Age-related effects on the incorporation of acetate into rat liver histones.
Incorporation of sodium [3H]acetate into histones of rats was examined as a function of age. Incorporation was observed to decline with age up to 24 months, at which time a levelling occurred. Controls indicated that this decrease in histone acetylation could not be attributed to variability in isotope delivery to the liver or to alterations in intracellular 'pools' available for acetylation. Polyacrylamide gel electrophoresis established that, in all cases, acetate was incorporated primarily into histone fractions H3 and H4 and the pattern of incorporation exhibited age-dependent phenomena. H4 was predominantly labelled in 2 months animals, while in 12, 16, and 24 months animals H3 was more highly labelled; at 27 months the two fractions were labelled equally. Assessment of histone acetylase and deacetylase activities indicates that deacetylase activity increased with age.


XCP1 cleaves Pathogenesis-related protein 1 into CAPE9 for systemic immunity in Arabidopsis.
Proteolytic activation of cytokines regulates immunity in diverse organisms. In animals, cysteine-dependent aspartate-specific proteases (caspases) play central roles in cytokine maturation. Although the proteolytic production of peptide cytokines is also essential for plant immunity, evidence for cysteine-dependent aspartate-specific proteases in regulating plant immunity is still limited. In this study, we found that the C-terminal proteolytic processing of a caspase-like substrate motif "CNYD" within Pathogenesis-related protein 1 (PR1) generates an immunomodulatory cytokine (CAPE9) in Arabidopsis. Salicylic acid enhances CNYD-targeted protease activity and the proteolytic release of CAPE9 from PR1 in Arabidopsis. This process involves a protease exhibiting caspase-like enzyme activity, identified as Xylem cysteine peptidase 1 (XCP1). XCP1 exhibits a calcium-modulated pH-activity profile and a comparable activity to human caspases. XCP1 is required to induce systemic immunity triggered by pathogen-associated molecular patterns. This work reveals XCP1 as a key protease for plant immunity, which produces the cytokine CAPE9 from the canonical salicylic acid signaling marker PR1 to activate systemic immunity.


Cytokine profiles of sentinel lymph nodes draining the primary melanoma.
The sentinel lymph node (SLN) draining the primary melanoma is the first echelon node where micrometastasis is established. SLNs may be the initial sites of antigen presentation associated with immune responses. A portion of each SLN from 68 melanoma patients undergoing selective SLN dissection was processed for enzyme-linked immunospot (ELISPOT) assay determination of interferon gamma (IFN-gamma), interleukin-2 (IL-2), granulocyte macrophage colony-stimulating factor (GM-CSF), and interleukin-10 (IL-10) secretion. The control was the adjacent non-SLN. Lymphocytes were stimulated with staphylococcal enterotoxin A (SEA) prior to ELISPOT assay. No significant difference was noted in the production of IL-10 between the SLNs and non-SLNs. Significant production of IFN-gamma, IL-2, and GM-CSF was noted in the SLNs when compared to the non-SLNs in the overall group. Patients with no micrometastasis (n = 60) had elevated secretion of all cytokines in the SLNs. However, patients harboring lymph node micrometastasis (n = 8) showed no increase of cytokine secretion in the SLNs. Significant Th1 and Th2 response was induced in melanoma-free SLNs. SLNs without micrometastasis may be activated by submicroscopic cells or soluble tumor antigens, while cytokine production may be down-regulated by micrometastasis. Future studies should be directed towards identifying the specific SLN T cells recognizing the tumor antigens.


Effectiveness of Acapella along with institutional based chest physiotherapy techniques on pulmonary functions and airway clearance in post-operative CABG patients.
Patients undergoing Coronary Artery Bypass Graft (CABG) surgery often develop pulmonary complications in the early post-operative period as result of decreased lung function and impaired cough. Conventional physiotherapy in early post-operative period aims at increasing lung volumes and airway clearance. This study aimed to determine the effectiveness of the addition of Acapella to conventional chest physiotherapy in improving lung volumes and secretion clearance in early post-operative CABG patients. Twenty patients of both genders (40-70 years) who had undergone CABG and were in Phase I of Cardiac Rehabilitation were involved in this pilot randomized control trial (9 control, 11 experimental). Post-surgery intervention commenced on post-operative day 2 (POD 2) and continued till POD 6. Patients in the control group were given conventional physiotherapy that included breathing exercises, incentive spirometry and manual techniques. Patient in the experimental group used an Acapella device along with the conventional intervention. Outcome measures considered were pulmonary function parameters (FVC, FEV1 & PEFR) and amount of sputum expectorated. A significant increase in lung volumes was observed in both the groups on POD 6 as compared to POD 2 (both<0.01). However, the increase was significantly greater on POD 6 in experimental group than the control group [mean difference (95% CI) FVC: 0.44 L (0.24-0.63), FEV1: 0.43 L (0.19-0.66), PEFR: 0.86 L/s (0.57-1.14)]. The amount of sputum expectoration significantly greater in the experimental group as compared to the control group [2.71 mL (0.53-4.90)]. The addition of Acapella enhanced the effect conventional physiotherapy in improving lung volumes and airway clearance in the early post-operative period for CABG patients.


IspG-catalyzed positional isotopic exchange in methylerythritol cyclodiphosphate of the deoxyxylulose phosphate pathway: mechanistic implications.
H(2)(18)O under the bridge: Recently, the deoxyxylulose phosphate (DXP) pathway was discovered to be a second pathway supplying isoprenoid biosynthetic precursors. One of steps is an IspG-catalyzed reductive deoxygenation of methylerythritol cyclodiphosphate (MEcPP) to 4-hydroxyl-3-methyl-2-(E)-1-diphosphate (HMBPP). Using [2-(13) C,(18) O]-MEcPP, we detected the positional isotopic exchange for the bridging oxygen in MEcPP.


Method comparison and estimation of causal effects of insomnia on health outcomes in a survey sampled population.
Applying causal inference methods, such as weighting and matching methods, to a survey sampled population requires properly incorporating the survey weights and design to obtain effect estimates that are representative of the target population and correct standard errors (SEs). With a simulation study, we compared various approaches for incorporating the survey weights and design into weighting and matching-based causal inference methods. When the models were correctly specified, most approaches performed well. However, when a variable was treated as an unmeasured confounder and the survey weights were constructed to depend on this variable, only the matching methods that used the survey weights in causal estimation and as a covariate in matching continued to perform well. If unmeasured confounders are potentially associated with the survey sample design, we recommend that investigators include the survey weights as a covariate in matching, in addition to incorporating them in causal effect estimation. Finally, we applied the various approaches to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and found that insomnia has a causal association with both mild cognitive impairment (MCI) and incident hypertension 6-7 years later in the US Hispanic/Latino population.


Chronic hepatitis B in male and female children of HBsAg carrier mothers.
We have studied a group of children born to HBsAg+ mothers, resident in the English West Midlands; none of the children had sought medical attention for hepatitis B-related problems. Forty-two out of 48 children born to HBeAg+ mothers were HBsAg+. Among these children, the mean age of the HBeAg+ girls was significantly lower than that of the HBeAg+ boys (P = 0.05), suggesting that girls eradicate HBeAg at a younger age than boys. Among all children born to HBsAg+ mothers, liver function tests were normal except in 2 HBsAg+ boys who had elevated serum aminotransferase activities. Excluding these boys, serum alanine aminotransferase activity, while within the normal range, was significantly higher in HBeAg+ and anti-HBe+ children than in their immune (anti-HBs+) and non-infected siblings (P less than 0.01 and P less than 0.05). Waning infectivity was observed in many HBsAg+ mothers, giving rise to a typical pattern of infection within a family: older children, born to the still HBeAg+ mother, being HBeAg+ carriers, while younger siblings, born when the mother had become anti-HBe+, had no markers of infection. These younger children are vulnerable to 'horizontal' transmission.


Investigation of reaction intermediates of the urea-diacetylmonoxime reaction.
1. An investigation of the intermediates of the urea-diacetylmonoxime reaction and the isolation of the protochromogen has been described. A comparative spectral study of the protochromogen with that of the literature values suggested the structure of the protochromogen to be a diureide. 2. The diureides of 1-phenyl-1,2-propanedione-monoxime and 2,3-pentanedione were synthesized and their visible, U.V., I.R., NMR, and mass desorption spectrometry data were analyzed. The study suggests that the structure of each of these compound is that of a diureide. When these diureides were redissolved in acid media, they gave the color expected of the corresponding chromogens found from the respective diketones and urea. 3. The 3a-methyl-6a-phenyl-glycoluril was synthesized by a base-catalyzed reaction. When this glycoluril was dissolved in concentrated HCl, a pink color was obtained, similar to that of the corresponding diureide. These studies indicate that both the diureide and the glycoluril (if formed at all in acid-catalyzed reaction) are converted to the same chromogen, possibly via a rearrangement. 4. When 2,3-butanedionemonoximethiosemicarbazone was reacted with urea in acid medium, characteristic spectral data were obtained which were very similar to those of the urea-diacetylmonoximethiosemicarbazide reaction. This tends to indicate that the possible structures of the protochromogens are similar and of the open chain diureide type.


Indirubin alleviates bleomycin-induced pulmonary fibrosis in mice by suppressing fibroblast to myofibroblast differentiation.
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. Indirubin, a compound obtained from indigo-bearing plants or mollusks of the family Muricidae, has various bioactivities, including anti-tumor activity and anti-inflammation effect. However, whether indirubin could mediate its therapeutic effects on bleomycin (BLM)-induced pulmonary fibrosis has not been addressed. The impacts of indirubin on bleomycin (BLM)-induced pulmonary fibrosis were evaluated by pathological staining, western blot, RT-PCR and immunofluorescent staining. The effects of indirubin on fibroblast differentiation and related signaling were next investigated to demonstrate the underlying mechanisms. The results indicated that indirubin-treated mice exhibited a definitively improved survival rate than that of the BLM-induced mice in a dose-depend manner. Additionally, administration of indirubin significantly alleviated inflammatory cells infiltration in BLM mice. Importantly, indirubin provided protection for mice against BLM-induced pulmonary fibrosis as manifested by the attenuating expression of fibrotic hallmarks, including fibronectin, collagen I and α-smooth muscle actin (α-SMA). Subsequently, we providedin vitro evidence revealing that indirubin suppressed fibroblast to myofibroblast differentiation by repressed TGF-β/Smad signaling in a dose-dependent manner. Notably, our data showed that indirubin seemed to be safe in mice and fibroblasts. Overall, indirubin could protect the mice against BLM-induced pulmonary fibrosis by alleviated fibroblast differentiation and may be therapeutically beneficial for IPF patients.


