World Workshop on Oral Medicine VI: Patient-reported outcome measures and oral mucosal disease: current status and future direction.
This systematic review aimed to (1) explore the patient-reported outcome measures (PROMs) currently used in the oral mucosal disease literature and report on the type and context of the use of these instruments and (2) provide a future direction for PROMs in Oral Medicine practice and research. A systematic review of published English-language articles relating to the use of PROMs in the oral mucosal diseases literature was performed in November 2013. In total, 131 articles met the inclusion criteria; these articles addressed the following oral mucosal conditions: lichen planus (75); recurrent aphthous stomatitis (30); mucous membrane pemphigoid/pemphigus vulgaris (14); orofacial granulomatosis (1); and multiple oral mucosal diseases (11). The most commonly used instruments were visual analog scales (VAS) and the oral health impact profile (OHIP). Limited progress has been achieved with use of PROMs in Oral Medicine in the last few decades in both clinical practice and a research setting. With the engagement of allied medical disciplines in PROM usage and the promotion of PROMs by national health care bodies globally, advancement of PROMs is imperative for Oral Medicine. Exposure through the World Workshop on Oral Medicine (WWOM), along with potential involvement in the Core Outcome Measures in Effectiveness Trials (COMET) or other such initiatives, will enable worldwide collaboration to promote the development and utilization of valid and reliable PROMs in oral medicine, and improve patient care.


Cutoff values of body mass index for severe obesity in Korean children and adolescents: the 99th percentile versus 120% of the 95th percentile.
Several definitions for severe obesity have been used, primarily the 99th percentile of the body mass index (BMI) and 120% of the 95th BMI percentile. This study aimed to establish a standardized definition for severe obesity in children and adolescents in Korea. The 99th BMI percentile line and 120% of the 95th BMI percentile line were constructed using 2017 Korean National Growth Charts. To compare these 2 cutoff points for severe obesity, we included 9,984 individuals (5,289 males and 4,695 females) aged 10-18 years with anthropometric data available from the Korean National Health and Nutrition Examination Survey 2007-2018. Although 120% of the 95th percentile of BMI is widely used as a definition of severe obesity, the 99th percentile is almost identical to 110% of the 95th percentile in Korea, according to the latest national BMI growth chart for children and adolescents. The prevalence rates of high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, and high alanine aminotransferase in the participants whose BMI was ≥120% of the 95th percentile were higher than in those whose BMI was ≥99th percentile (P<0.001). A cutoff value for severe obesity of ≥120% of the 95th percentile is appropriate in children and adolescents in Korea. To provide follow-up care for severely obese children and adolescents, it is necessary to add a new line at 120% of the 95th percentile to the national BMI growth chart.


Algorithmic decomposition for efficient multiple nuclear spin detection in diamond.
Efficiently detecting and characterizing individual spins in solid-state hosts is an essential step to expand the fields of quantum sensing and quantum information processing. While selective detection and control of a few 13C nuclear spins in diamond have been demonstrated using the electron spin of nitrogen-vacancy (NV) centers, a reliable, efficient, and automatic characterization method is desired. Here, we develop an automated algorithmic method for decomposing spectral data to identify and characterize multiple nuclear spins in diamond. We demonstrate efficient nuclear spin identification and accurate reproduction of hyperfine interaction components for both virtual and experimental nuclear spectroscopy data. We conduct a systematic analysis of this methodology and discuss the range of hyperfine interaction components of each nuclear spin that the method can efficiently detect. The result demonstrates a systematic approach that automatically detects nuclear spins with the aid of computational methods, facilitating the future scalability of devices.


Genetic and dietary control of plasma tissue kallikrein secretion and urinary kinins exretion in man.
Tissue kallikrein is a major kinin-forming enzyme involved in artery and kidney functions. Urinary tissue kallikrein activity (UKLKa) reflects renal tissue kallikrein activity and depends on Na and K intake, and genetic factors, especially the tissue kallikrein-inactivating polymorphism, R53H. The effect of these factors on the level of kinin peptides is, however, not known. Moreover, a circulating form of tissue kallikrein is present in human plasma but its origin and regulation are unknown. We used a crossover study to investigate UKLKa, plasma tissue kallikrein (pTK), and urinary kallidin peptides and metabolites (Uki) in 10 R53H and 30 R53R normotensive male subjects randomly assigned to either a 1-week low Na-high K or a high Na-low K diet. UKLKa was 50-60% lower in R53H than R53R subjects and was increased by the low Na-high K diet. pTK was also 45-55% lower in R53H than R53R subjects and was increased by the low Na-high K diet. Uki was slightly but significantly higher under the low Na-high K than the high Na-low K diet, but did not differ between genotypes. These observations indicate that pTK levels are genetically determined and regulated by Na and K diet, in parallel with UKLKa; this suggests that circulating tissue kallikrein originates mainly from the kidney, and can contribute to circulatory adaptation to dietary ions. Uki is influenced by the Na and K diet, suggesting that kinins participate in renal adaptation to ion intake, but do not quantitatively reflect tissue kallikrein activity in urine, or presumably, in the kidney.


Anti-Helicobacter pylori activity of bioactive components isolated from Hericium erinaceus.
The fungus Hericium erinaceus (Bull.) Pers is used in Chinese traditional medicine to treat symptoms related to gastric ulcers. Different extracts from the fungus were assessed for anti-Helicobacter pylori activity to investigate the antibacterial activity of the ethanol extracts from H. erinaceus and verify the traditional indication of use. The fruiting bodies of H. erinaceus were concentrated with ethanol by HPD-100 macroporous resin and the whole extract was partitioned by petroleum ether and chloroform to afford fractions with using a silica gel column. Several pure compounds of petroleum ether extracts were obtained and analyzed using nuclear magnetic resonance (NMR). The activity of the extracts and fractions towards H. pylori was assessed by the microdilution assay and by the disk diffusion assay in vitro. From the most active fraction, two pure compounds were isolated and identified as the main components with anti-H. pylori activity from the fungus H. erinaceus. The cytotoxicity of these two compounds against the human erythroleu-kemia cell line K562 was also evaluated. The crude ethanol extracts from the fungus H. erinaceus were inhibitory to H. pylori. The petroleum ether extracts (PE1s, PE2s) and the chloroform extracts (TEs) demonstrated strong inhibition to H. pylori. The inhibition of H. pylori was observed through an agar dilution test with minimal inhibition concentration (MIC) values from 400μg/mL to 12.5µg/mL. Two pure compounds, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid were isolated from the petroleum ether fractions and identified using (1)H NMR and (13)C NMR spectra analysis. The MIC value for 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone was 12.5-50µg/mL and the MIC value for 2,5-bis(methoxycarbonyl)terephthalic acid was 6.25-25µg/mL. Both two compounds showed weak cytotoxicity against K562 with IC50<200mM. This study revealed that the extracts from petroleum ether contribute to the anti-H. pylori activity. The compounds obtained from petroleum ether extracts, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid, inhibit the growth of H. pylori.


Drug-resistant epicrania fugax: Responding to onabotulinumtoxinA.
Epicrania fugax (EF) is a primary headache consisting of brief paroxysms of pain, lasting 1-10 s, that move through different nerve territories of one hemicranium with a linear or zigzag trajectory, although there are some clinical variants. Preventive therapy with anti-seizure medication such as gabapentin and lamotrigine are most commonly used in patients presenting with frequent and non-remitting attacks. In some cases, greater occipital nerve blockades are used for short- or long-term relief. Here, we report two patients with a paroxysmal EF-type pain who meet the criteria for EF of the International Classification of Headache Disorders, 3rd edition, with clear triggers and autonomic ocular signs and who failed multiple preventive treatments, but had a sustained response to onabotulinumtoxinA.


Unfolding the Role of BDNF as a Biomarker for Treatment of Depression.
Depression is a well-known disabling mental illness characterized by sadness, loss of interest in activities, and decreased energy. The symptoms of depression are usually recurrent in vulnerable individuals, and persistence of symptoms significantly impairs individuals' quality of life. The exact pathophysiology of depression remains ambiguous, though many hypotheses have been proposed. Brain-derived neurotrophic factor (BDNF) has recently been reported to play a vital role in the pathophysiology of depression. BDNF is an important neurotrophic factor found in the human brain and is involved in neuronal growth and proliferation, synaptic neurotransmission, and neuroplasticity. The neurotrophic theory of depression proposes that depression results from reduced BDNF levels in the brain, which can be treated with antidepressants to alleviate depressive behavior and increase BDNF levels. The aim of this review is to provide broad insight into the role of BDNF in the pathogenesis of depression and in antidepressant therapy. The studies mentioned in this review article greatly support the role of BDNF in the pathogenesis of depression and treatment of this disorder with antidepressants. Since abnormalities in BDNF levels lead to the production of diverse insults that amplify the development or progression of depression, it is important to study and explore BDNF impairment in relation to depression, neuroplasticity, and neurogenesis, and increasing BDNF levels through antidepressant therapy, showing positive response in the management of depression.


Exploring allele specific methylation in drug dependence susceptibility.
Drug dependence is a neuropsychiatric condition that involves genetic, epigenetic and environmental factors. Allele-specific methylation (ASM) is a common and stable epigenetic mechanism that involves genetic variants correlating with differential levels of methylation at CpG sites. We selected 182 single-nucleotide polymorphisms (SNPs) described to influence cis ASM in human brain regions to evaluate their possible contribution to drug dependence susceptibility. We performed a case-control association study in a discovery sample of 578 drug-dependent patients (including 428 cocaine-dependent subjects) and 656 controls from Spain, and then, we followed-up the significant associations in an independent sample of 1119 cases (including 589 cocaine-dependent subjects) and 1092 controls. In the discovery sample, we identified five nominal associations, one of them replicated in the follow-up sample (rs6020251). The pooled analysis revealed an association between drug dependence and rs6020251 but also rs11585570, both overcoming the Bonferroni correction for multiple testing. We performed the same analysis considering only cocaine-dependent patients and obtained similar results. The rs6020251 variant correlates with differential methylation levels of cg17974185 and lies in the first intron of the CTNNBL1 gene, in a genomic region with multiple histone marks related to enhancer and promoter regions in brain. Rs11585570 is an eQTL in brain and blood for the SCP2 and ECHDC2 genes and correlates with differential methylation of cg27535305 and cg13461509, located in the promoter regions of both genes. To conclude, using an approach that combines genetic and epigenetic data, we highlighted the CTNNBL1, SCP2 and ECHDC2 genes as potential contributors to drug dependence susceptibility.


