A mammalian pexophagy target.
Protein ubiquitylation in mammals is known to trigger selective autophagy of peroxisomes through a process termed pexophagy. The physiological peroxisomal target for pexophagy-related ubiquitylation has been controversial, but two studies have now identified the protein PEX5 as the real candidate.


Novel TBXAS1 variants in two Indian children with Ghosal hematodiaphyseal dysplasia: A concise report.
Ghosal hematodiaphyseal dysplasia (GHDD) is a rare, autosomal recessive condition characterised by diaphyseal dysplasia of long bones with defective haematopoiesis. We describe 2 such cases with clinical and radiological evidence of GHDD. Molecular analysis revealed novel variants in TBXAS1 gene in both of them. Suspicion and confirmation of this entity is crucial in cases of refractory anemia with bony deformities, as the clinical manifestations in this entity are usually well responsive to corticosteroids.


Role of heteroplasmic mutations in the mitochondrial genome and the ID4 gene promoter methylation region in the pathogenesis of chronic aplastic anemia in patients suffering from Kidney yin deficiency.
To analyze changes in gene amplification in the mitochondrial genome and in the ID4 gene promoter methylation region in patients with chronic aplastic anemia (CAA) suffering from Kidney (Shen) yin deficiency or Kidney yang deficiency. Bone marrow and oral epithelium samples were collected from CAA patients with Kidney yin deficiency or Kidney yang deficiency (20 cases). Bone marrow samples were collected from 20 healthy volunteers. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and PCR products were used for sequencing and analysis. Higher mutational rates were observed in the ND1-2, ND4-6, and CYTB genes in CAA patients suffering from Kidney yin deficiency. Moreover, the ID4 gene was unmethylated in bone marrow samples from healthy individuals, but was methylated in some CAA patients suffering from Kidney yin deficiency (positive rate, 60%) and Kidney yang deficiency (positive rate, 55%). These data supported that gene mutations can alter the expression of respiratory chain enzyme complexes in CAA patients, resulting in energy metabolism impairment and promoting the physiological and pathological processes of hematopoietic failure. Functional impairment of the mitochondrial respiration chain induced by gene mutation may be an important reason for hematopoietic failure in patients with CAA. This change is closely related to maternal inheritance and Kidney yin deficiency. Finally, these data supported the assertion that it is easy to treat disease in patients suffering from yang deficiency and difficult to treat disease in patients suffering from yin deficiency.


Prediction of Postoperative Risks in Laparoscopic Partial Nephrectomy Using RENAL, Mayo Adhesive Probability and Renal Pelvic Score.
To evaluate the Mayo Adhesive Probability (MAP) score, renal pelvis score, and RENAL nephrometry score for the prediction of surgical outcome in patients with renal masses undergoing laparoscopic partial nephrectomy at a single center. A total of 280 patients who underwent laparoscopic partial nephrectomy were identified retrospectively. Thirty-eight patients were excluded because of a lack of preoperative imaging. The outcome measures included surgical technique, patient characteristics, MAP score, renal-pelvis-score, RENAL nephrometry score, and complication rates according to the Clavien-Dindo classification. Regression analysis was performed for assessment of the predictive value of the given scores. Complications occurred after 32 (13%) operations. There was a significant positive association between the development of complications and RENAL nephrometry score (p=0.003). Prediction of complications was improved by the RENAL nephrometry score [area under the curve (AUC) =0.675] and the MAP score (AUC=0.655): With an increasing MAP score, there was a significantly increased operative time (p=0.033). The renal pelvis score had a minor predicitive role (AUC=0.516) and no correlation was found with postoperative urine leakage. The MAP score and RENAL nephrometry score seem to be able to predict a complex or complicated intra- and postoperative course, while the renal pelvis score is not suitable for predicting postoperative complications, especially urine leakage.


Pulmonary coccidioidomycosis found in healthy Japanese individuals.
Coccidioidomycosis is endemic in the south-western USA. This study described the clinicopathological features of pulmonary coccidioidomycosis found in otherwise healthy Japanese individuals. Four male patients with pulmonary coccidioidomycosis were assessed by clinical examination, serology, PCR assay, high-resolution computed tomography and histopathological findings. All patients had returned to Japan from the USA and all presented with an abnormal CXR during routine assessment; two of the patients were symptomatic. High-resolution computed tomography showed a well-defined homogenous nodule or mass adjacent to the pleura. All patients underwent surgical wedge resection. Histopathological examination revealed encapsulated caseating epithelioid cell granulomas containing spherules and endospores. Serum IgG antibody was negative in all patients, but PCR assay using DNA from resected specimens demonstrated the presence of coccidioides-specific DNA. Pulmonary coccidioidomycosis is very rare in Japan, but it can be found incidentally during routine evaluation. The main high-resolution computed tomography findings are a well-defined homogenous nodule adjacent to the pleura, reflecting the histological feature of encapsulated granulomas. PCR assay is useful for confirming the presence of coccidioides.


Assessing Chinese coach drivers' fitness to drive: The development of a toolkit based on cognition measurements.
Road traffic accidents resulting in group deaths and injuries are often related to coach drivers' inappropriate operations and behaviors. Thus, the evaluation of coach drivers' fitness to drive is an important measure for improving the safety of public transportation. Previous related research focused on drivers' age and health condition. Comprehensive studies about commercial drivers' cognitive capacities are limited. This study developed a toolkit consisting of nine cognition measurements across driver perception/sensation, attention, and reaction. A total of 1413 licensed coach drivers in Jiangsu Province, China were investigated and tested. Results indicated that drivers with accident history within three years performed overwhelmingly worse (p<0.001) on dark adaptation, dynamic visual acuity, depth perception, attention concentration, attention span, and significantly worse (p<0.05) on reaction to complex tasks compared with drivers with clear accident records. These findings supported that in the assessment of fitness to drive, cognitive capacities are sensitive to the detection of drivers with accident proneness. We first developed a simple evaluation model based on the percentile distribution of all single measurements, which defined the normal range of "fit-to-drive" by eliminating a 5% tail of each measurement. A comprehensive evaluation model was later constructed based on the kernel principal component analysis, in which the eliminated 5% tail was calculated from on integrated index. Methods to categorizing qualified, good, and excellent coach drivers and criteria for evaluating and training Chinese coach drivers' fitness to drive were also proposed.


Common reversal agents/antidotes in small animal poisoning.
Different antidotes counteract the effect of a toxicant in several different ways. Antidotes can reverse, decrease, or prevent action of a toxicant. They can also help in achieving stabilization of vital signs, directly or indirectly, and promote excretion of a toxicant. However, overreliance on an antidote can be unrealistic and dangerous. While expectations of rapid recovery from antidotes are usually high, in a real life situation, there are many impediments in achieving this goal. The timing of its use, availability, cost, and sometimes adverse effects from the antidote itself can influence the results and outcome of a case. The majority of toxicants do not have a specific antidote therapy indicated and patients in these cases equally benefit from supportive care. In this chapter, commonly used antidotes and reversal agents in small animals are listed in a table form. The table lists generic name along with brand name of an antidote/reversal agent whenever available, main indications for their use, and provides comments or cautions in their use as needed. After stabilizing the patient and establishing the etiology, the clinicians must review more detailed management of that particular toxicant discussed here or in other references.


Intronic PRRT2 mutation generates novel splice acceptor site and causes paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) in a three generation family.
Mutations in PRRT2 cause autosomal dominant paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC). A previously not recognized intronic PRRT2 mutation (c.880-35G > A; p.S294Lfs*29) was found in an 18 month old girl with IC and in her mother with classical presentation of PKD. The mutation results in a novel splice acceptor site in intron 2 of PRRT2. Due to frameshift and a subsequent premature stop-codon the resulting transcript appears to render the PRRT2 protein non/dysfunctional and is the likely cause of disease in this family. Our findings expand the mutational spectrum of this disease.


Voltage-dependent phosphorylation may recruit Ca2+ current facilitation in chromaffin cells.
Bovine chromaffin cells have two components of whole-cell Ca2+ current: 'standard' Ca2+ currents that are activated by brief depolarizations, and 'facilitation' Ca2+ currents, which are normally quiescent but can be activated by large pre-depolarizations or by repetitive depolarizations to physiological potentials. The activation of protein kinase A can also stimulate Ca2+ current facilitation, indicating that phosphorylation can play a part in facilitation. Here we investigate the role of protein phosphorylation in the recruitment of facilitation Ca2+ currents by pre-pulses or repetitive depolarizations. We find that recruitment of facilitation by depolarization is a rapid first-order process which is suppressed by inhibitors of protein phosphorylation or by injection of phosphatase 2A into cells. Recruitment of facilitation Ca2+ current by voltage is normally reversible but phosphatase inhibitors render it irreversible. Our results indicate that recruitment of these Ca2+ currents by pre-pulses or repetitive depolarizations involves voltage-dependent phosphorylation of the facilitation Ca2+ channel or a closely associated regulatory protein. Voltage-dependent phosphorylation may therefore be a mechanism by which membrane potential can modulate ion channel activity.


Revealing the structural chemistry in Na6-2xFex(SO4)3 (1.5 ≤ x ≤ 2.0) for low-cost and high-performance sodium-ion batteries.
Fe-based polyanionic sulfate materials are one of the most promising candidates for large-scale applications in sodium-ion batteries due to their low cost and excellent electrochemical performance. Although great achievements have been gained on a series of Na6-2xFex(SO4)3 (NFSO-x, 1.5 ≤ x ≤ 2.0) materials such as Na2Fe2(SO4)3, Na2Fe1.5(SO4)3, and Na2.4Fe1.8(SO4)3 for sodium storage, the phase and structure characteristics on these NFSO-x are still controversial, making it difficult to achieve phase-pure materials with optimal electrochemical properties. Herein, six NFSO-x samples with varied x are investigated via both experimental methods and density functional theory calculations to analyze the phase and structure properties. It reveals that a pure phase exists in the 1.6 ≤ x ≤ 1.7 region of the NFSO-x, and part of Na ions tend to occupy Fe sites to form more stable frameworks. The NFSO-1.7 exhibits the best electrochemical performance among the NFSO-x samples, delivering a high discharge capacity (104.5 mAh g-1 at 0.1 C, close to its theoretical capacity of 105 mAh g-1), excellent rate performance (81.5 mAh g-1 at 30 C), and remarkable cycle stability over 10,000 cycles with high-capacity retention of 72.4%. We believe that the results are useful to clarify the phase and structure characteristics of polyanionic materials to promote their application for large-scale energy storage.


