Survival of patient with late onset hepatic failure by living-related liver transplantation from maternal donor with incompatible blood type.
A 14-year-old girl with blood type B with late onset hepatic failure (LOHF) of unknown cause has survived through living-related liver transplantation (LRLT). No hepatitis virus, including HAV, HBV, HCV, and HGV, was positive at the onset of LOHF. Autoimmune hepatitis was thought to be the cause because of positive results for serum anti-nuclear antibody at 80 times dilution and elevated gamma-globulin, but treatment with glucocorticoid did not suppress the progressive hepatic failure. Supportive therapy, including pulse therapy with 1g methylprednisolone for 3 days, ursodesoxycholic acid, branched-chain amino acid, and azathioprine did not resolve the hepatic failure. She was treated by repeated plasmapheresis and plasma absorption for 10 months, and then received the left lobe of her mother's liver. (Her mother's blood type was AB). The patient had been well, being treated with tacrolimus and prednisolone, although the serum titer of anti-blood type B antibody was high just after LRLT and mild liver dysfunction continued for more than 3 years after LRLT. Follow-up biopsy 3 years after LRLT revealed chronic hepatitis and progression to liver cirrhosis. Re-transplantation is now under consideration; the patient is now aged 19 years.


Proofreading through spatial gradients.
Key enzymatic processes use the nonequilibrium error correction mechanism called kinetic proofreading to enhance their specificity. The applicability of traditional proofreading schemes, however, is limited because they typically require dedicated structural features in the enzyme, such as a nucleotide hydrolysis site or multiple intermediate conformations. Here, we explore an alternative conceptual mechanism that achieves error correction by having substrate binding and subsequent product formation occur at distinct physical locations. The time taken by the enzyme-substrate complex to diffuse from one location to another is leveraged to discard wrong substrates. This mechanism does not have the typical structural requirements, making it easier to overlook in experiments. We discuss how the length scales of molecular gradients dictate proofreading performance, and quantify the limitations imposed by realistic diffusion and reaction rates. Our work broadens the applicability of kinetic proofreading and sets the stage for studying spatial gradients as a possible route to specificity.


Presence of intact and gonadectomized juveniles and the reduction of fighting between adult male rats.
Research is reported which investigated the aggressive interactions between adult male rats in the presence of 17-27 day old juvenile conspecifics. Following a brief exposure to an inaccessible juvenile male, juvenile female, estrous adult female, or empty compartment, the males of Experiment 1 were allowed to interact with another adult male. Results were that the presence of both genders of juveniles reduced fighting between the adult males, and pre-pubertal females were particularly effective as an aggression-inhibitor. The hormonal bases for those sex differences were examined in Experiment 2 using juveniles gonadectomized on Postnatal Day 10. Adult males were more aggressive following exposure to intact juvenile males than to castrated juvenile males; the latter males, intact juvenile females, and ovariectomized juvenile females provoked similar and low rates of fighting between adult males. These data suggest that the sexual dimorphism is a function of testicular hormones present during the juvenile stage which modify the stimulus characteristics of a pre-pubertal male rat.


11C-labeled stilbene derivatives as Abeta-aggregate-specific PET imaging agents for Alzheimer's disease.
A series of stilbene derivatives as potential diagnostic imaging agents targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and evaluated. The syntheses of the stilbenes were successfully achieved by a simple Wadsworth-Emmons reaction between diethyl (4-nitrobenzyl)phosphonate and 4-methoxybenzaldehyde. 4-N,N-dimethylamino-4'-methyoxy and the corresponding 4-N-monomethylamino-, 4'-hydroxy stilbenes showed good binding affinities towards Abeta aggregates in vitro (K(i) < 10 nM). The (11)C labeled 4-N-methylamino-4'-hydroxystilbene, [(11)C]4, was prepared by (11)C methylation of 4-amino-4'-hydroxystilbene. The [(11)C]4 displayed a moderate lipophilicity (log P = 2.36), and showed a very good brain penetration and washout from normal rat brain after an iv injection. In vitro autoradiography of transgenic AD mouse brain sections showed a high specific labeling of beta-amyloid plaques, whereas the control sections showed no binding. Taken together the data suggest that a relatively simple stilbene derivative, [(11)C]4, N-[(11)C]methylamino-4'-hydroxystilbene, may be useful as a positron emission tomography (PET) imaging agent for mapping Abeta plaques in the brain of patients with Alzheimer's disease.


Transoral robotic surgery vs. non-robotic surgeries for oropharyngeal squamous cell carcinoma: systematic review and meta-analysis.
To compare the effectiveness of transoral robotic surgery (TORS) and non-robotic surgeries (NRES) in patients with oropharyngeal squamous cell carcinoma (OPSCC), medical databases were searched including PubMed, Web of Science, Medline, Embase, and Cochrane Library up to January 2023. The methodology follows PRISMA guidelines, including the PRISMA flow diagram. Data from the included studies were extracted independently by two researchers. Seven studies involving five hundred seventy-seven patients were included. Of these, 275 underwent TORS and 302 underwent NRES. The disease-free survival rate was significantly higher in the TORS group than in the NRES group (OR = 3.43, 95% CI 1.92-6.15, P < 0.0001). However, there were no significant differences in positive surgical margins, hospital stays, operation time, blood loss, postoperative bleeding rate, perioperative tracheostomy, perioperative feeding tube, and overall survival rate. These findings can initially guide the preoperative counseling of TORS in patients with OPSCC, and preliminarily confirm that the adoption of TORS deserves careful consideration.


[Children can present with liver disease without elevation of liver-specific enzymes].
In children, liver diseases are rarely suspected without elevated levels of liver transaminases. We describe two cases of portal hypertension of children who presented with gastrointestinal bleeding, splenomegaly and cytopenia. Both cases had normal levels of liver transaminases; thus haematological conditions initially were suspected. An elevated alanine aminotransferase level should always lead to further examination to detect liver diseases in early stages, in order to limit development of cirrhosis.


The effects of sucrose, fructose, and high-fructose corn syrup meals on plasma glucose and insulin in non-insulin-dependent diabetic subjects.
We have previously shown that fructose and sorbitol given with a standard meal cause less increment in plasma glucose than sucrose and high fructose corn syrup (HFCS) in patients with NIDDM. However, there was no direct comparison of sucrose with HFCS. Sixteen men and one woman aged 54-67) with NIDDM were given either 35 g sucrose, 35 g fructose, or 43.75 g HFCS containing 35 g carbohydrate as part of a 400-calorie test meal. Blood samples were obtained at frequent intervals up to 3 h and were analyzed for glucose and insulin. As compared with a fructose meal, the mean increment in plasma glucose (delta PG) after a sucrose meal was significantly higher at 45 min and after an HFCS meal it was significantly higher at 30 and 45 min, but sucrose and HFCS meals did not differ. When delta PGs were compared in nine patients with basal PG greater than 140 mg/dl and in eight patients with basal PG less than 140 mg/dl, differences in delta PG after sucrose and HFCS versus fructose meals became more significant but still did not differ from each other. The integrated total areas under the delta PG curves after sucrose, HFCS, and fructose meals were not statistically different. However, the areas under the curves up to 90 min after sucrose and HFCS meals, which did not differ, were greater than the fructose meal. The mean delta IRI after sucrose meals was markedly elevated at 45, 60, and 75 min (P less than 0.05) and after HFCS meals at 45 min as compared with fructose meals.(ABSTRACT TRUNCATED AT 250 WORDS)


UPF1 regulates FOXO1 protein expression by promoting PBK transcription in non-small cell lung cancer.
Up-frameshift protein 1 (UPF1) is essential for nonsense-mediated messenger RNA decay (NMD). It is best known for its cytoprotective role in degrading aberrant and specific RNAs. UPF1 is dysregulated in multiple tumors, which correlates with poor prognosis and low overall survival.However,the role of UPF1 in lung cancer remains unclear.Current study shows that UPF1 could be a potential target for oncology therapies. The results also demonstrated the potential efficiency of UPF1 in regulating the proliferation and metastasis of lung cancer. Our findings suggest that those functions can be attributed to the inhibition of the stability of FOXO1 protein. In addition, PBK participates in the regulation of FOXO1 by UPF1.This result provides a new therapeutic strategy for lung cancer patients.


Quantitative determination of mutton adulteration with single-copy nuclear genes by real-time PCR.
Mitochondrial genes were generally adopted for PCR-based meat adulteration authentication due to their excellent specificity to species and numerous copies in one cell. However, the number of mitochondrial gene copies varies according to cells and tissues, which leads to quantification errors for meat adulteration. To address this problem, single-copy nuclear genes were selected to develop a quantitative method for identifying mutton adulteration in this study. Both single-copy genes specific to sheep species and single-copy reference genes show good linearity between Ct values and series diluted DNA concentrations, with the correlation coefficients of 0.9999 and 0.9993, respectively. Meanwhile, a constant (correction factor) was introduced to transform DNA concentrations into mutton proportions in adulterated meat. With this method, simulated mutton-pork, mutton-chicken and mutton-duck adulteration samples could be accurately quantified with the recovery rates of 89.56%, 107.13% and 95.20%, respectively.


Effects of low doses of ochratoxin A after intratesticular injection in the rat.
The toxic effect of various doses of ochratoxin A on the rat testis was investigated after a single intratesticular injection. At time of sacrifice (day 10) degenerating changes occur in the testicular tissues: seminiferous tubules dilatation, cytolysis of the seminiferous epithelium, hyperplasia of the interstitial tissue, vascular thrombosis. The relations between the blood supply disturbances and the observed lesions are discussed.