Biomagnification profiles of tributyltin (TBT) and triphenyltin (TPT) in Japanese coastal food webs elucidated by stable nitrogen isotope ratios.
The measurement of organotins in the various biotas of coastal food webs with stable nitrogen isotope ratios (delta(15)N), which increase 3.4 per thousand per trophic level, can provide a biomagnification profile of organotins through food web. In this study, various biological samples were collected from three localities in Western Japan between 2002 and 2003 for analyses. Tributyltin (TBT) and triphenyltin (TPT) were still detected with a maximum of 99.5 and 8.7 ng wet weight g(-1), respectively. Unlike TBT, significant biomagnification of TPT through the food web (expressed by delta(15)N) was found in all three localities. The log transformed octanol-water partition coefficient (log K(ow)) of TPT of 2.11-3.43 was overlapped by, but was slightly lower than, that of TBT of 3.70-4.70. Thus, this study demonstrates that although these chemicals have a log K(ow) lower than 5, at least TPT undergoes significant biomagnification through the food web.


Determining the optimal inner air cell pressure for the effective reduction of interface pressure.
Alternating-pressure air mattresses can reduce interface pressure and prevent pressure ulcer development. However, bottoming out sometimes occurs, resulting in an increase in interface pressure. Therefore, optimal settings should be determined based on interface pressures and inner air cell pressures. The purpose of this study was to investigate the most effective inner air cell pressure to reduce interface pressure without causing bottoming out. A new alternating air mattress was used, which comprised three layers: a base layer, fitting (F) layer, and alternating layer. The alternating layer comprises inflated (I) cells and deflating (D) cells. The study participants were 13 healthy volunteers over 18 years of age, each of whom adopted supine position on the mattress. The pressures in the D cells were gradually deflated under different I cell and F layer pressure settings. We measured peak sacral pressure and inner air cell pressure to obtain the bottoming out cut-off values by using receiver-operating-characteristic (ROC) curves. We then investigated the effectiveness of different settings to reduce the peak sacral pressures. A number of test conditions were evaluated. Results indicated that the D cell pressure cut-off points were 1.26 kPa and 1.21 kPa, for phases 1 (F = 4 kPa, I = 4 kPa) and 4 (F = 1 kPa, I = 4 kPa), respectively. These settings significantly reduced the interface pressure (P < 0.001, P = 0.026, respectively). Our results suggest that appropriate configuration of inner air cell pressure could reduce interface pressure without causing bottoming out.


Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy.
To quantify the dose-time fractionation factors in preoperative radiation therapy for microscopic pelvic deposits of rectal cancer. This provides a biologic basis for understanding and improving the results of adjuvant therapies for this disease. The reduction in incidence of pelvic relapses as a function of radiation dose and overall treatment time was determined from the literature. The displacement of dose-response curves to higher doses reflects the growth during radiation treatment of subclinical pelvic deposits which are beyond the future surgical margins. Dose-response curves are steep if the effect of overall duration of radiation therapy is accounted for. The time-related displacement of these steep dose-response curves is consistent with a median doubling time for malignant clonogenic cells of about 4 or 5 days, much faster than the growth rate of the average primary tumor at diagnosis. This rapid growth is evident within the first few days of irradiation, implying that the natural growth rate of these microscopic deposits if fast, and/or that an acceleration of growth follows initiation of radiation injury with a very short lag time. Subclinical pelvic deposits of rectal cancer grow rapidly during preoperative radiation therapy with an adverse influence on the rate of pelvic tumor control from protracting the duration of adjuvant treatment. Low doses only offer clinically relevant reduction in risk of pelvic relapses if the overall radiation treatment time is short. For a given overall treatment duration there is a relatively steep dose-response curve, predicting that significant improvements in tumor control are possible.


Heat transfer considerations in design of a batch tube reactor for biomass hydrolysis.
Biologic conversion of inexpensive and abundant sources of cellulosic biomass offers a low-cost route to production of fuels and commodity chemicals that can provide unparalleled environmental, economic, and strategic benefits. However, low-cost, high-yield technologies are needed to recover sugars from the hemicellulose fraction of biomass and to prepare the remaining cellulose fraction for subsequent hydrolysis. Uncatalyzed hemicellulose hydrolysis in flow-through systems offers a number of important advantages for removal of hemicellulose sugars, and it is believed that oligomers could play an important role in explaining why the performance of flow-through systems differs from uncatalyzed steam explosion approaches. Thus, an effort is under way to study oligomer formation kinetics, and a small batch reactor is being applied to capture these important intermediates in a closed system that facilitates material balance closure for varying reaction conditions. In this article, heat transfer for batch tubes is analyzed to derive temperature profiles for different tube diameters and assess the impact on xylan conversion. It was found that the tube diameter must be <0.5 in. for xylan hydrolysis to follow the kinetics expected for a uniform temperature system at typical operating conditions.


Transformation of vibration signals in rotary blood pumps: the diagnostic potential of pump failure.
Although non-destructive and continuous monitoring is indispensable for long-term circulatory support with rotary blood pumps, a practical monitoring system has not yet been developed. The objective of this study was to investigate the possibility of detecting pump failure caused by thrombus formation through the monitoring of vibration signals. The data acquisition equipment included vibration pickups, a charge amplifier, vibration analysis systems, and exclusive hardware. A pivot-bearing centrifugal pump with a mock circuit was investigated for vibration analysis. To simulate the four common areas of thrombus formation, we used a piece of silicon attached to each of the following four locations: the total area of the bottom of the impeller, an eccentric shape on the bottom of the impeller, a circular shape around the shaft top, and an eccentric shape on the top of the impeller. Vibration signals were picked up, and the power spectrum density analysis was performed at pump rotational speeds of 2100, 2400, and 3000 rpm. In this study, pump failure could be detected, and the types of imitation thrombi could be determined. We conclude that vibration detection with a computerized analysis system is a potentially valuable diagnostic tool for long-term circulatory support with rotary blood pumps.


Effect of coping materials zirconia or polyetheretherketone with different techniques of fabrication on vertical marginal gap and fracture resistance of posterior crowns with composite veneering.
Insufficient research has been conducted in the literature assessing the performance of zirconia and polyetheretherketone (PEEK) crowns in relation to the essential requirements of successful restorations, such as fracture resistance or margin adaptation. The purpose of this study was to evaluate the effect of the coping materials zirconia or PEEK with different fabrication techniques on the vertical marginal gap and fracture resistance of posterior crowns with composite veneering. Ceramic copings (n = 18) restoring mandibular first molar were fabricated from zirconia (Zircon.x, Presidentdental, Germany), milled PEEK (PEEK CAD) (breCAM.BioHPP, Bredent, Germany) and pressed PEEK (PEEK Press) (BioHPP Granules, Bredent, Germany) six specimens each (n = 6). The copings were veneered with high impact polymer composite (HIPC) material (breCAM.HIPC, Bredent, Germany). The vertical marginal gap was captured under a magnification of 40X. Five equidistant marks on each surface of the die distinguished the points of measurement for a total of 20 readings per sample. The analysis was completed using an image analysis system (ImageJ 1.53t, National Institute of Health, USA). The specimens were loaded to failure at a crosshead speed of 1 mm/min and the load at failure was recorded to measure the fracture resistance. The marginal gap was analyzed using one-way ANOVA followed by Tukey's post hoc test. Fracture resistance was analyzed using Welch one-way ANOVA followed by the Games-Howell post hoc test. Marginal gap values showed a significant difference between the tested groups, with zirconia having significantly lower gap values (48.67 ± 11.98 µm) than both the PEEK CAD (108.00 ± 20.08 µm) and Press groups (108.00 ± 25.10 µm) (p < 0.001). However, the results of fracture resistance showed no significant difference (p = 0.06) with 1687.47 ± 253.29 N, 2156.82 ± 407.64 N, 2436.72 ± 725.93 N for zirconia, PEEK CAD, and Press, respectively. The significance level was p < 0.05. Zirconia framework crowns have a smaller vertical marginal gap than milled and pressed PEEK crowns. Crowns fabricated from zirconia, PEEK CAD, or PEEK Press frameworks and veneered with composite resin have comparable fracture resistance lower than the maximum biting force in the posterior region. Posterior crowns with zirconia frameworks are preferred over milled and pressed PEEK frameworks regarding margin adaptation, although all can safely survive the maximum occlusal forces without fracture.


In vivo pharmacological evaluation of compound 48/80-induced airways oedema by MRI.
Allergen-induced airways oedema in actively sensitized rats has been studied earlier by magnetic resonance imaging (MRI). We used MRI to follow the consequences of non-immunological mast cell activation induced by compound 48/80 in the rat lungs in vivo. Male naïve rats were scanned by MRI prior to and at several time points following intratracheal administration of the mast cell secretagogue, compound 48/80. The effects of a range of drugs on the response induced by compound 48/80 were studied. Strong fluid signals were detected by MRI in the lungs at 24 h after compound 48/80, correlating with increased protein concentration and inflammatory cell infiltration in bronchoalveolar lavage, and with perivascular oedema observed histologically. Pharmacological intervention demonstrated that the increase in MRI signal volume induced by compound 48/80 24 h after challenge was blocked by disodium cromoglycate and the glucocorticoid, budesonide. Pretreatment with wortmannin, capsazepine, DNK333 (a dual neurokinin (NK) 1 and NK2 antagonist) or the anti-allergy drug CGS8515, but not indomethacin, resulted in partial inhibition. Compound 48/80 induced a complex inflammatory reaction which did not solely involve mast cell degranulation but also activation of sensory nerves and was qualitatively similar to allergen challenge. Changes observed by MRI correlated with decreases in protein concentration in BAL fluid. However, the magnitude of the changes detected was greater using MRI. Our results demonstrate that MRI is a sensitive and efficient tool to assess the effects of drugs on lung inflammation.