Differences between patients with ventricular tachycardia and ventricular fibrillation as assessed by signal-averaged electrocardiogram, radionuclide ventriculography and cardiac mapping.
This study examined 65 patients with ventricular tachycardia or fibrillation late after myocardial infarction to determine whether they differed with respect to duration of ventricular activation in sinus rhythm and left ventricular ejection fraction. Patients with spontaneous ventricular tachycardia had a longer ventricular activation time in sinus rhythm than did patients with spontaneous ventricular fibrillation. This difference was detected with the signal-averaged electrocardiogram (ECG) (tachycardia 181 +/- 33 ms, fibrillation 152 +/- 23 ms, p less than 0.001) and at epicardial mapping (tachycardia 210 +/- 17 ms, fibrillation 192 +/- 17 ms, p less than 0.02). Left ventricular ejection fraction was lower in patients with spontaneous ventricular tachycardia (0.22 +/- 0.09) than in patients with spontaneous ventricular fibrillation (0.27 +/- 0.09) (p less than 0.05). The patients with both spontaneous and inducible ventricular fibrillation had a shorter ventricular activation time on the signal-averaged ECG (129 +/- 17 ms) and a higher ejection fraction (0.36 +/- 0.05) than did either patients with spontaneous ventricular fibrillation and inducible ventricular tachycardia (158 +/- 21 ms and 0.25 +/- 0.08, respectively, each p less than 0.01) or patients with both spontaneous and inducible ventricular tachycardia (181 +/- 33 ms and 0.22 +/- 0.09, respectively, each p less than 0.001). Of the patients with inducible ventricular tachycardia, presentation with tachycardia rather than fibrillation was associated with a longer ventricular activation time on the signal-averaged ECG (181 +/- 33 versus 158 +/- 21 ms, p less than 0.02) and a longer cycle length of inducible ventricular tachycardia (290 +/- 61 versus 259 +/- 44 ms, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Mercury in various tissues of three mustelid species and other trace metals in liver of European otter from Eastern Finland.
Mercury concentrations were monitored in European otter (Lutra lutra), European polecat (Mustela putorius) and European pine marten (Martes martes) collected in Eastern Finland during the period 1972-2008. Otters mainly eat fish, which is an important reason to monitor the bioaccumulation of mercury in this predator. In this species, the highest concentrations were found in fur followed by liver and kidney, and the mercury concentrations increased with increasing age and body weight. Males showed in general higher concentrations than females of otters. The food of European polecat consists of small mammals, frogs, birds and insects from both aquatic and terrestrial food chains. The mercury concentrations were lower than in otters without significant differences related to body weight or sex. In European pine martens, the concentrations were rather evenly distributed except for two specimens with high concentrations. Also, concentrations of some other metals (Al, Cd, Cu, Fe, Mn, Ni, Pb and Zn) were analysed from liver samples of otter. Possible adverse effects of mercury on the Finnish populations of these mustelids are discussed.


Effects of p,p'-DDE on the mRNA and protein expressions of vimentin, N-cadherin and FSHR in rats testes: an in vivo and in vitro study.
To elucidate the mechanism underlying the testicular effects of 1,1-dichloro-2,2bis(p-chlorophenyl)ethylene (p,p'-DDE), the expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor mRNA and proteins were measured in vivo and in vitro. Sprague-Dawley rats were dosed with p,p'-DDE at 0, 20, 60 and 100 mg/kg every other day by intraperitoneal injection for 10 days, and Sertoli cells were treated with p,p'-DDE (0, 10, 30, and 50 μM) for 24 h. Results indicated that the survival rate of Sertoli cells was decreased with increasing doses of p,p'-DDE. In vitro and in vivo studies, p,p'-DDE could increase the expression of neural cadherin, follicle-stimulating hormone receptor mRNA, while decrease the levels of vimentin, neural cadherin and follicle-stimulating hormone receptor proteins. Moreover, immunohistochemistry analysis revealed that the protein expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor in pubertal rat testes were disrupted by treatment with p,p'-DDE. Taken together, these results suggested that p,p'-DDE exposure could induce testicular toxicity through the changes of the mRNA and protein expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor in vitro and in vivo.


Mechanisms for metoclopramide-mediated sensitization and haloperidol-induced catalepsy in rats.
Typical antipsychotics such as the dopamine D(2) receptor antagonist, haloperidol are known to cause movement disorders or catalepsy in experimental animals. Catalepsy is believed to result from blockade of dopamine D(2) receptors. In this study two drugs that differ in antipsychotic potency but are similar in blocking dopamine D(2) receptors were used to investigate the mechanism for catalepsy and its sensitization. Metoclopramide is a strong postsynaptic dopamine D(2) receptor blocker with no antipsychotic potency. At low doses of 5 or 10 mg/kg given subcutaneously (s.c.), metoclopramide did not produce catalepsy or movement disturbance for seven days after drug treatment. Also metoclopramide at 10 mg/kg given for five days, failed to induce catalepsy. Haloperidol, another potent dopamine D(2) receptor blocker at 0.5 mg/kg (s.c.) rapidly produced catalepsy and suppressed movement 1 h after a single dose of the drug. Chronic as well as acute treatment with metoclopramide caused sensitization of haloperidol-induced catalepsy. Neurochemical analyses revealed significant dopamine D(2) receptor up-regulation in both frontal cortex and striatum of rats chronically treated with metoclopramide. However, no changes in dopamine D(2) receptor numbers were noted in these areas after chronic treatment with low doses of haloperidol. Significant increases in N-methyl-D-aspartate (NMDA) receptor numbers were observed in both frontal cortex and striatum of metoclopramide treated animals, while haloperidol elicited significant decreases in NMDA receptor numbers in both brain areas. These observations plus previous reports have led us to propose a model for catalepsy and its sensitization. According to this model the increase in NMDA receptors by metoclopramide sensitizes the brain to haloperidol-induced catalepsy. Thus, catalepsy appears to be elicited by simultaneous activation of glutamatergic NMDA and dopamine D(1) receptors as well as a blockade of dopamine D(2) receptors.


Biological factors influencing depression in later life: role of aging processes and treatment implications.
Late-life depression occurring in older adults is common, recurrent, and malignant. It is characterized by affective symptoms, but also cognitive decline, medical comorbidity, and physical disability. This behavioral and cognitive presentation results from altered function of discrete functional brain networks and circuits. A wide range of factors across the lifespan contributes to fragility and vulnerability of those networks to dysfunction. In many cases, these factors occur earlier in life and contribute to adolescent or earlier adulthood depressive episodes, where the onset was related to adverse childhood events, maladaptive personality traits, reproductive events, or other factors. Other individuals exhibit a later-life onset characterized by medical comorbidity, pro-inflammatory processes, cerebrovascular disease, or developing neurodegenerative processes. These later-life processes may not only lead to vulnerability to the affective symptoms, but also contribute to the comorbid cognitive and physical symptoms. Importantly, repeated depressive episodes themselves may accelerate the aging process by shifting allostatic processes to dysfunctional states and increasing allostatic load through the hypothalamic-pituitary-adrenal axis and inflammatory processes. Over time, this may accelerate the path of biological aging, leading to greater brain atrophy, cognitive decline, and the development of physical decline and frailty. It is unclear whether successful treatment of depression and avoidance of recurrent episodes would shift biological aging processes back towards a more normative trajectory. However, current antidepressant treatments exhibit good efficacy for older adults, including pharmacotherapy, neuromodulation, and psychotherapy, with recent work in these areas providing new guidance on optimal treatment approaches. Moreover, there is a host of nonpharmacological treatment approaches being examined that take advantage of resiliency factors and decrease vulnerability to depression. Thus, while late-life depression is a recurrent yet highly heterogeneous disorder, better phenotypic characterization provides opportunities to better utilize a range of nonspecific and targeted interventions that can promote recovery, resilience, and maintenance of remission.


In vitro antiplasmodial activity of spiro benzofuran compound from mangrove plant of Southern India.
To find out the in vitro antiplasmodial activities of mangrove leaf extracts. In vitro antiplasmodial assay was carried out with 13 different mangrove plants. Column chromatography was performed with the most potent Agecerious corniculatum (A. corniculatum) by using various solvent extractions. GC-MS was also preformed with the most potent ethanolic fraction of the A. corniculatum extract. Of the 13 mangroves plants, A. corniculatum showed maximum percentage of parasitemia suppression (94.98 ± 1.16)%. Column chromatography was performed with A. corniculatum with different solvents and the methanolic extract showed maximum percentage (99.73±1.63)% of parasitemia inhibition at 150 μg/mL concentration with the IC(50) value of (29.28±3.23) μg/mL concentration. The results of the GC-MS analysis observed that, the most potent methanolic extract showed maximum retention time (30.687 RT) and the chemical class was identified as Spiro [benzofuran-2(3 H), 1'(3 cyclohexane)-2',3-dione, 7-chloro-4',6] which was responsible for the antiplasmodial activity. It is concluded from the present study that, the chemical constituents of A. corniculatum collected from Pichavaram mangrove forest can be used as a putative antiplasmodial drugs in future.


Successful recovery from COVID-19 in three kidney transplant recipients who received convalescent plasma therapy.
Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease that typically presents with greater severity in patients with underlying medical conditions or those who are immunosuppressed. We present a novel case series of three kidney transplant recipients with COVID-19 who recovered after receiving COVID-19 convalescent plasma (CCP) therapy. Physicians should be aware of this potentially useful treatment option. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical and allograft outcomes associated with CCP use in this population.


Bipolar Disorder Course and Outcome Study from India (BiD-CoIN study): Sample Description & Methods.
This multicentric study from India aimed to evaluate the long term course and outcome of bipolar disorder (BD). Seven hundred and seventy-three participants diagnosed with BD, attending 14 outpatient clinic centers across the country, were evaluated using the National Institute of Mental Health- Retrospective Life Charts to assess the long term course of BD. The mean age of onset of the first episode of illness of the study sample was 26.3 (8.54) years, and mean duration of illness at the time of assessment was 233.05 (94.55) months. In terms of the total number of lifetime episodes, the mean number of manic episodes (mean: 3.68; SD: 4.75) exceeded the mean number of depressive episodes (mean: 3.36; SD: 5.51). The mean numbers of total lifetime episodes were 8.58 (10.6%). When the number of episodes per year was computed, the mean number of manic episodes per year exceeded that of the mean number of depressive episodes. Compared to females, a higher proportion of males had a history of comorbid substance dependence. The course was assessed retrospectively and the study was limited to participants attending the outpatient clinics. The course of BD in India differs from that described from developed countries in the form of a number of manic episodes exceeding the depressive episodes.


