, during a hospitalization for NSTEMI, were analyzed. The utilization of CABG was steady over the years. The data show increasing prevalence of individual co-morbidities as well as cases with Deyo Co-morbidity Index ≥2 (p <0.001). High, 26.4%, complication rate was driven mainly by cardiac and pulmonary complications. The mortality rate declined from 3.6% in 2003 to an average of 2.4% during 2010 to 2015. Older age, female gender, heart failure, and delayed CABG timing were independent predictors of adverse outcomes. In conclusion, utilization of in-hospital CABG as the primary revascularization strategy in patients with NSTEMI remained steady over the years. These data reveal the raising prevalence of co-morbidities during the study. High complication rate was recorded; however, the mortality declined over the years to about 2.4%. Delaying CABG was associated with small but statistically significant worsening in outcomes.


Maintenance of dihydrofolate reductase enzyme after disappearance of DHFR mRNA during muscle cell differentiation.
Terminally differentiating mouse muscle cells were used to examine the relationship between myogenic withdrawal from the cell cycle and the levels of dihydrofolate reductase (DHFR) mRNA and DHFR activity. Differentiation was induced by removal of fibroblast growth factor activity from the medium. DHFR mRNA was measured by a RNase protection assay. DHFR activity was measured by a spectrophotometric assay and by a [3H]methotrexate binding assay. Proliferative myoblasts contained four DHFR mRNA molecules and 1.8 X 10(5) DHFR enzyme molecules. By 12.5 h after induction, when [3H]thymidine labeling indices showed all cells had withdrawn from the cell cycle, DHFR mRNA levels had declined to 0.7 copies per cell. In contrast, myogenic withdrawal did not result in reduced DHFR activity. Qualitatively similar results, i.e. down-regulation of mRNA and constitutive expression of activity, were observed in a methotrexate-selected muscle cell line with greater than 50-fold amplification of the DHFR gene. Enzyme synthesis rate and stability measurements indicated that persistence of DHFR activity in postreplicative cells was due to a long enzyme lifetime rather than to continued synthesis from residual normal DHFR mRNA or an alternative mRNA species not detected by the RNase protection assay. Unlike DHFR, thymidine kinase (TK) activity disappeared rapidly as muscle cells differentiated. Both DHFR mRNA and TK mRNA are expressed in a replication-dependent manner; however, the enzymes encoded by these messages are subject to different fates in postreplicative cells.


Ovarian antral follicles metabolize imidacloprid in vitro.
Neonicotinoid insecticides are synthetic nicotine derivatives that have high affinity for invertebrate nicotine receptors and low affinity for mammalian nicotine receptors. However, imidacloprid (IMI), the most commonly used neonicotinoid, can be bioactivated by the liver in mammals to desnitro-imidacloprid, an intermediate metabolite that effectively binds and activates mammalian receptors. However, it is not known if other tissues such as the ovaries can metabolize IMI. Thus, the present study tested the hypothesis that ovarian antral follicles metabolize and bioactivate IMI. Antral follicles were dissected from the ovaries of CD-1 mice and cultured in media containing dimethyl sulfoxide or IMI (0.2-200 µg/ml) for 48 and 96 h. Media were subjected to liquid chromatography-mass spectrometry for detection of phase I IMI metabolites. Follicles from the cultures were used for gene expression analysis of metabolic enzymes associated with IMI metabolism. All IMI metabolites were detected at 48 and 96 h. Oxidized IMI intermediates were detected in media from cultured follicles, but not environmental controls. Reduced IMI intermediates were detected in media from cultured follicles and the environmental controls. At 48 h, IMI did not affect expression of any metabolic enzymes compared with control. At 96 h, IMI induced Cyp2e1 and Cyp4f18 compared with control. These data indicate that mouse ovarian follicles metabolize IMI and that IMI induces ovarian Cyp expression over time.


Respiratory responses to short term hypoxia in the snapping turtle, Chelydra serpentina.
Among vertebrates, turtles are able to tolerate exceptionally low oxygen tensions. We have investigated the compensatory mechanisms that regulate respiration and blood oxygen transport in snapping turtles during short exposure to hypoxia. Snapping turtles started to hyperventilate when oxygen levels dropped below 10% O(2). Total ventilation increased 1.75-fold, essentially related to an increase in respiration frequency. During normoxia, respiration occurred in bouts of four to five breaths, whereas at 5% O(2), the ventilation pattern was more regular with breathing bouts consisting of a single breath. The increase in the heart rate between breaths during hypoxia suggests that a high pulmonary blood flow may be maintained during non-ventilatory periods to improve arterial blood oxygenation. After 4 days of hypoxia at 5% O(2), hematocrit, hemoglobin concentration and multiplicity and intraerythrocytic organic phosphate concentration remained unaltered. Accordingly, oxygen binding curves at constant P(CO(2)) showed no changes in oxygen affinity and cooperativity. However, blood pH increased significantly from 7.50+/-0.05 under normoxia to 7.72+/-0.03 under hypoxia. The respiratory alkalosis will produce a pronounced in vivo left-shift of the blood oxygen dissociation curve due to the large Bohr effect and this is shown to be critical for arterial oxygen saturation.


Effect of obturators on facial form following surgery for head and neck cancer and impact on the perception of appearance.
To describe the correlation between changes in the surface area and depth of the face in individuals wearing an obturator compared with it not being in place, and self-reported Quality of Life in relation to appearance. Difference images were created from stereophotogrammetry images recorded from research participants with and without their obturators in place. On the difference images of the face, surface areas and mean depths were calculated. Oral health impact profile questionnaires (OHIP-49) were completed. Data from 19 research participants were recorded. The mean size of the outlined area of the face when the obturators were present compared to when they were not was 1411 mm2 (SD ± 848). Similarly the mean depth differences ranged up to 6.14 mm. Although a proportion of the individuals reported effects in relation to their quality of life, there were no statistically significant relations between the surface areas and mean depths with the participants' responses to the quality of life questions. There are clear changes in facial tissues, both in relation to surface area and depths when obturators are worn compared to when they are not. There is no simple relationship between the extent of facial change with and without an obturator and quality of life around appearance. The determinants of changed quality of life in this group of patients require greater exploration.