Determination of fast neutron RBE using a fully mechanistic computational model.
This work presents a model previously developed for estimating relative biological effectiveness (RBE) associated with high-LET particles. It is based on the combination of Monte Carlo simulations of particle interactions when traversing an atomic resolution DNA geometrical model. In addition, the model emulates the induction of lethal damage from the interaction of two sublethal lesions, taken as double-strand breaks. The Geant4-DNA package was used for simulations with liquid water as the transport medium. The RBE of neutron beams with energies ranging from 0.1 MeV up to 14 MeV was studied. The model succeeded in reproducing the general behavior of RBE as a function of neutron energy, including the RBE peak reported by experiments at approximately 0.4 MeV. Furthermore, the results of the model agree rather well with some experimental works. However, our results underestimate RBE for neutron energies above approximately 5 MeV due to the current limitations of Geant4-DNA for the tracking of heavy ions below 0.5 MeV/u.


Value of shared preclinical safety studies - The eTOX database.
A first analysis of a database of shared preclinical safety data for 1214 small molecule drugs and drug candidates extracted from 3970 reports donated by thirteen pharmaceutical companies for the eTOX project (www.etoxproject.eu) is presented. Species, duration of exposure and administration route data were analysed to assess if large enough subsets of homogenous data are available for building in silico predictive models. Prevalence of treatment related effects for the different types of findings recorded were analysed. The eTOX ontology was used to determine the most common treatment-related clinical chemistry and histopathology findings reported in the database. The data were then mined to evaluate sensitivity of established in vivo biomarkers for liver toxicity risk assessment. The value of the database to inform other drug development projects during early drug development is illustrated by a case study.


New pharmacological treatment strategies for relapse prevention.
Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit from those developments.


Predictive accuracy of physicians' estimates of outcome after severe stroke.
End-of-life decisions after stroke should be guided by accurate estimates of the patient's prognosis. We assessed the accuracy of physicians' estimates regarding mortality, functional outcome, and quality of life in patients with severe stroke. Treating physicians predicted mortality, functional outcome (modified Rankin scale (mRS)), and quality of life (visual analogue scale (VAS)) at six months in patients with major disabling stroke who had a Barthel Index ≤6 (of 20) at day four. Unfavorable functional outcome was defined as mRS >3, non-satisfactory quality of life as VAS <60. Patients were followed-up at six months after stroke. We compared physicians' estimates with actual outcomes. Sixty patients were included, with a mean age of 72 years. Of fifteen patients who were predicted to die, one actually survived at six months (positive predictive value (PPV), 0.93; 95% CI, 0.66-0.99). Of thirty patients who survived, one was predicted to die (false positive rate (FPR), 0.03; 95%CI 0.00-0.20). Of forty-six patients who were predicted to have an unfavorable outcome, four had a favorable outcome (PPV, 0.93; 95% CI, 0.81-0.98; FPR, 0.30; 95% CI; 0.08-0.65). Prediction of non-satisfactory quality of life was less accurate (PPV, 0.63; 95% CI, 0.26-0.90; FPR, 0.18; 95% CI 0.05-0.44). In patients with severe stroke, treating physicians' estimation of the risk of mortality or unfavorable functional outcome at six months is relatively inaccurate. Prediction of quality of life is even more imprecise.


Procathepsin d involvement in chemoresistance of cancer cells.
The role of pCD in cancer has been studied for a long time. We have focused on the hypothesis that increased expression and/or secretion of pCD in cancer cells causes increased chemoresistance to apoptosis inducing molecules. The aim was to evaluate the effects of pCD expression/release on chemoresistance. We tested the LC(50) values for various transfectants of breast cancer cell line MDA-MB-231 as well as effects of exogenous additions of pCD, its mutants, pepstatine, antibodies, and Brefeldin on the resistance. We found that pCD levels can be correlated with chemoresistance, the pro-resistant activity seems to be localized outside the cells, proteolytic activity is not involved, and PI3-Akt signaling has an important role in antiapoptotic effects of pCD. We can conclude that overexpression of pCD has strong influence on increased resistance of tumor cells. This could, in fact, be an important contribution in the possible use of pCD level determination for prognostic and/or therapeutic purposes.


Effect of TLR4/MyD88/NF-kB axis in paraventricular nucleus on ventricular arrhythmias induced by sympathetic hyperexcitation in post-myocardial infarction rats.
Sympathetic activation after myocardial infarction (MI) leads to ventricular arrhythmias (VAs), which can result in sudden cardiac death (SCD). The toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-kB) axis within the hypothalamic paraventricular nucleus (PVN), a cardiac-neural sympathetic nerve centre, plays an important role in causing VAs. An MI rat model and a PVN-TLR4 knockdown model were constructed. The levels of protein were detected by Western blotting and immunofluorescence, and localizations were visualized by multiple immunofluorescence staining. Central and peripheral sympathetic activation was visualized by immunohistochemistry for c-fos protein, renal sympathetic nerve activity (RSNA) measurement, heart rate variability (HRV) analysis and norepinephrine (NE) level detection in serum and myocardial tissue measured by ELISA. The arrhythmia scores were measured by programmed electrical stimulation (PES), and cardiac function was detected by the pressure-volume loop (P-V loop). The levels of TLR4 and MyD88 and the nuclear translocation of NF-kB within the PVN were increased after MI, while sympathetic activation and arrhythmia scores were increased and cardiac function was decreased. However, inhibition of TLR4 significantly reversed these conditions. PVN-mediated sympathetic activation via the TLR4/MyD88/NF-kB axis ultimately leads to the development of VAs after MI.


Proteomic changes at 8 weeks after infection are associated with chronic liver pathology in experimental schistosomiasis.
Chronic Schistosoma mansoni infection can present as a moderate or severe disease, termed intestinal or hepatosplenic schistosomiasis, respectively. Similarly, either moderate splenomegaly or hypersplenomegaly syndrome develops in CBA/J mice by 20weeks of infection and is similar to intestinal or hepatosplenic schistosomiasis respectively. Using this mouse model and two-dimensional differential in gel electrophoresis, the liver proteomic signatures of uninfected mice and mice infected for 6, 8, 12, or 20weeks were compared, and significant protein spots identified using mass spectrometry. We found the greatest number of changes at 12weeks suggesting that this period represents the peak time of change. Pathway analysis identified specific proteins and pathways that correlated to the pathological changes indicative of severe disease, and these pathways were involved as early as 8weeks after infection. These findings provide insight into the development of severe liver pathology in schistosomiasis and may aid in developing biomarkers for hepatosplenic schistosomiasis.


Increasing access to erectile dysfunction treatment via pharmacies to improve healthcare provider visits and quality of life: Results from a prospective real-world observational study in the United Kingdom.
The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) formally reclassified sildenafil citrate 50 mg tablets as a pharmacy medicine (sildenafil-P) in 2017 for adult men with erectile dysfunction (ED). A 1-year prospective real-world observational study was conducted to track men's health behaviour, particularly their healthcare resource utilisation (HCRU) and quality of life (QoL) before and after the availability of sildenafil-P. Adult men with ED aged ≥18 years provided data at baseline (prior to launch of sildenafil-P) and every 3 months after the launch. Demographics, health characteristics, treatments at baseline and HCRU, including number of pharmacist and physician/nurse practitioner visits over time are reported. QoL-related outcomes were assessed via the Self-Esteem and Relationship Questionnaire (SEAR), 2-Item Patient Health Questionnaire and ratings of sexual satisfaction. Generalised linear models were used to assess the association of sildenafil-P use with total physician/nurse practitioner and pharmacist visits and QoL-related outcomes at 12 months. Overall, 1162 men completed the survey at all 5 time points. The mean ± SD age was 59.02 ± 12.06 years; 55.42% reported having a moderate-to-severe ED. Hypertension (37.52%) and hypercholesterolaemia (31.50%) were the most common risk factors for ED. At baseline, 62.99% were not using any ED treatment. After adjusting for baseline visits/other covariates, mean physician/nurse practitioner (3.68 vs 2.87; P = .003) and pharmacist visits for any reason (2.10 vs 1.34; P < .001) at 12 months were significantly higher among sildenafil-P users than those who never used sildenafil-P. Sildenafil-P users also had significantly higher SEAR total and domain (sexual relationship and self-esteem) scores at 12 months. Following the reclassification to a pharmacy medicine in the UK, sildenafil-P was associated with a higher number of physician/nurse practitioner and pharmacist visits for any reason. Sildenafil-P use was also associated with better QoL, although group differences were small in magnitude.


The technology of microalgal culturing.
This review outlines the current status and recent developments in the technology of microalgal culturing in enclosed photobioreactors. Light distribution and mixing are the primary variables that affect productivities of photoautotrophic cultures and have strong impacts on photobioreactor designs. Process monitoring and control, physiological engineering, and heterotrophic microalgae are additional aspects of microalgal culturing, which have gained considerable attention in recent years.


Autoimmune encephalitis as an increasingly recognised cause of non-convulsive status epilepticus: A retrospective, multicentre evaluation of patient characteristics and electroencephalography (EEG) results.
Status epilepticus (SE) is a severe condition of unrelenting seizures requiring urgent identification and treatment. SE may be unprovoked, occurring in someone with epilepsy, or may be provoked by acute intracranial disease or metabolic derangement. Increasingly encephalitis, particularly autoimmune types, is reported to cause refractory seizures. Whilst convulsive SE is readily identified, non-convulsive SE (NCSE) can be difficult to identify clinically, and electroencephalography (EEG) is required. Therefore, it is critical to identify the key clinical features associated with NCSE on EEG to inform future use of EEG. We conducted a multicentre, retrospective analysis of EEG requests from four general and one specialist neurology hospital in the Northwest of England (2015-2018). Cases were identified from EEG requests for patients with suspected NCSE or other indications such as encephalopathy. We compared demographic and clinical characteristics between EEG-confirmed cases of NCSE and a randomly selected sample of negative controls. 358 EEGs were reviewed, and 8 positive cases of NCSE were identified. Epilepsy was identified as the aetiology in 2 of these cases, and autoimmune encephalitis another 2 cases (one patient with N-methyl-d-aspartate receptor antibodies and another with voltage gated potassium channel antibodies). Previous alcohol excess (p = 0.005) and subtle motor signs (p = 0.047) on examination were observed more frequently in patients with NCSE compared to controls. Physicians should have a low threshold for urgent EEG in patients with suspected or previous encephalitis, especially if autoimmunity is suspected or subtle motor signs are present.


