When less is more: novel mechanisms of iron conservation.
Disorders of iron homeostasis are very common, yet the molecular mechanisms of iron regulation remain understudied. Over 20 years have passed since the first characterization of iron-regulatory proteins (IRP) as mediators of cellular iron-deficiency response in mammals through iron acquisition. However, little is known about other mechanisms necessary for adaptation to low-iron states. In this review, we present recent evidence that establishes the existence of a new iron-regulatory pathway aimed at iron conservation and optimization of iron use through suppression of nonessential iron-consuming processes. Moreover, we discuss the possible links between iron homeostasis and energy metabolism uncovered by studies of iron-deficiency response.


Switch from IL-5 to IL-5-Receptor α Antibody Treatment in Severe Eosinophilic Asthma.
Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy. In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under anti-IL-5 therapy) and timepoint 2 (T2, under anti-IL-5Rα therapy). Of 665 patients treated with anti-IL-5 antibodies, 70 were switched to anti-IL-5Rα and 60 were included in the analysis. Median treatment duration was 8 months [IQR 5; 15] for anti-IL-5 and 5 months [IQR 4; 6] for anti-IL-5Rα therapy. FEV1 was 61% of predicted at BL [IQR 41; 74], 61% [IQR 43; 79] at T1 and 68% [IQR 49; 87] at T2 (pT1-T2=0.011). ACT score was 10 [IQR 8; 13], 16 [IQR 10; 19] and 19 [IQR 14; 22], respectively (both p<0.001). The number of patients requiring OCS was reduced from 41 (BL) to 32 (T1) and 19 (T2) (both p<0.001). Ten patients discontinued anti-IL-5Rα therapy due to insufficient efficacy (n=7) and adverse events (n=3). Switching from anti-IL-5 to anti-IL-5Rα therapy in patients with inadequate response was associated with significantly improved FEV1, asthma control and OCS reduction.


Atopic Dermatitis Severity, Patient Perception of the Disease, and Personality Characteristics: How Are They Related to Quality of Life?
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that greatly affects patients' quality of life, psychological condition, and social relationships. To analyze different aspects of AD patients' quality of life, we used the SCORing Atopic Dermatitis (SCORAD) index (for AD severity), the Dermatology Life Quality Index (DLQI), the World Health Organization Quality of Life Brief Version (WHOQOL-BREF), the Brief Illness Perception Questionnaire (Brief IPQ), and the Crown-Crisp Experiential Index (CCEI) to analyze personality traits. The study included 84 AD patients, 42 with clinical manifestations and 42 in remission. SCORAD values correlated positively and linearly with DLQI (r = 0.551; p < 0.001) and with disease impact on life, disease control, and disease symptoms (r = 0.350-0.398; p ≤ 0.023). DLQI was also related to certain personality characteristics (free-floating anxiety disorder, obsession, somatization, and depression (p ≤ 0.032)). Symptomatic AD patients had a significantly more impaired DLQI than asymptomatic patients (p < 0.001) and the two groups differed in some IPQ dimensions, but they did not differ significantly concerning the WHOQOL-BREF dimensions and personality traits (CCEI). Since AD patient quality of life was dependent not only on disease severity but was also influenced by patient personality characteristics (anxiety disorder, obsession, somatization, depression), many factors need to be taken into account to create effective, patient-specific therapy regimens.


Multistimulus-Responsive Supramolecular Hydrogels Derived by in situ Coating of Ag Nanoparticles on 5'-CMP-Capped β-FeOOH Binary Nanohybrids with Multifunctional Features and Applications.
The present manuscript reports the synthesis of multistimulus-responsive smart supramolecular hydrogels derived by in situ coating of silver nanoparticles (Ag NPs) on colloidal cytidine-5'-monophosphate-capped β-FeOOH nanohybrids (β-FeOOH@5'-CMP) under physiological conditions forming a polycrystalline building block (Ag-coated β-FeOOH@5'-CMP). The presence of Ag in the binary nanohybrids induces the puckering of ribose sugar, bringing a change in its conformation from C2'-endo to C3'-endo, which enhanced the supramolecular interactions among different moieties of other building blocks to construct a porous network of hydrogels in the self-assembly via the formation of a micellar structure. Such a supramolecular network in hydrogel is also evidenced by the reversible sol⇌gel transformation under multistimulus-responsiveness in a narrow range of pH, temperature, and sonication, as well as by the manifestation of rapid self-healing and injectability features. As-synthesized hydrogels exhibiting shear-thinning behavior under higher strain and converting back into the sol under low strain, suggests their potential for localized drug delivery. The presence of Ag NPs in the hydrogel enhanced its viscoelastic properties, % swelling (580) and loading capabilities (590 mg g-1) for methylene blue (MB), and its controlled release over days (∼2-30) as a function of pH. It displayed excellent surface-enhanced Raman spectroscopy activity allowing to detect MB-like drug molecules at ≤10-12 M. Thus, the as-synthesized hydrogels represent a unique superparamagnetic nanosystem consisting of all greener components (5'-CMP/β-FeOOH/Ag) with superior viscoelastic, sensing, and antimicrobial properties, displaying multistimulus-responsiveness (pH/temperature/sonication), thereby suggesting their vast potential for biomedical and environmental applications.


The N-terminal domain of SV40 large T antigen represses the HER2/neu-mediated transformation and metastatic potential in breast cancers.
HER2/neu is known to be overexpressed in approximately 40% of human breast and ovarian cancers and it is associated with increased metastasis and poor prognosis. We have shown previously that the N-terminal domain of simian virus 40 large T antigen (LT425) can act as a transforming suppressor of the HER2/neu oncogene in human ovarian cancer. In the present study, we demonstrate that LT425 can also repress the transforming properties of HER2/neu-overexpressing human breast cancer cells. In addition, the results of a chemotaxis assay and an in vitro chemoinvasion assay further suggest that LT425 can also suppress the metastatic potential of the HER2/neu-transformed breast cancer cells. Taken together, these data clearly suggest that the inhibition of the expression of p185 HER2/neu tyrosine kinase by LT425 is capable of suppressing the HER2/neu-mediated transformation and metastatic potential in breast cancers.