Aortic augmentation index in endurance athletes: a role for cardiorespiratory fitness.
Endurance exercise improves cardiovascular health and reduces mortality risk. Augmentation index (AIx) reflects adverse loading exerted on the heart and large arteries and predicts future cardiovascular disease. The purpose of this study was to establish whether endurance athletes possess lower AIx and aortic blood pressure compared to healthy controls, and to determine the association between AIx and cardiorespiratory fitness. Forty-six endurance athletes and 43 healthy controls underwent central BP and AIx measurements by non-invasive applanation tonometry before a maximal exercise test. Peak oxygen uptake ([Formula: see text]) was assessed by pulmonary analysis. Relative to controls, athletes had significantly lower brachial diastolic blood pressure (BP, -4.8 mmHg, p < 0.01), central systolic BP (-3.5 mmHg, p = 0.07), and AIx at a heart rate of 75 beats min(-1) (AIx@75, -11.9 %, p < 0.001). No AIx@75 differences were observed between athletes and controls when adjusted for age and [Formula: see text] [athletes vs controls mean (%) ± SE: -6.9 ± 2.2 vs -5.7 ± 2.3, p = 0.76]. Relative to men with low [Formula: see text], those with moderate and high [Formula: see text] had lower age-adjusted AIx@75 (p < 0.001). In women, those with high [Formula: see text] had lower AIx@75 than those with low and moderate [Formula: see text] (p < 0.01). The lower AIx@75 in endurance athletes is partly mediated by [Formula: see text]. While an inverse relationship between AIx@75 and [Formula: see text] was found in men, women with the highest [Formula: see text] possessed lowest AIx@75 compared to females with moderate or poor cardiorespiratory fitness. We recommend aerobic training aimed at achieving a minimum [Formula: see text] of 45 ml kg(-1) min(-1) to decrease the risk of future cardiovascular events and all-cause mortality.


Live-Cell High-Throughput Screen for Monitoring Autophagy Flux.
Autophagy is a cellular process implicated in the renewal of cellular components and the maintenance of cellular hemostasis and therefore associated with various types of diseases. In addition, autophagy belongs to the stress response pathways and is frequently activated by chemical compounds harboring characteristics of cell toxicity. High-throughput screens analyzing autophagy flux are therefore applied in both, the field of compound identification for targeting autophagy and compound characterization for analyzing compound toxicity. In this chapter, we describe a live-cell, fluorescent-based, high-throughput screening method in 384-well format for the fast and accurate measurement of autophagy flux over time suitable for academic research, pharmacological applications, and drug discovery.


Acral persistent papular mucinosis.
Acral persistent papular mucinosis has recently been proposed as a distinct form of cutaneous mucinosis. We describe a patient and review the literature. We conclude that acral persistent papular mucinosis is a distinct clinical entity, clearly separable from most other forms of cutaneous mucinosis except for one variant of lichen myxedematosus, from which it is less easily distinguished.


Nonadherence to antiasthmatic medications and its predictors among asthmatic patients in public hospitals of Bahir Dar City, North West Ethiopia: using ASK-12 tool.
Globally, adequate asthma control is not yet achieved. The main cause of uncontrollability is nonadherence to prescribed medications. The objective of this study is to assess asthmatic patients' non-adherence to anti-asthmatic medications and the predictors associated with non-adherence. An institution-based cross-sectional study was conducted in three governmental hospitals in Bahir Dar city from September 5 to December 12, 2021. The data was collected using the Adherence Starts with Knowledge-12 tool (ASK-12). Systematic random sampling was applied to select study participants. Bivariable and multivariable logistic regression analyses were used to identify predictors of non-adherence. All statistical tests were analyzed using STATA version 16. P-values less than 0.05 were considered statistically significant. A total of 422 asthmatic patients were included in the study. Most of the study participants (55.4%) did not adhere to their prescribed anti-asthmatic medicines. The educational status of the study participants (AOR = 0.03, 95% CI = 0.00-0.05), family history of asthma (AOR = 0.13, 95% CI = 0.04-0.21), and disease duration that the patients were living with (AOR = 0.01, 95% CI = 0.00-0.01) were the predictors of non-adherence to anti-asthmatic medications. The level of nonadherence to treatment among patients with asthma was high. Religion, educational status of study participants, family history of asthma, and duration of the disease were the predictors of non-adherence of asthmatic patients to their antiasthmatic medications. Therefore, the Ministry of health, health policy makers, clinicians, and other healthcare providers should pay attention to strengthening the adherence level to antiasthmatic medications, and country-based interventions should be developed to reduce the burden of non-adherence to anti-asthmatic medications.


Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test for Improved Patient Management Decisions and Disease-Related Outcomes when Combined with Current Clinicopathological Risk Factors for Cutaneous Squamous Cell Carcinoma (cSCC): Case Series.
While improvements have been made to risk assessment of cutaneous squamous cell carcinoma (cSCC) patients, there is a critical need for a uniform and more precise stratification system of their care. To address this unmet clinical need, a prognostic 40-gene expression profile (40-GEP) test has recently been developed and independently validated to show improved stratification of metastatic risk in high-risk cSCC patients compared with current staging systems. Two cSCC cases, both male with similar patient profiles and the same staging status across two different staging systems, yet with opposing outcomes, were chosen for retrospective review of their primary biopsy using the 40-GEP test. Case 1 declined further treatment, even when presented with evidence of a small focus of cSCC found in the last layer of nonmarginal tissue obtained from Mohs micrographic surgery (MMS). Case 1 remained recurrence free, and retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 1 result (low likelihood of metastasis). Case 2, even with subsequent clearing of the primary cSCC with MMS, noted another metastatic cSCC 3 months later. Case 2, after multimodal adjuvant treatments, died due to disease progression. Retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 2B result (high likelihood of metastasis). The cases discussed highlight the utility in 40-GEP to provide additional information to guide treatment decisions and improve outcomes. Integrating novel molecular prognostication with traditional clinicopathological risk factors can improve stratification of high-risk cSCC patients and may inform selection of risk-appropriate treatment and surveillance strategies.


Perinatal outcome in Berlin (Germany) among immigrants from Turkey.
Are there differences regarding important perinatal outcome-parameters in Berlin relating to ethnicity? A database was available covering 152,193 single deliveries in all hospitals in Berlin/Germany in the period 1993-1999, including 132,555 German women and 19,638 women of other ethnicities. Comparisons were made between a total of four pairs of sub-groups matched in terms of parity and social status (significance level P < 0.01). Pregnant migrants come for their first antenatal check-up significantly later, thus delaying the initiation of necessary diagnostic or therapeutic measures. Migrants show higher rates of prepartal and also postpartal anemia than the German women. In all sub-groups the German women had a significantly higher frequency of planned cesarean sections. Migrants were significantly less likely to receive an epidural anesthesia during delivery. It is also noticeable that the rate of congenital malformations of neonates is significantly higher in the migrant collectives. Important perinatal quality parameters such as infant and maternal mortality and rates of premature delivery have largely converged between German and Turkish migrant mothers. The differences found (e.g., rates of planned cesarean section, epidural anesthesia, or anemia) could be interpreted as indications of persistent differences in quality of care for migrants.


Infection rates and pathogenicity of trypanosomatid gut parasites in the water strider Gerris odontogaster (Zett.) (Heteroptera: Gerridae).
Trypanosomatid flagellates are common protozoan gut parasites of a wide range of insect species. Water striders (Gerridae) harbour the trypanosomatid Blastocrithidia gerridis. Three different populations of the water strider Gerris odontogaster in northern Sweden were sampled to assess the infection rate dynamics of trypanosomatids. The initially very low infection rates (0%-15%) early in the season were followed by a rapid increase during the reproductive period of the water striders, reaching very high levels (80%-90%). The pathogenic effects of trypanosomatids on G. odontogaster adults were studied in laboratory experiments. The parasites caused a general reduction of host vigour. Male skating endurance was negatively correlated with the intensity of the trypanosomatid infection. However, infection of trypanosomatids increased the mortality among adults only when the water striders were subjected to food stress. The trypanosomatids did not reduce the fecundity of females provided with food. We suggest that trypanosomatid gut parasites may be an important mortality factor in water strider populations. Since the pathogenicity of the parasites is enhanced by stress, parasitism by trypanosomatids may contribute to the regulation of host populations.


Noncompetitive immunoassay optimized for pharmacokinetic assessments of biologically active efruxifermin.
Efruxifermin (EFX) is a homodimeric human IgG1 Fc-FGF21 fusion protein undergoing investigation for treatment of liver fibrosis due to nonalcoholic steatohepatitis (NASH), a prevalent and serious metabolic disease for which there is no approved treatment. Biological activity of FGF21 requires its intact C-terminus, which enables binding to its obligate co-receptor β-Klotho on the surface of target cells. This interaction is a prerequisite for FGF21 signal transduction through its canonical FGF receptors: FGFR1c, 2c, and 3c. Therefore, the C-terminus of each FGF21 polypeptide chain must be intact, with no proteolytic truncation, for EFX to exert its pharmacological activity in patients. A sensitive immunoassay for quantification of biologically active EFX in human serum was therefore needed to support pharmacokinetic assessments in patients with NASH. We present a validated noncompetitive electrochemiluminescent immunoassay (ECLIA) that employs a rat monoclonal antibody for specific capture of EFX via its intact C-terminus. Bound EFX is detected by a SULFO-TAG™-conjugated, affinity purified chicken anti-EFX antiserum. The ECLIA reported herein for quantification of EFX demonstrated suitable analytical performance, with a sensitivity (LLOQ) of 20.0 ng/mL, to support reliable pharmacokinetic assessments of EFX. The validated assay was used to quantify serum EFX concentrations in a phase 2a study of NASH patients (BALANCED) with either moderate-to-advanced fibrosis or compensated cirrhosis. The pharmacokinetic profile of EFX was dose-proportional and did not differ between patients with moderate-to-advanced fibrosis and those with compensated cirrhosis. This report presents the first example of a validated pharmacokinetic assay specific for a biologically active Fc-FGF21 fusion protein, as well as the first demonstration of use of a chicken antibody conjugate as a detection reagent specific for an FGF21 analog.


Alignment in implementation of evidence-based interventions: a scoping review.
Alignment (i.e., the process of creating fit between elements of the inner and outer context of an organization or system) in conjunction with implementation of an evidence-based intervention (EBI) has been identified as important for implementation outcomes. However, research evidence has so far not been systematically summarized. The aim of this scoping review is therefore to create an overview of how the concept of alignment has been applied in the EBI implementation literature to provide a starting point for future implementation efforts in health care. We searched for peer-reviewed English language articles in four databases (MEDLINE, Cinahl, Embase, and Web of Science) published between 2003 and 2019. Extracted data were analyzed to address the study aims. A qualitative content analysis was carried out for items with more extensive information. The review was reported according to the preferred reporting items for systematic reviews and meta-analyses extension for scoping review (PRISMA-ScR) guidelines. The database searches yielded 3629 publications, of which 235 were considered potentially relevant based on the predetermined eligibility criteria, and retrieved in full text. In this review, the results of 53 studies are presented. Different definitions and conceptualizations of alignment were found, which in general could be categorized as structural, as well as social, types of alignments. Whereas the majority of studies viewed alignment as important to understand the implementation process, only a few studies actually assessed alignment. Outcomes of alignment were focused on either EBI implementation, EBI sustainment, or healthcare procedures. Different actors were identified as important for creating alignment and five overall strategies were found for achieving alignment. Although investigating alignment has not been the primary focus of studies focusing on EBI implementation, it has still been identified as an important factor for the implementation success. Based on the findings from this review, future research should incorporate alignment and put a stronger emphasize on testing the effectiveness of alignment related to implementation outcomes.