Association of insulin use with LV remodeling and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: assessed by cardiac MRI.
Insulin is commonly used in type 2 diabetes mellitus (T2DM) to achieve glycemic control. However, recent evidence showed that insulin use is associated with poor outcomes in the context of heart failure (HF). Since heart failure with reduced ejection fraction (HFrEF) accounts for approximately 50% of cases in the general HF population, we aimed to evaluate the effect of insulin treatment on left ventricular (LV) remodeling and contractility abnormalities in a HFrEF cohort and assess whether insulin was a predictor of adverse outcomes in this entity. A total of 377 HFrEF patients who underwent cardiac MRI were included and divided according to diabetes status and the need for insulin treatment. LV structural and functional indices, as well as systolic strains, were measured. The determinants of impaired myocardial strains were assessed using linear regression analysis. The associated endpoints were determined using a multivariable Cox proportional hazards model. T2DM patients on insulin displayed a higher indexed LV end-diastolic volume and LV mass than those with T2DM not on insulin or those without T2DM, despite similar LV ejection fractions, accompanied by a higher three-dimensional spherical index (P < 0.01). Worse longitudinal and circumferential peak systolic strain was shown to occur in T2DM patients on insulin (P < 0.01). Insulin treatment was independently associated with impaired magnitudes of systolic strain. The median follow-up duration was 32.4 months (IQR, 15.6-43.2 months). Insulin treatment remained consistently associated with poor outcomes after adjustment for established confounders, with an adjusted hazard ratio of 3.11; (95% CI, 1.45-6.87; P = 0.009) in the overall cohort and 2.16 (95% CI, 1.08-4.59; P = 0.030) in the diabetes cohort. Insulin may further lead to adverse LV remodeling and contractile dysfunction in the context of HFrEF with T2DM. Considerable care should be taken when treating HFrEF patients with insulin.


After chronic opioid exposure sensory neurons become supersensitive to the excitatory effects of opioid agonists and antagonists as occurs after acute elevation of GM1 ganglioside.
Mouse sensory dorsal-root ganglion (DRG) neurons chronically exposed to 1 microM D-Ala2-D-Leu5-enkephalin (DADLE) for greater than 1 week in culture become tolerant to opioid inhibitory effects, i.e. shortening of the duration of the calcium-dependent component of the action potential (APD). Acute application of higher concentrations of DADLE (ca. 10 microM) to these treated neurons not only fails to shorten the APD but, instead, generally elicits excitatory effects, i.e. prolongation of the APD. The present study shows that chronic DADLE- or morphine-treated DRG neurons also become supersensitive to the excitatory effects of opioids. Whereas nM concentrations of dynorphin(1-13) are generally required to prolong the APD of naive DRG neurons, fM levels become effective after chronic opioid treatment. Whereas 1-30 nM naloxone or diprenorphine do not alter the APD of naive DRG neurons, both opioid antagonists unexpectedly prolong the APD of most of the treated cells. Similar supersensitivity to the excitatory effects of opioid agonists and antagonists was previously observed after acute treatment of naive DRG neurons with GM1 ganglioside. Our results suggest that both chronic opioid and acute GM1 treatments of DRG neurons greatly enhance the efficacy of opioid excitatory receptor functions so that even the extremely weak agonist properties of naloxone and diprenorphine become effective in prolonging the APD of these treated cells when tested at low concentrations, whereas their antagonist properties at inhibitory opioid receptors do not appear to be altered. Furthermore, whereas cholera toxin-B subunit (CTX-B; 1-10 nM) blocks opioid-induced APD prolongation in naive DRG neurons (presumably by interfering with endogenous GM1 modulation of excitatory opioid receptors functions), even much higher concentrations of CTX-B were ineffective in chronic opioid-treated as well as acute GM1-elevated neurons. These and related data suggest that opioid excitatory supersensitivity in chronic opioid-treated DRG neurons may be due to a cyclic AMP-dependent increase in GM1 ganglioside levels. Our results may clarify mechanisms of opioid dependence and the paradoxical supersensitivity to naloxone which triggers withdrawal symptoms after opiate addiction.


Data on alveolar mandibular bone thickness in Class I skeletal patient with bimaxillary protrusion.
The alveolar bone thickness influences both diagnosis and limitation of tooth movement, therefore significance retraction was commonly applied in treating patients with bimaxillary protrusion. This is a retrospective data collection of pre and post treatment lateral cephalographs from 18 to 40 years old patient treated with four premolars extraction. The alveolar mandibular bone thickness was identified in sagittal planes with Image-J software based on cephalometry lateral radiographs. Statistical analysis namely Wilcoxon test and Pearson correlation analysis coefficient were used to understand the correlation of alveolar mandibular bone thickness variables and mandibular incisors position to skeletal profile treated with first premolars extraction are presented. This data is essential for advancing in a further understanding of Class I skeletal patients with bimaxillary protrusion.


Mucosal activity patterns as a basis for olfactory discrimination: comparing behavior and optical recordings.
In over half a century numerous studies have demonstrated that different odorants produce individually different spatial patterns of neural receptor activity on the olfactory mucosa. However, the thought that these differential activity patterns could be the neural code underlying olfactory perception has not been tested directly. In the present study using operant techniques, rats were trained to differentially identify five odors from a homologous series of iso-intensive straight-chain aldehydes that differed serially by only one carbon atom, viz. hexaldehyde to decaldehyde. The rats identified each of the five odorants with greater than 90% correct identification. The degree of perceptual similarity between any pair of the five odorants was determined. Using multidimensional scaling techniques (MDS) the similarity measures yielded a two-dimensional perceptual odorant space. Optical techniques were used to record the olfactory mucosal activity patterns in response to these same five iso-intensive aldehydes. The mucosal activity elicited by each odorant revealed individually distinct band-like patterns that varied both within and across these bands. More importantly, the relative differential responsivity of the bands was related to chain length. An MDS analysis of the dissimilarity measure between all possible pairs of odorant induced activity patterns yielded a two-dimensional neurophysiologic odorant space. Further analysis indicated that the neurophysiologic and psychophysically determined odorant spaces were highly correlated (F(1,39)=23.9, P=nil). These results give additional credence to the concept that the odorant-induced mucosal activity patterns may serve as the substrate for the perception of odorant quality.


Molecular tools for studying the radial spoke.
Studies of cilia and flagella often entail biochemical analysis of axonemal complexes that either associate with the nine outer doublet microtubules or the two singlet microtubules in the 9+2 axoneme. Each complex contains multiple subunits, a few of which are ubiquitous vital proteins, while many are novel with prevalent domains that remain to be characterized. Investigation of axoneme biochemistry will continue providing insights into flagellar biology as well as molecular complexes in general. Yet, the complicated contents and extensive molecular interactions pose significant challenges in experimentation. As such, most biochemical studies remain limited to dynein motors and often require extensive training and expensive equipment. The rapid accumulation of high-throughput database and versatile research tools has now lessened the obstacles significantly. Here, we describe the strategies and methods that were used to circumvent some of the common difficulties to characterize the radial spoke in Chlamydomonas axoneme, some of which were tailored to students with little research experience. They could be adapted for the study of many other axonemal complexes and for classroom settings as well.


Experimental corroboration of the nonstationary strain estimation errors in elastography.
The nonstationary variation in the noise performance of the cross-correlation-based strain estimator due to frequency-dependent attenuation and lateral and elevational signal decorrelation have been addressed theoretically in recent papers using the strain-filter approach. In this paper, we present the experimental verification and corroboration of the nonstationary effects on the strain estimation results. The accuracy and precision of the strain estimate deteriorates with lateral position in the elastogram, due to the lateral motion of tissue scatterers, and with depth, due to frequency-dependent attenuation. The results illustrate that the best strain-estimation noise performance is obtained in the focal zone of the transducer and around the axis of symmetry of the phantom.


Effect of probucol on the composition of lipoproteins and on VLDL apoprotein B turnover.
We studied the effect of probucol on lipoprotein composition and VLDL apo B turnover. In 7 hypercholesterolemic subjects, probucol therapy lowered mean total cholesterol, HDL cholesterol and HDL triglycerides, raised LDL triglycerides and did not change LDL cholesterol. LDL cholesterol:LDL triglycerides mass ratios fell. In all 6 subjects studied by rate-zonal ultracentrifugation, the flotation rate of LDL decreased. The isolated LDL were depleted of cholesteryl esters relative to protein. Thus, there were changes in the physical and chemical properties of LDL. All 6 subjects had reductions in HDL2, with variable changes in HDL3 on zonal ultracentrifugation. Probucol did not cause significant alterations in VLDL apo B turnover in 4 patients. The results suggest that the alterations in HDL probably are not related to changes in the flux of VLDL plasma, but rather may be due to direct effects of the drug on HDL production or catabolism.


Biallelic PADI6 variants cause multilocus imprinting disturbances and miscarriages in the same family.
The term multilocus imprinting disturbance (MLID) describes the aberrant methylation of multiple imprinted loci in the genome, and MLID occurs in patients suffering from imprinting disorder carrying methylation defects. First data indicate that functional variants in factors expressed from both the fetal as well as the maternal genome cause MLID. Molecular changes in such genes of the maternal genome are called maternal effect variants, they affect members of the subcortical maternal complex (SCMC) in the oocyte which plays an important role during early embryonic development. Whereas the contribution of variants in the SCMC genes NLRP2, NLRP5, NLRP7, and KHDC3L to the etiology of reproductive failure and aberrant imprinting is widely accepted, the involvement of PADI6 variants in the formation of MLID is in discussion. We now report on the identification of biallelic variants in a woman suffering from different miscarriages and giving birth to two children with MLID. Thereby the role of PADI6 in maintaining the proper imprinting status during early development is confirmed. Thus, PADI6 variants do not only cause (early) pregnancy losses, but maternal effect variants in this gene cause the same spectrum of pregnancy outcomes as variants in other SCMC encoding genes, including chromosomal aberrations and disturbed imprinting. The identification of maternal effect variants requires genetic and reproductive counseling as carriers of these variants are at high risks for reproductive failure.