Acute scrotum due to Haemophilus influenzae type b.
The acute scrotum in infants and children is generally due to torsion of the spermatic cord, torsion of the appendix testis, or acute epididymitis. An infant is presented who was found to have epididymitis and a scrotal abscess due to Haemophilus influenzae type b at the time of surgical exploration for suspected torsion of the spermatic cord.


Natural History of Type 1 Spinal Muscular Atrophy in a Series of Argentinian Children.
SMA1 natural history is characterized by early development of chronic respiratory failure. Respiratory interventions in type 1 SMA infants are subject to great practice variability. Nusinersen, has been recently approved in Argentina. The advent of novel treatments has highlighted the need for natural history studies reporting disease progression in type 1 SMA. To analyze the progression, respiratory interventions and survival based on the type of respiratory support in type 1SMA patients, in a third level pediatric hospital in Argentina. Cohort of SMA1 patients followed at the Interdisciplinary Program for the Study and Care of Neuromuscular Patients (IPNM). Patient survival was analyzed by using the Kaplan-Meier method. Log-rank test was performed to compare the survival curve for three respiratory intervention groups. 59 patients. Mean age of symptom onset was 2.19 (±1.4) months, age at diagnosis was 3.9 (±2.1) months. Patients developed respiratory failure at 5.82 months (±2.32) and 13.8 months (±5.6) in Type 1B and Type 1C, respectively (p < 0.001) 53 p were SMA1B. Three copies were found in 1/6 SMA1C. Respiratory interventions: SRC 23 p (56.1%); SRC + NIV 8 p (19.5%); SRC + IV 10 p (24.4%). 8 patients were already on invasive ventilation when included in the IPNM. Patients with invasive ventilation showed longer survival. This series provides valuable information on respiratory intervention requirements and life expectancy in children with SMA1 before the implementation of novel treatments that increase the expression of the SMA protein.


Effects of biochar particle size and dosage on the desiccation cracking behavior of a silty clay.
Desiccation cracking can significantly change the integrity of soils, and potentially result in the instability of infrastructure as well as the migration of contaminants. Biochar is regarded as a promising low-carbon material for geotechnical applications, including cracking prevention. This study investigates the effects of biochar particle size and dosage on the desiccation cracking characteristics of a silty clay. For samples with fine biochar particles (<0.25 mm), coarser primary cracks initiate first, followed by finer secondary cracks regardless of biochar dosage. Quantitative analysis of the cracking characteristics at the stable stage shows that the surface crack ratio, the number of crack segments, the total length of cracks and the average width of cracks decreased by 31.29%, 30.78%, 14.18%, and 20.45% after 10% biochar addition. For samples with coarse biochar particles (>0.25 mm), cracks initiate simultaneously on the soil surface, and primary and secondary cracks are difficult to distinguish after drying, especially in high dosage samples. In the presence of 10% biochar, the surface crack ratio and average width of cracks decreased by 28.64% and 62.84%, but the number of crack segments and total length of cracks increased by 163.39% and 42.13%. Microstructure and image processing analysis of soil cracks indicate that biochar affects the crack initiation and propagation process by altering the soil microstructure and thereby the crack parameters. The contact between biochar and soil particles transitions from close contact to loose contact as the size of the biochar particles increases. In general, the application of 10% biochar with fine particle size had the best performance in inhibiting soil cracking.


The spectrum of clinicopathological features in pure autonomic neuropathy.
We assessed the clinicopathological features of nine patients with pure autonomic neuropathy, that is, neuropathy without sensory or motor deficits. The duration from symptom onset to diagnosis ranged from 1 month to 13 years. Of eight patients in whom serum antiganglionic acetylcholine receptor antibody was determined, four were positive. All patients who tested positive for this antibody manifested widespread autonomic dysfunction, with the exception of one patient who only experienced orthostatic hypotension. However, patients who were negative for the antiganglionic acetylcholine receptor antibody presented with partial autonomic failure. One of these patients had diffuse parasympathetic failure and generalized hypohidrosis but no orthostatic hypotension, which is clinically compatible with postganglionic cholinergic dysautonomia. Electron microscopic examination revealed a variable degree of reduction in unmyelinated fibers. Compared with normal controls, the patients had a significantly increased density of collagen pockets (p < 0.05). Additionally, the percentage of Schwann cell subunits with axons (out of the total number of Schwann cell subunits associated with unmyelinated fibers) was significantly decreased (p < 0.01). The density of unmyelinated fibers tended to decrease with increasing time between the onset of autonomic symptoms and biopsy (p < 0.05). In conclusion, the clinical and pathological features of pure autonomic neuropathy vary in terms of progression, autonomic involvement, presence of the antiganglionic acetylcholine receptor antibody, and loss of unmyelinated fibers.


Oral iron absorption test: should it be performed before starting treatment with ferrous preparations?
The oral iron absorption test is sometimes used in the assessment of ferrous preparation efficacy before therapeutic use in the treatment of patients with anemia. Overdoses of Fe can cause the production of free radicals that are dangerous because of chemical modifications and damage of proteins, lipids, carbohydrates, and nucleotides. We suggest that this test should not be performed with the recommended dose of iron because of the potential threat to the patients. We assessed the serum concentration of iron and total iron-binding capacity during the test. Before and after the test, the concentration of malonyldialdehyde, an end product of lipid peroxidation, was determined in serum. In most patients, we found an increase in malonyldialdehyde concentration, suggesting the enhanced production of free radicals. This increase was particularly marked in patients with an overabsorption of iron. The administration of iron in the dose recommended for the oral iron absorption test causes increase in serum malonyldialdehyde concentration, proving an overproduction of free radicals. This test should not be performed because of the evidence proving detrimental effects of free-radical overproduction on the human body.


The earliest electrocardiographic sign of acute transmural myocardial infarction.
A 43 year old man had serial 12-lead electrocardiograms (ECG) in the early phase of an acute anterior transmural myocardial infarction. In addition to the ST-segment elevation and hyperacute T waves, the patient's ECG displayed increase in the R wave voltage, decrease and final disappearance of the S wave, merging of the R wave with the elevated ST-segment and formation of monophonic curves. Such ECG patterns have been noted in the early phase of experimental coronary occlusion in the dog and in patients with Prinzmetal's angina. The clinical implication of this observation is discussed.


The role of physical and psychological symptoms in desire for death: a study of terminally ill cancer patients.
The current study assessed the attitudes of the desire for hastened death in terminally ill cancer patients and whether these are determined by their physical and psychological symptoms. The final sample consisted of 106 terminally ill cancer patients attending a Palliative Care Unit, in University of Athens, Greece, between June and October 2004. Significant associations were found between the desire for hastened death (D.H.D.) and 'pain' (r=0.469, p<0.005), 'fatigue' (r=0.591, p<0.0005), 'loss of appetite' (r=0.622, p<0.0005) and 'feeling sad' (r=0.635, p<0.0005). Statistically significant associations were also found between Schedule of Attitudes towards Hastened Death (SAHD) scores, age (r=0.300, p=0.002) and ECOG (p<0.0005). Twenty-six percent of the patients reported high D.H.D. while 41% reported moderate desire. In the prediction of SHAD the contribution of 'pain' (p=0.011), 'lack of appetite' (p=0.012) and 'sadness' (p=0.011) is high (42% of variance). Further findings suggest that D.H.D. is significantly related to 'feeling sad', 'lack of appetite', 'pain' and 'fatigue' after controlling for age, gender and performance status according to ECOG in terminally ill cancer patients.


Enhanced Production of Active Ecumicin Component with Higher Antituberculosis Activity by the Rare Actinomycete Nonomuraea sp. MJM5123 Using a Novel Promoter-Engineering Strategy.
Ecumicins are potent antituberculosis natural compounds produced by the rare actinomycete Nonomuraea sp. MJM5123. Here, we report an efficient genetic manipulation platform of this rare actinomycete. CRISPR/Cas9-based genome editing was achieved based on successful sporulation. Two genes in the ecumicin gene cluster were further investigated, ecuN and ecuE, which potentially encode a pretailoring cytochrome P450 hydroxylase and the core peptide synthase, respectively. Deletion of ecuN led to an enhanced ratio of the ecumicin compound EcuH16 relative to that of EcuH14, indicating that EcuN is indeed a P450 hydroxylase, and there is catalyzed hydroxylation at the C-3 position in unit12 phenylalanine to transform EcuH16 to the compound EcuH14. Furthermore, promoter engineering of ecuE by employing the strong promoter kasO*P was performed and optimized. We found that integrating the endogenous ribosome-binding site (RBS) of ecuE together with the RBS from kasO*P led to improved ecumicin production and resulted in a remarkably high EcuH16/EcuH14 ratio. Importantly, production of the more active component EcuH16 was considerably increased in the double RBSs engineered strain EPR1 compared to that in the wild-type strain, reaching 310 mg/L. At the same time, this production level was 2.3 times higher than that of the control strain EPA1 with only one RBS from kasO*P. To the best of our knowledge, this is the first report of genome editing and promoter engineering on the rare actinomycete Nonomuraea.


Life expectancy and burden of late complications after reduced intensity conditioning allogeneic transplantation.
Reduced intensity conditionings (RIC) before after allogeneic hematopoietic stem cell transplantation (HSCT) allow older or unfit patients of being transplanted, but survival expectancy and burden of late complications are poorly described in this setting. All patients (N = 456) who were alive and relapse-free 2 years after HSCT following RIC were included. Cumulative incidences (CI), standardized incidence, or mortality, ratio (SIR or SMR), and competing risk models were used. The 10-year CIs of relapse and non-relapse mortality incidences were 13.9 and 13.4%, respectively. Seventy-eight patients died, late relapse being the most frequent cause of death leading to a SMR of 6.38 (95% CI, 5.1-8.0; p < 0.001). Among non-relapsing patients (n = 412), 30 died (SMR 4.38; 95% CI, 3.3-5.8: p < 0.001). A total of 37 patients developed 41 SM leading to a 10-year cumulative incidence of 12.9%, and a significant SIR relative to the general population (1.4). Finally, we found high CI of cardiovascular (CVC) and venous thromboembolic complications (VTE) (10-year CI; 15.1% and 11.7%, respectively). Older age was the only significant risk factor for CVC and VTE in multivariable analysis. In conclusion, with life expectancy rate of 70%, late survivors after RIC warrants long-term follow-up and active intervention on averting cardiovascular disease and screening cancers.