Looking back, looking forward: Paleopathology in Andean South America.
Over the past twenty years, the field of Andean paleopathology has advanced significantly thanks to a new generation of scholars who have been attracted to this region and whose innovative research has expanded our knowledge substantially. The papers in this special issue demonstrate how the field of Andean paleopathology has diversified and grown to become what is today a truly interdisciplinary enterprise involving archaeology, ethnohistory, biological anthropology, geochemistry, medical imaging, and genetics. These studies apply theoretical approaches to research questions that are increasingly innovative and nuanced as well as analytical methods that were in their infancy when I wrote my 1997 survey of the field.


Safety of intracameral cefuroxime in pars plana vitrectomy.
Postoperative endophthalmitis is a rare, but serious complication of pars plana vitrectomy (PPV). Subconjunctival cefuroxime injection has been the traditional choice for post vitrectomy endophthalmitis prophylaxis. Its effectiveness and safety in this context are however poorly understood and cases of retinal toxicity have been reported. The traditional standard subconjunctival antibiotic prophylaxis has been superceded in cataract surgery by intracameral antibiotic prophylaxis. The primary aim of this three centre non-randomised retrospective database cohort study of 7,532 PPV procedures was to identify the rate of endophthalmitis in cohorts of patients treated with intracameral or subconjunctival cefuroxime. A secondary aim was to estimate the achieved intraocular antibiotic concentrations of cefuroxime in eyes with intracameral versus subconjunctival administration using mathematical modelling. The overall incidence of postoperative endophthalmitis was 0.07% (5/7532). There were no cases of endophthalmitis in eyes receiving intracameral cefuroxime alone or in combination with subconjunctival cefuroxime (0/5586). Patients receiving subconjunctival cefuroxime alone had a higher incidence of endophthalmitis (0.22%, 4/1835), and there was one case of endophthalmitis in eyes not receiving any perioperative antibiotics (0.9%, 1/111). No cases of cefuroxime toxicity were identified. With subconjunctival cefuroxime, in the presence of a sclerotomy leak, we estimated the vitreous drug concentration to be higher than that for intracameral cefuroxime and potentially toxic. Intracameral cefuroxime appears to be a safe and efficient choice for prophylaxis against endophthalmitis after PPV. Small eyes with intraocular tamponade seem to be at particular risk of drug toxicity if cefuroxime is administered via the subconjunctival route.


Neuronal and glial differentiation following culture of the human embryonic cortical stem cells.
To set up long-term in vitro culture system of the human neural stem cells (hNSC) and to study their biological properties. Human fetuses aged about 20 weeks following spontaneous abortion were adopted. A serum-free medium containing basic fibroblast growth factor and epidermal growth factor was used to make the hNSCs divide continuously in the culture. The growth curve of continually passaged cells was examined. The effects of long-term culture on the cell cycle, cell differentiation were analyzed. The cell cycles of these cells were analyzed using flow cytometry. The cells from the human embryonic cortical tissue could be maintained and propagated in the presence of growth factors. Neurospheres were generated continually. Only one month after the primary culture, the precursors could be effectively discarded. The cells could be cultured for ten months. The cells had an exponential, consistent growth. The cell cycle analysis indicated that the hNSCs maintained remarkable proliferation. Upon differentiation, the hNSCs gave rise to mature cells. The multi-lineage potential of differentiation after different passages remained unchanged. The hNSCs isolated from the human embryonic tissues retained their biological features after long-term culture in vitro.


Low pleural fluid amylase associated with spontaneous rupture of the esophagus.
All previously reported determinations of pleural fluid amylase in Boerhaave's syndrome have demonstrated elevated values. We treated a patient with Sjögen's syndrome who had a low pleural fluid amylase level and the concomitant unusual finding of leakage of esophageal contents into the right pleural space.


A rational approach to guide cost-effective de novo donor-specific antibody surveillance with tacrolimus immunosuppression.
De novo donor-specific antibody (dnDSA) after renal transplantation has been shown to correlate with antibody-mediated rejection and allograft loss. However, the lack of proven interventions and the time and cost associated with annual screening for dnDSA are difficult to justify for all recipients. We studied a well-characterized consecutive cohort (n = 949) with over 15 years of prospective dnDSA surveillance to identify risk factors that would help institute a resource-responsible surveillance strategy. Younger recipient age and HLA-DR/DQ molecular mismatch were independent predictors of dnDSA development. Combining both risk factors into recipient age molecular mismatch categories, we found that 52% of recipients could be categorized as low-risk for dnDSA development (median subclinical dnDSA-free survival at 5 and 10 years, 98% and 97%, respectively). After adjustment, multivariate correlates of dnDSA development included tacrolimus versus cyclosporin maintenance immunosuppression (hazard ratio [HR], 0.37; 95% CI, 0.2-0.6; P < .0001) and recipient age molecular mismatch category: intermediate versus low (HR, 2.48; 95% CI, 1.5-4.2; P = .0007), high versus intermediate (HR, 2.56; 95% CI, 1.6-4.2; P = .0002), and high versus low (HR, 6.36; 95% CI, 3.7-10.8; P < .00001). When combined, recipient age and HLA-DR/DQ molecular mismatch provide a novel data-driven approach to reduce testing by >50% while selecting those most likely to benefit from dnDSA surveillance.


Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma.
Hypoxic microenvironment is prominent in advanced esophageal squamous cell carcinoma (ESCC). However, it is unclear whether ESCC becomes hypoxic when it remains in the mucosal layer or as it invades the submucosal layer. We aimed to investigate whether intramucosal (Tis-T1a) or submucosal invasive (T1b) ESCC becomes hypoxic using endoscopic submucosal dissection samples. We evaluated the expression of hypoxia markers including hypoxia inducible factor 1α (HIF-1α), carbonic anhydrase IX (CAIX), and glucose transporter 1 (GLUT1) by H-score and vessel density by microvessel count (MVC) and microvessel density (MVD) for CD31 and α-smooth muscle actin (α-SMA) with immunohistochemical staining (n = 109). Further, we quantified oxygen saturation (StO2 ) with oxygen saturation endoscopic imaging (OXEI) (n = 16) and compared them to non-neoplasia controls, Tis-T1a, and T1b. In Tis-T1a, cccIX (13.0 vs. 0.290, p < 0.001) and GLUT1 (199 vs. 37.6, p < 0.001) were significantly increased. Similarly, median MVC (22.7/mm2 vs. 14.2/mm2 , p < 0.001) and MVD (0.991% vs. 0.478%, p < 0.001) were markedly augmented. Additionally, in T1b, the mean expression of HIF-1α (16.0 vs. 4.95, p < 0.001), CAIX (15.7 vs. 0.290, p < 0.001), and GLUT1 (177 vs. 37.6, p < 0.001) were significantly heightened, and median MVC (24.8/mm2 vs. 14.2/mm2 , p < 0.001) and MVD (1.51% vs. 0.478%, p < 0.001) were markedly higher. Furthermore, OXEI revealed that median StO2 was significantly lower in T1b than in non-neoplasia (54% vs. 61.5%, p = 0.00131) and tended to be lower in T1b than in Tis-T1a (54% vs. 62%, p = 0.0606). These results suggest that ESCC becomes hypoxic even at an early stage, and is especially prominent in T1b.


Epileptic seizure onset predicts its duration.
Epilepsy is characterized by recurrent seizures that have a variety of manifestations. The severity of, and risks for patients associated with, seizures are largely linked to the duration of seizures. Methods that determine seizure duration based on seizure onsets could be used to help mitigate the risks associated with what might be extended seizures by guiding timely interventions. Using long-term intracranial electroencephalography (iEEG) recordings, this article presents a method for predicting whether a seizure is going to be long or short by analyzing the seizure onset. The definition of long and short depends on each patient's seizure distribution. By analyzing 2954 seizures from 10 patients, patient-specific classifiers were built to predict seizure duration given the first few seconds from the onset. The proposed methodology achieved an average area under the receiver operating characteristic curve (AUC) performance of 0.7 for the 5 of 10 patients with above chance prediction performance (p value from 0.04 to 10-9 ). Our results imply that the duration of seizures can be predicted from the onset in some patients. This could form the basis of methods for predicting status epilepticus or optimizing the amount of electrical stimulation delivered by seizure control devices.


Silver nitrate irrigation for hematuria from sickle cell hemoglobinopathy.
Three patients with significant unilateral, gross hematuria owing to sickle cell hemoglobinopathy were treated successfully with retrograde instillation of 1 per cent silver nitrate. There have been no recurrences of gross hematuria during 11 to 15 months of followup. With standard endoscopic evaluation, verification of the etiology of hematuria from sickle hemoglobinopathy and effective treatment can be accomplished quickly and safely.


Relevance of vitamin D on NAFLD and liver fibrosis detected by vibration controlled transient elastography in US adults: a cross-sectional analysis of NHANES 2017-2018.
The connection between vitamin D to non-alcoholic fatty liver disease (NAFLD) is still unclear. Herein, the relationship of vitamin D with NAFLD and liver fibrosis (LF) detected by vibration controlled transient elastography was investigated in US adults. The National Health and Nutrition Examination Survey of 2017-2018 was employed for our analysis. Participants were categorized as having either vitamin D deficiency (<50 nmol/L) or vitamin D sufficiency (≥50 nmol/L). A controlled attenuation parameter score of ≥ 263 dB/m was employed to define NAFLD. Significant LF was identified by the liver stiffness measurement value of ≥ 7.9 kPa. Multivariate logistic regression was adopted to explore the relationships. Among the 3407 participants, the prevalence of NAFLD and LF was 49.63% and 15.93% respectively. Compared to participants without NAFLD, no significant difference in serum vitamin D was observed in NALFD participants (74.26 vs. 72.24 nmol/L; p = 0.21). Using multivariate logistic regression analysis, no obvious connection of vitamin D status to NAFLD (sufficiency vs. deficiency, OR 0.89, 95%CI 0.70-1.13) was discovered. However, among NAFLD participants, the sufficiency of vitamin D represents a lower LF risk (OR 0.56, 95%CI 0.38-0.83). When evaluated in quartiles, in comparison to the lowest quartile, high vitamin D represents low LF risk in a dose-dependent manner (Q2 vs. Q1, OR 0.65, 95%CI 0.37-1.14; Q3 vs. Q1, OR 0.64, 95%CI 0.41-1.00; Q4 vs. Q1, OR 0.49, 95%CI 0.30-0.79). No relationship was found between vitamin D and CAP-defined NAFLD. However, a positive connection of the high serum vitamin D to the reduced LF risk was found among NAFLD subjects.Key messages:Our study found no relationship between vitamin D and CAP-defined NAFLD in US adults.High serum vitamin D was inversely associated with liver fibrosis in a dose-dependent manner among NAFLD participants.