Acute and long-term effects of modified hemoglobin (HBOC-201) in a rat model of hypertension and chronic kidney disease.
The goal was to determine whether administration of the oxygen-therapeutic blood substitute HBOC-201 had any deleterious effect on renal function and/or structure in a rat model of chronic kidney disease (CKD). Longitudinal studies were conducted in the conscious chronically catheterized male Sprague-Dawley rat with rapidly progressing CKD produced by ablation-infarction of 5/6th of the functional renal mass. Experimental rats received a loading dose (after acute removal of 10% blood volume) and six subsequent daily maintenance doses of HBOC-201 at Weeks 4 to 5 after induction of CKD and were studied again at 6 weeks. Controls received isoosmotic human serum albumin (HSA, 13%) over the same period. Blood pressure (BP) and renal function were measured in acute experiments at Weeks 4, 5, and 6. Proteinuria and 24-hour creatinine clearance was measured longitudinally and renal pathology was assessed at killing. There were differences in the acute response to the infusions, with rats given HBOC-201 exhibiting an increase in BP and renal vascular resistance, whereas rats given HSA showed a decrease in BP. These changes did not persist, however, because mean BP, glomerular filtration rate, level of proteinuria, and glomerular pathology were all similar at the end of the study (6 weeks after induction of CKD) in rats given HBOC-201 and HSA. In this model of CKD, daily doses of HBOC-201 had no long-term damaging effects on renal function or structure, compared to rats given the osmotic control agent, 13 percent HSA.


Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia.
Severe COVID-19 is associated with innate immunopathology, and CD14, a proximal activator of innate immunity, has been suggested as a potential therapeutic target. We conducted the COVID-19 anti-CD14 Treatment Trial (CaTT), a Phase II randomized, double-blind, placebo-controlled trial at 5 US-sites between April 12, 2021 and November 30, 2021 (NCT04391309). Hospitalized adults with COVID-19 requiring supplemental oxygen (<30 LPM) were randomized 1:1 to receive 4 daily doses of intravenous IC14, an anti-CD14 monoclonal antibody, or placebo. All participants received remdesivir. The primary outcome was time-to-resolution of illness, defined as improvement on the 8-point NIH-Ordinal COVID-19 Scale to category ≤3. Secondary endpoints were safety and exploratory endpoints were pro-inflammatory and antiviral mediators in serum on days 0-5 & 7. The trial was stopped after 40 patients were randomized and treated due to slow enrollment. 40 participants were randomized and treated with IC14 (n = 20) or placebo (n = 20). The median time-to-recovery was 6 days (95% CI, 5-11) in the IC14 group vs. 5 days (95% CI, 4-10) in the Placebo group (recovery rate ratio: 0.77 (95% CI, 0.40, 1.48) (log-rank p = 0.435). The number of adverse events was similar in each group, and no IC14-attributable secondary infections occurred. In repeated-measures mixed-effects analyses, IC14 treatment increased serum sCD14 concentrations, an expected pharmacodynamic effect. Pre-planned, exploratory analyses suggested that IC14 treatment decreased the trajectories of circulating MIP-1β and TNF-α. IC14 treatment did not improve time-to-resolution of illness in hypoxemic patients with COVID-19 in this small trial. Results of exploratory analyses suggested IC14 had biologic effects that warrant future clinical investigation. National Institute of Allergy and Infectious Diseases.


Quantitative Gene Expression by Recurrence Score in ER-Positive Breast Cancer, by Age.
Breast cancer in young women (<50 years) has been associated with an increased risk of recurrence and decreased survival compared with patients older than 50. The objective of this analysis was to determine, from a large database of patients with early-stage breast cancer, if the Recurrence Score(®) result (Oncotype DX(®), Genomic Health, Inc, Redwood City, CA, USA) provided clinically meaningful differences in predicted risk of recurrence in younger-compared with older-patients. Tumor samples from patients with estrogen receptor (ER)-positive breast cancers that were successfully processed in the Genomic Health central lab between June 2004 and December 2013 for Recurrence Score and quantitative gene expression of ER, progesterone receptor (PR), and Her/2neu, were included. Descriptive statistics were used to describe the distribution of scores by age group: <40, 40-49, 50-59, 60-69, and ≥70 years, nodal status, and histologic subtype. Specimens from 394,031 patients [3.3% (n = 13,029) aged <40 years; 15.6% (n = 61,643) aged ≥70 years] were included; 81.6% of patients had invasive ductal carcinoma. Nodal status was specified for 362,001 patients (87.0% negative). Median Recurrence Score results were similar across risk groups. Low (<18)- and high (≥31)- risk Recurrence Score results were seen in 58.5% and 8.5% of patients, respectively. A greater proportion of patients aged <40 (14.1%) than ≥70 (8.8%) years had a high-risk score. ER expression increased as a function of age and PR single-gene and invasion gene group expression were similar across age groups. These data indicate that in patients with ER-positive breast cancer, age alone does not reflect the underlying individual tumor biology, suggesting that the Recurrence Score result may add potentially useful information for personalized treatment decisions. Genomic Health, Inc.


Microhabitat use by European rabbits (Oryctolagus cuniculus) in central Chile: Are adult and juvenile patterns the same?
Rabbits (Oryctolagus cuniculus) have been recently introduced to central Chile; adult rabbits have been previously reported to exhibit a release in their use of microhabitats due to lack of effective predation upon them. This paper shows that kittens and juvenile rabbits do not exhibit the same microhabitat use pattern as adults, in spite of the very low predation pressure upon them. These results suggest that small rabbits are ecologically comparable to native rodents.


A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer.
Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥ 1,500/mm(3), platelets ≥ 100,000/mm(3), creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase ≤ 2.5 × upper limit of normal. FDR-G (1000 mg/m(2)/100 min intravenously) was given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥ 3, neutropenic fever, or deterioration in performance status to ≥ 3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.


Comparative evaluation of the effect of 10%, 20%, and 30% guava seed extract on reversing compromised resin bond strength after enamel bleaching in 120 min, 10 min, and 5 min: An in vitro study.
Bonding of composite with enamel and dentin gets compromised if the tooth is restored with composite immediately post bleaching. The application of antioxidants has shown to have a positive effect on it. The aim of this study was to evaluate and compare the effect of guava seed extract solutions in various concentrations on the shear bond strength (SBS) of composite resin to bleached enamel when applied for 5 min, 10 min, and 120 min. Fifty-five maxillary incisors were procured, and labial surfaces of 50 specimens were bleached with 37.5% hydrogen peroxide. These specimens were divided into 3 experimental groups: Group 1-3 comprising 15 specimens each (n = 15), and the remaining specimens were divided into two groups: Group 4 (positive control group) and Group 5 (negative control group). Groups 1-3 were further divided into 3 subgroups according to the application period of antioxidant: subgroups A, B, and C. Specimens were stored in distilled water for 24 h. SBS testing was done using the universal testing machine. Data were tabulated and subjected to statistical analysis using a three-way analysis of variance with post hoc Tukey's test. Guava seed extract showed a complete reversal of the compromised bond strength, and promising results were seen with increased concentration. The use of antioxidants effectively reversed the compromised bond strength of bleached enamel, and an increase in the concentration of antioxidants reduces the duration of its application.