Fatal metabolic stroke in a child with propionic acidemia 11 years post liver transplant.
Propionic acidemia is a rare autosomal recessive inborn error of metabolism caused by a deficiency of propionyl CoA carboxylase which often manifests with frequent metabolic decompensations and risk of neurological injury. Outcomes with medical therapy remain suboptimal. Liver transplantation has been shown to be a therapeutic option for patients and results in a milder phenotype of the disease and partial correction of the enzyme defect. Liver transplantation has been increasingly reported over the last decade and experience in managing these patients is improving. Long-term outcomes are generally good; however, the risk of complications still exists despite transplantation. We report a child who presented with a fatal metabolic stroke 11 years post liver transplant without any biochemical evidence of decompensation. We highlight the need to closely monitor these patients lifelong despite liver transplantation and maintain multidisciplinary working between hepatology and metabolic clinicians.


Rapid onset of emphysema associated with diffuse parenchymal disease.
In experimental models pulmonary emphysema may be produced in hours to days; however, in human subjects emphysema commonly develops over a period of many years. In this report we document a case of severe emphysema which developed in less than six months in association with an unexplained illness characterized by dyspnea, hypoxemia and bilateral lung parenchymal disease. There was no hereditary predisposition. The diffuse alveolar injury syndrome must be considered as a potential cause of alveolar disruption.


Association of the + 45T>G adiponectin gene polymorphism with insulin resistance in non-diabetic Saudi women.
The human adiponectin gene variations are associated with obesity, insulin resistance, and diabetes. However, these associations have not been fully examined in a non-diabetic population in Saudi Arabia. We aimed to investigate the association of 45T>G single nucleotide polymorphism (SNP) in the adiponectin gene with total adiponectin levels, insulin resistance (IR), fasting blood glucose (FBG) and other markers of obesity in non-diabetic Saudi females. One hundred non diabetic Saudi females were enrolled in this study. They were further divided according to their body mass index (BMI) into two groups. Group I, 46 non diabetic subjects with normal body weight and group II, 54 overweight and obese females. Adiponectin 45T/G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum adiponectin was measured by ELISA. Obese women exhibited a higher distribution of TG/GG genotype compared with non-obese women. SNP +45T>G genotypes were associated with higher FBG, insulin levels and HOMA-IR with lower total adiponectin levels in obese Saudi women. Otherwise the all estimated variables revealed non-significant differences among the non-obese genotypes. The observed differences in insulin resistance markers were very significant among women with a higher body weight but not among normal body weight women, thus suggesting that SNP +45T>G effects on insulin sensitivity may depend upon body weight and body fat status. SNP +45T>G of adiponectin gene has a significant role in the development of insulin resistance in Saudi women possibly through an interaction with increase body weight and hypoadiponectinemia.


Methodologic issues in the use of workers' compensation databases for the study of work injuries with days away from work. I. Sensitivity of case ascertainment.
Case ascertainment costs vary substantially between primary and secondary data sources. This review summarizes information on the sensitivity of state administrative databases in workers' compensation systems for the ascertainment of days-away-from-work (DAFW) work injuries for use in modeling studies. Review of the literature supplemented by data from governmental or organizational reports or produced for this report. Employers currently appear to provide workers' compensation insurance coverage for 98.9% of wage and salary workers. Wage and salary jobs account for approximately 90% of jobs in the United States. In industries such as manufacturing, the fraction of covered jobs is probably closer to 98%. In Minnesota, the number of DAFW cases ascertained by the Bureau of Labor Statistics' annual survey of occupational injuries and illnesses is approximately 92-97% concordant with the number of wage compensation claims for injuries producing DAFW over the period 1992-2000, once adjustments are made to permit direct comparisons of the numbers. The workers' compensation databases provide information for more than 95% of the total DAFW resulting from work injuries. Covariate estimates are unaffected by this less than 5% loss because effects appear dependent on time from injury. Statewide workers' compensation administrative databases can have substantial utility for epidemiologic study of work injuries with DAFW because of their size, using high sensitivity for case ascertainment as the evaluative criterion.


In vitro responses of human prostate tumour cell lines to a range of antitumour agents.
Four human prostate tumour continuous cell lines were employed for in vitro drug sensitivity testing of nine cytotoxic drugs, X-irradiation and two hormonal preparations. Responses were assessed by measuring cell survival as judged by colony formation in agarose. A marked heterogeneity of responses was noted to many of the agents studied, including X-irradiation. However, in terms of ID70 values for 24-h drug exposures, comparable responses in all the cell lines tested, with values falling within a 1.4- to 2.9-fold range, were noted with actinomycin D, adriamycin, m-AMSA, dibromodulcitol, 5-fluorouracil, hydroxyurea and ICRF-159. In contrast, mixed responses to cis-platinum and methotrexate were particularly marked, with ID70 values differing by factors of 3.8 and 7.5 respectively. In addition, when higher drug concentrations of m-AMSA, cis-platinum, dibromodulcitol and ICRF-159 were employed, significant deviations in the four survival curves became apparent. Continuous exposure to diethylstilboestrol and medroxyprogesterone acetate caused negligible cell kill. Due to these variable responses it was not possible to predict that any agent tested might have specific value in the treatment of prostate cancer. However, preliminary in vitro screening with such a panel of cell lines may complement in vivo studies with models of prostatic cancer and prove useful in investigations of mechanisms of drug resistance.


Vesicoureteral Reflux Detected with (99m)Tc-DTPA Renal Scintigraphy during Evaluation of Renal Function.
Radionuclide techniques, as direct radionuclide cystography and (99m)Tc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic (99m)Tc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and (99m)Tc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control (99m)Tc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. (99m)Tc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR.


Burns and the toxic effects of a derivative of hydrazine.
Comments are presented on a case history of extensive burns associated with 1,1-dimethylhydrazine (UDMH) toxicity in a 31-year-old man. Neurological symptoms dominated early developments. Specific treatment with pyridoxine, while begun late, effected a quite rapid resolution and the subsequent progression of treatment was straightforward. In reviewing previous reported findings, the authors have clarified the distinctive characteristics of UDMH toxicity, the methods for its detection and modes of treatment. They draw conclusions, based on problems encountered, linked to the exceptional character of acute UDMH toxicity especially in its association with extensive burns.