First rhyncaphytoptine mite (Eriophyoidea, Diptilomiopidae) parasitizing American hazelnut (Corylus americana): molecular identification, confocal microscopy, and phylogenetic position.
The plant genus Corylus is an economically important crop, valued especially for its nuts. Numerous pathogens and harmful phytophagous arthropods are known to damage hazelnuts. We report on a new eriophyoid mite, Rhyncaphytoptus corylivagrans n. sp., and the first record of Coptophylla lamimani both collected from leaves of American hazelnut (Corylus americana) in North Carolina, USA. Including our new data, the complex of eriophyoids from Corylus comprises 15 species from three families: Phytoptidae (2 spp.), Eriophyidae (11 spp.), and Diptilomiopidae (2 spp.). We obtained sequences of three genes (Cox1, D1-D5 28S, and ITS1-5.8S-ITS2), applied BLAST and tree-based approaches for identification of R. corylivagrans n. sp., and performed the first molecular phylogenetic analysis focused on Rhyncaphytoptinae. Among the three genes, Cox1 showed better power when used for BLAST searches. Combined molecular phylogenetic analyses inferred R. corylivagrans n. sp. as sister to R. betulae, determined several moderately supported host-specific lineages of rhyncaphytoptines, and indicated a close relationship of the new species with members of the genus Rhinotergum. In two Rhinotergum spp. from Rosaceae, confocal microscopy revealed a new structure, the needle-like anterior process of the prodorsal shield, which is absent in R. corylivagrans n. sp. Additionally, the elements of the anal secretory apparatus presumably associated with silk-production and hypothesized as a synapomorphy of Eriophyoidea, were detected in the new species, providing the first documented report of this structure in Diptilomiopidae. Our study contributes to knowledge on the biodiversity of phytoparasites associated with hazelnuts and calls for future comparative phylogenetics of Diptilomiopidae.


Intestinal microcirculation and necrotizing enterocolitis: The vascular endothelial growth factor system.
Necrotizing enterocolitis (NEC), a leading cause of morbidity and mortality in preterm neonates, is a devastating disease characterized by intestinal tissue inflammation and necrosis. NEC pathogenesis is multifactorial but remains unclear. Translocation of bacteria and/or bacterial products across a weak intestinal barrier in the setting of impaired mucosal immunity leads to an exaggerated inflammatory response and secondary mucosal epithelial injury. In addition to prematurity, other risk factors for NEC include congenital heart disease, maternal pre-eclampsia with placental vascular insufficiency, severe anemia and blood transfusion - all conditions that predispose the intestine to ischemia. We recently found that maldevelopment of the intestinal microvasculature plays an important role in NEC pathogenesis. Here we review the evidence supporting a role for defective development of the intestinal mucosal microvasculature and perturbations of intestinal blood flow in NEC, emphasizing the importance of vascular endothelial growth factor (VEGF) and the VEGF receptor-2 signaling pathway.


The effect of phorbol ester treatment on migration of C3H 10T1/2 and BT5C glioma cells: possible application to carcinogenesis.
Treatment with the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) and the second-stage promoter 12-O-retinoylphorbol 13-acetate induced down-regulation of protein kinase C (PKC) and enhanced the migration of C3H 10T1/2 cells. In the case of BT5C glioma cells the same negative correlation was observed only after treatment with TPA. The negative control 4 alpha-phorbol affected neither PKC activity nor the migratory ability of both cell lines.


A computational strategy for predicting lineage specifiers in stem cell subpopulations.
Stem cell differentiation is a complex biological event. Our understanding of this process is partly hampered by the co-existence of different cell subpopulations within a given population, which are characterized by different gene expression states driven by different underlying transcriptional regulatory networks (TRNs). Such cellular heterogeneity has been recently explored with the modern single-cell gene expression profiling technologies, such as single-cell RT-PCR and RNA-seq. However, the identification of cell subpopulation-specific TRNs and genes determining specific lineage commitment (i.e., lineage specifiers) remains a challenge due to the slower development of appropriate computational and experimental workflows. Here, we propose a computational method for predicting lineage specifiers for different cell subpopulations in binary-fate differentiation events. Our method first reconstructs subpopulation-specific TRNs, which is more realistic than reconstructing a single TRN representing multiple cell subpopulations. Then, it predicts lineage specifiers based on a model that assumes that each parental stem cell subpopulation is in a stable state maintained by its specific TRN stability core. In addition, this stable state is maintained in the parental cell subpopulation by the balanced gene expression pattern of pairs of opposing lineage specifiers for mutually exclusive different daughter cell subpopulations. To this end, we devised a statistical metric for identifying opposing lineage specifier pairs that show a significant ratio change upon differentiation. Application of this computational method to three different stem cell systems predicted known and putative novel lineage specifiers, which could be experimentally tested. Our method does not require pre-selection of putative candidate genes, and can be applied to any binary-fate differentiation system for which single-cell gene expression data are available. Furthermore, this method is compatible with both single-cell RT-PCR and single-cell RNA-seq data. Given the increasing importance of single-cell gene expression data in stem cell biology and regenerative medicine, approaches like ours would be useful for the identification of lineage specifiers and their associated TRN stability cores.


On the closing sounds of a mechanical heart valve.
In the 1994 Replacement Heart Valve Guidance of the U.S. Food and Drug Administration (FDA), in-vitro testing is required to evaluate the potential for cavitation damage of a mechanical heart valve (MHV). To fulfill this requirement, the stroboscopic high-speed imaging method is commonly used to visualize cavitation bubbles at the instant of valve closure. The procedure is expensive; it is also limited because not every cavitation event is detected, thus leaving the possibility of missing the whole cavitation process. As an alternative, some researchers have suggested an acoustic cavitation-detection method, based on the observation that cavitation noise has a broadband spectrum. In practice, however, it is difficult to differentiate between cavitation noise and the valve closing sound, which may also contain high-frequency components. In the present study, the frequency characteristics of the closing sound in air of a Björk-Shiley Convexo-Concave (BSCC) valve are investigated. The occluder closing speed is used as a control parameter, which is measured via a laser sweeping technique. It is found that for the BSCC valve tested, the distribution of the sound energy over its frequency domain changes at different valve closing speeds, but the cut-off frequency remains unchanged at 123.32 +/- 6.12 kHz. The resonant frequencies of the occluder are also identified from the valve closing sound.


A Case of Father-Son Juvenile Acute Myocardial Infarction.
Coronary artery ectasia (CAE) is a cause of juvenile myocardial infarction. The causes of CAE include arteriosclerosis, vasculitis such as Kawasaki disease, and genetic contribution. There are few reports about familial aggregation of CAE-related juvenile myocardial infarction. We report an unusual case of father-son juvenile myocardial infarction owing to CAE. (Level of Difficulty: Beginner.).


[Traumatic rupture of the isthmus of a horseshoe kidney (author's transl)].
In the light of an extremely rare case of rupture of the isthmus of a horseshoe kidney, the author described the operative technique used and the postoperative complications which, despite their gravity, could be controlled by conservative operative measures.


Transfer RNA-derived small RNA: an emerging small non-coding RNA with key roles in cancer.
Transfer RNAs (tRNAs) promote protein translation by binding to the corresponding amino acids and transporting them to the ribosome, which is essential in protein translation. tRNA-derived small RNAs (tsRNAs) are derived fragments of tRNAs that are cleaved explicitly under certain conditions. An increasing amount of research has demonstrated that tsRNAs have biological functions rather than just being degradation products. tsRNAs can exert functions such as regulating gene expression to influence cancer progression. Their dysregulation is closely associated with various cancers and can serve as diagnostic and prognostic biomarkers for cancer. This review summarizes the generation, classification, and biological functions of tsRNAs, and highlights the roles of tsRNAs in different cancers and their applications as tumor markers.


Extraction, characterization and antioxidant activity of polysaccharides of spent mushroom compost of Ganoderma lucidum.
To contribute toward effective exploitation and utilization of spent mushroom compost (SMC) of Ganoderma lucidum (SMC-G), a water-soluble polysaccharide of GPS was extracted, and then two fractions (GPS-1 and GPS-2) were purified from SMC-G. The optimum conditions for GPS extraction were optimized by the central composite design (CCD) and the GPS yield reached 3.84% at a ratio of water to material of 34.5, a precipitation time of 19.82h, and pH of 7.88. Characteristic analysis showed that GPS-1 and GPS-2 were heteropolysaccharides, and had glycosidic structures (OH, CH, CO and COC). Both GPS and its fractions showed potential antioxidant activities by scavenging hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and increasing the reducing power in vitro; and by improving the CAT activities, and lowing the LPO and MDA contents in vivo, respectively. The results provided a reference for the exploitation of SMC-G which would be significant to sustainable development of industry and agriculture, environmental protection and full utilization of resources.


Delayed surgery after hip fracture affects the incidence of venous thromboembolism.
Venous thromboembolism (VTE) is one of the most common complications of hip fracture surgeries, and it is unclear whether delayed surgery affects the incidence of VTE. This study aimed to examine the association between delayed surgery and VTE incidence by statistically adjusting for factors that may influence VTE incidence. We included 862 patients ≥ 65 years with hip fractures who underwent surgery between October 2010 and December 2020. We examined the effect of surgical delay 48 h after injury on postoperative VTE. Patients with and without VTE were assigned to groups V and NV, respectively. Those with and without proximal deep venous thrombosis (DVT) were assigned to PD and NPD groups, respectively. Univariate analysis was performed to identify factors that might influence DVT development. Risk factors for developing VTE and proximal DVT were analyzed using logistic regression analysis to determine whether delayed surgery was a risk factor. VTE was observed in 436 patients (40%) and proximal DVT in 48 patients (5.6%). Univariate analysis showed significant differences in the time from trauma to surgery between the V and NV groups and between the PD and NPD groups. In multivariate analysis, surgery 48 h later was also a risk factor for developing VTE and proximal DVT. A delay in surgery beyond 48 h after a hip fracture injury is a risk factor for developing VTE and proximal DVT.