Spatial distribution and changes of permafrost on the Qinghai-Tibet Plateau revealed by statistical models during the period of 1980 to 2010.
The Qinghai-Tibet Plateau (QTP), where is underlain by the highest and most extensive mid-altitude permafrost, is undergoing more dramatic climatic warming than its surrounding regions. Mapping the distribution of permafrost is of great importance to assess the impacts of permafrost changes on the regional climate system. In this study, we applied logistic regression model (LRM) and multi-criteria analysis (MCA) methods to map the decadal permafrost distribution on the QTP and to assess permafrost dynamics from the 1980s to 2000s. The occurrence of permafrost and its impacting factors (i.e., climatic and topographic elements) were constructed from in-situ field investigation-derived permafrost distribution patterns in 4 selected study regions. The validation results indicate that both LRM and MCA could efficiently map the permafrost distribution on the QTP. The areas of permafrost simulated by LRM and MCA are 1.23 × 106 km2 and 1.20 × 106 km2, respectively, between 2008 and 2012. The LRM and MCA modeling results revealed that permafrost area has significantly decreased at a rate of 0.066 × 106 km2 decade-1 over the past 30 years, and the decrease of permafrost area is accelerating. The sensitivity test results indicated that LRM did well in identifying the spatial distribution of permafrost and seasonally frozen ground, and MCA did well in reflecting permafrost dynamics. More parameters such as vegetation, soil property, and soil moisture are suggested to be integrated into the models to enhance the performance of both models.


Reliability of a White Striping Scoring System and Description of White Striping Prevalence in Purebred Turkey Lines.
To efficiently meet consumer demands for high-quality lean meat, turkeys are selected for increased meat yield, mainly by increasing breast muscle size and growth efficiency. Over time, this has altered muscle morphology and development rates, which are believed to contribute to the prevalence of myopathies. White striping is a myopathy of economic importance which presents as varying degrees of white striations on the surface of skinless breast muscle and can negatively affect consumer acceptance at the point of sale. Breeding for improved meat quality may be a novel strategy for mitigating the development of white striping in turkey meat; however, it is crucial to have a reliable assessment tool before it can be considered as a phenotype. Six observers used a four-category scoring system (0-3) to score severity in several controlled rounds and evaluate intra- and inter-observer reliability of the scoring system. After sufficient inter-observer reliability (Kendall's W > 0.6) was achieved, 12,321 turkey breasts, from four different purebred lines, were scored to assess prevalence of the condition and analyze its relationship with important growth traits. Overall, the prevalence of white striping (Score > 0) was approximately 88% across all genetic lines studied, with most scores being of moderate-severe severity (Score 1 or 2). As was expected, increased white striping severity was associated with higher slaughter weight, breast weight, and breast meat yield (BMY) within each genetic line. This study highlights the importance of training to improve the reliability of a scoring system for white striping in turkeys and was required to provide an updated account on white striping prevalence in modern turkeys. Furthermore, we showed that white striping is an important breast muscle myopathy in turkeys linked to heavily selected traits such as body weight and BMY. White striping should be investigated further as a novel phenotype in future domestic turkey selection through use of a balanced selection index.


Synergistic anticancer effects of curcumin and crocin on human colorectal cancer cells.
Curcumin, a polyphenol compound derived from the Curcuma longa L, and crocin, a hydrophilic carotenoid from Crocus Sativus Linnaeus, are traditionally used in food preparations in many countries and could act as chemopreventive compounds against several diseases, including cancer. In this study, the synergistic effect of curcumin and crocin was investigated for the first time on inducing apoptosis and suppressing colorectal cancer cells (SW-480 cell line). MTT, Annexin V-FITC/PI, and DAPI staining tests were employed to evaluate cell viability and apoptosis induction, respectively. The combined effect of curcumin and crocin on the expression of genes involved in apoptosis and proliferation was quantified using real-time PCR. The combination therapy effect on cell cycle progression was also evaluated by flow cytometry. Based on the obtained results, curcumin and crocin treatment could cooperatively reduce cell viability and induce apoptosis in SW-480 cells by modulating the expression of Bax, Bcl-2, Caspase-3, Caspase-8, Caspase-9, Jak2, Stat3, and Akt1 genes. Besides, curcumin and crocin were able to synergistically increase the cell cycle arrest at the sub G1 phase, induce autophagy and decrease the clonogenic ability of SW-480 cells. These results suggested that curcumin and crocin combination could be considered a more effective therapeutic strategy for inhibiting colorectal cancer.


Lipoprotein-associated and secretory phospholipase A2 in cardiovascular disease: the epidemiological evidence.
Among other lipid related biomarkers, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and type II secretory phospholipase A(2) (sPLA(2)) represent emerging candidates for refined assessment of future cardiovascular disease (CVD) risk. Indeed, emerging evidence from more than prospective 15 studies conducted since 2000, clearly demonstrate the prognostic ability of increased Lp-PLA(2) concentrations or elevated activity for risk of future coronary heart disease (CHD) and stroke. Moreover, Lp-PLA(2) might have similar predictive power for both, incident CHD in initially healthy subjects, as well as for recurrent events in those with clinically manifest atherosclerosis. By contrast, to date, there are only few prospective studies that have investigated the relationship of sPLA(2) with future CVD risk. However, most of them show a positive association between increased mass or elevated activity and future atherosclerotic complications. Nonetheless, since inhibitors of Lp-PLA(2) and sPLA(2) have already been developed, these enzymes may be considered as novel therapeutic targets to treat residual risk in certain high risk patient groups. This review summarizes the epidemiologic evidence on the association between increased mass or elevated activity of these two phospholipases and risk of CVD.


Radiation dose for normal organs by helical tomotherapy for lung cancer.
This study derived a simple equation of effective dose (E) versus normal organ of patients with varying body weights undergoing lung cancer treatment of helical tomotherapy (TOMO). Five tissue-equivalent and Rando phantoms were used to simulate lung cancer patients. This study then measured E and equivalent dose of organ or tissues (DT) using thermoluminescent dosimetry (TLD-100H). The TLD-100H was calibrated using TOMO 6MV photons, then inserted into phantom positions that closely corresponded with the position of the represented organs and tissues. Both E and DT were evaluated by ICRP 103. Peripheral doses varied markedly at positions close to the tumor center. The maximum statistical and total errors were 16.7-22.3%. This analytical result indicates that E of Rando and tissue-equivalent phantoms was in the ranged of 9.44±1.70 (10kg) to 4.58±0.83 (90kg)mSv/Gy. Notably, E decreased exponentially as phantom weight increased. Peripheral doses were also evaluated by TLD as a function of distance from the tumor center. Finally, experimental results are compared with those in literature. These findings will prove useful to patients, physicians, radiologists, and the public.


The impact of self-employment on mental health of the younger elderly in China.
With the prolongation of the life expectancy of the Chinese population and the intensification of the aging process of the population, the mental health problems of the elderly have become increasingly prominent. This study aims to explore whether self-employment can promote and how to promote the mental health of the elderly. Based on the 2018 China Longitudinal Aging Social Survey (CLASS) data, this paper uses OLS model and KHB method to verify the impact of self-employment on the mental health of the younger elderly and its mechanism. The results indicate that self-employment can significantly reduce the depression tendency of the younger elderly and promote their mental health. Heterogeneity analysis shows that self-employment has a more significant positive impact on the mental health of the younger elderly who are self-rated healthy, free of chronic diseases and low-level medical service utilization. The mechanism shows that self-employment can indirectly improve the mental health of the younger elderly through income growth effect and self-worth realization effect, in which the self-worth realization effect is greater than the economic effect. It illustrates that with the development of China's economy, the elderly are pursuing more intrinsic values brought by self-employment than economic benefits. In view of the above research results, it is suggested to encourage the elderly to actively participate in social activities, provide policy support for the younger elderly to engage in self-employment, increase government support as well as health guarantee level, and improve the subjective initiative of the elderly to participate in self-employment, so that the society can truly realize the healthy aging of "being useful and productive for the elderly".


Allergic bronchopulmonary aspergillosis associated with smoking moldy marihuana.
A 27-year-old man who habitually smoked marihuana developed clinical, laboratory, and radiologic findings consistent with allergic bronchopulmonary aspergillosis. Culture of the marihuana obtained from the patient's source yielded heavy mixed growths of Aspergillus. Treatment with corticosteroids was effective.


Variations in sulphur content and stable sulphur isotope composition of vegetation near a SO2 source at Fox Creek, Alberta, Canada.
The proportion of sulphur found in vegetation increases as an industrial sulphur dioxide emission source is approached, but this trend is modified by topographic extremes. Stable sulphur isotope analysis revealed that increased sulphur concentrations in arborcal and terricolous lichens, andPicea glauca needles were due to incorporation of sulphur emitted as sulphur dioxide by the Kaybob sour gas plant near Fox Creek, Alberta, Canada. It is confirmed thatPicea glauca gets its sulphur from both the soil and the air; arboreal lichens get their sulphur primarily from the atmosphere; and terricolous lichens get theirs from the air and particulate fallout. It is suggested that arboreal lichens selectively excrete isotopically light sulphur when thallus concentrations exceed 1,400 ppm. Accumulation of sulphur in vegetation is dependent, on fumigation episode duration, frequency, and concentration, as well as the plant's ability to avoid injury, but is not closely correlated with average sulphation rates. The implications of terrestrial moss-lichen carpet destruction is discussed.