Naproxen, meloxicam and methylprednisolone inhibit urokinase plasminogen activator and inhibitor and gelatinases expression during the early stage of osteoarthritis.
To test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA). Samples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). Gelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h. Naproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.


Measurement Properties of the Sedentary Behavior Questionnaire in Patients with Chronic Nonspecific Low Back Pain.
The Sedentary Behavior Questionnaire (SBQ) is a brief and easy instrument to measure time spent on sedentary activities; however, no study has investigated the reliability and validity of this questionnaire in people with chronic low back pain (LBP). To investigate the internal consistency, test-retest reliability, measurement error, construct validity, and interpretability of the SBQ against data derived from an accelerometer in patients with nonspecific chronic LBP. Cross-sectional study. Outpatient physiotherapy clinic. Seventy-five patients aged between 18 and 60 years (mean age, 42 years old) with nonspecific chronic LBP were recruited for this study. Not applicable. The Cronbach's α was calculated to investigate the internal consistency of the SBQ and the intraclass correlation coefficient (ICC) was calculated to investigate the reliability of the SBQ between two administrations separated by a 1-week interval. Measurement error was assessed calculating the SEM and minimal detectable change (MDC). Spearman correlation (r) was calculated to investigate the construct validity using hypothesis testing. Interpretability was investigated using ceiling and floor effects. The Cronbach's α of the SBQ total score was 0.92, indicating homogeneity among the items of the instrument. The reliability of the SBQ was excellent (ICC > 0.75), without any evidence of ceiling and floor effects. Regarding measurement error, the total score of the SBQ showed an SEM and MDC of 109.8 minutes per day and 304.4 minutes per day, respectively. However, there were no correlations of the SBQ domains or the total score with the accelerometer-measured sedentary time (r < 0.25). The SBQ is a reliable tool for quantifying time spent in sedentary activities of patients with chronic LBP. The SBQ showed poor construct validity compared to the accelerometer-measured sedentary time, which indicates that patients may underestimate their time spent in sedentary activities.


[Transcatheter closure of aorto-left atrial fistula using an Amplatzer device].
Aorto-left atrial fistulas are rare. We describe the case of a patient in whom transcatheter closure of an aorto-left atrial fistula was carried out using an Amplatzer septal occluder. The patient had previously undergone cardiac surgery twice because of a recurrent left atrial myxoma. Closure of this type of fistula using a transcatheter device should be considered when the location and size of the fistula are appropriate and there are no associated abnormalities. The risk of surgery must also be taken into account.


Charcoal hemoperfusion in the treatment of medically refractory pruritus in cholestatic liver disease.
Pruritus is a distressing symptom in a considerable proportion of cholestatic patients and a few of them do not respond to conventional treatment. Charcoal hemoperfusion (CH) is an extracorporeal technique that is effective in eliminating protein-bound substances which may have accumulated during cholestasis. Several case reports have shown significant reduction of bilirubin in mechanical jaundice and neonatal hemolytic jaundice. However, the published data of CH for the treatment of refractory pruritus in cholestatic patients are scarce. Procedure code "Charcoal hemoperfusion" (90997) was used to identify patients who received CH at Mayo Clinic, Rochester, from 1 January 2000 to 5 January 2015. Patients who received CH for refractory cholestatic pruritus were retrospectively reviewed. Thirteen patients were identified. A median of 5 (range 1-18) sessions for a total of 20 (1-72) h were performed. CH resulted in a significant decrease of pruritus in nine patients (69%). Two patients did not have significant relief and two patients did not pursue further treatments after having adverse reactions during the first session. Median pruritus numerical rating scale significantly decreased from 9/10 (9-10) to 4/10 (0-9) post-treatment (p = 0.004). Duration of symptom-free periods ranged from 8 to 90 days (median 18 days) in six patients who returned for follow-up. Most common adverse reactions were pain, bleeding from the catheter site and fever. CH temporarily improves the severity of medically refractory cholestatic pruritus in some patients. However, the improvement is not sustained and the short duration of benefit should be balanced with the invasive nature of the therapy and the relatively common adverse reactions.


Reactivity of scandium terminal imido complexes towards metal halides.
Reactions of scandium terminal imido complexes with CuI and [M(COD)Cl](2) (M = Rh, Ir) show two interesting reaction patterns, and the formed heterobimetallic complexes have intriguing structural features and show promising catalytic properties.


NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action.
NSAIDs inhibit cyclooxygenase, but their role in aging and other diseases is not well understood. Our group previously showed the potential benefit of NSAIDs in decreasing the risk of delirium and mortality. Concurrently, epigenetics signals have also been associated with delirium. Therefore, we sought to find differentially methylated genes and biological pathways related to exposure with NSAIDs by comparing the genome-wide DNA methylation profiles of patients with and without a history of NSAIDs use. Whole blood samples were collected from 171 patients at the University of Iowa Hospital and Clinics from November 2017 to March 2020. History of NSAIDs use was assessed through a word-search function in the subjects' electronic medical records. DNA was extracted from the blood samples, processed with bisulfite conversion, and analyzed using Illumina's EPIC array. The analysis of top differentially methylated CpG sites and subsequent enrichment analysis were conducted using an established pipeline using R statistical software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed several biological pathways relevant to NSAIDs' function. The identified GO terms included "arachidonic acid metabolic process," while KEGG results included "linoleic acid metabolism," "cellular senescence," and "circadian rhythm." Nonetheless, none of the top GO and KEGG pathways and the top differentially methylated CpG sites reached statistical significance. Our results suggest a potential role of epigenetics in the mechanisms of the action of NSAIDs. However, the results should be viewed with caution as exploratory and hypothesis-generating given the lack of statistically significant findings.


Profiling of Primary Metabolites and Volatiles in Apricot (Prunus armeniaca L.) Seed Kernels and Fruits in the Context of Its Different Cultivars and Soil Type as Analyzed Using Chemometric Tools.
The goal of this study was to assess nutrient primary metabolites and aroma determinants in Prunus armeniaca L. fruits and seed kernels grown in Egypt represented by its different cultivars and agricultural conditions i.e., two different soil types (muddy versus sandy). Two techniques were employed to assess non-volatile and volatile metabolites using gas chromatography mass-spectrometry (GC-MS) post silylation, and headspace solid-phase micro-extraction (HS-SPME) coupled GC-MS, respectively. A total of 36 peaks belonging to sugars, fatty acids/esters and organic acids were identified by GC-MS in various apricot fruits and seed kernels cultivars. Glucose and sucrose were enriched in apricot fruits compared to the seed kernels. A total of 70 volatiles were identified, with lactones, alcohols and esters representing the main classes of apricot volatiles accounting for its discrete aroma. (E)-Anethole, β-ionone, γ-decanolactone and methyl palmitate were the major peaks contributing to the discrimination between various fruit cultivars and providing novel insight on apricot metabolome.


Exercise training improves obesity-related lymphatic dysfunction.
Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR-3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity-induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications.


Pharmacist-led hormonal contraceptive prescribing service in a Federally Qualified Health Center: Initial implementation outcomes.
The United States has a higher rate of unintended pregnancy than many other developed countries, and Indiana's unintended pregnancy rate is above the national average. Unintended pregnancy rates are highest among low-income women. Federally Qualified Health Centers (FQHC) provide care for the underserved and uninsured patient population. To determine the acceptability, adoption, appropriateness, and feasibility of a pharmacist-led hormonal contraception prescribing service within a FQHC through a collaborative drug therapy management protocol. An explanatory mixed methods analysis included surveys followed by semistructured interviews. A survey was created and distributed to all patients who received the service and all providers (physicians and nurse practitioners) employed at the FQHC during service implementation. Semistructured interviews were conducted with a subset of patients and providers. A total of 11 patients and 8 providers completed the survey between January 1, 2022 and June 10, 2022. Of these participants, 4 patients and 4 providers completed an interview between May 1, 2022 and June 30, 2022. Both patients and providers perceived the service as acceptable and appropriate, and providers perceived implementation of the service within clinic as feasible. Ten patients received a prescription from the pharmacist; 1 patient was referred to a provider as the pharmacist was unable to prescribe the medication requested. Implementation of pharmacist prescribed hormonal contraception was perceived as acceptable, appropriate, and feasible by patients and providers. Pharmacists are perceived by patients and providers as an additional resource for hormonal contraception prescribing within a FQHC due to their clinical knowledge, efficiency, and attention paid to patients' concerns.


HMGB1 as a potential new marker of disease activity in patients with multiple sclerosis.
Neuroinflammation represents one of the two major pathological components of multiple sclerosis (MS). The aim of our study was to find the role of the late pro-inflammatory cytokine HMGB1 (high mobility group box) in MS pathogenesis. A total of 165 patients from three MS centers in Slovakia were enrolled in the study. Patients underwent a complex clinical investigation and their plasma levels of HMGB1 were analyzed by a sandwich ELISA test. MS patients had 4.5 times higher plasma level of HMGB1 (median, 13.529 ng/mL; IQR = 2.330-113.45) than healthy controls (median, 2.999 ng/mL; IQR = 1.686-9.844; P < 0.0001). The concentrations of HMGB1 were significantly associated with increased number of affected areas diagnosed by MRI (P < 0.0001) (the median for one affected area, 4.205 ng/mL; median for five affected areas, 17.843 ng/mL; P < 0.05). Patients with at least one active lesion in any of the affected areas in the brain had significantly higher plasma levels of HMGB1 (median, 20.118 ng/mL; IQR, 3.693-100.12) than those without any active lesion (median, 16.695 ng/mL; IQR, 3.255-113.45; P < 0.0235). We found also a very highly significant association of HMGB1 plasma levels with clinical condition expressed as EDSS (expanded disability status scale) (P < 0.0001); patients with higher EDSS had higher levels of HMGB1 (EDSS ≤ 2.5, 11.648 ng/mL vs. EDSS ≥ 3, 17.549 ng/mL; P = 0.0115). Our results suggest chronic low-grade inflammation in MS patients that correlates with clinical conditions of MS patients, and for HMGB1 as a possible target molecule in future therapy.