Increasing incidence of hypotension in the emergency department; a 12 year population-based cohort study.
The epidemiology of hypotension as presenting symptom among patients in the Emergency Department (ED) is not clarified. The aim of this study was to describe the incidence, etiology, and overall mortality of hypotensive patients in the ED. Population-based cohort study at an University Hospital ED in Denmark from January 1, 2000, to December 31, 2011. Patients aged ≥18 years living in the hospital catchment area with a first time presentation to the ED with hypotension (systolic blood pressure (SBP) ≤100 mm Hg) were included. Outcomes were annual incidence rates (IRs) per 100,000 person years at risk (pyar) and etiological characteristics by means of the International Classification of Diseases, Tenth Revision (ICD-10), as well as 7-day, 30-day, and 90-day all-cause mortality. We identified 3,268 of 438,198 (1 %) cases with a mean overall IR of 125/100,000 pyar (95% CI: 121-130). The IR increased 28% during the period (from 113 to 152 cases per 100,000 pyar). Patients ≥65 years had the highest IR compared to age <65 years (rate ratio for men 6.3 (95% CI: 5.6-7.1) and for women 4.2 (95% CI: 3.6-4.9)). The etiology was highly diversified with trauma (17%) and cardiovascular diseases (15%) as the most common. The overall 7-day, 30-day and 90-day mortality rates were 15% (95% CI: 14-16), 22 % (95% CI: 21-24) and 28% (95% CI: 27-30) respectively. During 2000-2011 the overall incidence of ED hypotension increased and remained highest among the elderly with a diversified etiology and a 90-day all-cause mortality of 28%.


Brain-responsive corticothalamic stimulation in the centromedian nucleus for the treatment of regional neocortical epilepsy.
The aim of the study was to determine if corticothalamic responsive stimulation targeting the centromedian nucleus of the thalamus (CMT) is a potential treatment for neocortical epilepsies with regional onsets. We assessed efficacy and safety of CMT and neocortical responsive stimulation, detection, and stimulation programming, methods for implantation, and location and patterns of electrographic seizure onset and spread in 7 patients with medically intractable focal seizures with a regional neocortical onset. The median follow-up duration was 17 months (average: 17 months, range: 8-28 months). The median % reduction in disabling seizures (excludes auras) in the 7 patients was 88% (mean: 80%, range: 55-100%). The median % reduction in all seizure types (disabling + auras) was 73% (mean: 67%, range: 15-94%). There were no adverse events related to implantation of the responsive neurostimulator and leads or related to the delivery of responsive stimulation. Stimulation-related contralateral paresthesias were addressed by adjusting stimulation parameters in the clinic during stimulation testing. Electrographic seizures were detected in the CMT and neocortex in all seven patients. Four patients had simultaneous or near simultaneous seizure onsets in the neocortex and CMT and three had onsets in the neocortex with spread to the CMT. In this small series of patients with medically intractable focal seizures and regional neocortical onset, responsive neurostimulation to the neocortex and CMT improved seizure control and was well tolerated. Responsive corticothalamic neurostimulation of the CMT and neocortex is a potential treatment for patients with regional neocortical epilepsies.


Efficacy and safety of caspofungin therapy in elderly patients with proven or suspected invasive fungal infections.
Invasive fungal infections (IFIs) are serious complications in elderly adults. Caspofungin may provide a useful therapeutic option for elderly patients with or at high risk for IFIs. We retrospectively compared efficacy and safety outcomes in elderly (> or = 65 years of age) and non-elderly patients in three clinical trials of caspofungin: a double-blind, randomized trial versus amphotericin B for documented invasive candidiasis (IC); an open-label, non-comparative study of definite or probable invasive aspergillosis (IA); and a double-blind, randomized trial versus liposomal amphotericin B as empirical therapy (ET) in febrile neutropenic patients. A total of 159 elderly patients with a median age of 71 years (range, 65-84) received caspofungin in these studies. The median duration of caspofungin therapy was 12 days for IC and ET, and 28 days for IA. Point estimates for the favorable response rates to caspofungin were numerically higher in elderly versus non-elderly patients with IC (83% vs. 68%) or IA (64% vs. 44%) and were similar in patients receiving ET (36% vs. 34%). Adverse events related to caspofungin occurred in generally similar proportions of elderly versus non-elderly patients with IC (clinical, 33% vs. 27%; laboratory, 17% vs. 29%), with IA (clinical, 7% vs. 13%; laboratory, 13% vs. 14%), or receiving ET (clinical, 47% vs. 47%; laboratory, 24% vs. 22%). Nephrotoxicity and infusion-related toxicity developed in comparable proportions of elderly and non-elderly caspofungin recipients in all three studies. In this post-hoc analysis, caspofungin appeared to be as efficacious and well tolerated in elderly patients as in non-elderly patients.


Anthropo-entomophagy: quantitatively chemical assessment of some edible arthropods, bought from an e-shop.
Eating edible arthropods is not associated with rural life anymore. The emerging industry of edible arthropods is trying to change that. The best shopping spot to buy well-known edible arthropods is online today. Consumers can find numerous outlet options to buy edible arthropods from the Internet. With worldwide growing threats to food security, today, gastronomy, especially in western countries, is trying to develop a more positive view to arthropods' nutritional value. In this paper, non-crustacean arthropods (armor tail scorpion, black scorpion, black ant, flying termites, giant waterbug, June beetle, diving beetles, rhino beetles, silkworm pupae, sago worm, bamboo worm), bought from online edible insect market, were evaluated in terms of availability of some hazardous chemical. Energy Dispersive X-Ray Fluorescence (EDXRF) spectroscopy was used for determining the concentrations of heavy metals/metalloids in the total body of the arthropods. Concentration of the elements (Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br, Rb, Sr, Pb) were measured quantitatively in all samples. The results showed that the chemicals like Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br, Rb, Sr, and Pb have highly been measured in the black scorpion, black ant, flying termites, giant waterbug, June beetle, sago worm, and bamboo worm.


Stimulus size mediates Gestalt processes in object perception - evidence from simultanagnosia.
Simultanagnosia caused by posterior temporo-parietal brain damage is characterized through an inability to recognize a global Gestalt from an arrangement of single objects while perception of single objects appears widely intact. We asked whether recognition of single objects in simultanagnosia is still intact if objects are really large, i.e. if they exceed the size of a usual computer screen. Single objects were presented in three different sizes: 'regular', 'medium', and 'large'. Simultanagnosia patients demonstrated a decrease of recognition performance with increasing object size; recognition of 'large' objects was significantly impaired while perception of 'regular' sized objects was unaffected. The results argue against the traditional view of preserved recognition of single objects in simultanagnosia. They provide evidence for a more general perceptual impairment that emerges irrespective of presenting single or multiple objects, but whenever the visual system has to assemble information over larger spatial distances or other demanding viewing conditions. It appears that perception of large single objects requires intact abilities of dorsal Gestalt processing, in addition to regular functions of ventral object recognition.