Noninvasive high frequency oscillatory ventilation through nasal prongs: bench evaluation of efficacy and mechanics.
Noninvasive high frequency oscillatory ventilation through nasal prongs (nHFOV) has been proposed as a new respiratory support in neonatology. We studied the effect of ventilation parameters and nasal prongs on nHFOV efficacy and mechanics. Customized sealed circuits connecting a SM3100A oscillator to a neonatal lung model were developed to evaluate the effect of applying HFOV via two different sized nasal prongs on delivered tidal volume and pressure. Measurements were made across a range of frequencies and pressures; amplitude was set to obtain visible lung oscillation. Volume delivered by peak-to-peak oscillation, ventilation, and pressure significantly differed among the interfaces, being higher for large cannulae and the control circuit (p < 0.0001). The interposition of a large or small nasal prong reduced volume to 56 and 26%, ventilation to 32 and 9%, and mean pressure to 83 and 79%, respectively, of the values measured for the direct connection of the oscillator to the test lung. Volume and ventilation were inversely related to frequency, which was particularly evident with larger diameter circuits due to higher delivered tidal volume (R (2) > 0.9). Increasing ventilation was associated with larger tidal volume and nasal prong diameter (adjusted R (2) = 0.97). nHFOV using common nasal prongs is technically possible. Efficiency of tidal volume delivery is significantly affected by prong diameter.


The purification and partial characterisation of two novel metalloproteinases from the venom of the West African carpet viper, Echis ocellatus.
Separation of previously uncharacterised Echis ocellatus venom by phenyl-Superose FPLC (Fast Liquid Protein Chromatography) yielded eight protein fractions. Three of these displayed high proteolytic activity when assayed by in vivo and in vitro assays (including enzyme linked immunosorbant assay), and were further separated using Superdex 75 and Mono-Q FPLC. This resulted in the purification of a non-haemorrhagic 24 kDa metalloproteinase (EoVMP1, pI 7.0), and a haemorrhagic 56 kDa metalloproteinase (EoVMP2, pI 5.5). Following tryptic digest, short amino acid sequences of EoVMP1 and EoVMP2 were obtained using Edman degradation. Both sequences displayed homology when aligned with existing snake venom metalloproteinases (SVMPs). The strong homology observed among previously well-characterised SVMPs suggests that principles governing the interaction of substrates and inhibitors are likely to be similar for EoVMP1, EoVMP2 and all members of the reprolysin family.


Addition of dexmedetomidine to ropivacaine improves cervical plexus block.
To investigate the sensory block onset time, duration time, and side effects of adding dexmedetomidine to ropivacaine for cervical plexus block. Forty American Society of Anesthesiologists (ASA) Class I or II adult patients who were scheduled to undergo thyroid surgery were randomly allocated to the following groups to receive cervical plexus block: 30 mL of 0.375% ropivacaine combined with 1 μg kg(-1) of dexmedetomidine; 30 mL of 0.375% ropivacaine combined with saline (control). The sensory block onset time, duration of analgesia, mean arterial pressure (MAP), heart rate (HR), and the incidences of side effects, such as hypotension, bradycardia, and hypoxemia were recorded. The addition of dexmedetomidine to ropivacaine (Group D) shortened the sensory block onset time compared with the ropivacaine group (Group C) (95% confidence interval [CI] 4.18-5.26; p < 0.05). The duration of analgesia of cervical plexus block in Group D was significantly longer than that in Group C (95% CI 295.96-311.12; p < 0.05). The Ramsay sedation score at 5, 10, 20, 40, 60, 90, and 120 minutes after local anesthetic administration in Group D was significantly higher than that in Group C (p < 0.05). MAP level and HR level in Group D were significantly lower than that in Group C (p < 0.05). The addition of 1 μg kg(-1) dexmedetomidine to ropivacaine for cervical plexus block could shorten the sensory block onset time and extend the duration of analgesia, and increased the quality of analgesia, with the patients being sedated and arousable.


Protocol for an evaluation of adherence monitoring and support interventions among people initiating antiretroviral therapy in Cape Town, South Africa-a multiphase optimization strategy (MOST) approach using a fractional factorial design.
South Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed. Standard care only allows for suboptimal adherence detection when routine testing indicates unsuppressed virus. Several adherence interventions are known to improve HIV outcomes, yet few are implemented in routinely due to the resources required. Therefore, determining scalable evidence-based adherence support interventions for resource-limited settings (RLS) is a priority. The multiphase optimization strategy (MOST) framework allows for simultaneous evaluation of multiple intervention components and their interactions. We propose to use MOST to identify the intervention combination with the highest levels of efficacy and cost-effectiveness that is feasible and acceptable in primary care clinics in Cape Town. We will employ a fractional factorial design to identify the most promising intervention components for inclusion in a multi-component intervention package to be tested in a future randomized controlled trial. We will recruit 512 participants initiating ART between March 2022 and February 2024 in three Cape Town clinics and evaluate acceptability, feasibility, and cost-effectiveness of intervention combinations. Participants will be randomized to one of 16 conditions with different combinations of three adherence monitoring components: rapid outreach following (1) unsuppressed virus, (2) missed pharmacy refill collection, and/or (3) missed doses as detected by an electronic adherence monitoring device; and two adherence support components: (1) weekly check-in texts and (2) enhanced peer support. We will assess viral suppression (<50 copies/mL) at 24 months as the primary outcome; acceptability, feasibility, fidelity, and other implementation outcomes; and cost-effectiveness. We will use logistic regression models to estimate intervention effects with an intention-to-treat approach, employ descriptive statistics to assess implementation outcomes, and determine an optimal intervention package. To our knowledge, ours will be the first study to use the MOST framework to determine the most effective combination of HIV adherence monitoring and support intervention components for implementation in clinics in a RLS. Our findings will provide direction for pragmatic, ongoing adherence support that will be key to ending the HIV epidemic. ClinicalTrials.gov NCT05040841. Registered on 10 September 2021.


Effects of two serine proteases from Bothrops pirajai snake venom on the complement system and the inflammatory response.
The present study aimed to evaluate the effects of two serine proteases from Bothrops pirajai snake venom, named BpirSP27 and BpirSP41, on the complement system and the inflammatory response. The effects of these enzymes on the human complement system were assessed by kinetic hemolytic assays, evaluating the hemolysis promoted by the classical/lectin (CP/LP) and alternative (AP) pathways after incubation of normal human serum with the serine proteases. The results suggested that these enzymes were able to induce modulation of CP/LP and AP at different levels: BpirSP41 showed higher inhibitory effects on the hemolytic activity of CP/LP than BpirSP27, with inhibition values close to 40% and 20%, respectively, for the highest concentration assayed. Regarding AP, both enzymes showed percentages of inhibition of the hemolytic activity around 20% for the highest concentrations tested, indicating similar effects on this complement pathway. The proinflammatory effects of B. pirajai serine proteases were evaluated regarding their ability to induce paw edema, variations in the pain threshold and leukocyte recruitment at the site of injection. Both showed mild effects on these inflammatory processes, leading to low levels of increase of paw volumes and decrease in pain thresholds in rats up to 6 h after injection, and inducing neutrophil recruitment without significant increases in the total number of leukocytes in the inflammatory exudates after 6 and 24 h of administration into mice peritoneal cavity. These results suggest that serine proteases must present a minor role in the inflammation caused by B. pirajai snake venom.


Comparison with Magnetic Resonance Three-Dimensional Sequence for Lumbar Nerve Root with Intervertebral Foramen.
Prospective study based on magnetic resonance (MR) imaging of the lumbar spinal root of the intervertebral foramen. This study was to compare MR three-dimensional (3D) sequences for the evaluation of the lumbar spinal root of the intervertebral foramen. The diagnosis of spinal disorders by MR imaging is commonly performed using two-dimensional T1- and T2-weighted images, whereas 3D MR images can be used for acquiring further detailed data using thin slices with multi-planar reconstruction. On twenty healthy volunteers, we investigated the contrast-to-noise ratio (CNR) of the lumbar spinal root of the intervertebral foramen with a 3D balanced sequence. The sequences used were the fast imaging employing steady state acquisition and the coherent oscillatory state acquisition for the manipulation of image contrast (COSMIC). COSMIC can be used with or without fat suppression (FS). We compared these sequence to determine the optimized visualization sequence for the lumbar spinal root of the intervertebral foramen. For the CNR between the nerve root and the peripheral tissue, these were no significant differences between the sequences at the entry of foramen. There was a significant difference and the highest CNR was seen with COSMIC-FS for the intra- and extra-foramen. In this study, the findings suggest that the COSMIC-FS sequences should be used for the internal or external foramen for spinal root disorders.


Effects of wildfire ashes on aquatic invertebrates: First molecular approach on Chironomus riparius larvae.
The wildfire magnification in recent years has raised increasing concern about their adverse impacts on the environment. Wildfires are recognized as an important source of diffuse pollution for the nearby aquatic systems being potentially toxic to aquatic life. Albeit previous studies with wildfire runoff/ashes observed effects in aquatic organisms, to date, different severity origins of ashes and their impact at the sub-organismal level on aquatic biota have not been assessed. In this work, the molecular response of Chironomus riparius exposed to wildfire with low (LS) and high (HS) severity ashes from burnt Pine plantations was evaluated by employing an array of 42 genes related to crucial metabolic pathways by Real time-PCR. IV instar larvae were exposed for 72 h to aqueous extract of ashes (12.5 %, 25 %, 50 %, 75 % and 100 %) prepared from LS and HS ashes. Mn, Zn, and Pb were the metals found at highest concentration in both ash extracts, for HS notable Cd, Mn and Cr presence. From the 42 genes studied only 4 were not altered (22 genes modulated their response by LS and 38 genes in the case of HS) showing the opposite response at 100% with downregulated by LS and upregulated by HS. The 12.5 %, 25 %, 100 % HS and 25 % LS were the main modulators, confirmed by the integrative biomarkers response (IBR). Remarkable genotoxicity was generated by ashes even activating the apoptosis response, and endocrine disruption observed could modify the development. Moreover, detoxification and stress response were strongly activated, limiting the organism's future response to external aggressions. The employment of this novelty approach with molecular tools act as early alarm signal preventing greater damages. Overall, wildfire ashes showed to be a significant environmental disruptor to C. riparius even at lower concentration and the short exposure time employed, emphasizing the strong impact of wildfires on aquatic systems.