Determination of 5-nitroimidazole residues in milk by capillary electrochromatography with packed C18 silica beds.
This work presents a novel methodology for analysing 5-nitroimidazole residues in milk samples by capillary electrochromatography using lab-made packed columns, produced by carrying out a high pressure packing procedure using acetone as driving solvent and C18 silica uncapped particles (5 µm particle size) as packing material. Column frits resulted from sintering the proper stationary phase by heating the packed material for 20s with a nichrome ribbon (80% Ni-20% Cr, 28 cm × 2 mm × 0.2 mm, electric resistance 1.3 Ω) connected to a 7 V AC power supply. Lab-made C18 silica packed capillaries (40 cm x 50 µm i.d.) were employed for the determination of 5-nitroimidazole drugs. Milk samples were treated by a salting-out assisted liquid-liquid extraction followed by a solid phase extraction with Oasis®HLB cartridges prior to their injection. Samples were hydrodynamically injected into the column for 120 s at 11.5 bar. Afterwards eight 5-nitroimidazole compounds were separated in isocratic mode under an applied voltage of 27 kV and a temperature of 30 °C. The selected mobile phase consisted of a mixture 60:40 acetonitrile:ammonium acetate (2.5 mM, pH=5). Separation was monitored at 320 nm and it was performed in less than 15 min. The method was characterized in terms of linearity (R(2)≥0.993) and precision (repeatability, RSD≤12.2% and reproducibility, RSD≤14.5%), obtaining detection limits lower than 29 µg/L for all compounds under study.


Exploring the mitochondrial genome of Caridina pseudogracilirostris: a comparative analysis within the Atyidae Family.
Caridina pseudogracilirostris is a highly adaptive estuarine species found in brackish waters and marshes along the southwestern and southern coastal regions of India. The whole mitochondrial genome of C. pseudogracilirostris is 15,451 bp in length with 59.3% AT content and encodes 37 genes, including 22 tRNAs, 13 protein-coding genes, and two rRNAs, which are arranged in a distinctive pattern similar to most crustaceans. ML and BI methods were used for phylogenetic analysis of C. pseudogracilirostris clustered with other Caridina species, supporting the monophyly of the Caridina genus within the Atyidae family. The fully annotated mitochondrial genome of C. pseudogracilirostris was submitted to GenBank under accession number OQ534868.1. We are the first to report on the C. pseudogracilirostris whole mitochondrial genome, which provides a valuable resource for future research on genetics, evolution, phylogenetics, etc., among Caridina species and other species. The phylogenetic investigation supports the monophyly of the Caridina genus within the Atyidae family and emphasizes the value of mitochondrial genome data in determining the evolutionary relationships among crustaceans.


Treatment refusal in a rootless individual with medical problems.
A multidisciplinary case conference was held concerning an elderly woman who was hospitalized repeatedly because of progressive cardiac and pulmonary disease. The patient was unable to understand her illness and did not comply with the treatment regimen. The case demonstrates the usefulness of the multidisciplinary approach and the complexities of caring for someone who does not accept treatment. The dilemma is in how to preserve an individual's freedom and right to refuse treatment when organic impairment and past history interfere and pose a threat to health.


Reclaiming abandoned mine tailings ponds for agricultural use: Opportunities and challenges.
Tailings ponds, large man-made structures conceived during the mining process for waste storage, often become deserted post-mining, leaving behind a stark, contaminated landscape. This paper posits that these forsaken tailings ponds can be rejuvenated into fertile agricultural land through adept reclamation efforts. Serving as a discussion paper, it engages in a stimulating exploration of the environmental and health risks linked to tailings ponds. It sheds light on the potential and impediments in the transformation of these ponds into agricultural land. The discussion concludes that despite the substantial hurdles in repurposing tailings ponds for agriculture, there are encouraging prospects with the application of multifaceted efforts.


Floating treatment wetlands for the bioremediation of oil spills: A review.
Conventional oil spill recovery may cause significant damage to shoreline habitats during the removal of oiled material and from human and equipment interaction. In addition, these methods are costly and can leave a significant amount of residual oil in the environment. Biological remediation strategies may be a less invasive option for recovering oil from sensitive regions, with potential to increase recovery. Floating treatment wetlands are a growing area of interest for biodegradation of oil facilitated by plant-bacterial partnerships. Plants are able to stimulate microbial colonization in the rhizosphere, creating greater opportunity for contaminant interaction and degradation. A literature review analysis revealed thirteen articles researching this topic, and found that floating treatment wetlands have high potential to degrade oil contaminants. In some instances, plants and inoculated bacteria exhibited the highest degradation potential, however, plants alone had higher degradation potential than bacteria alone. Research is needed to explore how floating treatment wetlands perform in field-based trials and under variable environmental conditions.


Who should provide the uterus? The ethics of live donor recruitment for uterus transplantation.
Uterus transplantation (UTx) is an experimental surgery likely to face the issue of organ shortage. In my article, I explore how this issue might be addressed by changing the prevailing practices around live uterus donor recruitment. Currently, women with children - often the mothers of recipients - tend to be overrepresented as donors. Yet, other potentially eligible groups who may have an interest in providing their uterus - such as transgender men, or cisgender women who do not wish to gestate or to have children - tend to be excluded as potential donors. Moving forward, I recommend that donor inclusion criteria for UTx be broadened to be more inclusive of these latter groups.