Defibrillation efficacy and pain perception of two biphasic waveforms for internal cardioversion of atrial fibrillation.
Efficacy and Pain Perception of Two Biphasic Waveforms. We evaluated the influence of the peak voltage of waveforms used for internal cardioversion of atrial fibrillation on defibrillation efficacy and pain perception. A low peak voltage biphasic waveform generated by a 500-microF capacitor with 40% tilt was compared to a standard biphasic waveform generated by a 60-microF capacitor with 80% tilt. In 19 patients with paroxysmal atrial fibrillation (79% male, age 55 +/- 11 years, 21% with heart disease), the atrial defibrillation threshold (ADFT) was determined during deep sedation with midazolam for both waveforms in a randomized fashion using a step-up protocol. Internal cardioversion with a single lead (shock vector: coronary sinus to right atrium) was successful in 18 (95%) of 19 patients. ADFT energy and peak voltage were significantly lower for the low-voltage waveform (2.1 +/- 2.4 J vs 3.5 +/- 3.9 J, P < 0.01; 100 +/- 53 V vs 290 +/- 149 V, P < 0.01). Sedation then was reversed with flumazenil after ADFT testing. Two shocks at the ADFT (or a 3-J shock if ADFT >3 J) were administered to the patient using each waveform in random order. Pain perception was assessed using both a visual scale and a numerical score. ADFTs were above the pain threshold in 17 (94%) of 18 patients, even though the ADFT with the 500-microF waveform was <100 V in 63% of the patients. Pain perception was comparable for both waveforms (numerical score: 6.5 +/- 2.4 vs 6.3 +/- 2.6; visual scale: 5.4 +/- 2.6 vs 5.2 +/- 3.1; P = NS, 500-microF vs 60-microF). The second shock was perceived as more painful in 88% of the patients, independent of the waveform used. Despite a 66% lower peak voltage and a 40% lower energy, the 40% tilt, 500-microF capacitor biphasic waveform did not change the pain perceived by the patient during delivery of internal cardioversion shocks. Pain perception for internal cardioversion probably is not influenced by peak voltage alone and increases with the number of applied shocks.


Comparative study of cardiovascular profiles of milrinone and amrinone by use of isolated, blood-perfused dog heart preparations.
The cardiac and coronary vasodilator effects of milrinone and amrinone were compared in isolated, blood-perfused papillary muscle and sinoatrial (SA) node and atrioventricular (AV) node preparations of dogs. Milrinone (0.3-100 nmol) and amrinone (0.01-3 mumol) were administered intra-arterially. Both drugs increased the force of contraction of paced and unpaced papillary muscles and the rate of automaticity of the latter; they increased sinus rate and accelerated AV nodal conduction. However, both drugs were not homogeneously effective on cardiac variables but affected them in the following order: The force of contraction of the ventricular muscle greater than SA nodal automaticity divided by AV nodal conduction greater than ventricular automaticity. In producing these cardiac effects, milrinone was 30-60 times more potent than amrinone. Both drugs increased (coronary) blood flow in all preparations. In this respect milrinone was about ten times more potent than amrinone. As a result, milrinone can be characterized as having almost equal cardiotonic and coronary vasodilatory effects, whereas amrinone is more coronary vasodilatory than cardiotonic. These differences in cardiovascular profile may contribute to their differential salutary mechanisms in the treatment of heart failure. Both drugs induced neither AV nodal tachycardia nor ventricular arrhythmia.


Assessing the impact of transcatheter aortic valve replacement on myocardial work indices and left ventricular diastolic function in aortic valve stenosis patients.
Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load-independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention. To evaluate the reliability of MWI in AS patients and the changes in MWI and LV diastolic function after transcatheter aortic valve replacement (TAVR). We enrolled 53 consecutive patients with severe AS undergoing TAVR admitted between March 2021 and November 2021. MWIs and LV diastolic function were assessed before and after TAVR for each patient. All MWIs and LV diastolic function indices improved after TAVR. The degree of MWIs improvement was higher in patients with lower prior-TAVR MWI values, while the more severe the impairment of diastolic function, the greater the post-TAVR benefit. The introduction of myocardial work parameters into the routine assessment of patients with AS could improve our understanding of cardiac performance and aid in identifying the optimal timing for surgical or percutaneous treatment.


Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats.
We investigate the effect of nobiletin on vascular and renal alterations and possible mechanisms involved in high-fat diet (HFD)-fed rats. Male Sprague-Dawley rats were fed a HFD with fructose 15% in drinking water for 16 weeks. HFD-fed rats were treated with nobiletin (20 or 40 mg/kg/day) or vehicle for the last 4 weeks. HFD-fed rats treated with nobiletin was significantly reduced obesity, hypertension, dyslipidemia and hyperinsulinemia. Nobiletin improved vascular endothelial function, restored creatinine clearance, and reduced plasma urea and creatinine levels, as well as urinary protein excretion. Nobiletin markedly alleviated vascular medial cross-sectional area (CSA) and collagen deposition, glomerular extracellular matrix (ECM) accumulation, and renal fibrosis. Nobiletin significantly elevated plasma adiponectin levels, together with upregulated adiponectin receptor 1 (AdipoR1) and suppressed transforming growth factor-β1 (TGF-β1) expression in kidney. In addition, an increase of plasma tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was significantly attenuated after nobiletin treatment. Our results suggest that nobiletin attenuates HFD-induced vascular and renal alterations in rats, which is possibly related to the modulation of AdipoR1 and TGF-β1expression, and suppression of inflammation.


An automated system for predicting detection limit and precision profile from a chromatogram.
This paper presents a basic model of an automated system for predicting the detection limit and precision profile (plot of relative standard deviation (RSD) of measurements against concentration) in chromatography. The fundamental assumption is that the major source of response errors at low sample concentrations is background noise and at high concentrations, it is the volumes injected into an HPLC system by a sample injector. The noise is approximated by the mixed random processes of the first order autoregressive process AR(1) and white noise. The research procedures are: (1) the description of the standard deviation (SD) of measurements in terms of the parameters of the mixed random processes; (2) the algorithm for the parameter estimation of the mixed processes from actual background noise; (3) the mathematical distinction between noise and signal in a chromatogram. When compounds are chromatographically separated, each obtained signal is given the detection limit and precision profile on laboratory-made software. A file of a chromatogram is the only requirement for the theoretical prediction of measurement uncertainty and therefore the repeated measurements of real samples can be dispensed with. The theoretically predicted RSDs are verified by comparing them with the statistical RSDs obtained by repeated measurements. Signal shapes on noise are illustrated at the detection limit and quantitation limit, the signal-to-noise ratios of which are close to the widely adopted values, 3 and 10, respectively.


Ciliates as model systems for cellular graviperception.
Ciliates are unicellular organisms, which have been subject of physiological studies since the 19th century. As they show distinct gravireactions, they are useful model organisms for investigation of the cellular gravitransduction chain.


Systemically administered cholecystokinin affects an evoked potential in the hippocampal dentate gyrus.
Cholecystokinin was administered systemically while recordings were taken of the evoked action potential in the hippocampal dentate gyrus to stimulation of the medial entorhinal cortex. The sulphated octapeptide and t. BOC CCK-4, but not the unsulphated octapeptide or tetrapeptide, increased the amplitude of the evoked action potential in a dose-dependent manner, whereas the unsulphated octapeptide decreased it. Bilateral vagotomy did not block the effect of the sulphated octapeptide. CR 1409 was also found to increase the amplitude of the evoked response and did not block the effect of subsequent administration of sulphated octapeptide. These results are consistent with action at a central receptor locus.


Automated headspace-solid-phase micro extraction-retention time locked-isotope dilution gas chromatography-mass spectrometry for the analysis of organotin compounds in water and sediment samples.
An automated method for the simultaneous determination of six important organotin compounds namely monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), monophenyltin (MPhT), diphenyltin (DPhT) and triphenyltin (TPhT) in water and sediment samples is described. The method is based on derivatization with sodium tetraethylborate followed by automated headspace-solid-phase micro extraction (SPME) combined with GC-MS under retention time locked (RTL) conditions. Home-synthesized deuterated organotin analogues were used as internal standards. Two high abundant fragment ions corresponding to the main tin isotopes Sn118 and Sn120 were chosen; one for quantification and one as qualifier ion. The method was validated and excellent figures of merit were obtained. Limits of quantification (LOQs) are from 1.3 to 15 ng l(-1) (ppt) for water samples and from 1.0 to 6.3 microg kg(-1) (ppb) for sediment samples. Accuracy for sediment samples was tested on spiked real-life sediment samples and on a reference PACS-2 marine harbor sediment. The developed method was used in a case-study at the harbor of Antwerp where sediment samples in different areas were taken and subsequently screened for TBT contamination. Concentrations ranged from 15 microg kg(-1) in the port of Antwerp up to 43 mg kg(-1) near a ship repair unit.


Guillain-Barré Syndrome Associated With Acute Toxoplasmosis in a 3-Year-old Boy.
Few clinical cases of Guillain-Barré syndrome have been described following acute Toxoplasma gondii infection, all in adult patients. We report a case of a 3-year-old boy who developed this syndrome with a good response to antiparasitic treatment.


Who loses public health insurance when states pass restrictive omnibus immigration-related laws? The moderating role of county Latino density.
In the United States, there is widespread concern that state laws restricting rights for noncitizens may have spillover effects for Latino children in immigrant families. Studies into the laws' effects on health care access have inconsistent findings, demonstrating gaps in our understanding of who is most affected, under what circumstances. Using comparative interrupted time series methods and a nationally-representative sample of US citizen, Latino children with noncitizen parents from the National Health Interview Survey (2005-2014, n = 18,118), this study finds that living in counties with higher co-ethnic density placed children at greater risk of losing Medicaid and Children's Health Insurance Program coverage when their states passed restrictive state omnibus immigrant laws. This study is the first to demonstrate the importance of examining how the health impacts of immigration-related policies vary across local communities.