The organization of nucleus tegmenti pedunculopontinus neurons projecting to basal ganglia and thalamus: a retrograde fluorescent double labeling study in the rat.
The organization of nucleus tegmenti pedunculopontinus (PPN) projections to the basal ganglia and thalamus was studied in the rat by using retrograde transport of fluorescent dyes. Fast blue was injected into the substantia nigra (SN) while Nuclear yellow was delivered to one of the following nuclei: globus pallidus (GP), entopeduncular nucleus, subthalamic nucleus (STN) or parafascicular nucleus of the thalamus. Retrogradely labeled cells were observed throughout the PPN without topographical arrangement. The cells labeled from the SN outnumbered those labeled from other structures. In all cases the majority of cells were single labeled and only a few cells double labeled from SN-GP or SN-STN were found. Labeled cells were either fusiform or multipolar in shape. These data suggest that distinct PPN cells project to their basal ganglia and thalamic targets without a prominent branched organization.


Immunoglobulin M and immunoglobulin G secretion by human B cells exposed to RU 41.740, a glycoprotein extract from Klebsiella pneumoniae.
RU 41.740, a glycoprotein extract from Klebsiella pneumoniae, was seen to activate human B cells to immunoglobulin secretion in vitro. The effects of RU 41.740 on human B cells were compared to those induced by pokeweed mitogen, a T-cell-dependent polyclonal B-cell activator, and Epstein-Barr virus, a T-cell-independent polyclonal B-cell activator. Exposure of human B cells to all of these agents resulted in increased immunoglobulin M (IgM) and immunoglobulin G (IgG) secretion. IgM and IgG secretion induced by RU 41.740 appeared to be T cell dependent when B cells were isolated from human peripheral blood. However, this activity may have been T cell independent when B cells were isolated from human spleen. RU 41.740-induced IgM secretion by peripheral blood B cells was seen to peak after 6 days in culture; IgG secretion peaked after 7 days in culture. The optimal concentration of RU 41.740 for the induction of IgM and IgG secretion by human B cells in vitro was seen to be 200 micrograms/ml.


A short-term memory trace persists for days in the mouse hippocampus.
Active recall of short-term memory (STM) is known to last for a few hours, but whether STM has long-term functions is unknown. Here we show that STM can be optogenetically retrieved at a time point during which natural recall is not possible, uncovering the long-term existence of an STM engram. Moreover, re-training within 3 days led to natural long-term recall, indicating facilitated consolidation. Inhibiting offline CA1 activity during non-rapid eye movement (NREM) sleep, N-methyl-D-aspartate receptor (NMDAR) activity, or protein synthesis after first exposure to the STM-forming event impaired the future re-exposure-facilitated consolidation, which highlights a role of protein synthesis, NMDAR and NREM sleep in the long-term storage of an STM trace. These results provide evidence that STM is not completely lost within hours and demonstrates a possible two-step STM consolidation, first long-term storage as a behaviorally inactive engram, then transformation into an active state by recurrence within 3 days.


Introducing a model for optimal design of sequential objective structured clinical examinations.
In a sequential OSCE which has been suggested to reduce testing costs, candidates take a short screening test and who fail the test, are asked to take the full OSCE. In order to introduce an effective and accurate sequential design, we developed a model for designing and evaluating screening OSCEs. Based on two datasets from a 10-station pre-internship OSCE and considering three factors, namely, the number of stations, the criteria for selecting the stations, and the cut-off score, several hypothetical tests were proposed. To investigate their accuracy, the positive predictive value (PPV), the pass rate, and the negative predictive value (NPV) were calculated. Also, a "desirable" composite outcome was defined as PPV = 100 %, pass rate ≥50 %, and NPV ≥25 %. Univariate and multiple logistic regression analyses were conducted to estimate the effects of independent factors on the occurrence of the desirable outcome. In half of the screening tests no false positive result was detected. Most of the screening OSCEs had acceptable levels of pass rate and NPV. Considering the desirable composite outcome 20 screening OSCEs could have successfully predicted the results of the corresponding full OSCE. The multiple regression analysis indicated significant contributions for the selection criteria (p values = 0.019) and the cut-off score (p values = 0.017). In order to have efficient screening OSCEs with the lowest probability of the error rate, careful selection of stations with high values of discrimination or item total correlation, and use of a relatively stringent cut-off score should be considered.


Digital artery diameters: an anatomic and clinical study.
This study measured the diameter of the arteries at the level of the diaphysis of the proximal phalanges of the index, long, ring, and small fingers. We measured the diameter of the vessel on ten normal arteriograms and on six amputated specimens. The larger vessel was usually on the ulnar border of the index and long fingers and on the radial border of the ring and small fingers. By the Hagen-Poiseuille equation, we assume that the larger vessel has the greater flow and, therefore, represents the dominant vessel to the digit. This observation may have clinical relevance in the reimplantation and revascularization of digits.


[An interesting experience on the use of information and population data bases].
In order to support decisions and analyze outcomes, the Spanish Health System has shown a great interest in developing data bases and high quality information systems. Nevertheless the use of these data bases are limited, not very systematized and, some times, their accessibility may be difficult. We describe in this review the experience in using the Institute for Clinical Evaluative Science (ICES, Ontario, Canada) as an efficient model to improve the usefulness of these data bases. Under restrictive conditions of confidentiality and privacy, the ICES has the legal capacity to use several population based data bases, for research projects and reports. ICES's functional structure (with an administrative and scientific level) is an interesting framework since it guarantees its independent and economic assessment. To date, its scientific production has been high in many areas of knowledge and open to those interested, with points of view of many health care professionals (including management), for whom the quality of research is of the ultimate importance, to be able to access these resources.


Phosphorylation-dependent activity of the deubiquitinase DUBA.
Addition and removal of ubiquitin or ubiquitin chains to and from proteins is a tightly regulated process that contributes to cellular signaling and protein stability. Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. The crystal structure of the ubiquitin aldehyde adduct of active DUBA reveals a marked cooperation between phosphorylation and substrate binding. An intricate web of interactions involving the phosphate and the C-terminal tail of ubiquitin cause DUBA to fold around its substrate, revealing why phosphorylation is essential for deubiquitinase activity. Phosphoactivation of DUBA represents an unprecedented mode of protease regulation and a clear link between two major cellular signal transduction systems: phosphorylation and ubiquitin modification.


Alpha-adrenoceptors involved on the cardiovascular response induced by mianserin in the pithed rat.
1. The effects of the antidepressant drug mianserin on the cardiovascular responses induced by preganglionic electrical stimulation, and i.v. infusion of the adrenergic agonists noradrenaline (NA, alpha 1 and alpha 2), phenylephrine (alpha 1) and xylazine (alpha 2) in the pithed normotensive rat were studied. 2. Mianserin inhibited in a dose-dependent manner the pressor effect caused by electrical stimulation of spinal cord (Th7-Th9) and the infusion of NA, phenylephrine and xylazine. Cocaine increased the inhibitory effect of mianserin on the pressor effect caused by electrical stimulation and NA. 3. Mianserin blocked the xylazine-induced inhibition of cardiac nerve stimulation effect. 4. These results suggest that mianserin blocks the NA uptake, and it is more effective in blocking presynaptic alpha 2- than postsynaptic alpha-adrenoceptors.


Studies on the control of respiration and behaviour during development in ewe-reared lambs.
Radiotelemetric recordings have been made in a series of newborn lambs with implanted electrodes and transducers and an external back-pack transmitter. Cardiac, respiratory and behavioural data have been gathered. These data have been analysed firstly with respect to age. The cardiac and respiratory data have then been related to both sleep state and age. An unexpected rise in both heart and respiratory rates was found after birth and marked differences were obvious in respiratory control in REM and non-REM sleep states.


Clinical utility of aVR lead T-wave in electrocardiogram of patients with ST-elevation myocardial infarction.
aVR lead is often neglected in routine clinical practice largely because of its undefined clinical utility specifications. Nevertheless, positive T-wave in aVR lead has been reported to be associated with poor clinical outcomes in some cardiovascular diseases. This study aimed to prospectively investigate the prognostic value and clinical utility of T-wave amplitude in aVR lead in patients with acute ST-elevation myocardial infarction (STEMI). A total of 340 STEMI patients admitted to a tertiary heart center were consecutively included. Patients were categorized into four strata, based on T wave amplitude in aVR lead in their admission ECG (i.e. < - 2, - 1 to - 2, - 1 to 0, and ≥ 0 mV). Patients' clinical outcomes were also recorded and statistically analyzed. In-hospital mortality, re-hospitalization, and six-month-mortality significantly varied among four T wave strata and were higher in patients with a T wave amplitude of ≥ 0 mV (p 0.001-0.002). The groups of patients with higher T wave amplitude in aVR, had progressively increased relative risk (RR) of in-hospital mortality (RRs ≤ 0.01, 0.07, 1.00, 2.30 in four T wave strata, respectively). T wave amplitude in the cutoff point of - 1 mV exhibited a sensitivity and specificity of 95.83 (95% CI 78.88-99.89) and 49.68 (95% CI 44.04-55.33). Our study demonstrated a significant association of positive T wave in aVR lead and adverse clinical outcomes in STEMI patients. Nevertheless, the clinical utility of T-wave amplitude at aVR lead is limited by its low discriminative potential toward prognosis of STEMI.