Relationship between cytokine levels in serum and gingival crevicular fluid (GCF) in pregnant women.
Periodontal disease has been linked to systemic diseases/disorders and a low-grade systemic inflammatory status originated from periodontitis has been proposed as a possible explanation for this association. This study evaluates the relationship, early in pregnancy, between gingival crevicular fluid (GCF) and serum levels of a panel of cytokines that have been implicated in PTB and periodontal disease. One hundred pregnant women aged 18-35 years old with a gestational age up to 20 weeks were included (mean±SD gestational age:16.1±3.5 weeks). Four periodontal sites per subject were randomly selected for GCF collection. Serum and GCF levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were analyzed using a cytometric bead array. Regression and correlation analyses were used to assess the relationship between serum and GCF cytokine levels. Participants had widespread periodontal inflammation but limited periodontal destruction. Cytokine levels were significantly higher in GCF than serum for all cytokines but IL-10. GCF levels had small but significant effect on serum levels for IL-10 (β=0.34±0.09, p<0.01), IL-12p70 (β=0.48±0.08, p<0.01) and TNF-α (β=0.29±0.09, p<0.01). Periodontal probing depth and bleeding on probing were significantly associated with GCF levels for IL-1β, IL-6 and IL-8; however, they had negligible effect on serum cytokine levels. Correlation between GCF and serum levels was non-significant, except for IL-12p70, which showed a significant but small correlation between the two sources (r=0.32, p=0.001). GCF cytokine levels were not strongly associated with serum cytokine levels in pregnant women with widespread periodontal inflammation but limited periodontal destruction.


[Telemedicine-assisted treatment of a 76-year-old man with heart failure].
The case of a patient with dilated cardiomyopathy and severely impaired left ventricular function is reported. With existing complete left bundle branch block and the patient being on optimal medical therapy, a cardiac resynchronization device with an integrated defibrillator was implanted and the patient was included in our telemonitoring program. During monitoring, an increase in ventricular premature beats with a decrease in biventricular pacing percentage was noticed. Consequently, radiofrequency ablation of the ventricular premature beats which originated in the left ventricle was performed. After ablation we could demonstrate a significant increase in biventricular pacing percentage. This case shows the importance of telemedicine and the complexity in the rhythmological treatment of heart failure patients.


Intrahepatic pyogenic abscesses: treatment by percutaneous drainage.
During a 6 year period, 18 liver abscesses in 12 patients were identified by computerized tomography. Five patients had presumed hematogenous seeding. Five patients previously had bilioenteric anastomoses, stents, or both to relieve obstructive jaundice. Four patients with abscesses had recent abdominal operations. Diagnosis was established by guided needle aspiration and treatment was provided by percutaneous catheter drainage. Organism-specific antibiotics were administered to all patients. Patients were evaluated for recurrence by serial computerized tomographic studies and were clinically followed up for a minimum of 15 months. Ten of 12 patients (83 percent) and 16 of 18 abscesses (89 percent) were successfully treated by percutaneous catheter drainage. Two failures required operative intervention. In summary, the low morbidity and high success rate in treating hepatic abscesses by percutaneous drainage suggests that this therapy be tried before operative intervention is considered.


Magnetic hydroxyapatite coatings as a new tool in medicine: A scanning probe investigation.
Hydroxyapatite films enriched with magnetite have been fabricated via a Pulsed Plasma Deposition (PPD) system with the final aim of representing a new platform able to disincentivate bacterial adhesion and biofilm formation. The chemical composition and magnetic properties of films were respectively examined by X-ray photoelectron spectroscopy (XPS) and Superconducting Quantum Interference Device (SQUID) measurements. The morphology and conductive properties of the magnetic films were investigated via a combination of scanning probe technologies including atomic force microscopy (AFM), electrostatic force microscopy (EFM), and scanning tunneling microscopy (STM). Interestingly, the range of adopted techniques allowed determining the preservation of the chemical composition and magnetic properties of the deposition target material while STM analysis provided new insights on the presence of surface inhomogeneities, revealing the presence of magnetite-rich islands over length scales compatible with the applications. Finally, preliminary results of bacterial adhesion tests, indicated a higher ability of magnetic hydroxyapatite films to reduce Escherichia coli adhesion at 4h from seeding compared to control hydroxyapatite films.


Neuronal injury, but not microglia activation, is associated with ketamine-induced experimental schizophrenic model in mice.
Schizophrenia is a chronic debilitating psychiatric disorder affecting as many as 1% of the population worldwide. Unfortunately, its etiology and pathophysiology are poorly defined. Previous studies have shown that neuronal injury and microglia activation were observed in the schizophrenic patients. The present study aims to evaluate the role of neurons and microglia in ketamine-induced experimental schizophrenic model to further understand its pathophysiology. Firstly, ketamine was used to simulate the behavior abnormalities associated with schizophrenia. The effects of ketamine on mouse locomotor activity, Y-maze task, novel object recognition, and forced swimming test were studied. The results showed that ketamine (25, 50, and 100mg/kg i.p.) administered acutely or repeatedly (for 7 days) can increase the locomotor number significantly. In Y-maze task, ketamine (25, 50, and 100mg/kg) impaired spontaneous alternation after both acute and repeated treatments. In novel object recognition test, acute or chronic ketamine treatment showed no significant effect on mouse exploratory preference behavior. In forced swimming test, repeated treatment of ketamine (100mg/kg) enhanced the immobility duration. Secondly, immunohistochemical method was used to study the changes of neurons and microglia. The results showed that acute treatment of ketamine (100mg/kg) had no effect on neurons in the prefrontal cortex or hippocampus (1, 3, 5, and 7 days after the treatment). In contrast, repeated treatment of ketamine caused neuronal impairment in mouse hippocampus (3rd day, 5th day and 7th day after the final administration). The results of immunohistochemistry demonstrated that microglia in the prefrontal cortex and hippocampus were not affected after acute or repeated administration of ketamine. Finally, the neuronal impairment caused by repeated administration of ketamine was further investigated from the oxidative stress aspects. The results showed that repeated administration of ketamine increased nitric oxide (NO) and nitric oxide synthase (NOS) in prefrontal cortex, hippocampus and serum, while decreased SOD in hippocampus and serum. In summary, chronic ketamine treatment to mice successfully mimics the core behavioral deficits in schizophrenia. It is demonstrated for the first time that neuronal injury was associated with the chronic ketamine-induced experimental schizophrenic model, while microglial cells may play little role in this model. Oxidative stress may contribute to the significant neuronal injury in mouse brain induced by chronic ketamine treatment.


Dietary Risk Factors for Pediatric Kidney Stones: A Case-Control Study.
Data are scarce regarding dietary risk factors for pediatric nephrolithiasis. Our objective was to perform a case-control study (nonmatched) of the association of dietary nutrients with pediatric urolithiasis. We obtained dietary information from pediatric urolithiasis patients (from stone clinic in 2013-2016) and healthy controls (well-child visit at primary care in 2011-2012). Survey results were converted to standard nutrient intakes. Children younger than 5 years of age and those with extreme calorie intake values (<500 or >5,000 kcal/day) were excluded. The association of individual nutrients with urolithiasis was assessed by bivariate analysis results and machine-learning methods. A multivariable logistic regression model was fitted using urolithiasis as the outcome. We included 285 patients (57 stones/228 controls). Mean±SD age was 8.9±3.6 years (range 5-20). Of the patients 47% were male. After adjusting for age, sex, body mass index (obese/overweight/normal), calorie intake and oxalate, urolithiasis was associated with higher dietary sodium (OR=2.43 [95% CI=1.40-4.84] per quintile increase, p=0.004), calcium (OR=1.73 [95% CI=1.07-3.00] per quintile increase, p=0.034) and beta carotene (OR=2.01 [95% CI=1.06-4.18] per quintile increase, p=0.042), and lower potassium (OR=0.31 [95% CI=0.13-0.63] per quintile increase, p=0.003). Sensitivity analysis was performed by removing oxalate from the model and limiting the sample to patients aged 5-13 years, with similar results. In our cohort, higher dietary intake of calcium, sodium and beta carotene, and lower potassium intake were associated with pediatric urolithiasis. This is the first study using a detailed dietary survey to identify dietary risk factors for pediatric urolithiasis. Further research is warranted to delineate the mechanisms and to generate a lower risk diet profile for pediatric urolithiasis.


Synthesis and evaluation of anticancer activity of 6-pyrazolinylcoumarin derivatives.
A series of novel 6-pyrazolinylcoumarins has been synthesized via multi-step protocol. The synthetic procedure was based on the acetylation of hydroxycoumarins; Fries rearrangement and Claisen-Schmidt condensation; the target 6-[5-aryl-4,5-dihydropyrazol-3-yl]-5-hydroxy-7-methylcoumarins (33-49) were obtained under reactions of hydrazine and 2-aryl-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-diones as the last phase of the protocol. Anticancer activity screening in NCI60-cell lines assay allowed identification of compound 47 with the highest level of antimitotic activity with mean GI50 value of 10.20 μM and certain sensitivity profile toward the Leukemia cell lines CCRF-CEM and MOLT-4 (GI50/TGI values 1.88/5.06 μM and 1.92/4.04 μM respectively).


Implementation of subcritical water extraction with natural deep eutectic solvents for sustainable extraction of phenolic compounds from winemaking by-products.
In attempt to recover valuable phenolic compounds from grape pomace by-products, a new implemented methodology has been proposed. The subcritical water extraction technique has been implemented with the use of emerging eco-solvents such as natural deep eutectic solvents (NADESs). The extraction efficiency of different NADESs were screened. Among them, choline chloride containing urea as hydrogen bond donor was selected (ChClU). However, due to pressurised system and the viscosity of NADESs, ChClU could not be used as truly solvent but as a solvent modifier in an promising percentage of 30%. The optimum extraction temperature for the isolation of phenolic compounds was 100 °C since extractions above this temperature implied the loss of the original composition of grape pomace due to thermaldegradation reactions and neoformation of Maillard compounds. The employ of subcritical water combined with 30% of ChClU led to a significant rise of extracted phenolic compounds quantities in comparison with the solely use of subcritical water. Among them, the extraction of catechin and epicatechin suffered an increase of 45.05 and 47.98% respectively, so this implementation led to highly efficient and truly eco-friendly extraction method. The implementation of subcritical water with NADESs to extract valuable compounds from winery by-products has not been applied until now.