MRI signal intensity ratio reflects the quality of the anterior talofibular and calcaneofibular ligaments in patients with chronic lateral ankle instability.
Ligament quality can affect clinical outcomes of ligament repair in chronic lateral ankle instability (CLAI). Magnetic resonance imaging (MRI) is used to assess the morphological changes of ligaments, but the measurement of signal intensity enables quantitative evaluation, which can evaluate the degree of the ligament quality. This study aimed to evaluate the qualitative diagnostic capacity for anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) injuries of the signal intensity on MRI. Thirty-eight and 20 ankles with and without CLAI, respectively, were included. The regions of interest (ROIs) were set in the ATFL, CFL, and tibialis anterior tendon (TAT) on MRI, and the signal intensities were measured. The signal intensities of the ATFL and CFL were corrected using TAT as the signal intensity ratio (SIR). The SIRs of the ATFL and CFL in the control and CLAI groups were compared. The relationship between the SIR of the ATFL and the arthroscopic findings was analyzed. Finally, the SIRs of the CFL in CLAI with and without CFL repair were compared. The mean SIR of the ATFL in the CLAI group (6.1 ± 2.4) was significantly higher than that in the control (2.1 ± 0.4) (P < 0.01). The SIR of the ATFL was associated with the arthroscopic grading. The mean SIR of the CFL in the CLAI groups (4.1 ± 2.5) was significantly higher than that in the control (1.7 ± 0.4) (P < 0.01). The SIR of the CFL in patients with the requirement of the CFL repair (6.2 ± 1.9) was significantly higher than that without the CFL repair (2.1 ± 0.5) (P < 0.05). The SIR is useful for evaluating the quality of the ATFL and CFL, which enables the decision of the treatment strategy of the CLAI.


The effect of hyaluronic acid incorporation on fibroblast spreading and proliferation within PEG-diacrylate based semi-interpenetrating networks.
The nanometer-scale mesh size of many synthetic crosslinked hydrogel networks restricts encapsulated cells to a rounded morphology that can inhibit cellular processes such as proliferation and migration that are essential for the early stages of remodeling and tissue formation. The objective of these studies was to investigate an approach for accelerating cellular remodeling based on the creation of semi-interpenetrating networks (IPNs) composed of hydrolytically degradable poly(ethylene glycol) (PEG) diacrylate macromers and native, enzymatically degradable extracellular matrix (ECM) components (collagen, gelatin and hyaluronic acid (HA)). Among the three ECM components investigated, addition of HA at concentrations of 0.12% w/v and greater supported fibroblast spreading throughout the three-dimensional network and significantly increased proliferation relative to control hydrogels without HA. Incorporation of HA resulted in relatively small changes in hydrogel physical/chemical properties such as swelling, degradation rate, and elastic modulus. Fibroblast spreading was eliminated by the addition of hyaluronidase inhibitors, demonstrating that cell-mediated enzymatic degradation of HA is a necessary mechanism responsible for the observed increases in fibroblast activity. By accelerating early cellular remodeling and growth, these semi-IPNs may be useful vehicles for cell transplantation in a variety of tissue engineering applications.


Perceptual fluency can be used as a cue for categorization decisions.
Learning in the prototype distortion task is thought to involve perceptual learning in which category members experience an enhanced visual response (Ashby & Maddox. Annual Review of Psychology, 56, 149-178, 2005). This response likely leads to more-efficient processing, which in turn may result in a feeling of perceptual fluency for category members. We examined the perceptual-fluency hypothesis by manipulating fluency independently from category membership. We predicted that when perceptual fluency was induced using subliminal priming, this fluency would be misattributed to category membership and would affect categorization decisions. In a prototype distortion task, the participants were more likely to judge stimuli that were not members of the category as category members when the nonmembers were made perceptually fluent with a matching subliminal prime. This result suggests that perceptual fluency can be used as a cue during some categorization decisions. In addition, the results provided converging evidence that some types of categorization are based on perceptual learning.


Domain size control in all-polymer solar cells.
In all polymer solar cells (all-PSCs), the domain size is critical for device performance. In highly crystalline polymer blends, however, precisely adjusting the domain size remains a significant challenge because of the simultaneous crystallization of both components. Herein, a strategy that promotes acceptor and donor to crystallize separately was proposed. Take PBDB-T/N2200 blends for instance; the solution state and confined crystallization were combined, which induced the crystallization of N2200, and PBDB-T occurred during the film-forming process and at thermal annealing stage. This separated crystallization process lowers the driving force of phase separation without affecting the degree of crystallinity of the blends. Thus, an interpenetrating network with high crystallinity and proper domain size was obtained, which boosted the power conversion efficiency to 7.59%. Importantly, the relation between pre-aggregation and domain size was established, which may be a guide to precisely adjust the active layer's domain size in all-PSCs.


Overexpression of STARCH BRANCHING ENZYME II increases short-chain branching of amylopectin and alters the physicochemical properties of starch from potato tuber.
Starch is biosynthesised by a complex of enzymes including various starch synthases and starch branching and debranching enzymes, amongst others. The role of all these enzymes has been investigated using gene silencing or genetic knockouts, but there are few examples of overexpression due to the problems of either cloning large genomic fragments or the toxicity of functional cDNAs to bacteria during cloning. The aim of this study was to investigate the function of potato STARCH BRANCHING ENZYME II (SBEII) using overexpression in potato tubers. A hybrid SBEII intragene consisting of potato cDNA containing a fragment of potato genomic DNA that included a single intron was used in order to prevent bacterial translation during cloning. A population of 20 transgenic potato plants exhibiting SBEII overexpression was generated. Compared with wild-type, starch from these tubers possessed an increased degree of amylopectin branching, with more short chains of degree of polymerisation (DP) 6-12 and particularly of DP6. Transgenic lines expressing a GRANULE-BOUND STARCH SYNTHASE (GBSS) RNAi construct were also generated for comparison and exhibited post-transcriptional gene silencing of GBSS and reduced amylose content in the starch. Both transgenic modifications did not affect granule morphology but reduced starch peak viscosity. In starch from SBEII-overexpressing lines, the increased ratio of short to long amylopectin branches facilitated gelatinisation, which occurred at a reduced temperature (by up to 3°C) or lower urea concentration. In contrast, silencing of GBSS increased the gelatinisation temperature by 4°C, and starch required a higher urea concentration for gelatinisation. In lines with a range of SBEII overexpression, the magnitude of the increase in SBEII activity, reduction in onset of gelatinisation temperature and increase in starch swollen pellet volume were highly correlated, consistent with reports that starch swelling is greatly dependent upon the amylopectin branching pattern. This work reports the first time that overexpression of SBEII has been achieved in a non-cereal plant. The data show that overexpression of SBEII using a simple single-intron hybrid intragene is an effective way to modify potato starch physicochemical properties, and indicate that an increased ratio of short to long amylopectin branches produces commercially beneficial changes in starch properties such as reduced gelatinisation temperature, reduced viscosity and increased swelling volume.


Infertility and multiple urogenital abnormalities in a male with mosaic 46,XY/45,XO/47,XXY karyotype and mixed phenotype.
We hereby present a rare case of a 46,XY/45,XO/47,XXY mosaic male patient with a predominance of the XY cell line. The patient, who exhibited phenotypic stigmata of both XO gonadal dysgenesis and Klinefelter syndromes, suffered from infertility and multiple urogenital abnormalities, as our investigation revealed.