Functional neurosurgery in the treatment of epilepsy in The Netherlands. Aspects of presurgical evaluation and the contribution of subdural and stereotactically implanted depth electrodes in the Dutch Workgroup for Functional Surgery.
In the Netherlands all patients who are considered candidates for surgical treatment of their epilepsy are referred to the Dutch Workgroup for Functional Neurosurgery. Resective neurosurgery in partial epilepsy is a focus of special interest of national health authorities. Annually 15-20 patients can now be operated upon. Presurgical evaluation includes a.o. 18/FDG PET. For depth-EEG recording a specially designed method of "Combined Subdural and Depth-EEG Recording" is used which has been described previously. 70 patients underwent depth-EEG recording with the combined method. In 4.2% of the patients there were transient complications, in 1.4% there was a possibly permanent slight neurological deficit caused by the method. Fifty-six patients were evaluated at least one year after their surgical treatment (median follow-up 3 years). In the frontal lobe group comprising 9 patients 56% were seizure-free, 76% benefited from the treatment. In the temporal lobe group with 47 patients 68% were seizure-free and 92% benefited. No patient deteriorated from the resection. Permanent morbidity was nil.


[Acute anterior myocardial infarction as presenting feature of antiphospholipid syndrome related lupus arthritis].
Antiphospholipid syndrome is an autoimmune disorder causing venous and arterial thrombosis. Acute coronary complications are rare but potentially dramatic. We report a 39-year-old woman who presented with an acute anterior myocardial infarction after intravenous corticosteroids as part of the treatment of lupus arthritis and revealing antiphospholipid syndrome. Emergency coronary angiography was performed with drug-eluting stent angioplasty despite the need for anticoagulation and dual antiplatelet therapy. Antiplatelet and anticoagulant therapy management is pivotal in patients with antiphospholipid syndrome and acute coronary syndrome to prevent thrombosis recurrence.


Two-dimensional layered carbon-based catalytic ozonation for water purification: Rational design of catalysts and an in-depth understanding of the interfacial reaction mechanism.
This review renewed insight into the existing complex and contradictory mechanisms of catalytic ozonation by two-dimensional layered carbon-based materials (2D-LCMs) for degradation toxic refractory organics in aqueous solution. Migration and capture of active electrons are central to catalytic ozonation reactions, which was not studied or reviewed more clearly. Based on this perspective, the catalytic ozonation potential of 2D-LCMs synthesized by numerous methods is firstly contrasted to guide the design of subsequent carbon based-catalysts, and not limited to 2D-LCMs. Matching ROS to active sites is a key step in understanding the catalytic mechanism. The structure-activity relationships between reported numerous active sites and ROS evolution is then constructed. Result showed that OH could be produced by -OH, -C=O, -COOH groups, defective sites, immobilized metal atoms, doped heteroatoms and photo-induced electrons; and O2- could be produced by -OH groups and sp2-bonded carbon. The normalized model further be used to visually compare the contribution degree of various regulatory methods to performance improvement. More importantly, this review calls for 2D-LCMs-based catalytic ozonation to be studied without circumventing the issue of structural stability, which would lead to many proposals of catalysts and its involved catalytic reaction mechanism being meaningless.


Sonotubometric measurement of the eustachian tube function by means of band noise. A clinical view of the acoustic measurement of the eustachian tube.
The Eustachian tube is well known as an organ serving the ventilation and drainage of the tympanic cavity and mastoid. Ventilation is carried out by the opening and closing of the Eustachian tube accompanying swallowing movements. Until now there has been no instrument to quantify these motor activities of the tube necessary for its function as a ventilator. The author developed a generally applicable sonotubometer Model WIO-01 with the help of Siemens Hearing Institute K.K. for automatic measurement of the aforesaid tubal function with the use of 7 kHz full-octave band noise. In a sonotubometric trial with 32 adult female subjects, the duration of patency of the Eustachian tube was 288.5 +/- 1.38.5 ms, and the amplitude eliciting response was 16.4 +/- 8.3 dB. The positive response rate was 89.1%. In 89 children aged 4-12 years, a positive response was detected in 117 ears (61.9%). The mean duration of patency was 337.7 +/- 154.4 ms, and the amplitude 16.3 +/- 7.2 dB. It is physiological to have tubal opening and closing during natural swallowing. It is therefore important to understand the tubal function when dealing with tympanoplasty and diseases caused by tubal dysfunction.


Hepatitis in fatal infectious mononucleosis.
A detailed clinicopathologic analysis of 30 patients with sporadic fatal infectious mononucleosis and 31 males with fatal infectious mononucleosis and the X-linked lymphoproliferative syndrome was performed to determine the extent of hepatic dysfunction in these cases. At death, the median age of patients with sporadic infectious mononucleosis was 10.7 yr vs. 2.4 yr for X-linked lymphoproliferative syndrome. The median survival time was 8 wk for sporadic infectious mononucleosis and only 4 wk for X-linked lymphoproliferative syndrome. The male to female ratio was 3:2 in sporadic infectious mononucleosis; all patients with X-linked lymphoproliferative syndrome were males. Fever, sore throat, lymphadenopathy, hepatomegaly, and splenomegaly were prominent findings. Hepatic dysfunction was uniformly present and caused death in 13 of 30 sporadic infectious mononucleosis cases and 18 of 31 X-linked lymphoproliferative syndrome cases. Diagnosis of infectious mononucleosis was confirmed by heterophile antibody titers or Monospot, Epstein-Barr virus antibody studies, viral culture, molecular hybridization studies, clinical and histologic findings, and pedigree analysis.


Endoscopic treatment of transnasal intracranial penetrating foreign body.
Transnasal intracranial penetrating injury is rare. We report a case of transnasal intracranial penetrating metallic chopstick, which was removed successfully by endoscopic approach, and management of transnasal intracranial penetrating injuries.


Hypersensitivity reaction to high-dose methotrexate and successful rechallenge in a pediatric patient with osteosarcoma.
Hypersensitivity reactions to methotrexate are rare, but have been reported. Methotrexate has shown activity against many malignancies, and omission of methotrexate therapy may increase the risk of cancer-related death in some patients. Therefore, rechallenging patients with methotrexate following hypersensitivity may be beneficial. We report a case of a child with metastatic osteosarcoma who experienced a hypersensitivity reaction to high-dose methotrexate and was successfully rechallenged with methotrexate using a 6-hour infusion. Using this regimen, adequate peak methotrexate plasma concentrations were achieved and no further hypersensitivity reactions were noted.


Water and heat stresses during grain formation affect the physicochemical properties of waxy maize starch.
Maize is frequently subjected to simultaneous water (drought or waterlogging) and heat (HS) stresses during grain formation in southern China. This work examined the effect of high temperature combined with drought (HD) or waterlogging (HW) during grain formation on the starch physicochemical properties of two waxy maize hybrids, namely Suyunnuo5 (SYN5) and Yunuo7 (YN7). Heat stress enlarged the starch granule size, and water stresses aggravated this effect. Heat stress reduced the ratio of small molecular weight fractions for both hybrids, and HD aggravated this reduction only in SYN5. Relative crystallinity in SYN5 was increased by stresses but in YN7 it was unaffected by HD, reduced by HS, and increased by HW. Fourier-transform infrared (FTIR) spectrometry results showed that the 1045/1022 cm-1 ratio in SYN5 was not influenced by HW but was increased by other stresses, and that in YN7 it was increased by all stresses, with the highest value induced by HW. Peak viscosity was decreased, whereas gelatinization temperatures and retrogradation percentage were increased by all of these stresses. These effects were exacerbated by combined heat and water stresses. The maximum decomposition rate was severely increased by HW. Drought or waterlogging at grain formation stage aggravated the detrimental effects of HS on the starch physicochemical properties of waxy maize. © 2020 Society of Chemical Industry.


Evaluation of dental arch dimensions in 12 year-old Vietnamese children - A cross-sectional study of 4565 subjects.
This study aimed to define the width and length of the dental arch in 12-year-old Vietnamese children, and to elucidate differences between genders and among ethnic groups. A cross-sectional study was conducted in 4565 12 years-old children from the 4 major ethnic groups in Vietnam (Kinh, Muong, Thai, and Tay), with a healthy and full set of 28 permanent teeth that had never had any orthodontic treatment and with no reconstructive materials at the measured points. The mean variables in all subjects were 36.39 mm for upper inter-canine width; 46.88 mm for upper inter-first molar width; 59.43 mm for upper inter-second molar width; 10.41 mm for upper anterior length; 32.15 mm for upper posterior length 1; 45.52 mm for upper posterior length 2; 28.31 mm for lower inter-canine width; 41.63 mm for lower inter-first molar width; 54.57 mm for lower inter-second molar width (LM2W); 7.06 mm for lower anterior length (LAL); 26.87 mm for lower posterior length 1 (LP1L); and 41.29 mm for lower posterior length 2. Significant differences in these parameters between genders were found in all ethnic groups, except for LAL in the Kinh and Thai groups, and LP1L in the Tay group. Significant ethnic differences were also found in almost all parameters except LM2W in both males and females. Taken together, the representative sizes of dental arches of 12-year-old Vietnamese children have been defined. Our data indicate that there are some variations in dental arch dimensions among ethnic groups and between genders.


Endobronchial blood-patch: A novel technique for a persistent pleural air leak.
Patients with severe COVID-19 Pneumonia requiring prolonged mechanical ventilation have an increased incidence of pneumothorax. Mechanically ventilated patients who are critically ill and develop a persistent air leak from pneumothorax are poor candidates for surgical repair. As the persistent air leak can be a significant barrier to vent-weaning and clinical stability, these patients present a unique clinical challenge. A 65-year-old male intubated and on prolonged mechanical ventilation for severe COVID-19 Pneumonia developed a pneumothorax complicated by a persistent alveolar-pleural fistula with a persistent air-leak. Given his critical state with ongoing pressor requirements and elevated vent requirements, surgical repair was not an option. A bedside bronchoscopy occlusion study with isolation of the air leak, and subsequent autologous endobronchial blood-patch repair with thrombin was performed with rapid and definitive resolution of the air leak. The patient progressed favorably, ultimately being weaned from the ventilator, decannulated, and walking out of the hospital. In critically ill ventilated patients with pneumothorax complicated by a persistent air-leak, bedside endobronchial evaluation and blood-patch repair is a feasible approach to management.