The structural characteristics of radiation oncology in Japan in 2003.
To ascertain the basic structural characteristics of radiation oncology facilities in Japan, we conducted a national survey on their status in 2003. The aims of the survey included the following: present status of radiation treatment facilities, equipment, personnel, patient loads, and other factors. A mail survey verified each potential facility delivering megavoltage radiation therapy and collected data on treatment devices, other equipment, personnel, new patients, and so on. Responses were obtained from 100% of potential facilities. A total of 726 facilities delivered radiation therapy, with 859 megavoltage devices, 203 RALS (remote after-loading system) and other radioactive sources, with 941 FTE (full-time employee) radiation oncologists including 369 FTE Japanese Society of Therapeutic Radiation Oncology-certified radiation oncologists, 1555 FTE radiation therapists, and 70 FTE physicists in 2003. Megavoltage devices included two heavy ion units and four proton units. In total, there were 149,793 new patients and 146,351 (98%) by external irradiation; 4379 (3%) were treated by brachytherapy with or without external irradiation. Eighty-six percent of the facilities had treatment-planning computers, but 4% had no treatment-planning capability. Six percent (44 facilities) of all facilities used hyperthermia, 12% (85 facilities) intraoperative radiation therapy, and 2% (12 facilities) intensity-modulated radiation therapy. Facilities surveys continue to provide a source of census data on radiation oncology in Japan, allowing comparisons among facility groups and over time.


Effects of digitalis on resting and isometric exercise myocardial perfusion in patients with coronary artery disease and left ventricular dysfunction.
Digitalis has been shown to improve the impaired ventricular function associated with coronary artery disease as well as to increase myocardial oxygen consumption and produce coronary vasoconstriction. To elucidate the net result of these contrasting effects, six patients with coronary artery disease and left ventricular ejection fractions less than 0.50 had 1.0 mCi thallium-201 injected intravenously at rest and during three minutes of 33% of maximal handgrip, off and on 0.25 mg daily maintenance digoxin. Thallium-201 scintigram images were taken 30 minutes later and were computer processed with orthogonal linearly interpolated background subtraction and maximal count density equalization. Processed images were visually graded on a 0, 1, or 2 scale for 18 sectors--nine from the AP projections and nine from the 40 degrees left anterior oblique projections. A score resulting from the summation of the 18 sector grades was made for each study, the maximum score being 36. Off digitalis, patients performing handgrip exercise decreased their scintigram scores from 25.7 +/- 1.5 (mean +/- SEM) to 23.0 +/- 1.0, P less than 0.05. When patients were on maintenance digoxin, scores did not change significantly during handgrip exercise. Post exercise scores were significantly higher on digoxin than off (P less than 0.05), whereas, resting scores were unaffected by digoxin. These data suggest that myocardial perfusion, as measured by thallium-201 uptake, is improved in patients on digitalis who have coronary artery disease and left ventricular dysfunction.


Studies on antibody to hepatitis A virus in children and adults in London.
366 specimens of serum from children and adults without liver disease were screened for antibody to hepatitis A virus (anti-HAV) by means of radioimmunoassay. 56% were born in London, 26% came to London from various parts of the United Kingdom and the remainder (18%) from various parts of the world. The prevalence of antibody was related to increasing age, ranging from 7% in children under ten years of age to 77% in adults aged 50 years or more. The prevalence of anti-HAV was significantly higher in females, in the lower socio-economic class and in those not indigenous to London. In comparison to other urban populations such as those of the United States and Western Europe, the prevalence of anti-HAV was similar in terms of the overall prevalence and age distribution. By contrast, these findings were entirely different from the countries of Eastern Europe and the Middle East where the overall prevalence was higher but the anti-HAV was equal in all ages. Thus, the findings presented indicate that hepatitis A virus infection is common in London and also shows a clear relationship to advancing age, lower socioeconomic class and the country of origin.


A latent profile analysis of sleep disturbance in relation to mental health among college students in China.
This study aimed to examine the subtype classification characteristics of sleep disturbance (SD) in college students and their associations with sample characteristic factors and mental health outcomes. The sample comprised 4,302 college students (Mean age = 19.92 ± 1.42 years, 58.6% females). The Youth Self-Rating Insomnia Scale, Beck Depression Inventory, 8-item Positive Subscale of the Community Assessment of Psychic Experiences, and 10-item Connor-Davidson Resilience Scale were used to assess adolescents' sleep disturbance, depressive symptoms, psychotic-like experiences (PLEs), and resilience. Latent profile analysis, logistic regression, and liner regression analysis were used to analyze the data. Three subtypes of SD in college students were identified: the high SD profile (10.6%), the mild SD profile (37.5%), and the no SD profile (51.9%). Compared with college students in the "no SD" profile, risk factors for "high SD" include being male and poor parental marital status. Sophomores were found to predict the "high SD" profile or "mild SD" profile relative to the "no SD" profile. College students in the "mild SD" profile or "high SD" profile were more likely to have a higher level of depressive symptoms and PLEs, while a lower level of resilience. The findings highlighted that target intervention is urgently needed for male college students, sophomores, and those with poor parental marital status in the "mild SD" profile or "high SD" profile.


Relationship between compression time and long-term hypoesthesia in primary trigeminal neuralgia treated with percutaneous balloon compression.
Percutaneous balloon compression is a surgical method for the treatment of trigeminal neuralgia, but one of the surgical parameters, compression time, is inconclusive. To investigate the effect of compression time during balloon compression on long-term postoperative hypoesthesia in patients with primary trigeminal neuralgia and to provide guidance on relevant parameters for balloon compression in the treatment of primary trigeminal neuralgia, we conducted a nested case-control study. Patients with primary trigeminal neuralgia treated by balloon compression from March 2013 to September 2013 were divided into case group and control group according to whether there were still symptoms of hypoesthesia at present. The relationship between the compression time of balloon compression and long-term hypoesthesia was analyzed. A total of 289 trigeminal neuralgia patients treated with percutaneous balloon compression were included in this study. Multivariate logistic regression showed that compression time was significantly correlated with long-term hypoesthesia (OR = 1.91, 95% CI = 1.13-3.23, P = 0.02), and compression time was greater than one. The risk of hypoesthesia in the long-term when the compression time is longer than 1 min is 1.93 times that of 1 min. PBC is a safe and effective surgical method, and the long-term hypoesthesia is related to the compression time during operation. The longer the compression time during operation, the greater the risk of long-term hypoesthesia.


Determinants of bone specific metastasis in prostate cancer.
Prostate cancer is one of the most common type of cancer in Western countries. Although the majority of patients with PCa have a minimally aggressive disease, some of them will experience relapse and formation of metastasis. Bone metastasis are a major cause of quality of life impairment and death among patients with metastatic prostate cancer. Different "bone targeted therapies" and several follow-up strategies were developed in order to optimize bone metastasis prevention and treatment. Nevertheless there is still a great clinical need of identifying patients more likely to benefit from those interventions as not all patients will develop metastatic disease and not all patients with metastatic disease will develop bone metastasis. Here we review markers predictive of bone metastasis occurrence that have been tested in clinical settings, particularly focusing on the ability of such markers to predict bone metastasis over visceral metastasis occurrence.


Quenching of intrinsic tryptophan fluorescence in membranes of rat pituitary cells.
The GH4C1 strain of hormone-producing rat pituitary cells has specific receptors for the tripeptide thyrotropin-releasing hormone (TRH). Membranes prepared from GH4C1 cells show intrinsic tryptophan fluorescence which was quenched by low concentrations (10--100 nM) of TRH and Ntau-methyl TRH but not by biologically inactive analogs of TRH. Membranes from GH4C1 cells were subjected to thermal denaturation. A conformational transition was noted above 40 degrees C and an irreversible denaturation was observed at 52 degrees C. TRH-induced quenching of intrinsic fluorescence was lost completely in membranes previously incubated for 10 min at 30 degrees C while loss of [3H]-TRH binding was only about 20% at this temperature. Collisional quenching by iodide revealed that about 38% of the tryptophanyl residues in GH4C1 membranes were exposed to solvent. Quenching by TRH occurred with a shift in wavelength maximum from 336 to 342 nm suggesting that few of the tryptophanyl residues quenched by the tripeptide are totally exposed. Membranes prepared from cells preincubated with 20 nM TRH for 48 h, in which TRH receptors were decreased to 30% of control values, showed no quenching of tryptophan fluorescence in response to freshly added TRH. We conclude that the TRH-receptor interaction in GH4C1 cells is associated with a change in membrane conformation that can be measured by differential spectrofluorometry of intrinsic tryptophan fluorescence.


TRPV1 Gene Polymorphisms Are Associated with Type 2 Diabetes by Their Interaction with Fat Consumption in the Korean Genome Epidemiology Study.
Different transient receptor potential vanilloid 1 (TRPV1) variants may be differently activated by noxious stimuli. We investigated how TRPV1 variants modulated the prevalence of type 2 diabetes and specific gene-nutrient interactions. Among 8,842 adults aged 40-69 years in the Korean Genome Epidemiology Study, the associations between TRPV1 genotypes and the prevalence of type 2 diabetes as well as their gene-nutrient interactions were investigated after adjusting for the covariates of age, gender, residence area, body mass index, daily energy intake, and total activity. The TRPV1 rs161364 and rs8065080 minor alleles lowered HOMA-IR and the risk of type 2 diabetes after adjusting for covariates. There were gene-nutrient interactions between TRPV1 variants rs161364 and rs8065080 and preference for oily taste, intake of oily foods, and fat intake after adjusting for covariates. Among subjects with the minor alleles of TRPV1 rs161364 and rs8065080, the group with a high preference for oily foods had a lower odds ratio for type 2 diabetes. Consistent with the preference for taste, among subjects with the minor alleles, the group with high fat intake from oily foods also exhibited a lower risk of type 2 diabetes than subjects with the major alleles. People with the minor alleles of the TRPV1 single nucleotide polymorphisms rs161364 and rs8065080 have a lower risk of diabetes with a high-fat diet, but people with the major alleles are at a higher risk of type 2 diabetes when consuming high-fat diets. The majority of people should be careful about a high fat intake.