Biochemical Variations in Cytolytic Activity of Ortho- and Paramyxoviruses in Human Lung Tumor Cell Culture.
Human lung cancer cells (Calu-3 line) were studied for the development of apoptosis, necrosis, and autophagy in response to infection with ortho- and paramyxoviruses. Biochemical pathways underlying various mechanisms of cell death differed for different viruses. When infected with murine Sendai paramyxovirus, Calu-3 cells demonstrated typical necrotic features such as cell swelling (but not shrinkage), lack of chromatin DNA laddering, of caspase 3 and 8 activation, and of apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) protein; an activation of antiapoptotic protein kinase Akt was also revealed. In contrast, infection with avian influenza virus A/FPV/Rostock/34 (H7N1 subtype) or Newcastle disease virus (NDV, avian paramyxovirus) caused the development of typical apoptotic markers such as cell shrinkage, ladder-type chromosomal DNA fragmentation, caspase 3 and 8 activation, and proteolytic cleavage of PARP in the absence of Akt activation. Notably, no upregulation of p53 protein phosphorylation was observed in all infected cells, which indicates that p53 is not involved in the virus-induced death of Calu-3 cells. Cell death caused by the influenza virus was accompanied by overstimulation of autophagy, whereas no stimulation of autophagy was observed in the NDV-infected cells. Infection with Sendai virus caused moderate stimulation of autophagy, which suggests that the mechanism of the virus-induced cell death and the balance between autophagy and cell death in infected cancer cells depend on the virus type and might significantly differ even for closely related viruses. Therefore, an optimal strategy for oncolytic virus-mediated destruction of tumor cells in cancer patients requires selection of the most appropriate oncolytic virus based on the mechanism of its cytolytic action in a particular type of tumor.


Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome.
Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women and it is associated with overt metabolic derangement. Circulating lipids are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9) which blocks low density lipoprotein (LDL) receptors especially in the liver. The liver is highly vulnerable in dyslipidemia as lipid accumulation leads to progression of non-alcoholic fatty liver disease (NAFLD). An array of scientific endeavours hold that low-dose spironolactone (LDS) is beneficial as intervention for PCOS traits, but this claim is yet to be fully elucidated. The aim of this study was to investigate the effect of LDS on dyslipidemia and hepatic inflammation in rats with letrozole (LET)-induced PCOS and to assess the possible involvement of PCSK9 in these effects. Eighteen female Wistar rats were randomly assigned into 3 groups. The control group received vehicle (distilled water; p.o.), LET-treated group received letrozole (1 mg/kg; p.o.), LET+LDS-treated group received LET plus LDS (0.25 mg/kg, p.o.) for 21 days. Exposure to LET increased body and hepatic weights, plasma and hepatic total cholesterol (TC), TC/HDL, LDL, interleukin-6, MDA, PCSK9, ovarian degenerated follicles and hepatic NLRP3 intensity, reduced GSH and normal ovarian follicles. Interestingly, LDS averted dyslipidemia, NLRP3-dependent hepatic inflammation and ovarian PCOS traits. It is evident herein that LDS ameliorates PCOS traits and combats dyslipidemia and hepatic inflammation in PCOS by a PCSK9-dependent mechanism.


Patterns of tumor colony development over time in soft-agar culture.
Human tumors were cultured by the two-layer soft-agar technique and the time course of tumor colony development was evaluated during periods of up to 6 weeks in culture. All colony counting was performed with an automated tumor colony counter (Omnicon; Bausch and Lomb, Inc, Rochester, NY, USA). This instrument provided colony counts per culture plate in six size categories from greater than 60 microns diameter colonies to greater than 149 microns diameter colonies. Six to 24 culture plates were used for each "growth curve", generally 24. Control (non-drug-treated) cultures were obtained from 117 tumors, of which 25 also provided enough cells to allow evaluation of the time course of colony development after exposure to cytostatic agents. The development of colonies in non-drug-treated plates usually demonstrated a lag phase, a logarithmic growth phase to maximum colony development and a subsequent deterioration of colonies. In spite of clumps seeded into the agar, real colony growth could be recognized by frequent colony counting of culture dishes, although the temporal patterns of growth were sometimes different if pure single-cell suspensions were compared with suspensions containing clumps from the same tumor. Drug pre-incubation caused changes in the temporal pattern of colony growth as well as in the total number of colonies. Some cultures showed drug sensitivity when evaluated at certain time points while evaluation at later time points showed only borderline drug effect or none at all. The potential utility of tumor colony growth curves in the clinical applications of tumor colony cultures is discussed.


Comparison of papaverine and verapamil on frequency-dependent changes in Vmax of K-depolarized ventricular tissue.
The maximum upstroke velocity (Vmax) of K-depolarized guinea pig ventricular strips was used to indirectly measure frequency-dependent changes in slow inward current (Isi) caused by papaverine, verapamil, Ba2+, and isoproterenol. The effects of verapamil were studied after pretreatment with 0.8 mM Ba2+ to restore excitability of the K-depolarized tissue. Similar steady-state, frequency-dependent (0.1--4.0 Hz) changes in Vmax were observed in tissues exposed to papaverine (10(-5), Ba2+ (0.2 mM, 0.8 mM), or isoproterenol (5 x 10(-7) M). Verapamil (10(-7) M) caused a marked frequency-dependent inhibition of Vmax relative to the Ba2+-treated condition. Step increases in stimulation frequency resulted in a new steady state after only one to three depolarizations under all conditions except during exposure to verapamil. Vmax decreased exponentially after an increase in stimulation frequency during verapamil exposure, and therefore required many stimuli before a new quasi-steady-state was attained. The time constant for the recovery from inactivation of Isi determined by a paired pulse protocol was 169 +/- 16 ms for 10(-5) M papaverine, 185 +/- 14 ms for 0.8 mM Ba2+, and about 390 ms for 10(-7) M verapamil. The time required for half-recovery of Vmax after a train of 1-Hz stimuli (preceded by a rest period) was 2.5--3 s for papaverine or Ba2+ but 30--38 s for verapamil-treated preparations. The results show that papaverine is not a Ca antagonist like verapamil. The results also suggest that Ba2+ may be useful for restoring excitability in K-depolarized tissues to study the frequency-dependent changes in Vmax caused by drugs that alter Isi.


Prenatal ultrasonographic diagnosis of osteogenesis imperfecta.
Between 1982 and 1986, osteogenesis imperfecta was diagnosed by ultrasound in seven fetuses. The known heterogeneity of osteogenesis imperfecta was confirmed by the prenatal ultrasonographic findings. Dependent on the type of osteogenesis imperfecta, the appearance of the limbs varied from severely shortened and broad, with very low echogeneity and absent acoustic shadow (type IIA), to only moderately shortened and thin, with almost normal echogeneity and acoustic shadow but clearly visible fractures causing angulation of the bone (types IIC and III). Ultrasonography offers the possibility to detect or exclude the lethal and severe forms of osteogenesis imperfecta early (type IIA) or halfway (types IIB, IIC, and III) through the second trimester. Prenatal diagnosis of the disease allows the option of elective abortion or may prevent unnecessary obstetric intervention.


CT findings in a case of laryngeal sarcoidosis.
Laryngeal sarcoidosis is a rare manifestation of systemic sarcoidosis. It affects mainly the supraglottic larynx. Involvement of the glottic and subglottic levels are exceptional. We present the case of a 56-year-old man with a 2-year history of systemic sarcoidosis, involving the mucosa of paranasal sinuses, a joint, and mediastinal lymph nodes, who developed laryngeal sarcoidosis. We emphasize the CT appearance of laryngeal sarcoidosis.


Dual trajectories of depression and social participation among Chinese older adults.
This study aimed to investigate the dual trajectories of social participation (SP) and depression among older adults, and explore common factors that may influence both trajectories. The study utilized data from four waves of the China Health and Retirement Longitudinal Study (CHARLS, 2011 to 2018). The dual-trajectory model was employed to estimate the dual trajectories of SP and depression. This study identified two SP and three depression trajectories. The results revealed that the reciprocal relationship between SP and depression trajectories is confirmed in all sub-groups of the dual trajectories. Our study identified six distinct sub-groups of individuals based on their SP and depression trajectories and some commen risk factors of SP and depression trajectories. Related intervention policies should consider the dual trajectories of SP and depression and focus on subgroups with high vulnerability, such as high depression but low SP. Additionally, attention should be given to addressing the common risk factors that underlie these trajectories.


Scaling responses of leaf nutrient stoichiometry to the lakeshore flooding duration gradient across different organizational levels.
Most wetlands have been subject to changes in flooding regimes by climate change and human activities, resulting in widespread alteration of wetland plants at different organizational levels. However, scaling the responses of wetland plants to changes in flooding regimes is still challenging, because flooding could indirectly affect wetland plants through affecting environment factors (e.g. soil properties). During the non-flooding period, we investigated leaf N and P stoichiometry at three organizational levels (intra-species, inter-species, inter-community) along a flooding duration gradient in a lakeshore meadow of Poyang Lake floodplain, China. At the intra-species level, leaf N and P stoichiometry showed species-specific responses to flooding duration. At the inter-species level, leaf N or P contents or N:P ratio showed no significant response to flooding duration. At the inter-community level, leaf N and P contents significantly increased with flooding duration, while leaf N:P ratio decreased. At each organizational level, leaf N and P stoichiometry showed poor correlation with soil N and P stoichiometry. Moreover, intra-specific responses of leaf N and P contents to flooding duration and soil nutrient content increased with mean flooding duration of species distribution, which was the index of species hydrological niche. Intraspecific variation had lower contribution than species turnover to variations in community leaf nutrient stoichiometry. In all, flooding duration affected leaf N and P stoichiometry mainly through direct pathway at the intra-species and inter-community level, rather than the indirect pathway via soil nutrient stoichiometry. Therefore, our results have implications for scaling up from environmental conditions to ecosystem processes via wetland plant communities.