Making a mountain out of a molehill: NRAS, mosaicism, and large congenital nevi.
Linking phenotypic patterns of melanocytic neoplasia to specific gene mutations allows more precise predicting of clinical behavior and response to targeted therapy. In this issue, Kinsler et al. provide evidence that multiple congenital nevi with central nervous system lesions are likely exclusively the result of mosaic mutations in NRAS. We discuss the link between mosaic NRAS mutations, cellular senescence, and clinical phenotype in these nevi.


Effectiveness of Platelet-ich Plasma Based on Gene Expression in Knee Osteoarthritis.
Intra-articular injection of Platelet-rich plasma (PRP) is an effective method for the treatment of patients with knee osteoarthritis (OA). This study aimed to assess the effects of PRP injection on OA, based on gene expression analysis. A sample of 30 subjects with knee OA was asked to complete the Persian versions of the Intermittent and Constant Osteoarthritis Pain (ICOAP) and Knee and Osteoarthritis Outcome Score (KOOS). Thereafter, the expression of IGF-1, HIF-1, cartilage oligometric matrix protein (COMP), and bone morphogenetic proteins (BMP2) were compared in the patient before and 1 month after PRP injection using real-time polymerase chain reaction (PCR). According to the results of the study, the expression of IGF-1, HIF-1, COMP and BMP2 were reported to be higher in subjects with PRP injection; however, only the up-regulation of IGF-1 was statistically significant (P<007). Moreover, the significant change in the KOOS and ICOAP scores was attributed to PRP injection (P<0.01). Intra-articular injections of PRP were reported to ease the pain, decrease the stiffness, and improve quality of life in patients with knee OA through the promotion of IGF-1 expression.


Experimental cerebral infarction. Part 2: Electroencephalographic changes produced by experimental thalamic infarction in dogs.
Previously, one of the authors developed a reliable experimental model in dogs for producing cerebral infarction. The EEG increased detection of experimental cerebral infarction, and was useful in predicting ischemic regions or infarction.


Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer.
NDRG2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.


Common variable immunodeficiency syndrome with right aortic arch: a case report.
Common variable immunodeficiency syndrome predominantly affects adults. It is characterized by low production of all the major classes of immunoglobulins. We report a case of common variable immunodeficiency syndrome with right aortic arch. An association of right-sided arch and common variable immunodeficiency syndrome has not been previously reported. A 41-year-old female patient presented with a history of recurrent pneumonia, sinusitis, otitis media, diarrhoea, cystitis since childhood. Biochemical and immunocytochemical analysis revealed common variable immunodeficiency syndrome and radiological evaluation confirmed right aortic arch and aberrant left subclavian artery. Common variable immunodeficiency syndrome syndrome is a clinical entity that should be kept in mind in patients with recurrent infections of different sites.


Cowpox: How dangerous could it be for humans? Case report.
Cowpox is a rare zoonosis transmitted to humans mainly from cats. The disease usually causes skin lesions; however, the ocular form may lead to other serious complications. We describe a case of cowpox in a rare location of the upper eyelid of an immunocompetent male, which lead to necrosis of the upper eyelid, keratitis and leucomatous opacity, and the neovascularization of the cornea. The patient underwent several surgeries, including reconstruction surgery of the eyelids, correction of the medial canthus, and corneal neurotization with supraorbicular nerve transplantation. Suspicion of cowpox should be made in patients where there are poorly healing skin lesions accompanied by a painful black eschar with erythema and local lymphadenopathy. Ocular cowpox may lead to serious complications and possibly mimic anthrax. Diagnosis of cowpox can be confirmed by detection of cowpox virus DNA by polymerase chain reaction. Patients should be advised to protect themselves while handling sick animals.


CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development.
CHARGE (coloboma, heart defect, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities, and/or hearing loss defect) syndrome consists of a combination of congenital malformations including genital hypoplasia and retarded growth. The objective of the study was to study gonadotropic axis function and growth parameters in CHARGE syndrome. This was a retrospective study. The study included 32 children with CHARGE syndrome. Nineteen of 20 affected boys had micropenis and/or cryptorchidism, consistent with hypogonadotropic hypogonadism during fetal life. None of the boys was of pubertal age. Seven of nine boys tested before the age of 5 months during the neonatal peak period had extremely low testosterone levels. LH response to GnRH stimulation was variable during the first year of life and not correlated with existing clinical abnormalities. None of the girls over the age of 12 yr (n = 7) had begun puberty spontaneously, and a lack of response to GnRH stimulation was documented in five of them. Olfactory evaluation (n = 10) and magnetic resonance imaging (n = 18) of the forebrain revealed defective sense of smell and abnormal olfactory bulbs in all cases. Cardiorespiratory and nutritional problems were corrected, but the mean height of the 25 children who had reached 5 yr of age was -2 +/- 0.2 sd score. Height was not correlated with birth length or body mass index. GH deficiency was diagnosed in only three children. These findings suggest that CHARGE syndrome includes the main features of Kallmann syndrome, which is defined by hypogonadotropic hypogonadism combined with a defective sense of smell and abnormal olfactory bulb development. This forebrain abnormality, if confirmed in a larger group of patients, could serve as a major new criterion for the diagnosis of CHARGE syndrome.


Proton magnetic resonance spectroscopy and diffusion-weighted imaging in intracranial cystic mass lesions.
The differential diagnosis of various intracranial cystic lesions is sometimes difficult on the basis of CT or MRI findings. Our objective was to evaluate (1)H MRS and DWI in the differential diagnosis of these lesions and in comparison with conventional MRI. Fifty patients with intracranial cystic lesions (21 pyogenic abscesses, 23 tumor cysts, 3 epidermoid cysts, and 3 arachnoid cysts) were evaluated with conventional MRI, DWI, and in vivo (1)H MRS. Preoperative diagnosis of the lesions was based on the results of DWI and in vivo MRS. All DWI and (1)H MRS studies were performed with a clinical 1.5-T system. The DWI was performed using single-shot spin-echo echo-planar pulse sequence with b = 1000 s/mm(2). The ADC value was measured. Diagnostic accuracy of conventional MRI, DWI, and in vivo (1)H MRS was calculated with respect to a final diagnosis of brain abscess vs nonabscess cystic tumor. Lactate and cytosolic amino acids with/without succinate, acetate, and alanine were observed in 18 of 21 cases of abscesses on MRS. In 3 cases of epidermoid cysts, lactate was observed and could be differentiated from 3 cases of arachnoid cysts, which showed only minimal lactate. Only lactate was seen in 14 of 23 patients with tumor cysts, whereas both lipid/lactate and choline were visible in 9 patients with tumor cysts. Increased signal was seen in 20 of 21 patients with abscesses and 3 patients with epidermoid cysts on DWI. Decreased signal was observed in 22 of 23 patients with tumor cysts and 3 patients with arachnoid cyst on DWI. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of conventional MRI for the differentiation of brain abscess from nonabscess cystic tumor were 61.4%, 61.9%, 60.9%, 59.1%, and 63.6%, respectively, whereas they were 93.2%, 85.7%, 100%, 100%, and 88.5% with MRS; 95.5%, 95.2%, 95.7%, 95.2%, and 95.7% with DWI; and 97.7%, 95.2%, 100%, 100%, and 95.8% with MRS and DWI. Magnetic resonance imaging, when combined with in vivo MRS and DWI, accurately predicted the diagnosis in 47 (94%) of 50 and 48 (96%) of 50 of the cases, respectively. Proton MRS and DWI are useful as additional diagnostic modalities in differentiating intracranial cystic lesions. Combination of DWI with calculated ADC values and metabolite spectrum acquired by MRS add more information to MRI in the differentiation of intracranial cystic mass lesions.


Targeting Th17 cells in HIV-1 remission/cure interventions.
Since the discovery of HIV-1, progress has been made in deciphering the viral replication cycle and mechanisms of host-pathogen interactions that has facilitated the implementation of effective antiretroviral therapies (ARTs). Major barriers to HIV-1 remission/cure include the persistence of viral reservoirs (VRs) in long-lived CD4+ T cells, residual viral transcription, and lack of mucosal immunity restoration during ART, which together fuel systemic inflammation. Recently, T helper (Th)17-polarized cells were identified as major contributors to the pool of transcriptionally/translationally competent VRs. In this review, we discuss the functional features of Th17 cells that were elucidated by fundamental immunology studies in the context of autoimmunity. We also highlight recent discoveries supporting the possibility of extrapolating this knowledge toward the identification of new putative Th17-targeted HIV-1 remission/cure strategies.


Solitary fibrous tumor arising in the sphenoethmoidal recess: a case report and review of the literature.
Recently, solitary fibrous tumors (SFTs) have been reported in the head and neck area, such as the nasal cavity, thyroid, salivary gland, etc. We present a rare case of SFT which arose from the sphenoethmoidal recess of the nasal cavity, penetrating into the sphenoid sinus, and which showed different intensities on magnetic resonance imaging (MRI) according to the occupied locations. T2 weighted magnetic resonance (MR) images showed low intensity in the nasal cavity, and iso-intensity in the sphenoid sinus. Enhancement with gadolinium contrast on T1-weighted images was more remarkable in the sphenoid sinus than in the nasal cavity. While the tumor in the nasal cavity showed abundant collagen and high cellularity in microscopic examination, numerous small vessels and dilated vascular spaces were remarkable in the tumor of the sphenoid sinus. MRI findings corresponded to pathological findings. We review SFTs in the head and neck area in the English literature.


Noise-Induced Hearing Loss: Permanent Versus Temporary Threshold Shifts and the Effects of Hair Cell Versus Neuronal Degeneration.
For decades, research on permanent noise-induced hearing loss has concentrated on the death of sensory hair cells and the associated threshold elevations. Recent work has shown that cochlear neurons are actually more vulnerable to noise, and even after exposures causing only temporary threshold elevation and no loss of hair cells, there is a rapid and irreversible loss of synaptic connections between cochlear neurons and hair cells followed by a slow degeneration of cochlear nerve cell bodies and central axons. Although this noise-induced neuropathy does not affect the audiogram, it likely reduces performance on more complex auditory tasks such as speech discrimination in noise.