Gallbladder volvulus with gangrene. Case report and review of the literature.
Volvulus of the gallbladder is an unusual event. Over 300 cases have appeared in the literature since first reported by Wendel in 1898, ranging in age from 2 to 100 years old. Unusual mobility of the gallbladder due to congenital anomalies is a constant factor in all occurrences. This is a report of a laparoscopic cholecystectomy in an 82-year-old white female with volvulus of the gallbladder presenting with a chief complaint of chest pain. The patient had an uneventful recovery and was discharged within 72 hours after surgery, indicating that with the proper technique laparoscopic cholecystectomy is both feasible and safe in gallbladder volvulus.


Health professionals' acceptance and willingness to pay for hepatitis B virus vaccination in Gondar City Administration governmental health institutions, Northwest Ethiopia.
Hepatitis B virus (HBV) infection is a global public health problem. The burden of the disease is high in low and middle income countries like Ethiopia. However, for highly vulnerable groups such as health professionals, vaccination coverage is a major issue in the developing countries where health professionals are expected to pay for vaccination. Therefore, the objective of this study was to assess health professionals' acceptance and willingness to pay (WTP) and associated factors for vaccination against HBV. Cross-sectional study was conducted from March to April, 2017 in Gondar city administration governmental health institutions among 423 health professionals. Simple random sampling method was employed to select the study participants. Data were collected using self- administered questionnaire. Tobit model was used to analyze the determinants of WTP and the maximum amount of money the individuals might pay for HBV vaccination. P-value < 0.05 was considered statistically significant. A total of 423 health professionals (physicians, nurses, midwives, laboratory technicians/technologists, and others) participated in the study with a response rate of 100, and 62.4% of them were willing to pay for HBV vaccination. The mean amount of money the participants might pay for HBV vaccination was 325.83 ± 283.46 ETB (US$ 14.39 ± 12.52). The study indicated that the WTP for HBV vaccination of health professionals from health centers was 179.41 ETB less compared to health professionals from hospital. The WTP for HBV vaccination of the participants who had no experience of seeing previous patients with HBV was 157.87 ETB less compared to participants who had experience of seeing previous patients with HBV. As monthly income of the study participants increased by one ETB, the WTP was increased by 0.027 ETB. The study revealed that the mean amount of money the participants might pay for HBV vaccination was much less than the market price for HBV vaccination. Type of workplace and experience of seeing/observing patients with HBV, and income were the predictors of WTP for HBV vaccination. Availing the vaccine with affordable cost in governmental health institutions may increase WTP of health professionals for HBV vaccination.


Definitive characterization of uric acid as an interferent in peroxidase indicator reactions and a proposed mechanism of action.
We have characterized and identified uric acid as an interferent to peroxidase catalyzed reactions where hydrogen peroxide is generated at relatively low concentrations. The implications of these findings are important for those utilizing peroxidase as an indicator reaction where low primary substrate concentrations require their preliminary extraction or chemical modification. We have shown that the elimination of uric acid as an interferent from biologic fluid obviates the necessity for such treatment. In amniotic fluid, our data suggests that uric acid represents the only interference to peroxidase-catalyzed reactions, especially when using p-substituted phenols as proton donors. The removal of uric acid has been shown to eliminate hydrogen peroxide reduction and should allow for an increase in sensitivity and specificity for measurements incorporating a peroxidase-coupled indicator reaction, hence, more effective use of these reaction sequences. To our knowledge, this is the first report of a mechanism to eliminate hydrogen peroxide reduction in amniotic fluid.


The effects of 100 nm pure boron nanoparticles on the primary antioxidant system of Nile tilapia (Oreochromisniloticus).
In this study, the effects of 100 nm boron nanoparticles (B-NPs) on the primary antioxidant status of Nile tilapia were researched via analysis of enzyme activities and related gene expressions. This is a new study which focuses on the relationship between B-NPs and oxidative stress that contribute to the literature in terms of its scope. Fish (n = 15) for each group were exposed to three different concentrations as 5, 25 (n2) and 125 (n3) mg/L during 96 h to see the response of the primary antioxidant system. According to the results, SOD expressions differed in all treatment groups compared to the control group (P < 0.05). CAT expressions were different in 5 and 125 mg/L groups compared to control and 25 mg/L groups (P < 0.05). GPX expressions were only different in 125 mg/L group (P < 0.05). The changes in enzyme activities of SOD and CAT were significantly different in 25 mg/L groups. GPX enzyme activities were not significant (P > 0.05). TBARS concentrations in 25 mg/L group were significantly different from those in the control and 125 mg/L groups (P < 0.05).


Comparison between single-photon emission computed tomography/computed tomography and ultrasound in preoperative detection of parathyroid adenoma: retrospective review of an institutional experience.
The aim of this study was to evaluate the accuracy of technetium- 99m-methoxyisobutylisonitrile (Tc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) and ultrasound in preoperative localization of single parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (pHPT) who would be suitable for minimally invasive parathyroidectomy (MIP). A retrospective study of 143 consecutive patients with biochemical evidence of hyperparathyroidism who underwent preoperative localization of parathyroid lesions using Tc-MIBI SPECT/CT and ultrasound, and proceeded to parathyroid surgery at our institution from January 2013 to January 2018. Of these, 125 had single adenomas and are the subject of this study. The sensitivity, positive predictive value (PPV) and accuracy of the two imaging techniques for the accurately identification and lateralization of PTAs were determined using histopathology as the criterion standard. Of 125 PTAs, the correct identification and lateralization were significantly higher by SPECT/CT than ultrasound. SPECT/CT and ultrasound detected lesions with histopathologically proven PTAs in 116 and 95 patients, respectively. The sensitivity, PPV and accuracy were 92.17, 94.64 and 87.60%, respectively, for SPECT/CT and 75.89, 90.43 and 70.25%, respectively, for ultrasound in lateralization analysis. The results of our study indicate that Tc-MIBI SPECT/CT is more accurate than ultrasound for the preoperative identification of single PTAs in patients with pHPT who are candidates for MIP.


Livedo reticularis in association with acute lymphocytic leukemia. Report of a case.
A case of livedo reticularis of relatively short duration associated with severe pain in the legs is presented. The skin condition preceded the onset of a fulminant and fatal acute lymphocytic leukemia in this patient by a period of fourteen months.


Drivers behind co-occurrence patterns between pathogenic bacteria, protozoa, and helminths in populations of the multimammate mouse, Mastomys natalensis.
Advances in experimental and theoretical work increasingly suggest that parasite interactions within a single host can affect the spread and severity of wildlife diseases. Yet empirical data to support predicted co-infection patterns are limited due to the practical challenges of gathering convincing data from animal populations and the stochastic nature of parasite transmission. Here, we investigated co-infection patterns between micro- (bacteria and protozoa) and macroparasites (gastro-intestinal helminths) in natural populations of the multimammate mouse (Mastomys natalensis). Fieldwork was performed in Morogoro (Tanzania), where we trapped 211 M. natalensis and tested their behaviour using a modified open-field arena. All animals were checked for the presence of helminths in their gastro-intestinal tract, three bacteria (Anaplasma, Bartonella, and Borrelia) and two protozoan genera (Babesia and Hepatozoon). Besides the presence of eight different helminth genera (reported earlier), we found that 19% of M. natalensis were positive for Anaplasma, 10% for Bartonella, and 2% for Hepatozoon species. Hierarchical modelling of species communities was used to investigate the effect of the different host-related factors on these parasites' infection probability and community structure. Our results show that the infection probability of Bartonella increased with the host's age, while the infection probability of Anaplasma peaked when individuals reached adulthood. We also observed that less explorative and stress-sensitive individuals had a higher infection probability with Bartonella. Finally, we found limited support for within-host interactions between micro-and macroparasites, as most co-infection patterns could be attributed to host exposure time.


A new test of random walks in heterogeneous environments.
Environmental heterogeneities can change animal movement in two different manners. First, they can modify movement characteristics (move lengths or turning angles), in which case the movement remains of the diffusive kind. Second, they can bias displacement towards a particular direction in which case it becomes non-diffusive. We propose in this paper a simple method that only requires computing the mean length of a sample of trajectories in some bounded area to distinguish between these two kinds of movement. We show through simulations that the method allows to detect the presence of heterogeneities that orient animal movement. We apply it to experimental trajectories of Messor sancta ants engaged in corpse aggregation to show that their displacement is oriented at the contact of the formed corpse piles and that their trajectories become non-diffusive.


Experimental and Numerical Studies on the Behaviors of Autoclaved Aerated Concrete Panels with Insulation Boards Subjected to Wind Loading.
Autoclaved aerated concrete panels (AACP) are lightweight elements in civil engineering design. In this paper, experiments and numerical analyses were conducted to study the flexural behavior of an enclosure system that consisted of AACPs and a decorative plate. A full-scale test was conducted to investigate the behavior of the enclosure system under wind suction. Load-deflection curves and load-strain relationships under different wind pressures were recorded and discussed. The effects of thickness, reinforcement ratio, and strength grade on the flexural behavior of AACPs were numerically investigated. Based on the numerical results, we found that the flexural behavior of AACPs can be improved by increasing the thickness or the reinforcement ratio. A comparison of finite element and theoretical results calculated using American and Chinese design formulae was conducted, and the results indicated the existing design formulae can conservatively estimate the major mechanical indices of AACPs.


Transcatheter management of mid-aortic syndrome secondary to myofibroma presenting in infancy with severe left ventricular dysfunction: a case report.
In this study, we summarise a case of a myofibroma causing mid-aortic syndrome due to obstruction of the distal thoracic and abdominal aorta leading to severe left ventricular dysfunction. The patient was managed with percutaneous intervention via balloon dilation and stent placement. On follow-up, the patient has normalisation of ventricular function, is off anti-hypertensives, and is being monitored for re-stenosis.