Purification of Par j I, the major allergen of Parietaria judaica pollen.
A component of Parietaria judaica pollen extract, previously identified as the major allergen, then reported as Pj10 and hereafter denominated Par j I has been isolated by a combination of 65% ammonium sulphate salt precipitation and gel filtration and an Ultrogel AcA54 column. The purified allergen appeared essentially homogeneous on gel filtration HPLC. The mol. wt of Par j I was estimated by electrophoretic and chromatographic techniques. All results gave values in a range from 13 K to 25 K. Analysis in SDS-PAGE under reducing conditions revealed a broad band corresponding to a mol. wt of 10 K, which retained allergenicity when tested with a patients serum pool. CIE and CRIE patterns of the isolated Par j I displayed the two precipitating lines already reported as those exhibiting the highest IgE-binding ability. Par j I showed a specific allergenic activity about 10-fold higher than that of the whole extract and was demonstrated to be the major allergen of Parietaria judaica as assessed in 25 sensitive human sera.


Upfront treatment of locally advanced cervical cancer with intensity modulated radiation therapy compared to four-field radiation therapy: a cost-effectiveness analysis.
Radiation can be delivered via four-field box (BOX-RT) or intensity modulated radiation therapy (IMRT). We sought to evaluate the cost-effectiveness (C/E) of IMRT relative to BOX-RT for the treatment of locally advanced cervical cancer. A three-year Markov model with eight-week cycles was developed to compare IMRT to BOX-RT. A proportion (25%) received extended-field radiation therapy (EFRT) to include para-aortic nodes. The model assumed equal overall survival (OS). The model captured costs and utility estimates for BOX-RT, IMRT, and each complication. Modeled complications included acute and chronic toxicities. Baseline model assumptions were obtained by literature review and supplemented by expert opinion. Costs were based on Medicare reimbursement rates and the Agency for Healthcare Research and Quality Database. Treatment strategies were compared using an incremental cost-effectiveness ratio (ICER). One-way, probabilistic and structural sensitivity analyses were performed to account for uncertainty in assumptions. The C/E of each strategy was evaluated from the perspective of the health care system. C/E analysis revealed an ICER for IMRT of $182,777/quality adjusted life year (QALY) gained. Although this value was higher than the willingness to pay threshold of $100,000/QALY, sensitivity analysis revealed several modifications that would make IMRT a C/E option relative to BOX-RT. For patients requiring EFRT, IMRT was C/E with an ICER of $91,580/QALY. Although IMRT was not C/E at the $100,000 willingness-to-pay threshold, in those requiring EFRT, IMRT was C/E relative to BOX-RT. A randomized trial comparing IMRT to BOX-RT for the treatment of locally advanced cervical cancer is warranted.


Biomaterials for intervertebral disc regeneration and repair.
The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to pathology with age and injury. Engineering strategies that rely upon synthetic materials or composite implants that do not interface with the biological components of the disc have not met with widespread use or desirable outcomes in the treatment of intervertebral disc pathology. Here we review bioengineering advances to treat disc disorders, using cell-supplemented materials, or acellular, biologically based materials, that provide opportunity for cell-material interactions and remodeling in the treatment of intervertebral disc disorders. While a field still in early development, bioengineering-based strategies employing novel biomaterials are emerging as promising alternatives for clinical treatment of intervertebral disc disorders.


Clinical features and risk factors for early recurrence after esophagectomy following neoadjuvant chemotherapy for esophageal cancer.
The purpose of this study was to clarify the clinical features and outcomes of patients with recurrence after esophagectomy following neoadjuvant chemotherapy (NAC) related to the timing of recurrence. We reviewed 240 consecutive patients who underwent NAC followed by esophagectomy for clinical stage II/III esophageal squamous cell carcinoma between 2009 and 2014. We compared the clinical features and survival after recurrence among groups of patients stratified by the timing of recurrence diagnosis and identified the risk factors for early recurrence (ER). Recurrence was identified within 1 year in 61 patients and after 1 year in 23 patients. Significant differences were observed between the patients with recurrence within 1 year (early recurrence; ER) and those with recurrence after 1 year (late recurrence; LR). The ER patients had more advanced tumors and higher pretreatment serum squamous cell antigen (SCC-Ag) levels and less experienced downstaging than patients without recurrence (no recurrence; NR). Overall survival was significantly worse for the ER patients than for the LR patients. Multivariate analysis revealed that cN2-3, increased serum SCC-Ag levels, and clinical response to NAC were independent predictors of ER. The ER patients had distinctive clinical features from the LR and NR patients. Extensive lymph node metastasis, an elevated SCC-Ag, and inadequate response to NAC were identified as predictors of ER.


Periodontitis as a promoting factor of T2D: current evidence and mechanisms.
Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response. Epidemiologically, periodontitis is closely related to the occurrence, development, and poor prognosis of T2D and is recognized as a potential risk factor for T2D. In recent years, increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D, including islet β-cell dysfunction and insulin resistance (IR). However, the related mechanisms have not been well summarized. This review highlights periodontitis-derived virulence factors, reviews how these stimuli directly or indirectly regulate islet β-cell dysfunction. The mechanisms by which IR is induced in insulin-targeting tissues (the liver, visceral adipose tissue, and skeletal muscle) are explained, clarifying the influence of periodontitis on the occurrence and development of T2D. In addition, the positive effects of periodontal therapy on T2D are overviewed. Finally, the limitations and prospects of the current research are discussed. In summary, periodontitis is worthy of attention as a promoting factor of T2D. Understanding on the effect of disseminated periodontitis-derived virulence factors on the T2D-related tissues and cells may provide new treatment options for reducing the risk of T2D associated with periodontitis.


Predicting extinction phenotype to optimize fear reduction.
Fear conditioning is widely employed to study dysregulations of the fear system. The repeated presentation of a conditioned stimulus in the absence of a reinforcer leads to a decrease in fear responding-a phenomenon known as extinction. From a translational perspective, identifying whether an individual might respond well to extinction prior to intervention could prove important to treatment outcomes. Here, we test the hypothesis that CO2 reactivity predicts extinction phenotype in rats, and that variability in CO2 reactivity as well as extinction long-term memory (LTM) significantly predicts orexin activity in the lateral hypothalamus (LH). Our results validate a rat model of CO2 reactivity and show that subcomponents of behavioral reactivity following acute CO2 exposure explain a significant portion of the variance in extinction LTM. Furthermore, we show evidence that variability in CO2 reactivity is also significantly predictive of orexin activity in the LH, and that orexin activity, in turn, significantly accounts for LTM variance. Our findings open the possibility that we may be able to use CO2 reactivity as a screening tool to determine if individuals are good candidates for an extinction/exposure-based approach.


Baroreceptor reflex sensitivity in human neonates: the effect of postmenstrual age.
We performed a cross-sectional study in human infants to determine if indices of R-R interval variability, systolic blood pressure (SBP) variability, and baroreceptor reflex sensitivity change with postmenstrual age (PMA: gestational age+postnatal age). The electrocardiogram, arterial SBP and respiration were recorded in clinically stable infants (PMA, 28-42 weeks) in the quiet sleep state in the first days after birth. (Cross-)spectral analyses of R-R interval series and SBP series were performed to calculate the power of low-frequency (LF, indicating baroreceptor reflex activity, 0.04-0.15 Hz) and high-frequency (HF, indicating parasympathetic activity, individualized between the p-10 and p-90 values of respiratory frequency) fluctuations, and transfer function phase and gain. The mean R-R interval, and LF and HF spectral powers of R-R interval series increased with PMA. The mean SBP increased with PMA, but not the LF and HF spectral powers of SBP series. In the LF range, cross-spectral analysis showed high coherence values (>0.5) with a consistent negative phase shift between R-R interval and SBP, indicating a approximately 3 s lag in R-R interval changes in relation to SBP. Baroreceptor reflex sensitivity, calculated from LF transfer gain, increased significantly with PMA, from 5 (preterm) to 15 ms mmHg-1 (term). Baroreceptor reflex sensitivity correlated significantly with the (LF and) HF spectral powers of R-R interval series, but not with the LF and HF spectral powers of SBP series. The principal conclusions are that baroreceptor reflex sensitivity and spectral power in R-R interval series increase in parallel with PMA, suggesting a progressive vagal maturation with PMA.


Highly Efficient Organic Solar Cells with Improved Vertical Donor-Acceptor Compositional Gradient Via an Inverted Off-Center Spinning Method.
A novel, yet simple solution fabrication technique to address the trade-off between photocurrent and fill factor in thick bulk heterojunction organic solar cells is described. The inverted off-center spinning technique promotes a vertical gradient of the donor-acceptor phase-separated morphology, enabling devices with near 100% internal quantum efficiency and a high power conversion efficiency of 10.95%.


Corrigendum: Gender Gap in Unhealthy Life Expectancy: The Role of Education Among Adults Aged 45.
[This corrects the article DOI: 10.3389/ijph.2022.1604946.].


Effect of Eel Biscuit Supplementation on Height of Children with Stunting Aged 36-60 Months: A Pilot Study.
Stunting is a major health problem in developing countries. Animal-based supplements can increase the height of children with stunting. This study was aimed at determining the effect of eel biscuit supplementation on increase in the height of children with stunting aged 36-60 months. A pilot study with pretest-post-test design. The study was conducted in two villages in the Priangan Region, West Java Province, Indonesia. The participants were divided into two groups: intervention group (10 supplemented eel biscuit pieces) and control group (biscuits from the government's biscuit programme). A total of 56 children aged 36-60 months with the height-for-age z-score of <-2 SD were recruited voluntarily for sampling. The initial height-for-age z-score of the intervention group was -3.45 SD and that of the control group was -3.11 SD. After 3 months of supplemented eel biscuit consumption, the height-for-age z-score of the intervention group changed to -2.52 SD and that of the control group changed to -2.51 SD. The average shift of the height-for-age z-score after 3 months of supplemented eel biscuit consumption was 0.93 SD in the intervention group and 0.6 SD in the control group. There were significant differences in delta and percent increase in the height-for-age z-score between both groups. Consumption of supplemented eel biscuits for 3 months increased the height-for-age z-score of children with stunting aged 36-60 months by 0.93 SD.