Unraveling the Nature of Excellent Potassium Storage in Small-Molecule Se@Peapod-Like N-Doped Carbon Nanofibers.
The potassium-selenium (K-Se) battery is considered as an alternative solution for stationary energy storage because of abundant resource of K. However, the detailed mechanism of the energy storage process is yet to be unraveled. Herein, the findings in probing the working mechanism of the K-ion storage in Se cathode are reported using both experimental and computational approaches. A flexible K-Se battery is prepared by employing the small-molecule Se embedded in freestanding N -doped porous carbon nanofibers thin film (Se@NPCFs) as cathode. The reaction mechanisms are elucidated by identifying the existence of short-chain molecular Se encapsulated inside the microporous host, which transforms to K2 Se by a two-step conversion reaction via an "all-solid-state" electrochemical process in the carbonate electrolyte system. Through the whole reaction, the generation of polyselenides (K2 Sen , 3 ≤ n ≤ 8) is effectively suppressed by electrochemical reaction dominated by Se2 molecules, thus significantly enhancing the utilization of Se and effecting the voltage platform of the K-Se battery. This work offers a practical pathway to optimize the K-Se battery performance through structure engineering and manipulation of selenium chemistry for the formation of selective species and reveal its internal reaction mechanism in the carbonate electrolyte.


Closed-intraoral wound suction: a prospective analysis of 65 cases and a review of the literature.
Minimizing postsurgical swelling, edema, and pain are important to the patient because of the elective nature of orthognathic surgical procedures. Closed-intraoral wound suction was placed following mandibular osteotomies in 65 consecutive patients. The volume of drainage ranged from 35 to 285 mL (mean of 113 mL). The use of closed-intraoral wound suction only minimally increased the incidence of postsurgical infection and at the same time resulted in considerable subjective improvement in postoperative facial appearance and a decrease in tissue edema and pain.


Efficacy and safety of sarolaner (Simparica™) against fleas on dogs presented as veterinary patients in the United States.
The efficacy and safety of a novel isoxazoline parasiticide, sarolaner (Simparica™), for the control of fleas on dogs was evaluated in a randomized, controlled clinical study conducted in 19 general veterinary practices throughout the United States. Four hundred and seventy nine (479) dogs from 293 households were enrolled. Each household was randomly assigned to treatment with either sarolaner oral tablets (Simparica™, Zoetis) at the proposed label dose or an approved comparator product at the label dose (spinosad, Comfortis(®), Elanco). Dogs were dosed by their owners at home on Day 0 and on approximately Days 30 and 60. Dogs were examined at the clinics for general health, flea and tick infestation, and clinical signs of flea allergy dermatitis (FAD) at the initial visit and Days 14, 30, 60 and 90. Blood was collected for clinical pathology at screening and Day 90. Sarolaner was well-accepted by dogs with the majority of flavored chewable tablets (91.5%) accepted free choice, by hand or in food. Geometric mean live flea counts were reduced by >99% at the first time measured (14 days) after initiation of treatment and continued to reduce through the study. Treatment success (proportion of dogs with ≥90% reduction in fleas) for the sarolaner-treated dogs was superior to that for spinosad-treated dogs at Days 14 and 30 and non-inferior on Days 60 and 90 (P≤0.025) The rapid reduction in flea infestations resulted in a similar rapid resolution of the clinical signs associated with FAD. Sarolaner chewable tablets were well tolerated with no treatment related adverse reactions. Most of the clinical signs reported were consistent with allergies and dermatitis or sporadic occurrences of conditions commonly observed in the general dog population. A wide variety of concomitant medications, including many commercially available heartworm preventatives and other anthelmintic drugs, were administered to study dogs and all were well tolerated. Sarolaner administered orally to provide a minimum dosage of 2.0mg/kg (range 2-4mg/kg) once monthly for three consecutive treatments was safe and effective in the treatment and prevention of natural infestations of fleas and resulted in a substantial improvement of clinical signs associated with FAD.


DNA repair in lung cancer: a large-scale quantitative analysis for polymorphisms in DNA repairing pathway genes and lung cancer susceptibility.
The results of associations between single nucleotide polymorphisms (SNPs) of genes in DNA repairing pathway and lung cancer (LC) risk are inconsistent. We applied allele, dominant and recessive models to explore the risk of researched variants to LC in total LC and subgroups by ethnicity or LC subtypes with a cutoff point of p < 0.05. A total of 76,935 cases and 88,649 controls from 192 articles were included. Among the analyzed 40 variants from 20 genes, we found 9 statistically significant variants in overall populations by allele model, including five SNPs (rs1760944, rs9344, rs13181, rs1001581, and rs915927) increasing LC risk (odd ratios [ORs] = 1.10-1.71) and four SNPs (rs1042522, rs3213245, rs11615, and rs238406) decreasing the risk (ORs = 0.75-0.94). We identified rs1042522 and rs13181 as significant variants for LC in three models. Additionally, we identified differential significant SNPs in ethnic and subtype's analysis with comparison to total population. There are five SNPs in DNA repairing pathway associated with increased LC risk and four others decreased LC risk. Besides, the risky SNPs in different ethnicities and various LC subtypes were partly different, and the contribution of different genotypes to risk alleles were various as well.


Development of a scale to assess practitioner knowledge in providing integrated dual disorders treatment.
As mental health providers increasingly adopt evidence-based practices, tools are needed to assess practitioner knowledge of these practices. We describe the development and psychometric evaluation of a paper-and-pencil test to assess provider attitudes and knowledge about Integrated Dual Disorders Treatment (IDDT). In this sample of clinicians who were implementing IDDT in two mental health centers, the test showed good internal consistency, inter-rater reliability, and for a subsample who took the test twice, significant improvement over time. Higher scores on the scale were correlated with greater education, but not greater experience or lower burnout. This test is a promising tool for assessing provider knowledge of a specific evidence-based practice.


Expression of the early lymphocyte activation antigen CD69, a C-type lectin, is regulated by mRNA degradation associated with AU-rich sequence motifs.
CD69 is the earliest inducible cell surface glycoprotein acquired during lymphoid activation both in vitro and in vivo under physiological conditions and inflammation. This molecule is involved in lymphocyte proliferation, and functions as a signal-transmitting receptor in T and B lymphocytes, NK cells and platelets. Molecular cloning of CD69 cDNA revealed that this antigen is a type-II integral membrane protein with a C-type lectin domain in the extracellular region. The expression time course of CD69 mRNA has previously been reported to be transient, peaking around 3 h after induction in T lymphocytes, and declining to nearly resting levels by 8 h. We describe herein studies on the stability of the CD69 mRNA in phorbol ester-activated T lymphocytes. The level of CD69 mRNA in these cells declined rapidly with a half-life of less than 60 min. This finding is consistent with the presence of several AU-rich sequence motifs in the 3' untranslated region (3'UTR), which have been implicated in the selective destabilization of short-lived mRNA of mammalian cytokines, and proto-oncogenes. We have therefore introduced a fragment of the 3'UTR of the human CD69 cDNA, which contains the AU-rich sequence motifs, into the 3'UTR of the rabbit beta-globin gene. This inserted sequence causes the otherwise stable beta-globin mRNA to become unstable in vivo. A similar destabilizing effect is observed when the 51-nucleotide AU sequence from the mRNA of the human cytokine granulocyte/macrophage colony-stimulating factor is used as a positive control. Furthermore, the introduction of 194-bp fragment from the CD69 3'UTR containing most of the AU-rich motifs was sufficient to induce the destabilizing effect. We propose that the selective degradation pathway involved in the regulation of the expression of cytokines and proto-oncogenes is implicated in the rapid degradation of CD69 mRNA in activated T lymphocytes. This pathway may constitute a general mechanism to regulate the expression of inducible molecules involved in inflammatory processes.


Comparative study of the efficacy of fluconazole versus amphotericin B/flucytosine in surgical patients with systemic mycoses.
In an open, prospective, randomized study, the efficacy of fluconazole was compared with that of the combination amphotericin B/flucytosine. Forty surgical patients with deep-seated mycoses were included in the study. Absolute inclusion criteria were histological finding of fungi in a tissue sample taken during surgery from e.g. peritoneum, pancreas, lungs or trachea, a positive blood culture or candida lesion of the eye. According to the random list 20 patients received up to 0.5 mg amphotericin B per kg body weight in combination with 3 x 2.5 g flucytosine (5-FC) daily and 20 patients received fluconazole, 400 mg on the first day and then 300 mg daily. The two therapy groups were comparable in terms of age, sex and underlying diseases. Gastrointestinal perforations (27 times) were the most frequent underlying diseases. Candida albicans was the fungus most frequently detected microbiologically (34 times). The pathogens were eliminated from 12 patients in the fluconazole group and 14 patients in the combination group. The median elimination time was 8.5 days in the fluconazole group and 5.5 days in the amphotericin B/5-FC group. Six patients died in the fluconazole group, whereas five patients died in the comparison group. Side effects which necessitated switching of therapy occurred twice in the combination group. In deep-seated candida mycoses, surgical patients receiving the combination therapy with amphotericin B/5-FC showed an earlier elimination than patients on monotherapy with fluconazole. With respect to cure rates there was no difference between these two regimens.