Immune electron microscopic localization of dinitrophenyl-modified ribosomal protein S19 in reconstituted Escherichia coli 30 S subunits using antibodies to dinitrophenol.
Escherichia coli small ribosomal subunits have been reconstituted from RNA and high performance liquid chromatography-purified proteins including protein S19 that had been modified at its amino-terminal proline residue with 1-fluoro-2,4-dinitrobenzene. As detailed in the accompanying paper (Olah, T. V., Olson, H. M., Glitz, D. G., and Cooperman, B. S. (1988) J. Biol. Chem. 263, 4795-4800), dinitrophenyl (DNP)-S19 was efficiently incorporated into the site ordinarily occupied by S19. Antibodies to DNP bound effectively to the reconstituted subunits and did not cause dissociation of the modified protein from the subunit. Electron microscopy of the immune complexes was used to localize the modified protein on the subunit surface. More than 95% of the antibody binding sites seen were consistent with a single location of protein S19 on the upper portion or head of the subunit, on the surface that faces the 50 S particle in a 70 S ribosome, and in an area relatively distant from the subunit platform. The S19 site is close to the region in which 30 S subunits are photoaffinity labeled with puromycin. Protein S19 is thus near protein S14 in the small subunit and in proximity to the peptidyl transferase center of the 70 S ribosome.


Impact of body mass index and metabolic syndrome on sperm DNA fragmentation in males from infertile couples: A cross-sectional study from Vietnam.
This study investigated the relationship between body mass index (BMI) and metabolic syndrome on sperm DNA fragmentation (SDF) in males from infertile couples. This cross-sectional study was performed from September 2018 to September 2019 at the Hue Center for Reproductive Endocrinology and Infertility (HUECREI), Vietnam. The study included men from couples with at least one year of infertility, who were subjected to semen analysis and SDF assay (Halosperm). We also performed a 2-h oral glucose tolerance test and measured lipidemia. Metabolic syndrome (MetS) was defined based on the NHLBI/AHA-ATP III guidelines. The mean age of the patients was 35.26 ± 5.87 years and 53.8% of them had a BMI ≥23.0 kg/m2. The DNA fragmentation index was significantly associated with overweight (p = 0.024). Men without MetS had a higher rate of big halos and a lower rate of small halos, no halos, and degraded semen compared to that in men with MetS, but the differences were not significant (p > 0.05). By performing multivariable analysis, we found that the SDF value was significantly different among the two groups with either overweight or normal weight. In males from infertile couples with a relatively young mean age, BMI can be an independent indicator for SDF. MetS thus has a significant role in the development of sperm DNA fragmentation, at least in overweight individuals; it should thus be assessed under the scope of BMI, for better/earlier detection of increased SDF.


Value of adjuvant whole-pelvis irradiation after Wertheim hysterectomy for early-stage squamous carcinoma of the cervix with pelvic nodal metastasis: a matched-control study.
In a retrospective study, 185 patients with previously untreated stage IB or IIA (International Federation of Gynecology and Obstetrics) squamous cell carcinoma of the cervix were found to have pelvic nodal metastasis at the time of Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Of these patients, 103 received adjuvant whole-pelvis irradiation and 82 received no adjuvant therapy. Median dose of pelvic irradiation was 5000 cGy. Among the irradiated patients, in 75% the dose was 5000 cGy or greater. Matching irradiated and nonirradiated patients according to stage, tumor size, and number and location of positive nodes yielded 60 pairs. Mean length of follow-up was 3.9 years for the 60 irradiated patients and 5.8 years for the non-irradiated patients. Kaplan-Meier overall and cancer-specific survival estimates for the two groups were not significantly different (P greater than 0.30). During the follow-up period, 21 surgery-only patients and 22 patients treated with adjuvant radiotherapy had recurrence, but adjuvant radiotherapy decreased the proportion of recurrences occurring in the pelvis alone--27% compared with 67% in the surgery-only group (P = 0.01).


Adoptive T-cell therapy for fungal infections in haematology patients.
The prolonged immune deficiency resulting from haematopoietic stem cell transplant and chemotherapy predisposes to a high risk of invasive fungal infections. Despite the recent advances in molecular diagnostic testing, early initiation of pre-emptive antifungal therapy and the use of combination pharmacotherapy, mortality from invasive mould infections remain high among recipients of allogeneic stem cell transplant. The increasing incidences of previously rare and drug-resistant strains of fungi present a further clinical challenge. Therefore, there is a need for novel strategies to combat fungal infections in the immunocompromised. Adoptive therapy using in vitro-expanded fungus-specific CD4 cells of the Th-1 type has shown clinical efficacy in murine studies and in a small human clinical study. Several techniques for the isolation and expansion of fungus-specific T cells have been successfully applied. Here we discuss the incidence and changing patterns of invasive fungal diseases, clinical evidence supporting the role of T cells in fungal immunity, methods to expand fungus-specific T cells in the laboratory and considerations surrounding the use of T cells for fungal immunotherapy.


Safety of Tranexamic Acid During Pediatric Trauma: A Nationwide Database Study.
The present study aimed to examine the association between tranexamic acid use and adverse effects (seizures, thromboembolism, and renal dysfunction) in a pediatric trauma population using a national inpatient database in Japan. We also assessed the association between tranexamic acid use and in-hospital mortality. A nationwide, retrospective cohort study using propensity score analyses. Japanese Diagnosis Procedure Combination inpatient database. Pediatric patients less than or equal to 12 years old admitted in hospital with the diagnosis of trauma between July 2010 and March 2014 (n = 61,779). None. Propensity score matching created 1,914 pairs of patients with and without tranexamic acid administration. Propensity-matched analysis showed that the proportion of seizures was significantly higher in the tranexamic acid group than in the nontranexamic acid group (7/1,914, 0.37% vs 0/1,914, 0%; difference, 0.37%; 95% CI, 0.10-0.64; p = 0.008). However, none of the other outcomes were significantly different between the groups. Tranexamic acid use is associated with a significantly increased risk of seizures. However, no difference exists among any other outcomes between the tranexamic acid and nontranexamic acid groups.


Establishment of a multilayered 3D cellular model of the retinal-blood barrier.
Retinal disorders are leading causes of blindness. Still, treatment strategies are limited and the challenging anatomical barriers of the eye limit the evaluation and development of new therapeutics. Among these layers of barriers is the blood-retinal barrier, which separates the retina from the choroid by the Bruch's membrane. This work aimed to establish a 3D cellular model that recapitulates barrier properties of the BRB and diffusion through the vitreous, the main barriers encountered upon intravitreal injection. Several parameters were evaluated namely co-culture time of ARPE-19 and HUVECs and different biomaterial compositions of hydrogels to better mimic the human vitreous. The developed vitreous mimic has viscoelastic properties similar to human vitreous. Co-culture of human retinal and endothelial cells showed increased transepithelial resistance with longer co-culture times concomitant with reduced permeability to FITC-dextran 40 kDa. The proposed models lay the foundation of a platform for faster assessment of a large number of samples and without the use of animals.


Personal control after a breast cancer diagnosis: stability and adaptive value.
This longitudinal study aims to gain more insight in both the changes in personal control due to a breast cancer diagnosis, as well as in the stress-buffering effect of personal control. Personal control and distress were assessed in breast cancer patients not treated with chemotherapy (n=47), breast cancer patients treated with chemotherapy (n=32) and in healthy women (n=58) at 3, 9 and 15 months after diagnosis. Results indicate that personal control was affected only in patients treated with chemotherapy, particularly right after the completion of treatment. Furthermore, the cross-sectional and longitudinal results provide modest support for the stress-buffering potential of control. The findings and future directions of research on the role of personal control in the adjustment to cancer will be discussed.


The spatio-temporal pattern of Wallerian degeneration in the rhesus monkey optic nerve.
Three patterns of degeneration were distinguished in the Rhesus monkey optic nerve following eye enucleation. A traumatic zone, extending for 1 to 2 mm from the site of transection and characterized by a rapid infiltration of haematogenous macrophages, the rapid degeneration and removal of all neural elements and the formation of astrocytic scar tissue within 35 days. A conical zone, closely associated with the central retinal blood vessels, in which the pattern of degeneration was similar to the traumatic zone except that the onset was delayed and the removal of debris was slower. There was extensive vesiculation of myelin sheaths in these two zones which was indicative of haematogenous cell infiltration. The remainder of the nerve underwent classical Wallerian degeneration in which endogenous cells slowly phagocytosed the degenerating nerve fibres. These observations are considered relevant to the controversy concerning the identification of the macrophage involved in Wallerian degeneration; many studies have described the macrophage within the area of trauma rather than the macrophage involved at some distance from the site of trauma.


Thoracic and lower cervical spine involvement in a case of rheumatoid arthritis.
The authors report a case of spine involvement in a severe case of rheumatoid arthritis treated with corticosteroids. First, the patient developed acute back pain, related to costovertebral joints arthritis at levels T9-T10. Then, neck pain and cord involvement yielded to diagnosis of cervical interapophyseal joints arthritis; there was a C5-C6 subluxation which necessitated surgical treatment. The conjunction of these two rheumatoid localizations is an uncommon feature. Study by the CT scan is valuable when rheumatoid arthritis of the spine is suspected. Lower cervical spine subluxation, even severe, may be well tolerated. Surgery is necessary when there is medullary involvement.


A Big-Data-based platform of workers' behavior: Observations from the field.
Behavior-Based Safety (BBS) has been used in construction to observe, analyze and modify workers' behavior. However, studies have identified that BBS has several limitations, which have hindered its effective implementation. To mitigate the negative impact of BBS, this paper uses a case study approach to develop a Big-Data-based platform to classify, collect and store data about workers' unsafe behavior that is derived from a metro construction project. In developing the platform, three processes were undertaken: (1) a behavioral risk knowledge base was established; (2) images reflecting workers' unsafe behavior were collected from intelligent video surveillance and mobile application; and (3) images with semantic information were stored via a Hadoop Distributed File System (HDFS). The platform was implemented during the construction of the metro-system and it is demonstrated that it can effectively analyze semantic information contained in images, automatically extract workers' unsafe behavior and quickly retrieve on HDFS as well. The research presented in this paper can enable construction organizations with the ability to visualize unsafe acts in real-time and further identify patterns of behavior that can jeopardize safety outcomes.