Role of the locus coeruleus in transmission onto anterior colliculus neurons.
The present study was an attempt to elucidate the role of locus coeruleus (LC) on neuronal activities in the anterior colliculus of rats anesthetized with alpha-chloralose. The spike latency of neurons in the deep grey and white layers of anterior colliculus elicited by stimulation of the optic chiasm (OC), lateral geniculate body (LGB) and visual cortex (VC) was longer than that of neurons in the more superficial layers: optic and intermediate grey layers. When conditioning stimuli were applied to LC, a significant inhibition of spike generation upon OC, LGB and VC stimulation was observed on neurons of deep grey and white layers, but not on those of optic and intermediate grey layers. The conditioning stimulation did not alter spike generation, either in the neurons of deep grey and white layers or those of optic and intermediate grey layers, following stimulation of the superficial grey layer. These results strongly suggest that noradrenaline originating in the LC could produce an inhibition of neuronal activities in the deep grey and white layers, and such is probably the result of inhibition of neurons located in the superficial layer of the anterior colliculus.


Long-Term Recurrence-Free and Overall Survival Differ Based on Common, Proliferative, and Inflammatory Subtypes After Resection of Intrahepatic Cholangiocarcinoma.
While generally associated with poor prognosis, intrahepatic cholangiocarcinoma (ICC) can have a heterogeneous presentation and natural history. We sought to identify specific ICC subtypes that may be associated with varied long-term outcomes and patterns of recurrence after liver resection. Patients who underwent curative-intent resection for ICC from 2000 to 2020 were identified from a multi-institutional database. Hierarchical cluster analysis characterized three ICC subtypes based on morphology (i.e., tumor burden score [TBS]) and biology (i.e., preoperative neutrophil-to-lymphocyte ratio [NLR] and CA19-9 levels). Among 598 patients, the cluster analysis identified three ICC subtypes: Common (n = 300, 50.2%) (median, TBS: 4.5; NLR: 2.4; CA19-9: 38.0 U/mL); Proliferative (n = 246, 41.1%) (median, TBS: 8.8; NLR: 2.9; CA19-9: 71.2 U/mL); Inflammatory (n = 52, 8.7%) (median, TBS: 5.4; NLR: 12.6; CA19-9: 26.7 U/mL). Median overall survival (OS) (Common: 72.0 months; Proliferative: 31.4 months; Inflammatory: 22.9 months) and recurrence-free survival (RFS) (Common: 21.5 months; Proliferative: 11.9 months; Inflammatory: 9.0 months) varied considerably among the different ICC subtypes (all p < 0.001). Even though patients with Inflammatory ICC had more favorable T-(T1/T2, Common: 84.4%; Proliferative: 80.6%; Inflammatory: 86.5%) and N-(N0, Common: 14.0%; Proliferative: 20.7%; Inflammatory: 26.9%) disease, the Inflammatory subtype was associated with a higher incidence of intra- and extrahepatic recurrence (Common: 15.8%; Proliferative: 24.2%; Inflammatory: 28.6%) (all p = 0.01). Cluster analysis identified three distinct subtypes of ICC based on TBS, NLR, and CA19-9. ICC subtype was associated with RFS and OS and predicted worse outcomes among patients. Despite more favorable T- and N-disease, the Inflammatory ICC subtype was associated with worse outcomes ICC subtype should be considered in the prognostic stratification of patients.


Application of ionic liquid-based dispersive liquid phase microextraction for highly sensitive simultaneous determination of three endocrine disrupting compounds in food packaging.
Ionic liquid (IL) dispersive liquid-liquid microextraction (DLLME) method was successfully developed for extracting three endocrine disrupting compounds (EDCs) (bisphenol A, bisphenol AF and bisphenol AP) from the food packaging. 1-Octyl-3-methylimidazoliumhexafluorophosphate ([C8MIM][PF6]) was selected as extraction solution. The extraction procedure did not require a dispersive solvent. Three EDCs extraction kinetics were found to be very fast and the equilibrium was attained within 3.0 min following the pseudo-first-order model. The H-bonding and hydrophobic interactions play an important role in the partitioning of EDCs into IL from aqueous solution. The recovered IL could be reused for three runs without significant loss of extraction efficiencies. The spiked recoveries of three targets in food packaging were in the range of 97.8-103.1%. The limits of detection ranged from 0.50 to 1.50 ng mL(-1) (S/N=3). As a result, this method has been successfully applied for the sensitive detection of three EDCs in real samples.


Polysubstance use in inflammatory bowel disease.
We aimed to evaluate the incidence, predisposing factors and impacts of polysubstance use (PSU) (ie, the concurrent use or abuse of two or more drugs or substances) in inflammatory bowel disease (IBD). Data of patients enrolled between 1 January 2015 and 31 August 2019 from a single tertiary care referral center were retrospectively collected. Patients' baseline and clinical characteristics and their antidepressant and/or anxiolytic medications were abstracted. Associations between PSU and patients' characteristics were analyzed. Multivariate logistic regression models were fit, incorporating significant clinical factors. Altogether 315 patients with IBD (166 women, 149 men; 214 with Crohn's disease and 101 ulcerative colitis) were enrolled. Of them, 66 (21.0%) exhibited PSU (CD 21.5%, UC 19.8%); 37.5% had moderate to severe disease activity, 34.3% with extraintestinal manifestations (EIM), 41.6% with an anxious or depressed state and 69.8% had used healthcare resources in the prior 12 months. Moreover, 71.2% used two substances, while 27.3% used three substances. In the total cohort, EIM (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14-3.34, P = 0.019) and antidepressant or anxiolytic use (OR 2.51, 95% CI 1.45-4.39, P < 0.001) were positively associated with PSU on multivariate analysis. PSU was associated with increased rate of IBD-associated imaging (57.6% vs 47.0%, P < 0.05). PSU is common in IBD. EIM, antidepressant and/or anxiolytic use and imaging studies were independently associated with PSU. This study reinforces the importance of screening patients with IBD for substance use, particularly those with EIM and using antidepressants and/or anxiolytics.