Intact colonic motor response to sudden awakening from sleep in patients with chronic idiopathic (slow-transit) constipation.
There are few data about the relationships between colonic motor behavior and higher brain functions, such as sleep. Previous studies were done in healthy subjects, and it is unknown whether patients with functional motor disorders of the colon behave differently. This study was designed to characterize colonic motor activity in patients with constipation, both during sleep and after sudden awakening, and to compare it with that of healthy subjects. Our working hypothesis was that patients with constipation would have an impaired response to sudden awakening. Twelve chronically constipated women, 22 to 49 years old, were recruited for the study, and their data were compared with those obtained from 12 healthy female volunteers, 21 to 38 years old. Manometric studies were performed in the descending and sigmoid colon for 30 minutes during sleep (immediately before awakening) and 30 minutes after being awakened suddenly. A motility index was calculated before and after the stimulus. In both groups motility in the descending and the sigmoid colon was almost absent during sleep and significantly increased after sudden awakening. No difference in postawakening values was found between patients with constipation and controls. In patients with chronic constipation, the brain-gut control of some fundamental mechanisms governing colonic motility is preserved. These data suggest that the alterations of colonic motility described in chronic constipation may be caused by an intrinsic dysfunction of the viscus.


The role of tocilizumab in the treatment of inflammatory diseases of the eye and orbit: A useful alternative.
With uveitis being one of the leading causes of blindness worldwide, biological therapies have arisen as an option for the treatment of refractory cases based on good results shown in clinical practice. The goal of this study is to provide a systematic review of current knowledge of the role and possible uses of tocilizumab in the field of ophthalmology. We performed a search for records reporting the use of tocilizumab for various diseases in MEDLINE (PubMed and OVID). We conducted an analysis of several individual studies and their reported individual patient data (82 eyes of 45 patients) published from 2011 to 2017. Tocilizumab may prove to be an effective choice for the treatment of a variety of ocular conditions such as refractory uveitis, inflammatory macular edema, vitreo-retinal tumors and thyroid orbitopathy, leading to control of the inflammation in these patients. Further studies need to be conducted to establish its safety and efficacy.


Improved glycaemia in high-fat-fed neprilysin-deficient mice is associated with reduced DPP-4 activity and increased active GLP-1 levels.
Neprilysin, a widely expressed peptidase, is upregulated in metabolically altered states such as obesity and type 2 diabetes. Like dipeptidyl peptidase-4 (DPP-4), neprilysin can degrade and inactivate the insulinotropic peptide glucagon-like peptide-1 (GLP-1). Thus, we investigated whether neprilysin deficiency enhances active GLP-1 levels and improves glycaemia in a mouse model of high fat feeding. Nep +/+ and Nep -/- mice were fed a 60% fat diet for 16 weeks, after which active GLP-1 and DPP-4 activity levels were measured, as were glucose, insulin and C-peptide levels during an OGTT. Insulin sensitivity was assessed using an insulin tolerance test. High-fat-fed Nep -/- mice exhibited elevated active GLP-1 levels (5.8 ± 1.1 vs 3.5 ± 0.8 pmol/l, p < 0.05) in association with improved glucose tolerance, insulin sensitivity and beta cell function compared with high-fat-fed Nep +/+ mice. In addition, plasma DPP-4 activity was lower in high-fat-fed Nep -/- mice (7.4 ± 1.0 vs 10.7 ± 1.3 nmol ml-1 min-1, p < 0.05). No difference in insulin:C-peptide ratio was observed between Nep -/- and Nep +/+ mice, suggesting that improved glycaemia does not result from changes in insulin clearance. Under conditions of increased dietary fat, an improved glycaemic status in neprilysin-deficient mice is associated with elevated active GLP-1 levels, reduced plasma DPP-4 activity and improved beta cell function. Thus, neprilysin inhibition may be a novel treatment strategy for type 2 diabetes.


Bioconversion of Calophyllum inophyllum oilcake for intensification of rhamnolipid and polyhydroxyalkanoates co-production by Enterobacter aerogenes.
The biologically derived products are highly valued due to their biodegradability, low toxicity, and renewability. However, most production processes are exorbitant due to high raw material cost and the downstream processing required for product recovery and purification. Therefore, the present study utilized the low-cost lignocellulosic biomass, Calophyllum inophyllum oilcake for the simultaneous production of PHA and rhamnolipid by a facultative anaerobe Enterobacter aerogenes. Both the products are produced during the stationary phase and constitute β- hydroxyalkanoic acids, which makes it feasible for the co-production through a single fermentation process. From the batch fermentation studies, it was revealed that the under optimum condition rhamnolipid and PHA yield are 5.81 g/L and 4.2 g/L: 5%(v/v) of inoculum size, pH of 6.5, C:N ratio of 5:1 and urea are found to be the best nitrogen source for the fermentation process. Characterization studies for extracted PHA and RL was done using- FTIR, NMR and TGA analysis.


Astragaloside IV antagonizes the malignant progression of breast cancer induced by macrophage M2 polarization through the TGF-β-regulated Akt/Foxo1 pathway.
Astragaloside IV (AS‑IV) was used for breast cancer (BC) treatment in China from ancient times; however, the mechanism of the prevention effect of AS-IV on BC remains not entirely clear. qRT-PCR, western blot and flow cytometry were employed to validate the expression of gene and protein expressions. CCK-8 assay, scratch assay, and transwell assay were used to assess the BC cell proliferation, migration, and invasion. Co-culture of conditional medium from macrophages and BC were performed. AS-IV suppressed macrophage polarized to M2 phenotype and thereby inhibited M2 macrophage-induced BC progression. The inhibitory effect of AS-IV on M2 macrophage polarization was exerted via the deactivation of the Akt/Foxo1 signaling pathway in macrophages by suppressing TGF-β. The addition of TGF-β or the treatment with Akt activator SC79 reversed the regulatory effect of AS-IV on M2 macrophage polarization, which increased M2 macrophage polarization-induced BC cell proliferation, migration and invasion. This present study revealed a new mechanism of AS-IV inhibited M2 macrophage polarization-induced BC progression and may provide a potential target for the treatment of BC.