The protein LJM 111 from Lutzomyia longipalpis salivary gland extract (SGE) accounts for the SGE-inhibitory effects upon inflammatory parameters in experimental arthritis model.
Several studies have pointed out the immunomodulatory properties of the Salivary Gland Extract (SGE) from Lutzomyia longipalpis. We aimed to identify the SGE component (s) responsible for its effect on ovalbumin (OVA)-induced neutrophil migration (NM) and to evaluate the effect of SGE and components in the antigen-induced arthritis (AIA) model. We tested the anti-arthritic activities of SGE and the recombinant LJM111 salivary protein (rLJM111) by measuring the mechanical hypernociception and the NM into synovial cavity. Furthermore, we measured IL-17, TNF-α and IFN-γ released by lymph nodes cells stimulated with mBSA or anti-CD3 using enzyme-linked immunosorbent assay (ELISA). Additionally, we tested the effect of SGE and rLJM111 on co-stimulatory molecules expression (MHC-II and CD-86) by flow cytometry, TNF-α and IL-10 production (ELISA) of bone marrow-derived dendritic cells (BMDCs) stimulated with LPS, chemotaxis and actin polymerization from neutrophils. Besides, the effect of SGE on CXCR2 and GRK-2 expression on neutrophils was investigated. We identified one plasmid expressing the protein LJM111 that prevented NM in OVA-challenged immunized mice. Furthermore, both SGE and rLJM111 inhibited NM and pain sensitivity in AIA and reduced IL-17, TNF-α and IFN-γ. SGE and rLJM111 also reduced MHC-II and CD-86 expression and TNF-α whereas increased IL-10 release by LPS-stimulated BMDCs. SGE, but not LJM 111, inhibited neutrophils chemotaxis and actin polymerization. Additionally, SGE reduced neutrophil CXCR2 expression and increased GRK-2. Thus, rLJM111 is partially responsible for SGE mechanisms by diminishing DC function and maturation but not chemoattraction of neutrophils.


Neuronal primary cilia: a review.
Primary cilia in neurons have often been regarded as rare, vestigial curiosities. However, neuronal cilia are now gaining recognition as ubiquitous organelles in the mammalian brain, raising speculation about what their functions may be. They might have some features tailored for the nervous system and others that serve needs shared by a spectrum of other cell types. Here we review clues from the literature and present new data supporting several possibilities for the significance of neuronal cilia. Our immunocytochemical results show regional heterogeneity in neuronal cilia. Brain regions nearer to the cerebral ventricles had longer cilia, suggesting that they might sense chemicals such as peptides, originating from cerebrospinal fluid. In mutant Tg737(orpk)mice, most brain regions appeared to be missing cilia. The importance of intraflagellar transport proteins establishes a functional link between neuronal cilia and other primary cilia.


Pectate lyases: Their role in plants and importance in fruit ripening.
Plant cell walls are complex structures that are modified throughout development. They are a major contributor to the properties of plant structure and act as barriers against pathogens. The primary cell walls of plants are composed of polysaccharides and proteins. The polysaccharide fraction is divided into components cellulose, hemicelluloses and pectin, are all modified during fruit ripening. Pectin plays an important role in intercellular adhesion and controlling the porosity of the wall. A large number of pectin degrading enzymes have been characterised from plants and they are involved in numerous aspects of plant development. The role of pectate lyases in plant development has received little attention, probably because they are normally associated with the action of plant pathogenic organisms. However their importance in plant development and ripening is now becoming well established and new information about the role of pectate lyases in plant development forms the focus of this review.


Use of buserelin acetate in an in vitro fertilization program: a comparison with classical clomiphene citrate-human menopausal gonadotropin treatment.
A comparison has been established retrospectively between clomiphene citrate-human menopausal gonadotropin (CC-hMG) and buserelin acetate-hMG treatments in in vitro fertilization trials performed over a 3-year period. The analysis of 466 CC-hMG and 319 buserelin acetate-hMG trials shows that buserelin acetate-hMG stimulation generates a greater ovarian response resulting in higher numbers of oocytes being retrieved (6.2 + 3.8 versus 9.3 + 5.2) and fertilized (2.8 + 2.7 versus 4.3 + 3.8). More embryos are thus obtained, allowing a wider choice for intrauterine replacement and cryopreservation. Mean embryonic vitality scores do not differ (4.33 + 1.51 versus 4.44 + 1.54), implying that the embryonic quality remains similar in both treatments. A premature demise of the corpus luteum occurs in a large proportion of buserelin acetate-hMG cycles. However, when suppletive progesterone treatment is given, there is a trend toward a better implantation rate per embryo, and a significantly higher ongoing pregnancy rate is observed in relation to buserelin acetate-hMG treatment (20%) as compared with CC-hMG cycles (14%).


Dural ectasia in Marfan's syndrome: magnetic resonance imaging appearances and anaesthetic experience of three deliveries.
Neuraxial anaesthetic techniques are considered useful to minimise haemodynamic stress during labour. In Marfan's syndrome, connective tissue abnormalities not only affect the thoracic aorta but also predispose to dural ectasia. A dural ectatic sac may cause difficulties with neuraxial analgesia and anaesthesia. We discuss magnetic resonance imaging appearances and anaesthetic experience of three deliveries in a parturient with stable echocardiographic findings. We consider that epidural analgesia and anaesthesia are a safe and pragmatic solution for labour and delivery. Lumbo-sacral magnetic resonance imaging at presentation will define dural ectasia and assist in management.


The Association of Food Insecurity With Asthma Control in Adults During COVID-19.
Food insecurity has been associated with poorer asthma control in children, but research lacks in adults. To assess the frequency of food insecurity and its association with asthma control in adults during the coronavirus disease 2019 pandemic. An online cross-sectional survey study was conducted in US adults with asthma. Survey questions included how worried or concerned participants were about food security since the pandemic. Asthma control was assessed using the Asthma Control Test, with uncontrolled asthma defined as Asthma Control Test score less than or equal to 19. Self-report of food insecurity since the pandemic was assessed. Food insecurity variables were dichotomized into high insecurity (≥3) or low insecurity (<3). Descriptive statistics and bivariate analyses were performed. Of the total participants (N = 866), 82.79% were female; mean age of participants was 44 ± 15.05 years, their mean Asthma Control Test score was 19.25 ± 4.54, and 18.48% had high food insecurity. Participants with high food insecurity were more likely to have uncontrolled asthma (74.38%) compared with those with lower food insecurity (34.99%; P < .01). The relationship between asthma control and food insecurity remained significant after adjusting for age, education, sex, race, anxiety, and living stability concerns due to the pandemic. Food insecurity exists in adults with asthma and is associated with uncontrolled asthma. Providers should consider screening their patients for food insecurity when treating individuals with uncontrolled asthma.


Early childhood diarrhea and cardiometabolic risk factors in adulthood: the Institute of Nutrition of Central America and Panama Nutritional Supplementation Longitudinal Study.
Nutritional deficits in early life have been associated with a higher prevalence of the metabolic syndrome (MetS) in adulthood. Early childhood diarrhea contributes to undernutrition and may potentially increase the risk for adult noncommunicable diseases. Our objective was to examine associations between early childhood diarrhea burden and later development of MetS. We studied individuals who participated in the Institute of Nutrition of Central America and Panama Nutritional Supplementation Longitudinal Study (1969-1977) and were followed up in 2002-2004. We used logistic regression to determine associations of diarrhea burden at ages 0 to 6, 6 to 12, and 12 to 24 months with odds of MetS and elevations in its components as adults. Among 389 adults age 25 to 42 years at follow-up, the prevalence of MetS was 29%. Adjusting for several confounders including adult body mass index (BMI), each absolute 1% increase in diarrhea burden at age 0 to 6 months (but not at other time periods) was associated with increased odds of MetS (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06). This was attributable primarily to associations with elevated blood pressure (OR, 1.03; 95% CI, 1.00-1.06) and waist circumference (OR, 1.03; 95% CI, 1.00-1.06). Childhood diarrhea burden at 0 to 6 months is associated with MetS in adulthood after controlling for childhood growth parameters and adult BMI.


Anatomical and histological analyses reveal that tail repair is coupled with regrowth in wild-caught, juvenile American alligators (Alligator mississippiensis).
Reptiles are the only amniotes that maintain the capacity to regenerate appendages. This study presents the first anatomical and histological evidence of tail repair with regrowth in an archosaur, the American alligator. The regrown alligator tails constituted approximately 6-18% of the total body length and were morphologically distinct from original tail segments. Gross dissection, radiographs, and magnetic resonance imaging revealed that caudal vertebrae were replaced by a ventrally-positioned, unsegmented endoskeleton. This contrasts with lepidosaurs, where the regenerated tail is radially organized around a central endoskeleton. Furthermore, the regrown alligator tail lacked skeletal muscle and instead consisted of fibrous connective tissue composed of type I and type III collagen fibers. The overproduction of connective tissue shares features with mammalian wound healing or fibrosis. The lack of skeletal muscle contrasts with lizards, but shares similarities with regenerated tails in the tuatara and regenerated limbs in Xenopus adult frogs, which have a cartilaginous endoskeleton surrounded by connective tissue, but lack skeletal muscle. Overall, this study of wild-caught, juvenile American alligator tails identifies a distinct pattern of wound repair in mammals while exhibiting features in common with regeneration in lepidosaurs and amphibia.


To Continue or to Withhold Opioid Analgesics? An Ethical Dilemma Involving a 63-year-old Cancer Patient Who 'Broke the Pain Contract'.
[Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].


White matter NMDA receptors: an unexpected new therapeutic target?
Axons, their ensheathing myelin and supporting glia that make up the white matter in the mammalian brain and spinal cord are fundamentally important for the normal operation of the central nervous system. Prevalent human disorders such as stroke, vascular dementia, multiple sclerosis, brain and spinal cord trauma, HIV-associated dementia, periventricular leukomalacia of premature infants, and seemingly traditional 'gray matter disorders' such as Alzheimer's disease and schizophrenia, exhibit white matter pathology that contributes to morbidity and mortality. N-Methyl-D-aspartate (NMDA) receptors have been shown to have an important role in mediating Ca2+-dependent injury of oligodendrocytes and the myelin sheath; newly recognized family members of the NMDA receptor, known as NR3 subunits, seem to be involved. Recently developed uncompetitive NMDA channel blockers such as memantine hold therapeutic promise because these agents are well tolerated clinically and might prove to be effective at protecting certain white matter elements from a variety of insults.