The endoplasmic reticulum stress inhibitor salubrinal inhibits the activation of autophagy and neuroprotection induced by brain ischemic preconditioning.
To investigate whether endoplasmic reticulum (ER) stress participates in the neuroprotective effects of ischemic preconditioning (IPC)-induced neuroprotection and autophagy activation in rat brains. The right middle cerebral artery in SD rats was occluded for 10 min to induce focal cerebral IPC, and was occluded permanently 24 h later to induce permanent focal ischemia (PFI). ER stress inhibitor salubrinal (SAL) was injected via intracerebral ventricle infusion 10 min before the onset of IPC. Infarct volume and motor behavior deficits were examined after the ischemic insult. The protein levels of LC3, p62, HSP70, glucose-regulated protein 78 (GRP 78), p-eIF2α and caspase-12 in the ipsilateral cortex were analyzed using immunoblotting. LC3 expression pattern in the sections of ipsilateral cortex was observed with immunofluorescence. Pretreatment with SAL (150 pmol) abolished the neuroprotective effects of IPC, as evidenced by the significant increases in mortality, infarct volume and motor deficits after PFI. At the molecular levels, pretreatment with SAL (150 pmol) significantly increased p-eIF2α level, and decreased GRP78 level after PFI, suggesting that SAL effectively inhibited ER stress in the cortex. Furthermore, the pretreatment with SAL blocked the IPC-induced upregulation of LC3-II and downregulation of p62 in the cortex, thus inhibiting the activation of autophagy. Moreover,SAL blocked the upregulation of HSP70, but significantly increased the cleaved caspase-12 level, thus promoting ER stress-dependent apoptotic signaling in the cortex. ER stress-induced autophagy might contribute to the neuroprotective effect of brain ischemic preconditioning.


Student pharmacists' perceptions regarding pharmacist-prescribed hormonal contraceptives and their professional responsibility.
Currently, 13 U.S. jurisdictions allow for pharmacist-prescribed contraception; however, pharmacists' intention to use and ultimate uptake of this patient care opportunity have been variable. The objectives of this study were to (1) identify student pharmacists' attitudes toward pharmacist-prescribed hormonal contraception (HC), (2) identify student pharmacist perceived barriers regarding pharmacist-prescribed HC, and (3) explore what factors affect student pharmacists' viewpoints. An anonymous survey was administered using Qualtrics among third-year student pharmacists in a public health course. The survey was developed using the Theory of Planned Behavior (TPB) and previously published literature. TPB was developed to predict an individuals' intention to engage in a behavior at a specific time and place. All responses were anonymous. Survey responses were summarized using descriptive statistics, and Wilcoxon Mann-Whitney test was used to compare differences based on student pharmacist gender and religion. A total of 67 student pharmacists participated in the survey (response rate 80.7%). Most agreed-strongly agreed (n = 59, 88.1%) that pharmacists are capable of appropriately assessing and selecting HC therapies and believe it should be within a pharmacist's scope of practice (n = 53, 79.1%). Similarly, most agreed-strongly agreed that it is a professional responsibility for pharmacists to provide this service (n = 56, 83.6%). Potential barriers identified included limited access to patient medical records (n = 55, 82.1%), interruption to workflow (n = 51, 76.1%), and concerns for a decrease in well-women examinations (n = 51, 76.1%). Most identified with the Christian faith (n = 45, 67.2%) but said this did not influence their opinions (n = 40, 59.7%). Gender, age, and religion were not found to be associated with student pharmacists' attitudes. However, an increasing number of barriers were negatively associated with their attitudes. Student pharmacists believe it is within a pharmacist's scope of practice and a professional responsibly to prescribe HC. Student pharmacists were less supportive of pharmacist-prescribed HC if they reported a greater number of barriers.


Effects of triiodothyronine on insulin release from cultured neonatal and adult rat islets.
Insulin secretion from neonatal and adult rat islets maintained in culture for 7-9 days in the absence or in the presence of 10 nM T3 was measured. In both neonatal and adult islets T3 treatment tends to inhibit insulin secretion only in the absence or in the presence of low glucose concentrations.


Bilateral Internal Mammary Artery Use Can Be Safely Taught Without Increasing Morbidity or Mortality.
Evidence shows a likely survival benefit with the use of bilateral internal mammary arteries (BIMA) compared with a single internal mammary artery (SIMA). Nonetheless, BIMA use is often not used or taught because of a perceived increase in operative time and complexity. This study aimed to evaluate operative time, morbidity, and mortality in both resident and nonresident cases using BIMA compared with SIMA. Consecutive patients undergoing isolated coronary artery bypass grafting (October 2012 to April 2015) at a single institution were reviewed. Cases were stratified on the basis of the use of SIMA versus BIMA and resident teaching versus nonresident teaching cases. Primary outcomes included operative time, postoperative morbidity, and mortality. A total of 416 patients were identified; 335 of 416 (81%) patients received a SIMA, and 81 of 416 (19%) patients received BIMA. A total of 184 of 416 (44%) were resident cases: 143 of the 335 (43%) SIMA cases and 41 of the 81 (51%) BIMA cases. Use of BIMA in resident cases was associated with a longer operative and cardiopulmonary bypass (CPB) time than resident SIMA cases, but this increased time did not affect morbidity or mortality. Use of SIMA versus BIMA in nonresident cases had no significant difference on total operative time, CPB time, postoperative morbidity, or mortality. Overall, operative and 1-year mortality rates were similar in the SIMA and BIMA groups (SIMA: 1.2%, 1.8%, respectively; BIMA: 0%, 0%, respectively; p = NS). In the hands of an experienced surgeon, BIMA use can be effectively performed without an increase in operative or CPB time. In resident teaching cases, BIMA use may increase operative time, but it can be safely taught without affecting morbidity or mortality.


Continuous synthesis of hexanal by immobilized hydroperoxide lyase in packed-bed reactor.
This study aimed to develop an optimal continuous procedure of immobilized hydroperoxide lyase (HPL)-catalyzed synthesis of hexanal. A central composite design was used to study the combined effect of substrate concentration and the residence time of the reactant on hexanal concentration. The optimum conditions for hexanal synthesis included a 13-HPOD concentration of 43.54 mM and a residence time of 60.99 min. The maximum hexanal concentration was 3560 ± 130 mg/L when 16 U of immobilized HPLwas used. Furthermore, the stability of immobilized HPL was significantly improved in the packed-bed reactor, as evidenced by the slowed enzyme inactivation and prolonged operation time. The immobilized HPL remained activity until 40 mL substrate solution flowed past the packed-bed reactor. The catalyst productivity of hexanal in the packed-bed reactor was 5.35 ± 0.34 mg/U, much higher than that in the batch stirred reactor. This study was greatly meaningful for providing a green method to the large-scale production of hexanal.