Molecular mechanisms for understanding the association between TMPRSS2 and beta coronaviruses SARS-CoV-2, SARS-CoV and MERS-CoV infection: scoping review.
The aim of this scoping review was to identify knowledge gaps and to describe the current state of the research on the association between TMPRSS2 and the essential beta coronaviruses (Beta-CoVs) infection and the molecular mechanisms for this association. We searched MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). We included 13 studies. Evidence shows an essential role of TMPRSS2 in Spike protein activation, entry, and spread into host cells. Co-expression of TMPRSS2 with cell surface receptors (ACE2 or DPP4) increased virus entry. This serine protease is involved in the formation of large syncytia between infected cells. TMPRSS2 cleaved the Spike protein of SARS-CoV, SARS-CoV-2, and MERS-CoV, and increased virus propagation. Accumulating evidence suggests that TMPRSS2 is an essential protease for virus replication. We highlighted its critical molecular role in membrane fusion and the impact in viral mRNA replication, then promoting/driving pathogenesis and resistance.


Long-term heart transplant recipients: heart rate-related effects on augmented transfer function coherence during repeated squat-stand maneuvers in males.
Previous research has highlighted that squat-stand maneuvers (SSMs) augment coherence values within the cerebral pressure-flow relationship to ∼0.99. However, it is not fully elucidated if mean arterial pressure (MAP) leads to this physiological entrainment independently, or if heart rate (HR) and/or the partial pressure of carbon dioxide (Pco2) also have contributing influences. A 2:1 control-to-case model was used in the present investigation [participant number (n) = 40; n = 16 age-matched (AM); n = 16 donor control (DM); n = 8 heart transplant recipients (HTRs)]. The latter group was used to mechanistically isolate the extent to which HR influences the cerebral pressure-flow relationship. Participants completed 5 min of squat-stand maneuvers at 0.05 Hz (10 s) and 0.10 Hz (5 s). Linear transfer function analysis (TFA) examined the relationship between different physiological inputs (i.e., MAP, HR, and Pco2) and output [cerebral blood velocity (CBV)] during SSM; and cardiac baroreceptor sensitivity (BRS). Compared with DM, cardiac BRS was reduced in AM (P < 0.001), which was further reduced in HTR (P < 0.045). In addition, during the SSM, HR was elevated in HTR compared with both control groups (P < 0.001), but all groups had near-maximal coherence metrics ≥0.98 at 0.05 Hz and ≥0.99 at 0.10 Hz (P ≥ 0.399). In contrast, the mean HR-CBV/Pco2-CBV relationships ranged from 0.38 (HTR) to 0.81 (DM). Despite near abolishment of BRS and blunted HR following heart transplantation, long-term HTR exhibited near-maximal coherence within the MAP-CBV relationship, comparable with AM and DM. Therefore, these results show that the augmented coherence with SSM is driven by blood pressure, whereas elevations in TFA coherence as a result of HR contribution are likely correlational in nature.


Boar taint, meat quality and fail rate in entire male pigs and male pigs immunized against gonadotrophin releasing factor as related to body weight and feeding regime.
The objective of this experiment was to compare the pork quality of entire male pigs and pigs immunized against GnRF (IC males) at both light (64.8kg) and heavy (106kg) liveweights and two feeding regimes (restricted at 2.5 times maintenance and ad libitum). There was no difference in objective measurements (P>0.05) or eating pork quality (P>0.1) between entire male and IC males. Fail rates were reduced by 9.1% and 12% for pork from IC males for quality grade (P=0.007) and re-purchase intention (P=0.001), respectively, compared to pork from entire males. Skatole (P=0.001) and androstenone (P<0.001) levels in belly fat were higher in entire male than IC male pigs. In addition, 37.5% of the light entire male pigs fed ad libitum showed skatole levels that exceeded the sensory threshold of 0.2μg/g. This work confirms that immunization against GnRF is effective in eliminating boar taint and reducing pork quality fail rates by approximately 10% compared to pork from entire males.


Alternate wetting and drying irrigation increases water and phosphorus use efficiency independent of substrate phosphorus status of vegetative rice plants.
Sustainable approaches to rice cultivation that apply less irrigation and chemical fertilisers are required to increase crop resource use efficiency. Although alternate wetting and drying (AWD) has been widely promoted as a water-saving irrigation technique, its interactions with phosphorus (P) nutrition have attracted little attention. Vegetative rice plants were grown with two phosphorus levels, fertilised (HP) or un-fertilised (LP), and either continuous flooding (CF) or AWD irrigation. Treatment effects on substrate P bioavailability (measured by Diffusive Gradients in Thin films - DGT-P), plant and substrate water relations, and foliar phytohormone status, were assessed along with P partitioning in planta. Shoot biomass and leaf area under different irrigation treatments depended on substrate P status (significant P x irrigation interaction), since LP decreased these variables under CF, but had no significant effect on plants grown under AWD. AWD maintained DGT-P concentrations and increased maximal root length, but decreased root P concentrations and P offtake. Substrate drying decreased stomatal conductance (gs) and leaf water potential (Ψleaf) but re-flooding increased gs. AWD increased foliar abscisic acid (ABA), isopentenyl adenine (iP) and 1-aminocyclopropane-1-carboxylic acid (ACC) concentrations, but decreased trans-zeatin (tZ) and gibberellin A1 (GA1) concentrations. Low P increased ACC and jasmonic acid (JA) concentrations but decreased gibberellin A4 (GA4) concentrations. Across all treatments, stomatal conductance was negatively correlated with foliar ABA concentration but positively correlated with GA1 concentration. Changes in shoot phytohormone concentrations were associated with increased water and phosphorus use efficiency (WUE and PUE) of vegetative rice plants grown under AWD.


The effects of diacetate with nitrite, lactate, or pediocin on the viability of Listeria monocytogenes in turkey slurries.
The antilisterial effects of sodium diacetate (0.1, 0.3 and 0.5%) alone or in combination with sodium nitrite (30 ppm), sodium lactate (2.5%) or pediocin (5000 arbitrary units/ml) were evaluated in slurries (25% meat in sterile deionized H2O) prepared from vacuum-packaged, ready-to-eat turkey breast meat and challenged with Listeria monocytogenes. In the absence of food additives, counts of L. monocytogenes increased from 4.5 log10 cfu/ml to ca. 8 log10 cfu/ml within 1 day at 25 degrees C and within 14 days at 4 degrees C. Similarly, the pathogen grew to ca. 8 log10 cfu/ml within 1 d at 25 degrees C and within 28 days at 4 degrees C in slurries containing nitrite or lactate. In the presence of pediocin, after an initial decrease of 0.9 log10 cfu/ml, numbers of the pathogen reached ca. 8 log10 cfu/ml within 5 days at 25 degrees C and within 28 days at 4 degrees C. However, 0.3 and 0.5% diacetate in turkey slurries were listericidal at 4 and 25 degree C, respectively. In the presence of nitrite with diacetate, there was no appreciable difference in growth of L. monocytogenes compared with diacetate alone. Antilisterial activity was potentiated in treatments containing lactate with 0.3% diacetate at 25 degrees C and lactate with 0.1% diacetate at 4 degrees C, compared to similar treatments containing diacetate or lactate alone. A listericidal effect (ca. 7 log10 cfu/ml difference compared to slurries without additives) was observed in treatments containing pediocin with 0.5% diacetate at 25 degrees C and pediocin with 0.3% diacetate at 4 degrees C. The pH of slurries containing 0.3 or 0.5% diacetate was 5.5 and 5.2, respectively, whereas nitrite (pH 6.2), lactate (pH 6.3) or pediocin (pH 6.2) in slurries had a negligible effect on pH compared to the control (pH 6.2). The increased antilisterial activity in slurries with diacetate in combination with other additives was due to synergistic effects and not just pH. Thus, sodium diacetate alone can be used to delay growth of L. monocytogenes in turkey, and an additional level of safety can be achieved using diacetate in combination with sodium lactate or pediocin.