The Evaluation of Endothelin-1 and Endothelin Receptor Type A Gene Polymorphisms in Patients with Vitiligo.
Endothelin-1 (EDN1) and EDN receptor type A (EDNRA) are implicated in melanocyte functions. This study examines the role of EDN1 (G5665T and T-1370G) and EDNRA (C + 70G and G-231A) polymorphisms as a risk factor for vitiligo, and evaluates the relationship between genotypes and clinical characteristics of vitiligo patients. We analyzed genotype/allele distributions of EDN1 and EDNRA polymorphisms in 100 patients with vitiligo and 185 healthy controls by real-time polymerase chain reaction. There was no notable risk for vitiligo afflicted by studied polymorphisms. However, the presence of EDNRA +70 variant G allele was found to be related with decreased risk for development of generalized type of vitiligo (odds ratio [OR]: 0.42, 95% confidence interval [CI] = 0.21-0.86, pcorr = 0.03) and showed protective effect against associated diseases seen in vitiligo (OR: 0.49, 95% CI = 0.27-0.88, pcorr = 0.034). Haplotype analysis demonstrated a strong (disequilibrium coefficient = 0.73, r (2) = 0.405) linkage disequilibrium between EDN1 G5665T and T-1370G polymorphisms. The EDN1 5665/-1330 TT haplotype was over represented significantly in controls than in patients (P = 0.04). The studied polymorphisms do not seem to be a major risk for vitiligo. Haplotype analysis denoting protective effects against vitiligo may indicate an indirect interaction in the course of vitiligo. In addition, EDNRA + 70 polymorphism is protective against generalized type of vitiligo and associated diseases.


Manufacturing and characterization of Pd nanoparticles formed on immobilized bacterial cells.
To fabricate and analyse Pd nanoparticles on immobilized bacterial cells. Biological ceramic composites (biocers) were used as a template to produce Pd(0) nanoparticles. The metal-binding cells of the uranium mining waste pile isolate, Bacillus sphaericus JG-A12 were used as a biological component of the biocers and immobilized by using sol-gel technology. Vegetative cells and surface-layer proteins of this strain are known to bind high amounts of Pd(II) that can be reduced to Pd(0) particles by the addition of a reducing agent. Sorption of Pd(II) by the biocers from a metal complex solution was studied by inductively coupled plasma mass spectroscopy analyses. After embedding into sol-gel ceramics, the cells retained their Pd(II)-binding capability. Pd(0) nanoclusters were produced by the addition of hydrogen as reducing agent after the sorption of Pd(II). The interactions of Pd(0) with the biocers and the formed Pd(0) nanoparticles were investigated by extended X-ray absorption fine structure spectroscopy. The particles had a size of 0.6-0.8 nm. Bacterial cells that were immobilized by embedding into sol-gel ceramics were used as a template to produce Pd nanoclusters of a size smaller than 1 nm. These particles possess interesting physical and chemical properties. The use of embedded bacterial cells as template enabled the fabrication of immobilized Pd(0) nanoparticles. These particles are highly interesting for technical applications, such as the development of novel catalysts.


Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes.
Variable genomic sequences have been reported for RNA cloned from hepatitis C virus (HCV)-infected humans and chimpanzees. We found that four distinct genotypes of HCV could be differentially identified by PCR using type-specific primers. Full-length sequences have so far been reported for three of the four HCV genotypes, and we report herewith the sequence of the fourth type obtained from a Japanese blood donor. The entire nucleotide sequence of the HCV isolate (HC-J8) comprised 9481 bases plus a 3'-terminal poly(U) stretch of variable length. Like all previous isolates, the RNA contained a single, long open reading frame for a polyprotein of 3033 amino acids. HC-J8 differed from previously reported HCV isolates by 23.1-33.1% in nucleotide sequence and 15.9-28.8% in amino acid sequence. Based on genomic sequence homologies, a proposed phylogenetic tree of HCV, with a fourth branch represented by HC-J8, allowed a classification of all HCV isolates whose complete or partial sequences are now known. This classification suggests that all or most HCV genome sequences will fall into one of the proposed four types. The classification may be helpful in designing vaccine studies and for serological investigations of possible group- and type-specific antibodies.


Combination therapy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma: comparison with TACE or RFA monotherapy.
To compare the safety and efficacy of combined transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) with those of TACE or RFA monotherapy. This study included 34 combined TACE and RFA (TACE-RFA), 87 TACE, and 136 ultrasound-guided RFA, which were performed to treat HCC (≤ 3 cm, 3 or fewer) between March and August 2009. The safety (Child-Pugh score indicating hepatic functional reserve, patient discomfort requiring medication, duration of hospitalization, and complications) and efficacy (1-month, 6-month, and 1-year tumor responses) profiles of each treatment were evaluated and compared. TACE-RFA group showed longer hospital stay and more frequent patient discomfort requiring medication than TACE or RFA group (P < 0.001). The frequency of overall complications after TACE-RFA was higher than TACE (P = 0.006) or RFA (P = 0.009). There were no statistical differences in major complication rates between the three groups (P = 0.094). Child-Pugh score at 1-month follow-up showed no significant difference between the three groups (P = 0.162). 1-month, 6-month, and 1-year tumor responses of TACE-RFA were similar to those of RFA and better than those of TACE. TACE-RFA appears to result in more frequent patient discomfort requiring medication, longer hospital stay, and more frequent complications than TACE or RFA monotherapy. Tumor response of TACE-RFA seems to be similar to that of RFA and better than TACE monotherapy. Thus, TACE-RFA for treating small HCC may be required for the selected patients, especially patients with small HCC ineligible for RFA monotherapy.


Stereotactic Radiosurgery for Partially Resected Cerebral Arteriovenous Malformations.
Incomplete microsurgical resection of cerebral arteriovenous malformations (AVM) occurs uncommonly. However, such patients harboring postoperative residual nidi remain exposed to the risk of AVM hemorrhage and are therefore reasonable candidates for further intervention. The goals of this retrospective case-control study are to analyze the radiosurgery outcomes for partially resected AVMs and determine the effect of prior resection on AVM radiosurgery outcomes. We evaluated a prospective database of AVM patients treated with radiosurgery from 1989-2013. Previously resected AVMs with radiologic follow-up ≥2 years or nidus obliteration were selected for analysis and matched, in a 1:1 fashion and blinded to outcome, to previously unresected AVMs. Statistical analyses were performed to assess relationship between prior resection and AVM radiosurgery outcomes. The matching process yielded 88 patients in each of the previously resected and unresected AVM cohorts. In the resected AVM cohort, the actuarial AVM obliteration rates at 3 and 5 years were 47% and 75%, respectively; the rates of radiologic and symptomatic radiation-induced changes (RICs) were 10% and 3%, respectively; and the annual postradiosurgery hemorrhage risk was 1.1%. The lack of prior AVM resection (P < 0.001) and superficial AVM location (P = 0.009) were independent predictors of radiologic RIC. The actuarial rates of obliteration (P = 0.849) and postradiosurgery hemorrhage (P = 0.548) were not significantly different between the resected and unresected AVM cohorts. Radiosurgery affords a reasonable risk-to-benefit profile for incompletely resected AVMs. For those with a small-volume residual nidus after resection, radiosurgery should be considered an effective alternative to repeat resection.


High chlorpyrifos resistance in Culex pipiens mosquitoes: strong synergy between resistance genes.
We investigated the genetic determinism of high chlorpyrifos resistance (HCR), a phenotype first described in 1999 in Culex pipiens mosquitoes surviving chlorpyrifos doses ⩾1 mg l(-1) and more recently found in field samples from Tunisia, Israel or Indian Ocean islands. Through chlorpyrifos selection, we selected several HCR strains that displayed over 10 000-fold resistance. All strains were homozygous for resistant alleles at two main loci: the ace-1 gene, with the resistant ace-1(R) allele expressing the insensitive G119S acetylcholinesterase, and a resistant allele of an unknown gene (named T) linked to the sex and ace-2 genes. We constructed a strain carrying only the T-resistant allele and studied its resistance characteristics. By crossing this strain with strains harboring different alleles at the ace-1 locus, we showed that the resistant ace-1(R) and the T alleles act in strong synergy, as they elicited a resistance 100 times higher than expected from a simple multiplicative effect. This effect was specific to chlorpyrifos and parathion and was not affected by synergists. We also examined how HCR was expressed in strains carrying other ace-1-resistant alleles, such as ace-1(V) or the duplicated ace-1(D) allele, currently spreading worldwide. We identified two major parameters that influenced the level of resistance: the number and the nature of the ace-1-resistant alleles and the number of T alleles. Our data fit a model that predicts that the T allele acts by decreasing chlorpyrifos concentration in the compartment targeted in insects.


Ten-year outcomes following traumatic brain injury: a population-based cohort.
To quantify the 10 year health service use (HSU) and mortality outcomes for people with a traumatic brain injury (TBI). A population-based matched cohort study using linked administrative data from Manitoba, Canada (Manitoba Injury Outcome Study). An inception cohort (1988-1991) of hospitalized cases with TBI aged 18-64 years (n = 1290) was identified and matched to a non-injured comparison group (n = 1290). Survival analysis, Negative binomial and Poisson regression were used to quantify associations between injury and HSU/mortality outcomes for 10 years following the TBI event. The majority of deaths (47.2%) occurred in the first 60 days following injury. Excluding the first 60 days, the adjusted 10 year mortality remained elevated (mortality rate ratio = 1.48, 95% CI = 1.02-2.15). After adjusting for demographic characteristics and pre-existing health status, the TBI cohort had more post-injury hospitalizations (rate ratio (RR) = 1.54, 95% CI = 1.39-1.71), greater cumulative lengths of stay (RR = 5.14, 95% CI = 3.29-8.02) and a greater post-injury physician claims rate (RR = 1.44, 95% CI = 1.35-1.53) than the non-injured cohort. People who sustain a TBI and survive the initial acute phase of care experience substantially increased long-term morbidity compared to the general population, regardless of the level of injury severity.


Hematoporphyrin derivatives: an oligomeric composition study.
The oligomeric composition of HpD, Photofrin II and other hematoporphyrin derivatives useful for the diagnosis and therapy of tumors has been studied. Gel chromatographic procedures were used that excluded porphyrin aggregation. Photofrin and hematoporphyrin derivatives were shown to contain different quantities of monomer, dimer and other oligomeric porphyrins.