Spatiotemporal Characteristics of 360-Degree Basic Attention.
The spatiotemporal characteristics of basic attention are important for understanding attending behaviours in real-life situations, and they are useful for evaluating the accessibility of visual information. However, although people are encircled by their 360-degree surroundings in real life, no study has addressed the general characteristics of attention to 360-degree surroundings. Here, we conducted an experiment using virtual reality technology to examine the spatiotemporal characteristics of attention in a highly controlled basic visual context consisting of a 360-degree surrounding. We measured response times and gaze patterns during the 360-degree search task and examined the spatial distribution of attention and its temporal variations in a 360-degree environment based on the participants' physical position. Data were collected from both younger adults and older adults to consider age-related differences. The results showed the fundamental spatiotemporal characteristics of 360-degree attention, which can be used as basic criteria to analyse the structure of exogenous effects on attention in complex 360-degree surroundings in real-life situations. For practical purposes, we created spherical criteria maps of 360-degree attention, which are useful for estimating attending behaviours to 360-degree environmental information or for evaluating visual information design in living environments, workspaces, or other real-life contexts.


Lymphoscintigraphic analysis in chromoblastomycosis.
One of the main complications of chromoblastomycosis is lymphedema. The purpose of this study was to evaluate the lymphatic system of the limbs of patients with chromoblastomycosis using lymphoscintigraphy. It is a reliable, objective and noninvasive means of supporting the diagnosis of lymphedema. Lymphoscintigraphy was performed in seven patients with chromoblastomycosis, six with lesions in the lower limb and one in the upper limb. Tc-99 m dextran was injected into the interdigital spaces of the upper or lower extremities. The qualitative parameters analyzed were the visibilization of the lymph vessels and the lymph nodes, dermal backflow, and existence of collateral vessels. All patients were treated with the association of itraconazole and cryotherapy with liquid nitrogen. Three out of the 14 extremities examined had lymphedema clinically, and the lymphoscintigraphy showed abnormalities in the qualitative parameters; whereas these parameters were normal in the extremities without lymphedema. During the treatment of chromoblastomycosis, a second lymphoscintigraphy exam was performed on 10 limbs and did not show any improvement of the previous lymphoscintigraphic alterations. The qualitative lymphoscintigraphy was a reliable method to show the morphology of the lymph vessels and confirm objectively the diagnosis of lymphedema secondary to chromoblastomycosis. The association of oral itraconazole and cryotherapy did not modify the lymphatic alterations in chromoblastomycosis.


Surgical approach to the treatment of popliteal aneurysm.
Seventeen popliteal artery aneurysms were repaired at the Santa Barbara Cottage Hospital from 1975 to 1987. Fourteen patients were involved, with three having bilateral lesions. All but one were men with an average age of 67 years. Four of the aneurysms (three patients) presented with asymptomatic masses while the others were associated with arterial or venous obstructive symptoms. The aneurysms were repaired and there was no mortality. One patient developed a transient foot-drop. All patients with symptoms caused by their aneurysm were improved or became asymptomatic, postoperatively. We are impressed that the posterior approach to an uncomplicated popliteal artery aneurysm has several advantages over the bypass technique. The distal anastomosis can frequently be kept proximal to the knee joint, and since exposure of the aneurysm is excellent, aneurysmectomy is often possible thus eliminating pressure symptoms as well as the possibility of late rupture.


Characterization of the thyroid hormone transport system of isolated hepatocytes.
Transport of 3,5-[3'-125I]triiodo-L-thyronine ([125I]T3) was studied in isolated rat liver hepatocytes. T3 transport was temperature-sensitive, the initial velocity of uptake, at low substrate concentration, was 60 times higher at 25 degrees C than at 0 degrees C. The activation energy of cellular uptake (26 kcal/mol) was different from that of binding to cytosolic proteins (6 kcal/mol), indicating that the latter was not the rate-limiting step. Uptake obeyed simple Michaelis-Menten kinetics, with an apparent Km of 0.34 microM and a Vmax of 0.15 fmol/min/cell at 25 degrees C. No simple diffusion occurred. Unlabeled T3, L-thyroxine (T4), 3,5,3'-triiodo-D-thyronine, and triiodothyroacetic acid inhibited T3 uptake with Kl values of 0.32, 1.4, 4.1, and 5.4 microM, respectively, indicating specificity of uptake which was different from specificity of intracellular binding sites. [125I]T4 was also taken up by a saturable process (Km = 0.65 microM and Vmax = 0.16 fmol/min/cell at 25 degrees C). T3 was a better competitor than T4 for the uptake of [125I]T4, indicating that both hormones were taken up by the same carrier system. Metabolic inhibitors had either no effect on T3 uptake or inhibitory effects unrelated to cellular ATP depletion. Uptake was not affected by modification of the membrane potential or the sodium ion gradient. T3 and T4 uptake was pH-dependent. It is suggested that the un-ionized 4'-OH form of the hormones was preferentially taken up. Inhibition of uptake by various compounds was compared to inhibition of thyroid hormone binding to transthyretin, nuclear receptor, and cytosolic-binding proteins. We conclude that, in freshly isolated hepatocytes, thyroid hormones are taken up by a saturable, stereospecific, Na+-independent carrier system.


Phenylboronic acid-functionalized magnetic nanoparticles for one-step saccharides enrichment and mass spectrometry analysis.
In this work, 2-(2-aminoethoxy) ethanol-blocked phenylboronic acid-functionalized magnetic nanoparticles (blocked PMNPs) were fabricated for selective enrichment of different types of saccharides. The phenylboronic acid was designed for capturing the cis-diols moieties on saccharides molecules, and the 2-(2-aminoethoxy) ethanol can deplete the nonspecific absorption of peptides and proteins which always coexisted with saccharides. For mass spectrometry analysis, the PMNPs bound saccharides can be directly applied onto the MALDI plate with matrix without removing the PMNPs. By PMNPs, the simple saccharide (glucose) could be detected in pmol level. The complex saccharides can also be reliably purified and analyzed; 16 different N-glycans were successfully identified from ovalbumin, and the high-abundance N-glycans can be detected even when the ovalbumin was in very low concentration (2 μg). In human milk, ten different oligosaccharides were identified, and the lactose can still be detected when the human milk concentration was low to 0.01 μL.