The marriage of coherent Raman scattering imaging and advanced computational tools.
Coherent Raman scattering microscopy can provide high-contrast tissue and single-cell images based on the inherent molecular vibrations of the sample. However, conventional techniques face a three-way trade-off between Raman spectral bandwidth, imaging speed, and image fidelity. Although currently challenging to address via optical design, this trade-off can be overcome via emerging computational tools such as compressive sensing and machine learning.


Palatal shelf movement during palatogenesis: a fate map of the fetal mouse palate cultured in vitro.
Day-13 fetal mouse palates (plug day=day 0) were labeled with carbon particles at various sites of palatal shelves and cultivated in a chemically defined medium for up to 48 h. During the culture period, the bilateral palatal shelves came in contact and fused with each other, which simulated in vivo palatogenesis. The carbon study revealed that at the midpalatal region, the medial edge of the palatal shelf elevated to the horizontal plane, elongated toward the midline, and made contact with the medial edge of the opposing shelf. On the other hand, near the anterior and posterior ends of the shelf, some new tissue was formed at the medial edge of the shelf by remodeling and this newly formed tissue took part in palatal fusion. The results of the present study indicate that during mouse palatogenesis, the anterior and posterior regions of the palatal shelf behave differently from the midpalatal region. It seems that in the fetal mouse palate, the midpalate closes mainly by means of rotation and medial elongation of the shelf, whereas the anterior and posterior parts of the palate close mainly by tissue remodeling of the medial edge and partly by medial elongation of the shelf.


[Current status of research of a lymphatic system in the nervous system: initial trials with cerebral lymphography].
After having recognized the existence of post-mortem intra-cerebral circulation of a coloring substance with lymphatic resorption, the author is continuing his research by injecting a product sharing the same characteristics: Iotrolan. Brain X-rays show brain circulation from the cortex to the ventricular cavities and from the spinal cord to the bulbar area and to the cerebellum. One question deserves to be asked: what is this circulation?


Fast-Track in Bariatric and Metabolic Surgery: Feasibility and Cost Analysis Through a Matched-Cohort Study in a Single Centre.
Due to the rise in severe obesity in Western countries and the increase in bariatric surgery, enhanced recovery (ER) pathways should be developed and promoted. A monocentric prospective series of 103 bariatric surgery patients managed with the ER pathway (group ER) was compared with a retrospective and immediately previous series of 103 patients managed with standard care (group CS). The aim of the present study was to assess and compare the differences in terms of mean postoperative length of stay (LOS), costs for surgery and recovery, and the differences in terms of complications, readmission, and reoperation rate in the short term between the ER and CS groups. The mean LOS was 4.18 days in group CS and 1.79 days in group ER (p < 0.0001). The mean operative time (OT) per patient was 190.20 min in the group CS and 133.54 min in the group ER, resulting in an average cost of 7272.57€ per patient in group CS and 5424.09€ per patient in group ER. The average recovery cost was 1809.94€ for the group CS series and 775.07 for the group ER one. Overall complications (Clavien-Dindo up to II) occurred in 6 patients (5.8 %) in group CS and in 2 patients (1.9 %) in group ER (p = 0.149) and specific complications (Clavien-Dindo IIIb) occurred for 9 patients (8.7 %) in Group CS and for 14 patients (13.5 %) in group ER (p = 0.268) after hospital discharge within 1-month of follow-up. Twelve patients (11.5 %) in group CS and 13 (12.5 %) in group ER were readmitted after discharge (p = 0.831) within 1-month of follow-up; 8 patients (7.7 %) in group CS versus 9 patients (8.8 %) in group ER needed to be reoperated (p = 0.800) within 1-month follow-up. Enhanced recovery pathway reduces significantly LOS in bariatric surgical patients and shortens the mean OT of the procedure, with no significant differences in terms of surgical outcomes. Furthermore, recovery charges were lower and operative time was shorter allowing for procedural cost reduction.


Impact of microplastics on riverine greenhouse gas emissions: a view point.
In recent decades, microplastics (MPs < 5 mm) are ubiquitous and considered a serious emerging environmental problem. However, due to the limited recovery and long-lasting durability MPs, debris is frequently accumulating in riverine ecosystems, thereby impacting microbial activity and its communities. The presence of MPs may alter the microbial richness, variety, and population, thereby impacting the transformation of biogeochemical cycles. The occurrence, fate, and transport of MPs in marine and terrestrial ecosystems and their impact on biogeochemical or nutrient cycling are reported in the scientific fraternity. Yet, the global scientific community is conspicuously devoid of research on impact of MPs on riverine greenhouse gas (GHG) emissions. The presented view point provides a novel idea about the fate of MPs in the riverine system and its impact on GHG emissions potential. Literature reveals that DO and nutrients (organic carbon, NH4+, NO3-) concentrations play an important role in potential of GHG emission in riverine ecosystems. The proposed mechanism and research gaps provided will be highly helpful to the hydrologist, environmentalist, biotechnologist, and policymakers to think about the strategic mitigation measure to resolve the future climatic risk.