The use of postoperative irradiation for the prevention of heterotopic bone formation after total hip replacement.
Formation of heterotopic bone (HTB) following total hip replacement may partially or completely ankylose the joint space, causing pain and/or limiting the range of motion. Patients at high risk for formation of HTB postoperatively include those with previous HTB formation, heterotopic osteoarthritis, and active rheumatoid spondylitis. Patients in these high risk groups have a 63-69% incidence of post-operative HTB formation, usually seen radiographically by 2 months post-operation. From 1980-1986 twenty-nine hips in 28 consecutively treated patients were irradiated post-operatively at the UCLA Center for the Health Sciences. The indication for irradiation was documented HTB formation previously in 26 of the 27 hips presented below. From 1980-1982 patients received 20 Gray (Gy) in 2 Gy fractions; from 1982-1986 the dose was reduced to 10 Gy in 2 Gy fractions. Twenty-seven hips in 26 patients completed therapy and were available for evaluation, with a minimum of 2 month follow-up, and a median follow-up of 12 months. Three of 27 hips developed significant HTB (Brooker grade III or IV) post-operatively, whereas 5 of 27 hips developed minor, nonsymptomatic HTB (Brooker grade I). When irradiation was begun by postoperative day 4, 0 of 17 hips formed significant HTB. If irradiation began after post-operative day 4, 3 of 10 hips formed significant HTB (Brooker grade III or IV). These 3 hips received doses of 10 Gy in one hip and 20 Gy in the other 2 hips. There were no differences in the incidence or severity of side effects in the 10 Gy vs. the 20 Gy treatment groups. Eighteen hips received 10 Gy, 8 hips 20 Gy and, 1 hip 12 Gy. In conclusion, 10 Gy in 5 fractions appears as effective as 20 Gy in 10 fractions at preventing post-operative formation of HTB. For optimal results, treatment should begin as early as possible prior to post-operative day 4.


Finding a solution: Heparinised saline versus normal saline in the maintenance of invasive arterial lines in intensive care.
We assessed the impact of heparinised saline versus 0.9% normal saline on arterial line patency. Maintaining the patency of arterial lines is essential for obtaining accurate physiological measurements, enabling blood sampling and minimising line replacement. Use of heparinised saline is associated with risks such as thrombocytopenia, haemorrhage and mis-selection. Historical studies draw variable conclusions but suggest that normal saline is at least as effective at maintaining line patency, although recent evidence has questioned this. We conducted a prospective analysis of the use of heparinised saline versus normal saline on unselected patients in the intensive care of our hospital. Data concerning duration of 471 lines insertion and reason for removal was collected. We found a higher risk of blockage for lines flushed with normal saline compared with heparinised saline (RR = 2.15, 95% CI 1.392-3.32, p ≤ 0.001). Of the 56 lines which blocked initially (19 heparinised saline and 37 normal saline lines), 16 were replaced with new lines; 5 heparinised saline lines and 11 normal saline lines were reinserted; 5 of these lines subsequently blocked again, 3 of which were flushed with normal saline. Our study demonstrates a clinically important reduction in arterial line longevity due to blockages when flushed with normal saline compared to heparinised saline. We have determined that these excess blockages have a significant clinical impact with further lines being inserted after blockage, resulting in increased risks to patients, wasted time and cost of resources. Our findings suggest that the current UK guidance favouring normal saline flushes should be reviewed.


Dual functions of eicosapentaenoic acid-rich microalgae: enrichment of yolk with n-3 polyunsaturated fatty acids and partial replacement for soybean meal in diet of laying hens.
Microalgae (Nannochloropsis sp., NS), with high contents of eicosapentaenoic acid (EPA) and crude protein, may be one of the important n-3 polyunsaturated fatty acid (PUFA) sources and potential protein feed ingredient. The purposes of this study were to enrich yolk with n-3 PUFA by dietary EPA-rich NS supplementation and to evaluate whether it is feasible to partly substitute for soybean meal in laying hens diet. A total of 360 37-wk-old healthy Lohmann Brown laying hens, with similar laying rate and body weight, were randomly allotted to 5 groups (6 replicates, 12 birds/replicate) and fed 5 experimental diets (0, 1, 2, 4, and 8% NS) for 4 wk. The hen performance and egg quality (except yolk color) were not affected (P > 0.05) by the NS supplemental diets. Yolk color score was increased as NS supplementation in diets (P < 0.001), and peaked on about the seventh day in all NS supplemental groups. The concentration of total n-3 PUFA was increased (P < 0.001), while total n-6 PUFA and n-6/n-3 ratio were decreased (P < 0.001) in yolk with increasing NS levels in diets. The 8% NS group had highest docosahexaenoic acid (DHA) and total n-3 PUFA levels, reaching 111.6 mg DHA and 148.6 mg total n-3 PUFA per egg. Maximum DHA, total n-3 PUFA, very long-chain (LC-) n-3 PUFA, and LC-PUFA levels were all observed at day 13 of NS supplementation. In conclusion, dietary NS supplementation enriched yolk with n-3 PUFA (especially DHA) and enhanced yolk color score without adverse effects on performance and egg quality, and indicated the practical feasibility of partial replacement for soybean meal in laying hens diet.


Intracranial subdural hematoma: a rare complication following spinal anesthesia: case report.
Intracranial subdural hematoma is a rare complication following spinal anesthesia. The diagnosis is usually difficult because initial symptoms are the same of post-dural puncture headache. The objective was to report a case of early diagnosed subdural hematoma after spinal anesthesia performed with a fine-gauge needle and single puncture. 48-year old female patient, ASA I, undergoing spinal anesthesia for surgery to correct urinary incontinence. The spinal anesthesia was performed with 27G Quincke needle and single puncture. There was no unexpected event in the surgery and the patient was discharged. After 48 hours of spinal puncture, the patient reported sudden, strong headache, affecting especially the orbital region, but also the temporal region, with important improvement in dorsal decubitus and followed by two vomiting episodes. A cranial tomography was requested and revealed the presence of an acute left frontotemporoparietal subdural hematoma. A conservative treatment with analgesics, dexamethasone and hydantoin was indicated. After 17 days, the patient had intense headache, followed by dormancy and paresis of right upper limb and speech and behavior disorders. The hematoma was surgically drained. The patient evolved well and without sequelae. Headache is the most frequent complication after spinal anesthesia and it is considered of benign evolution. In many cases however, it leads to the late or absent diagnosis of potentially fatal conditions, like subdural hematoma. This case describes a rare case of an acute subdural hematoma following spinal anesthesia with fine-gauge needle in a patient without risk factors for bleeding.


Is America finally ready for reform?
All the talk this political season about fixing health care may feel like deja vu. Anybody remember the '90s? Skeptics beware: Reform could happen this time around.


Highly efficient UV/H2O2 technology for the removal of nifedipine antibiotics: Kinetics, co-existing anions and degradation pathways.
This study investigates the degradation of nifedipine (NIF) by using a novel and highly efficient ultraviolet light combined with hydrogen peroxide (UV/H2O2). The degradation rate and degradation kinetics of NIF first increased and then remained constant as the H2O2 dose increased, and the quasi-percolation threshold was an H2O2 dose of 0.378 mmol/L. An increase in the initial pH and divalent anions (SO42- and CO32-) resulted in a linear decrease of NIF (the R2 of the initial pH, SO42- and CO32- was 0.6884, 0.9939 and 0.8589, respectively). The effect of monovalent anions was complex; Cl- and NO3- had opposite effects: low Cl- or high NO3- promoted degradation, and high Cl- or low NO3- inhibited the degradation of NIF. The degradation rate and kinetics constant of NIF via UV/H2O2 were 99.94% and 1.45569 min-1, respectively, and the NIF concentration = 5 mg/L, pH = 7, the H2O2 dose = 0.52 mmol/L, T = 20 ℃ and the reaction time = 5 min. The ·OH was the primary key reactive oxygen species (ROS) and ·O2- was the secondary key ROS. There were 11 intermediate products (P345, P329, P329-2, P315, P301, P274, P271, P241, P200, P181 and P158) and 2 degradation pathways (dehydrogenation of NIF → P345 → P274 and dehydration of NIF → P329 → P315).


Patterns of bulbar respiratory neurons during and after artifical hyperventilation.
Single bulbar respiratory unit activity was recorded in urethane-anesthetized rabbits. During artificial ventilation, reflex contractions of the diaphragm were elicited by the forced deflations of the respirator. Out of 44 neurons, four I, one E and two EI units exhibited a shift of their discharge relative to the contractile phase of the diaphragm, compared to normal respiration. During hypocapnic apnea, some I, IE and E neurons became silent. Other cells belonging to all phase types, however, continued to fire tonically at a rate less than the peak rate in normal bursts. When rhythmic respiration resumed after termination of the apneic pause, five (I, IE and E) units exhibited a transient phase shift of their burst discharge compared to normal respiration. The results of simultaneous recordings of two neurons belonging to different phase types are compatible with the assumption that inspiratory units are periodically inhibited by inspiratory-expiratory cells.


Biomarkers for risk stratification of febrile neutropenia among children with malignancy: a pilot study.
Patients receiving myelosuppressive chemotherapy remain at increased risk for developing febrile neutropenia (FN). For this heterogeneous population, a biomarker based risk stratification of FN patients may be a useful clinical tool. We hypothesized that serum biomarkers during initial presentation of an FN event could be predictive of subsequent clinical outcome. Eighty-nine FN events from 36 non-consecutive subjects were analyzed. "High-risk" FN criteria included prolonged hospitalization (≥ 7 days), admission to pediatric intensive care unit (PICU) or a microbiology confirmed bacteremia. Patients with "low risk" FN had none of the above. Biomarkers measured during the first 2 days of FN hospitalization were analyzed and correlated with respective clinical outcome. Of the 89 FN events, 44 (49%) fulfilled pre-defined high-risk criteria and 45 (51%) were low-risk. Procalcitonin level (>0.11 ng/ml) was found to be associated with the high-risk FN outcome with sensitivity of 97%. With an increase in log scale by 1, the odds of being high-risk FN increased twofold. Hs-CRP >100 mg/L had sensitivity of 88% in predicting high-risk FN. The odds of a high-risk FN event increased by approximately 1.8-fold with an increase in the log scale of hs-CRP by 1 (10-fold). In univariate analysis, IL-6, IL-8, and IL-10 were statistically significant and associated with high-risk FN. However, no statistically significant difference was found for IL-1α, sIL-2Ra, IL-3, or TNF-α. Biomarkers with appropriate critical threshold values may be a useful clinical tool for appropriate risk stratification of children with FN.