Anti-patched-1 antibodies suppress hedgehog signaling pathway and pancreatic cancer proliferation.
The hedgehog (Hh) signaling pathway is aberrantly activated in many human carcinomas including pancreatic cancer and regulates tumor cell growth. Overproduction of sonic hedgehog (Shh), a ligand of the Hh signaling pathway, increases the Hh signaling activity through transmitting the signal to patched-1 (Ptch1), the receptor of the Hh signaling pathway. a-Ptch1 antibodies were raised against an oligo-peptide, designed according to the Ptch1 aminoacid sequence. The specificity of a-Ptch1 was examined by immunoblotting and immuno-fluorescence, and biological effects were detected by RT-PCR and cell proliferation assay using two pancreatic cancer cell lines, Panc1 and SUIT-2. a-Ptch1 recognized a 160 kDa protein as shown by immunoblotting and cell surface staining of pancreatic cancer cells. Incubation with a-Ptch1 suppressed Hh signaling activity and proliferation of pancreatic cancer cells. These results provide a new strategy for controling Hh dependent development of pancreatic cancer and other Hh related carcinomas.


A Sleepwalking Patient Presenting with Concomitant ACL, PCL, and Meniscal Root Avulsion Fractures: A Case Report.
Tibial-sided anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) avulsion fractures compose a rare subset of cruciate ligament injuries. Fixation strategies are mixed in the literature, particularly regarding the PCL, which has traditionally been addressed using an open approach. A 41-year-old male sustained avulsion fractures of the tibial eminence involving the ACL, PCL, and posterior medial meniscal root through an unknown mechanism while sleepwalking. Surgical treatment comprised of entirely arthroscopic reduction and transtibial suture fixation. Only seven cases of combined ACL/PCL avulsion fracture have been reported and all but one utilized open fixation for at least the PCL and restricted weight-bearing postoperatively. This previously unreported triad of injury was successfully managed arthroscopically, negating a posterior approach to the knee. Early post-operative weight-bearing and aggressive range of motion aided in swift recovery and a favorable outcome.


How Doula Care Can Advance the Goals of the Affordable Care Act: A Snapshot From New York City.
Doula care meets each of the triple aims of the Affordable Care Act: improving health outcomes for all, improving the experience of care, and lowering costs by reducing non-beneficial and unwanted medical interventions. Cost is the greatest barrier to use of doula support. Reimbursement for doula services by private insurance, Medicaid, and Medicaid managed care organizations would significantly increase access to doulas. Widespread availability of doula care could significantly reduce cesarean rates, and increased access to community-based doula programs could reduce entrenched health disparities.


Placental small extracellular vesicles: Current questions and investigative opportunities.
The discovery of regulated trafficking of extracellular vesicles (EVs) has added a new dimension to our understanding of local and distant communication among cells and tissues. Notwithstanding the expanded landscape of EV subtypes, the majority of research in the field centers on small and large EVs that are commonly termed exosomes, microvesicles and apoptotic cell-derived vesicles. In the context of pregnancy, EV-based communication has a special role in the crosstalk among the placenta, maternal and fetal compartments, with most studies focusing on trophoblastic EVs and their effect on other placental cell types, endothelial cells, and distant tissues. Many unanswered questions in the field of EV biology center on the mechanisms of vesicle biogenesis, loading of cargo molecules, EV release and trafficking, the interaction of EVs with target cells and the endocytic pathways underlying their uptake, and the intracellular processing of EVs inside target cells. These questions are directly relevant to EV-based placental-maternal-fetal communication and have unique implications in the context of interaction between two organisms. Despite rapid progress in the field, the number of speculative, unsubstantiated assumptions about placental EVs is concerning. Here we attempt to delineate existing knowledge in the field, focusing primarily on placental small EVs (exosomes). We define central questions that require investigative attention in order to advance the field.


Optimization of the spontaneous adsorption of food colors from aqueous medium using functionalized Chitosan/Cinnamaldehyde hydrogel.
Hydrogels are considered as practical and proficient materials in adsorption and removal of soluble lethal molecules from aqueous system. They are also rapid-decomposable and economical materials besides their diverse preventive claims. In current study, Cinnamaldehyde (C), a natural defensive compound and Chitosan (Ch), natural occurring bio-macromolecule are considered to develop bio-inspired hydrogel (ChC). The structural and surface characteristics of ChC (13C solid state NMR, FT-IR, UV-Vis and SEM) are investigated to confirm the successful grafting. The origami of gelation in ChC performs an excellent adsorption activity towards food dyes, Carmoisine (CA) and Tartrazine (TA), which are contaminated by the accumulation during excess release from catering and chemical industries in aqueous system. The adsorption performance is thoroughly screened by varying the pH, ChC dosage, dye concentration, contact time and temperature in aqueous system. Thermodynamic and Kinetics study suggest the natural tendency of adsorption with a good reusability up to 3 cycles. The main mechanism for spontaneous adsorption is initiated by capturing of TA/CA in porous surface followed by the ionic interactions and formation of H-bondings. ChC based adsorption is an excellent and potential approach to control the toxicants for the water-pollution and water-preservation.


Identification and characterization of a novel stress-responsive outer membrane protein Lip40 from Actinobacillus pleuropneumoniae.
Actinobacillus pleuropneumoniae, a Gram-negative bacterium, is the causative agent of porcine pleuropneumonia, a highly contagious and often fatal disease. Because current vaccines confer limited protection against A. pleuropneumoniae infection, the development of more effective vaccines is urgently required. The identification of immunogenic and protective antigens, such as an outer-membrane lipoprotein, will advance this purpose. Sixty putative lipoproteins were predicted from the genomic sequence of A. pleuropneumoniae using multiple algorithms. Here, we focused on the characteristics of the putative lipoprotein Lip40 from A. pleuropneumoniae strain SLW01 (serovar 1). Lip40 shares sequence similarity with many bacterial lipoproteins, and the structural prediction of Lip40 suggests that it is similar to A. pleuropneumoniae TbpB. The N-terminus of Lip40 contains an interesting tandemly repeated sequence, Q(E/D/P)QPK. Real-time RT-PCR indicated that the expression of lip40 was significantly upregulated at 42 °C, at 16 °C, and under anaerobic conditions. Recombinant Lip40 (rLip40) produced in Escherichia coli BL21(DE3) was specifically recognized by porcine convalescent serum directed against A. pleuropneumoniae. Lip40 was confirmed to localize at the bacterial outer membrane, and its expression was significantly stimulated when A. pleuropneumoniae was cultured under various stress conditions. Lip40 also protected 75% of mice from fatal virulent A. pleuropneumoniae infection. The immunogenic outer-membrane protein Lip40 is stress responsive, protects mice against infection, and might be a virulence determinant. Further investigation of Lip40 should expedite vaccine development and provide insight into the pathogenesis of A. pleuropneumoniae.