Complex interplay of lesion-specific DNA repair enzyme on bistranded clustered DNA damage harboring Tg:G mismatch in nucleosome core particles.
5,6-Dihydroxy-5,6-dihydrothymine (thymine glycol) and 7,8-dihydro-8-oxo-20-deoxyguanosine (8-oxodG) are major DNA damage lesions produced by endogenous oxidative stress, as well as inflicted by carcinogens and ionizing radiation. The processing of Tg:G mismatch and 8-oxodG in close proximity of each other in a bistranded clustered environment in DNA oligomer duplexes as well as in a nucleosome core particle (NCP) model are reported here. The processing of the lesions was evaluated by purified enzyme cocktails of hNTH1 and hOGG1 as well as with a HeLa cell extract. Interestingly, the yield of double-strand breaks (DSBs) resulting from the processing of the bistranded lesions are appreciably lower when the DNA is treated with the HeLa cell extract compared with the relevant purified enzyme cocktail in both models. Clustered bistranded lesions become more repair refractive when reconstituted as an NCP. This indicates a complex interplay between the repair enzymes that influence the processing of the bistranded cluster damage positively to avoid the formation of DSBs under cellular conditions. In addition to position and orientation of the lesions, the type of the lesions in the cluster environment in DNA along with the relative abundance of the lesion-specific enzymes in the cells strongly prevents the processing of the oxidized nucleobases.


Copper(I) Phosphinooxazoline Complexes: Impact of the Ligand Substitution and Steric Demand on the Electrochemical and Photophysical Properties.
A series of seven homoleptic CuI complexes based on hetero-bidentate P^N ligands was synthesized and comprehensively characterized. In order to study structure-property relationships, the type, size, number and configuration of substituents at the phosphinooxazoline (phox) ligands were systematically varied. To this end, a combination of X-ray diffraction, NMR spectroscopy, steady-state absorption and emission spectroscopy, time-resolved emission spectroscopy, quenching experiments and cyclic voltammetry was used to assess the photophysical and electrochemical properties. Furthermore, time-dependent density functional theory calculations were applied to also analyze the excited state structures and characteristics. Surprisingly, a strong dependency on the chirality of the respective P^N ligand was found, whereas the specific kind and size of the different substituents has only a minor impact on the properties in solution. Most importantly, all complexes except C3 are photostable in solution and show fully reversible redox processes. Sacrificial reductants were applied to demonstrate a successful electron transfer upon light irradiation. These properties render this class of photosensitizers as potential candidates for solar energy conversion issues.


Altered fractionation trials in head and neck cancer.
Advancement in radiobiological concepts has led to the development of two classes of new fractionation schedules for the treatment of head and neck cancers. These altered fractionation regimens are referred to as hyperfractionation and accelerated fractionation schedules. Hyperfractionation exploits the difference in fractionation sensitivity between tumors and normal tissues manifesting late morbidity. In contrast, accelerated fractionations attempt to reduce tumor proliferation as a major cause of radiotherapy failure. Although there are many permutations in accelerating radiation treatment, the existing schedules can be conceptually grouped into two categories, pure accelerated fractionations and hybrid accelerated regimens, depending on whether there are concurrent changes in other fractionation parameters. The results of 10 completed phase III clinical trials addressing different types of altered fractionation schedules in head and neck carcinomas are examined and summarized in this review article. The data of trials on hyperfractionation regimens applying 10% to 15% total dose increment over the standard 66 to 70 Gy consistently revealed a 10% to 15% improvement in the local control rate of a subset of intermediate-stage carcinomas without an appreciable increase in the incidence of late complications. The available data on accelerated fractionation regimens showed that tumor clonogen proliferation is a major cause of radiation failure. Completed studies, however, revealed that a 1- to 1.5-week treatment acceleration without total dose reduction achieved by administering 2-Gy fractions 6 times per week or concomitant boost schedule yielded an approximately 15% higher tumor control rate without increasing late toxicity. Shortening the overall time to less than 2 weeks with an associated total dose reduction did not seem to improve tumor control rate, with an exception perhaps for a small subset of patients with laryngeal carcinomas, but might decrease some late normal tissue injury. A weekly dose accumulation rate of 14 Gy or greater, or delivery of 3 fractions of 1.6 Gy/d, with 6 hour intervals, without total dose reduction, was found to increase morbidity beyond the acceptable level. Further treatment refinements building on these findings are being pursued.


Substance P-like immunoreactive nerves in the anterior segment of the rabbit, cat and monkey eye.
The indirect immunofluorescence technique demonstrates a substance P-like immunoreactive innervation to the anterior segment of the rabbit, cat and monkey eye. In all three species there is a sparse, but definite, corneal innervation. For the rabbit, substance P-like immunoreactive nerves to the aqueous outflow apparatus are found chiefly in the pectinate ligament. In the cat, this innervation is somewhat more extensive, being seen in the septae of the ciliary cleft as well. The monkey has a more plentiful innervation to the outflow apparatus than either the cat or the rabbit. Substance P-like immunoreactive nerves are visible in the trabecular meshwork and at the inner and outer walls of Schlemm's canal. For all three animals, the iris contains immunoreactive nerve fibers to the sphincter muscle, to the large blood vessels and to the anterior stromal melanocytes. In the ciliary body, the ciliary processes receive a constant innervation; it is somewhat more dense in the rabbit. Some of the large ciliary body blood vessels also are innervated. Ciliary body melanocytes are innervated; it was not possible to determine whether or not immunoreactive fibers innervate the ciliary muscle cells as well. The present study extends prior knowledge of the innervation of the eye. Taken with the known physiologic effects of substance P, it indicates a series of potential roles for this peptide in the vegetative processes of the eye.


DNA comparisons of Trypanosoma evansi (Indonesia) and Trypanosoma brucei spp.
Two clones from separate isolates of Trypanosoma evansi in Indonesia were found by polymerase chain reaction (PCR) analyses to contain 3 different repeated nuclear DNA sequences of Trypanosoma brucei spp: the consensus sequence for a highly repetitive 177 base pairs and the gene repeats encoding procyclin and the spliced leader. In addition, the 994 bp minicircle sequence of one of the clones was determined, and PCR amplification primers specific for minicircles of T. evansi were identified that do not amplify minicircle sequences in the T. brucei spp. clones tested.


Machine learning methods applied to triage in emergency services: A systematic review.
In emergency services is important to accurately assess and classify symptoms, which may be improved with the help of technology. One mechanism that could help and improve predictions from health records or patient flow is machine learning (ML). To analyse the effectiveness of ML systems in triage for making predictions at the emergency department in comparison with other triage scales/scores. Following the PRISMA recommendations, a systematic review was conducted using CINAHL, Cochrane, Cuiden, Medline and Scopus databases with the search equation "Machine learning AND triage AND emergency". Eleven studies were identified. The studies show that the use of ML methods consistently predict important outcomes like mortality, critical care outcomes and admission, and the need for hospitalization in comparison with scales like Emergency Severity Index or others. Among the ML models considered, XGBoost and Deep Neural Networks obtained the highest levels of prediction accuracy, while Logistic Regression performed obtained the worst values. Machine learning methods can be a good instrument for helping triage process with the prediction of important emergency variables like mortality or the need for critical care or hospitalization.