Determinants of quality of life in patients with refractory focal epilepsy who were not eligible for surgery or who rejected surgery.
The aim of the study was to assess the determinants of quality of life (QOL) in adult patients with refractory focal epilepsy who were not eligible for surgery or who rejected surgery after presurgical evaluation. The QOLIE-31, the Hospital Anxiety and Depression Scale and PESOS questionnaire were mailed in 2009 to all adult patients who had been evaluated for suitability for epilepsy surgery between 2001 and 2007 in the Bethel Epilepsy Center and had been deemed not eligible for surgery or had decided against surgery. Questionnaires were sent by post to 359 patients: 172 (47.9%) replied, and of these, 125 patients were eligible for this study. The remaining 47 patients were excluded mainly because they did not fulfill the criteria of refractory epilepsy. Out of the included 125 patients, 106 were considered to be poor surgical candidates for medical reasons, and 19 had decided against surgery. The mean follow-up was 4.1±2.1 years. In the past 6 months, 13.9% of the patients were seizure free, 12 of them (9.6%) were seizure free for one year, 10.7% had 1-2 seizures, 11.5% had 3-5 seizures, 27.0% had one or more seizures a month, 23.0% had one or more seizures a week, and 13.9% had one or more seizures a day. Patient-perceived changes in their seizures since presurgical evaluation were rated by 15.6% of the patients as 'improved significantly', by 28.7% as 'improved', by 46.7% as 'no change', by 6.6% as 'deteriorated' and by 2.5% as 'significantly deteriorated'. Quality of life in patients with refractory epilepsy was much lower compared to operated patients from our center. Multivariate analysis of QOL showed that depression and anxiety are strong predictors but not exclusively. Furthermore, tolerability and efficacy of AEDs are significant predictors of most QOLIE-31 subscales. Employment, seizure frequency, patient-perceived change in their seizures, number of AEDs and the degree of comorbidity appeared as predictors for some aspects of QOL as well. When excluding anxiety and depression, the most important predictors of QOL were tolerability of AEDs and employment. For other aspects of QOL, efficacy of AEDs, gender, number of AEDs, degree of comorbidity and a certificate of disability were additional predictors. The results of the multivariate analysis did not essentially change when seizure-free patients were excluded. Quality of life in non-operated patients with refractory epilepsy is significantly lower than in operated patients from the same center. Besides depression and anxiety, patient-rated tolerability and efficacy of AEDs, seizure frequency and employment are the main determinants of QOL.


Clinical analysis of delayed epistaxis following endoscopic sinus surgery.
To investigate the clinical characteristics and treatment methods associated with delayed epistaxis following endoscopic sinus surgery. The clinical data of 46 patients with delayed epistaxis following endoscopic sinus surgery were retrospectively analyzed. To explore the clinical features, pathogenesis, and treatment plan for delayed epistaxis, the postoperative bleeding time, bleeding inducements, systemic complications, surgical approach, the hemorrhage locations and responsible vessels, and treatment methods were analyzed. The average bleeding time was 16.34 ± 9.05 days after the operation, and 76.6% of the cases occurred 6-20 days after the operation. Sphenopalatal artery hemorrhage accounted for 69.6% (32/46), the most common of which was a posterior nasal septal artery hemorrhage (17/32). A total of 45 patients received endoscopic low-temperature plasma hemostasis following ineffective nasal packing, and no rebleeding in the ipsilateral nasal cavity was observed during the postoperative follow-up for 3 to 6 months. The peak of hemorrhaging in delayed epistaxis following endoscopic sinus surgery occurred at 6-20 days post-operatively. Bleeding of the posterior nasal septal artery from the sphenopalatine artery was the most common. Surgical methods were closely related to delayed postoperative hemorrhage. Treatment with low temperature plasma hemostasis under nasal endoscope was found to be effective.


Exploring pharmacological options for adolescent depression: a preclinical evaluation with a sex perspective.
There is an urgent need for developing novel pharmacological treatment options for adolescent depression, and to ensure an optimal translational outcome to the clinic, sex should be included as a biological variable in preclinical studies. In this context, the present study compared the antidepressant-like potential of ketamine and cannabidiol, with the clinical standard fluoxetine, in adolescent rats exposed to maternal deprivation (as a model of early-life stress), while including a sex perspective. Moreover, changes in drug efficacy over time were evaluated by re-exposing rats to the same dose regimens during adulthood. Antidepressant-like responses were scored through a battery of distinctive tests (forced-swim, novelty-suppressed feeding, and sucrose preference) across time. The main results proved an antidepressant-like potential for ketamine and cannabidiol in adolescent rats, although their efficacy was dependent on sex and prior stress exposure, as well as on treatment length and the behavioral feature analyzed. In general, while all tested antidepressants in male rats improved certain affective-like features, female rats were mainly unresponsive to the treatments performed (except for certain benefits induced by ketamine), demonstrating the need for further characterizing proper treatments for this particular sex. Moreover, when rats were re-exposed in adulthood to the same drug regimens as in adolescence, a drop in efficacy was observed. These findings may have translational ramifications in that ketamine or cannabidiol could be moved forward as antidepressants for the adolescent depressed population, but not before further characterizing their potential long-term safety and/or beneficial vs. harmful effects for both sexes.


Afferent and efferent connections of the parapineal organ in lampreys: a tract tracing and immunocytochemical study.
The neural connections of the parapineal organ of two species of lampreys were studied with the fluorescent dye 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) and with immunocytochemistry. The lamprey parapineal organ consists of a vesicle and a ganglion that are connected to the left habenula. Labeling experiments included the application of DiI to the parapineal organ, left and right fasciculus retroflexus, left habenula, and the left pretectal region. Afferent parapineal fibers run in the left fasciculus retroflexus to the interpeduncular nucleus. The parapineal fibers of this fascicle arose from parapineal ganglion cells, whereas DiI application to the left habenula labeled both neurons of this ganglion and bipolar cells in the parapineal vesicle. Efferent neurons were observed in the left habenula, and bilaterally in the subhippocampal nucleus and the dorsal pretectum. Labeling with DiI also revealed a hippocampal projection. Immunocytochemical study of the parapineal vesicle revealed serotonin-immunoreactive cells in both species of lamprey, as well as substance P-immunoreactive (SP-ir) cells in sea lamprey and choline acetyltransferase-immunoreactive (ChAT-ir) cells in the river lamprey. The SP-ir cells and ChAT-ir cells formed a rich neuropil in the parapineal ganglion. Calretinin-ir cells were numerous in the ganglion. Neuropeptide Y-immunoreactive and gamma-aminobutyric acid-immunoreactive efferent fibers were observed in the parapineal organ. Neuropeptide Y-immunoreactive fibers originate in the subhippocampal nucleus, whereas gamma-aminobutyric acid-immunoreactive fibers might also arise in the pretectal nucleus. A few galanin-ir fibers were observed. These results indicate that the parapineal connections are completely different from those of the pineal organ. The possible homology between parapineal organs of vertebrates is discussed.


Redox control and autoxidation of class 1, 2 and 3 phytoglobins from Arabidopsis thaliana.
Despite a recent increase in interest towards phytoglobins and their importance in plants, much is still unknown regarding their biochemical/biophysical properties and physiological roles. The present study presents data on three recombinant Arabidopsis phytoglobins in terms of their UV-vis and Raman spectroscopic characteristics, redox state control, redox potentials and autoxidation rates. The latter are strongly influenced by pH for all three hemoglobins - (with a fundamental involvement of the distal histidine), as well as by added anion concentrations - suggesting either a process dominated by nucleophilic displacement of superoxide for AtHb2 or an inhibitory effect for AtHb1 and AtHb3. Reducing agents, such as ascorbate and glutathione, are found to either enhance- (presumably via direct electron transfer or via allosteric regulation) or prevent autoxidation. HbFe3+ reduction was possible in the presence of high (presumably not physiologically relevant) concentrations of NADH, glutathione and ascorbate, with differing behaviors for the three globins. The iron coordination sphere is found to affect the autoxidation, redox state interconversion and redox potentials in these three phytoglobins.


Testing a new hypothesis: plant vigor and phylloxera distribution on wild grape in Arizona.
Longer, meaning more vigorous, shoots of a wild grape clone (Vitis arizonica) were more susceptible to attack by second and third generations of leaf-galling grape phylloxera,Daktulopsphaira vitifoliae, as the growing season progressed. Although there was no significant difference in mean shoot length between attacked and unattacked shoots within a clone at the beginning of shoot elongation, attacked shoots were significantly longer than unattacked shoots when elongation had ceased (P<0.01). Also, long attacked shoots had a significantly greater population of phylloxera galls than short attacked shoots (P<0.01) as the season progressed. The phylloxera population on long shoots increased rapidly while the population on short shoots remained the same. Longer shoots also produced significantly more axillary shoots than shorter shoots as the season progressed (P<0.001), and the number of axillary shoots accounted for 66 percent of the variance in number of attacked leaves on a shoot. Experimental evidence showed that there was a significantly greater percentage of available leaves attacked on long shoots than on short shoots (P<0.05) and the leaves on long shoots generally had a greater number of galls per leaf. The relationship between shoot length and probability of attack was also tested by comparing shoots lengths of 10 attacked clones and 10 unattacked clones at a second location. Mean shoot lengths of attacked clones were significantly longer than mean shoot lengths of unattacked clones (P<0.05), and mean shoot lengths of attacked shoots within a clone were significantly longer than unattacked shoots (P<0.001). Longer shoot length accounted for 81 percent of the variance in probability of attack. The reason for this pattern of attack was that long shoots produced newly expanding leaves over a longer time during the growing season and multivoltine phylloxera require undifferentiated tissue to initiate gall formation. Patterns of attack within a shoot were characterized by an uneven distribution of galls among leaves. This was due to development time between generations and the current availability of undifferentiated tissue at times of colonization. This study supports the hypothesis that some herbivore species are favored more by vigorous plants than by stressed plants.


Expert Reliability in Legal Proceedings: "Eeny, Meeny, Miny, Moe, With Which Expert Should We Go?"
Between Expert Reliability refers to the extent to which different experts examining identical evidence make the same observations and reach the same conclusions. Some areas of expert decision making have been shown to entail questions with relatively low Between Expert Reliability, but the disagreement between experts is not always communicated to the legal actors forming decisions on the basis of the expert evidence. In this paper, we discuss the issues of Between Expert Reliability in legal proceedings, using forensic age estimations as a case study. Across national as well international jurisdictions, there is large variation in which experts are hired to conduct age estimations as well as the methods they use. Simultaneously, age estimations can be fully decisive for outcomes e.g. in asylum law and criminal law. Using datasets obtained from the Swedish legal context, we identify that radiologists and odontologists examining knees or teeth images to estimate age seem to disagree within their own disciplines (radiologist 1 v. radiologist 2 or odontologist 1 v. odontologist 2) as well as across different disciplines (radiologist v. odontologist) relatively often. This may have large implications e.g. in cases where only one expert from the respective field is involved. The paper discusses appropriate ways for legal actors to deal with the possibility of lacking Between Expert Reliability. This is indeed a challenging task provided that legal actors are legal experts but not necessarily scientific experts.