Comparison of Outcomes From Delayed-Onset Bleb-Related Endophthalmitis Treated With Pars Plana Vitrectomy Versus Vitreous Biopsy.
Bleb-related endophthalmitis (BRE) is a serious complication of glaucoma filtration surgery. The current study reports similar visual and intraocular pressure (IOP) outcomes in eyes treated with pars plana vitrectomy (PPV) compared with vitreous biopsy and injection of intravitreal antibiotics (TI). The purpose of this study was to investigate the isolated organisms, visual acuity (VA), and IOP outcomes associated with delayed-onset BRE in eyes treated with PPV versus TI. A retrospective chart review was conducted at the Bascom Palmer Eye Institute (Miami, Florida) and the University of Florida (Gainesville, FL) identifying patients treated for BRE with at least 1 month of follow-up from the inception of an electronic health record (2014 and 2011, respectively) through 2021. All patients had undergone bleb-forming glaucoma surgery at least 1 month before endophthalmitis diagnosis. Thirty-nine eyes from 39 patients (33 from Bascom Palmer, 6 from University of Florida) were included. Trabeculectomy was performed in 34 of 39 eyes (87.2%). Streptococcus species (9 eyes, 23.1%) and Staphylococcus species (8 eyes, 20.5%) were the most common isolated organisms and were similar in both treatment groups ( P =0.49). Baseline VA was worse in the PPV group (logarithm of the minimum angle of resolution: 2.51 vs. 2.16, P =0.04), but VA at last follow-up was similar ( P =0.48) in both groups. After recovery from BRE, the average IOP in the PPV group was 15.1 mm Hg on 0.9 IOP-lowering medications compared with 12.6 mm Hg on 1.2 medications in the TI group (IOP: P =0.56; medications: P =0.80). Additional glaucoma surgery was performed in 44.4% of the PPV eyes and 16.7% of the TI eyes ( P =0.09). In eyes with delayed-onset BRE, isolated organisms, visual outcomes, and IOP control were similar after initial PPV compared with TI.


[Value and current role of anterior mediastinotomy in the diagnosis of mediastinal diseases. Apropos of a series of 100 cases].
One hundred anterior mediastinotomies performed between 1981 and 1987 resulted in the diagnosis of 90 malignant mediastino-hilar or anterior mediastinal tumours, 4 benign lymph node diseases and 6 non-specific lesions. This easy to perform biopsy technique was followed by low morbidity (7%) and one death after 48 hours due to major mediastinal compression. Its sensitivity and specificity make it a valuable alternative and, according to the authors, preferable to mediastinoscopy in the diagnosis of tumours of lymph node diseases in the anterior, pulmonary hila, especially on the left side, and anterior mediastinal lymph node chains.


Velocity Vector Imaging to Assess Longitudinal Wall Motion of Adult Carotid Arteries.
We aimed to assess longitudinal wall motion of the common carotid artery (CCA) using velocity vector imaging (VVI). From October 2018 to July 2019, we prospectively performed VVI of 204 CCAs (102 adult volunteers, 57 men, 45 women) in young (n = 40, 20-44 y), mid-age (n = 30, 45-64 y), and senior (n = 32, ≥65 y) groups. VVI parameters of CCA included longitudinal motion pattern, motion parameters (strain, strain rate, displacement), and time-to-peak motion parameters (time-to-peak strain, time-to-peak strain rate, time-to-peak displacement). Statistical analyses included one-way ANOVA post-hoc testing to examine the difference in VVI parameters among the 3 age groups and in paired groups; unpaired t tests to examine the difference in VVI parameters between CCAs with and without atherosclerotic plaque, between hypertensive and normotensive subjects without atherosclerotic plaque; linear regression to analyze correlations of VVI parameters to age, carotid intima-media thickness; and intraclass correlation coefficient to test inter- and intra-observer reliability in performing VVI of the CCA. Differences in VVI parameters and patterns among the 3 age groups, between hypertensive and normotensive, and CCAs with and without plaque were significant (p < .01). CCA motion- and time-to-peak motion parameters were correlated to age (R2 = 0.63-0.56) and carotid intima-media thickness (R2 = 0.29-0.22). CCA wall motion dyssynchrony was remarkable in seniors. The repeatability and reproducibility for performing carotid artery VVI were good (intraclass correlation coefficient > 0.85). VVI is feasible to assess changes in longitudinal CCA wall mechanical properties and synchrony with aging, atherosclerosis, and hypertension.


Optical tunneling effect calculation of a solid immersion lens for use in optical disk memory.
A solid immersion lens (SIL) has the advantage of easily decreasing the spot size for high data density in optical recording. To accurately obtain the optical tunneling effect for a high-N.A. SIL, we calculated the optical tunneling beam characteristics, using electromagnetic theory. Tunneling beam spot-size dependence on polarization direction and energy-transfer efficiency are also clearly shown.


An integrative review of measures of transitions and care coordination for persons living with dementia and their caregivers.
High rates of hospital visits and readmissions are common among persons living with dementia, resulting in frequent transitions in care and care coordination. This paper identifies and evaluates existing measures of transitions and care coordination for persons living with dementia and their caregivers. This integrative review builds off a prior review using a systematic search of online databases (PubMed, EBSCO, CINAHL, PsycInfo, and Scopus) to identify records and locate reports (or articles) that use measures of care transitions and care coordination. Identified measures were compared to the Alzheimer's Association's Dementia Care Practice Recommendations to evaluate strengths and weaknesses of the measure in this population, such as if measures were person- and family-centered. Seventy-one reports using measures of transitions in care and care coordination for persons living with dementia and their caregivers were identified. There were multiple measures identified in some reports. Three main areas of measures were classified into: identification of the population (3 measures, 8 reports), transitional care and care coordination delivery (14 measures, 17 reports), and transitional care and care coordination outcomes (e.g., health-care use, cost, and mortality; 17 measures, 60 reports). A strength of the three main areas of measures was that a portion of the measures were person- and family-centered. Variability in the operational definitions of some measures and time intensiveness of collecting the measure (e.g., number of items, the time it takes to complete the items) were common weaknesses. Transitions and care coordination measures are varied across studies targeted at persons living with dementia and their caregivers. Existing measures focus heavily on outcomes, specifically health-care resource use, and cost, rather than the elements of transitional care or care coordination. Future measure development focused on care transitions and service coordination is needed.


Natural killer and T cells of innate and adaptive immunity: lymphoid compartments with different requirements for common gamma chain-dependent cytokines.
A group of cytokines, including interleukin-2, -4, -7, -9 and -15, are related through the usage of a shared receptor subunit, the common cytokine receptor gamma chain, gamma c. gamma c-dependent cytokines critically affect the development and maintenance of the lymphoid system. This review will highlight our current knowledge on the gamma c-dependent cytokine network and on the non-redundant roles that these cytokines play in the development and homeostasis of T and natural killer cells involved in innate and adaptive immunity.


The calcium component of the action potential in spinal motoneurones of the rat.
Intracellular recordings were made from motoneurones of the neonatal rat (1-14 days old) spinal cord isolated and perfused in vitro. An increase in extracellular Ca2+ concentration from 2 to 20 mM produced an increase in the amplitude of the after-depolarization (a.d.p.), while replacement of Ca2+ by Mn2+ virtually abolished the a.d.p. These changes in the a.d.p. occurred in parallel with those in the after-hyperpolarization (a.h.p.). The amplitudes of the a.d.p. and the a.h.p. were dependent upon the membrane potential: hyperpolarization increased the a.d.p. and decreased the a.h.p.; the opposite effects were produced by depolarization. The presence of Ca2+ spikes was demonstrated either by suppression of the voltage-dependent K+ conductance with tetraethylammonium (TEA) or after blocking the Na+ spike. The Ca2+ spike was all-or-none in nature and blocked by Mn2+ or Co2+. The a.h.p. amplitude was dependent upon the extracellular K+ concentration but also correlated with the amplitude of the Ca2+-dependent response. It is concluded that the a.d.p. is a Ca2+-dependent potential whose amplitude is under normal conditions markedly reduced by the voltage-dependent K+ conductance; the a.h.p. seems to be produced by an increase in the Ca2+-dependent K+ conductance.


The amount of treatment versus quality of life in patients formerly treated for head and neck squamous cell carcinomas.
The aim of the present study was to investigate the association between the self-reported quality of life (QoL) versus the initial TNM stage and amount of primary and recurrent tumor therapy given in a population of formerly treated head and neck squamous cell carcinoma (HNSCC) patients. We determined QoL by the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ) C30/H&N35 by structured interview. One hundred and twenty-two patients less than 80 years old, who had been diagnosed with HNSCC in western Norway in the period from 1992 to1997, and who had survived until 2000, were identified. Of these patients, 106 were eligible to be included. Ninety-six of these patients agreed to be interviewed. For TNM stage as well as the type of therapy given (local surgery, neck dissection or radiation therapy), T stage predicted the general QoL scores. Both increased TNM stage and all given tumor therapy seemingly caused lower H&N symptom QoL scores. Of the various tumor treatments employed, neck radiation therapy and neck dissection were indicated to be the most closely associated with the H&N QoL scores. Having neck dissection performed seemingly caused impairment beyond what was explained by the initial TNM stage. In conclusion, tumor therapy to HNSCC should not be restricted due to general QoL considerations. Further study of how and when to perform neck treatment is suggested in order to avoid unnecessary reduced H&N QoL.


Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model.
Primary prevention with aminoguanidine-an inhibitor of advanced glycation end product (AGE) formation--has been successfully employed to prevent diabetic retinopathy in the rat. However, it is unknown whether inhibition of AGE formation is still effective in a secondary intervention strategy. The present study addresses this question by comparing secondary intervention with aminoguanidine with syngeneic islet transplantation in the rat model. After 6 months of diabetes, one group was treated with aminoguanidine (50 mg/100 ml drinking water; D-AG) while another group received syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection (Tx). After an additional 4 months, both groups were compared to a normal (NC 10) and diabetic (DC 10) control group. Retinal autofluorescence was increased 2.5-fold after 6 months and increased 3.7-fold after 10 months of diabetes (p < 0.001). Aminoguanidine and islet Tx retarded the further accumulation of autofluorescence equally (p < 0.001 vs DC 10), although the values were higher than those observed in DC at 6 months (p < 0.001). Diabetes was associated with a 2.7-fold increase in acellular capillaries after 6 months and a 4.1-fold increase after 10 months. Treatment with aminoguanidine or islet Tx reduced but did not completely attenuate the progression of vascular occlusion (p < 0.001 vs DC 10; D-AG vs DC 6, p < 0.05; Tx vs DC 6, p < 0.01). Both treatments reduced endothelial proliferation (22.4% after 10 months; p < 0.001) and completely arrested pericyte dropout (40% after 10 months; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)