Comparative Cadaveric Analysis for Surgical Corridor and Maneuverability: Far-Lateral Approach and Its Transcondylar Extension.
The necessity of partial occipital condyle (OC) resection for lesions in the ventral craniocervical junction is debatable. This study's purpose was to compare the surgical exposure of the classic far-lateral approach (FLA) and transcondylar FLA. The classic FLA and transcondylar FLA were performed in 12 human cadaveric heads (24 sides). The surgical corridor of 3 levels (a: vagus nerve, b: from the midpoint of proximal ends of the vagus and hypoglossal nerves to the midpoint of the distal ends of each nerve, c: hypoglossal nerve) and the maneuverability (the area between neurovascular structures that limits instrumental maneuvers) were measured after each approach. The surgical corridors were significantly greater in transcondylar FLA than in classic FLA (a: 14.4 ± 3.4 mm vs. 17.1 ± 4.4 mm, P < 0.001; b: 8.6 ± 2.9 mm vs. 11.2 ± 4.1 mm, P < 0.001; c: 5.5 ± 2.2 mm vs. 7.7 ± 2.8 mm, P < 0.001). Transcondylar FLA also provided greater maneuverability than classic FLA (73.2 ± 23.9 mm2 vs. 94.9 ± 32.2 mm2, P < 0.001). The increased length of the surgical corridor was greatest in a (a: 2.7 ± 2.3 mm, b: 2.6 ± 2.0 mm, c: 2.2 ± 1.4 mm). However, the rate of increase was greatest in c (a: 18.9 ± 16.4%, b: 30.4 ± 26.2%, c: 44.8 ± 27.2%). The area of increased maneuverability was 21.7 ± 20.3 mm2 (31.1 ± 27.8%) after partial OC resection. Transcondylar FLA can significantly increase surgical exposure compared with the classic FLA, although also increasing surgical complications. Therefore, the surgical approach should be individualized according to each lesion and patient. The results of our study may assist in surgical decision-making regarding the need for OC resection.


Prevention of experimental liver metastases by D-galactose.
The metastasis of malignant tumors from a primary site to near and distant secondary sites is probably the most important event in the pathogenesis of cancer and it accounts for most cancer deaths. Whereas advances in the treatment of primary cancer have led to increased patient survival, metastatic cancers are still the most difficult group of diseases to treat successfully. As organ-characteristic lectins play an important role in the organ manifestation of metastatic islets, it might be possible (e.g. during surgical operations on malignant tumors) to block those organ-characteristic lectins with the appropriate receptor-bearing glycoconjugates in order to inhibit the metastatic spread. Recent experiments have demonstrated that neuraminidase treatment of tumor cells (mouse sarcoma-1) alters in vivo (Balb/c-mice) the organotropic distribution of metastases; instead of being found exclusively in the lung, they are found both in lung and liver. However, pre-injection and regular application of D-galactose--the same holds for arabinogalactan--prevents the setting of metastases in the liver but does not influence the metastatic process to the lung, whereas mannan--as a galactose-free control substance--does not alter the initial pattern of metastasis to lung and liver.


[Postoperative necrotizing fasciitis: a rare and fatal complication].
Postoperative parietal complications can be exceptionally severe and serious threatening vital prognosis. Necrotizing fasciitis is a rare infection of the skin and deep subcutaneous tissues, spreading along fascia and adipose tissue. It is mainly caused by group A streptococcus (streptococcus pyogenes) but also by other bacteria such as Vibrio vulnificus, Clostridium perfringens or Bacteroides fragilis. Necrotizing fasciitis is a real surgical and medical emergency. We report, in this study, a very rare case of abdominal parietal gangrene occurring in a 75-year-old woman on the fifth day after surgery for an ovarian cyst. Evolution was marked by occurrence of a refractory septic shock with a rapidly fatal course on the third day of management.


Should time-lag and time-accumulation effects of climate be considered in attribution of vegetation dynamics? Case study of China's temperate grassland region.
Although the time-lag and time-accumulation effects (TLTAEs) of climatic factors on vegetation growth have been investigated extensively, the uncertainties caused by disregarding TLTAEs in the attribution analysis of long-term changes in vegetation remain unclear. This hinders our understanding of the associated changes in ecosystems and the effects of climate change. In this study, using multiple methods, we evaluate the biases of attribution analyses of vegetation dynamics caused by the non-consideration of TLTAEs in the temperate grassland region (TGR) of China from 2000 to 2019. Based on the datasets of the normalized difference vegetation index (NDVI), temperature (TMP), precipitation (PRE), and solar radiation (SR), the temporal reaction patterns of vegetation are analyzed, and the relationships among these variables under two scenarios (considering and disregarding TLTAEs) are compared. The results indicate that most areas of the TGR show a greening trend. A time-lag or time-accumulation effect of the three climatic variables is observed in most areas with significant spatial differences. The lagged times of the vegetation response to PRE are particularly prominent, with an average of 2.12 months in the TGR. When the TLTAE is considered, the areas where changes in the NDVI are affected by climatic factors expanded significantly, whereas the explanatory power of climate change on NDVI change increased by an average of 9.3% in the TGR; these improvements are more prominent in relatively arid areas. This study highlights the importance of including TLTAEs in the attribution of vegetation dynamics and the assessment of climatic effects on ecosystems.


Molecular Sexing and Species Detection of Antlered European Hunting Game for Forensic Purposes.
Molecular sexing techniques are widely applied in conservation biology, although the range of forensically validated methods is fairly limited. The primary aim of this work was to develop forensically validated assays, using two PCR panels for sex and species assignment for the abundant antlered European game species: red deer (Cervus elaphus), roe deer (Capreolus capreolus) and fallow deer (Dama dama). Segments of the SRY and Amelogenin X/Y genes for sex determination, additionally species-specific cytochrome b regions for species detection were targeted and separately amplified in two multiplex reactions. These assays can reliably analyze trace amounts of DNA. The results of both can easily be visualized and interpreted practically, either on agarose gel or by capillary electrophoresis. These simple, fast molecular assays are able to affect the early-stage resolution of disputed or unsolved poaching cases, without the need of individualization or sequencing of forensic samples.


Role of T cells in abscess formation.
A series of recent studies have shed new light on the strategy used by certain bacterial pathogens to induce a classic infectious process: abscess formation. This work describes how zwitterionic polysaccharides on the surface of these organisms interact with the host immune system in general, and with T cells in particular, to coordinate this pathobiologic response.


A survey of amniocentesis in 925 patients at high risk of fetal genetic disorder.
Over a nine-year period, 925 pregnancies at an Israeli medical centre were selected for investigation by amniocentesis for genetic reasons. In only 30 pregnancies did failure of laboratory methods or difficulty with amniocentesis lead to a lack of results with which to assess the normality of the fetus. The information obtained by examination of the amniotic fluid in the other 895 pregnancies is presented and discussed.


Probiotics as functional foods: How probiotics can alleviate the symptoms of neurological disabilities.
Neurological disorders are diseases of the central nervous system with progressive loss of nervous tissue. One of the most difficult problems associated with neurological disorders is that there is no clear treatment for these diseases. In this review, the physiopathology of some neurodegenerative diseases, etiological causes, drugs used and their side effects, and finally the role of probiotics in controlling the symptoms of these neurodegenerative diseases are presented. Recently, researchers have focused more on the microbiome and the gut-brain axis, which may play a critical role in maintaining brain health. Probiotics are among the most important bacteria that have positive effects on the balance of homeostasis via influencing the microbiome. Other important functions of probiotics in alleviating symptoms of neurological disorders include anti-inflammatory properties, short-chain fatty acid production, and the production of various neurotransmitters. The effects of probiotics on the control of abnormalities seen in neurological disorders led to probiotics being referred to as "psychobiotic. Given the important role of the gut-brain axis and the imbalance of the gut microbiome in the etiology and symptoms of neurological disorders, probiotics could be considered safe agents that positively affect the balance of the microbiome as complementary treatment options for neurological disorders.


Associations of Cost Sharing With Rheumatoid Arthritis Disease Burden.
To evaluate the regional variation of cost sharing and associations with rheumatoid arthritis (RA) disease burden in the US. Patients with RA from rheumatology practices in Northeast, South, and West US regions were evaluated. Sociodemographics, RA disease status, and comorbidities were collected, and Rheumatic Disease Comorbidity Index (RDCI) score was calculated. Primary insurance types and copay for office visits (OVs) and medications were documented. Univariable pairwise differences between regions were conducted, and multivariable regression models were estimated to evaluate associations of RDCI with insurance, geographical region, and race. In a cohort of 402 predominantly female, White patients with RA, most received government versus private sponsored primary insurance (40% vs. 27.9%). Disease activity and RDCI were highest for patients in the South region, where copays for OVs were more frequently more than $25. Copays for OVs and medications were less than $10 in 45% and 31.8% of observations, respectively, and more prevalent in the Northeast and West patient subsets than in the South subset. Overall, RDCI score was significantly higher for OV copays less than $10 as well as for medication copays less than $25, both independent of region or race. Additionally, RDCI was significantly lower for privately insured than Medicare individuals (RDCI -0.78, 95% CI [-0.41 to -1.15], P < 0.001) and Medicaid (RDCI -0.83, 95% CI [-0.13 to -1.54], P = 0.020), independent of region and race. Cost sharing may not facilitate optimum care for patients with RA, especially in the Southern regions. More support may be required of government insurance plans to accommodate patients with RA with a high disease burden.


The Dectin-2 family of C-type lectin-like receptors: an update.
Myeloid and non-myeloid cells express members of the C-type lectin-like receptor (CTLR) family, which mediate crucial cellular functions during immunity and homeostasis. Of relevance here is the dendritic cell-associated C-type lectin-2 (Dectin-2) family of CTLRs, which includes blood dendritic cell antigen 2 (BDCA-2), dendritic cell immunoactivating receptor (DCAR), dendritic cell immunoreceptor (DCIR), Dectin-2, C-type lectin superfamily 8 (CLECSF8) and macrophage-inducible C-type lectin (Mincle). These CTLRs possess a single extracellular conserved C-type lectin-like domain and are capable of mediating intracellular signalling either directly, through integral signalling domains, or indirectly, by associating with signalling adaptor molecules. These receptors recognize a diverse range of endogenous and exogenous ligands, and can function as pattern recognition receptors for several classes of pathogens including fungi, bacteria and parasites, driving both innate and adaptive immunity. In this review, we summarize our knowledge of each of these receptors, highlighting the exciting discoveries that have been made in recent years.


(E)-3-(2,4-Dimeth-oxy-phen-yl)-1-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one.
In the title chalcone derivative, C(20)H(22)O(6), the dihedral angle between the mean planes of the benzene rings is 15.77 (6)°. The H atoms of the central C=C double bond are in a trans configuration. There are a number of C-H⋯O interactions and a C-H⋯π interaction present in the crystal structure.