Long-Term Aesthetic Cicatrization Analysis of Lower Eyelid Incision for Orbital Floor Fracture Approach.
Orbital fractures are among the most frequent facial injuries. Of the 3 most widely described approaches in the literature, the lower eyelid approach is the authors' preference. This study retrospectively analyzed the patients treated at the Trauma Center of the Umberto I Hospital, Sapienza University of Rome from January 2010 to December 2020. Inclusion criteria were as follows: diagnosis of pure/impure orbital bone fracture, complete clinical and radiological documentation, and a minimum of 12 months follow-up. Sex, age, etiology, treatment, and associated complications were analyzed using IBM SPSS Statistics. Two internationally validated scales were used for the functional and esthetic long-term evaluation: the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver one. The scales were compiled by the patient himself and by 3 independent expert observers. Of the 543 patients who underwent surgery in the specified period, 208 fully met the inclusion criteria. One hundred forty-two (68.2%) were males and 66 (31.8%) were females, with a mean age of 40.68 years. The main cause was represented by assaults (33.1%). One hundred seventy-nine patients had a pure orbital fracture (83.8%) and 29 an impure one (16.2%). The most frequent symptoms at the time of diagnosis were diplopia (31.2%), followed by anesthesia of the second trigeminal branch (24.3%). Open reduction with internal fixation was the preferred treatment and proved to be effective in reducing the main signs and symptoms of the fracture in a statistically significant way ( P < 0.05). Long-term esthetic results of the lower eyelid, using the Vancouver and POSASs, were respectively as follows: Vancouver Scar Scale mean total score was 2.41 (range: 0-8), observer POSAS mean total score was 1.83 (range: 1.2-3.9), observer general opinion mean score was 1.66, patient POSAS mean total score was 2.23 (range: 1.33-3.7), and patient general opinion mean score was 2.87. The lower eyelid approach has proven to be reproducible, with a fast-learning curve and a low complication rate. The analysis conducted highlighted an excellent long-term esthetic-functional result. Further studies will be needed to statistically compare the results obtained with other orbital floor surgical approaches.


Relationship between oxidative stress and clinical-pathological aspects in dogs experimentally infected with Rangelia vitalii.
The aim of this study was to evaluate lipid peroxidation, protein oxidation and activity of enzymes that are indicators of oxidative stress in Rangelia vitalii infection in dogs. Animals were divided into two groups: negative control (n=5) and infected with R. vitalii (n=7). After inoculation, the parasitemia was estimated daily by microscopic examination of smears. Lipid peroxidation (TBARS) and advanced oxidation protein products (AOPP); and delta-aminolevulinate dehydratase (δ-ALA-D), superoxide dismutase (SOD) and catalase (CAT) activities in blood were evaluated. The samples were collected at days 10 and 20 post-inoculation (PI). TBARS and AOPP levels were higher in the infected group in both analyzed periods (P<0.01). The δ-ALA-D activity was reduced in blood of dogs infected with R. vitalii on days 10 and 20 PI. SOD activity was significantly increased (P<0.01) in the blood of dogs infected with R. vitalii at days 10 and 20 PI, while CAT activity was significantly increased (P<0.01) only at day 20 PI when compared to non-infected animals. A positive correlation was observed between the degree of parasitemia and TBARS and AOPP levels and activity of antioxidant enzymes. The δ-ALA-D activity was negatively correlated with the degree of parasitemia. Based on the increased levels of TBARS, AOPP, SOD and CAT activities, and inhibition δ-ALA-D activity, we concluded that dogs experimentally infected with R. vitalii develop a state of redox unbalance and that these changes might be involved in the pathophysiology of disease.


Consequence of use of lower dose flat plate fluoroscopy in pediatric patients undergoing ablation for supraventricular tachycardia.
Traditional imaging for ablation of supraventricular tachycardia has been fluoroscopy, although 3-dimensional electroanatomic mapping (3D) has been demonstrated to reduce radiation exposure. This study compares a technique for the reduction of radiation, low-dose fluoroscopy (LD), with standard-dose fluoroscopy (SD) and 3D with SD (3D-SD). This was a single institutional retrospective cohort study. All patients undergoing initial ablation for atrioventricular reentrant tachycardia (AVRT) or atrioventricular nodal reentrant tachycardia (AVNRT) from 2009 to 2012 were reviewed and divided into 3 groups: (1) SD, (2) 3D (CARTO or NavX) with SD, or (3) LD. LD uses the same equipment as SD but includes customized changes to the manufacturer's lowest settings by decreasing the requested dose to the detector. Primary outcomes were fluoroscopy time and dose area product exposure. One hundred eighty-one patients were included. The median age was 15.0 years (3.3-20.8); 59% had AVRT, 35% had AVNRT, and 6% had both AVRT and AVNRT. LD decreased the dose area product (DAP) compared with SD (637.0 vs 960.1 cGy*cm², p = 0.01) with no difference in fluoroscopy time. 3D-SD decreased fluoroscopy time compared with SD (9.9 vs 18.3 minutes, p <0.001) with DAP of 570.1.0 versus 960.1 cGy*cm² (p = 0.16). LD and 3D-SD had comparable DAP (637.0 vs 570.1 cGy*cm², p = 0.67), even though LD had significantly longer fluoroscopy time (19.9 vs 9.9 minutes, p <0.001). In conclusion, LD during catheter ablation of AVRT and AVNRT significantly reduced the DAP compared with SD and had similar radiation exposure compared with 3D with SD.


Impact of dust deposition on phytoplankton biomass in the Northwestern Pacific: A long-term study from 1998 to 2020.
Dust deposition can supply nutrients to the ocean and affect phytoplankton growth. However, the impact of dust deposition on phytoplankton biomass in varying trophic regions remains poorly evaluated. The Northwestern Pacific is located in the downwind area of East Asian dust and includes eutrophic regions (Yellow Sea, YS; East China Sea, ECS), high-nutrient low-chlorophyll waters (subarctic Northwestern Pacific, SNWP) and low-nutrient low-chlorophyll waters (Northwestern Pacific subtropical gyre, NWPSG), which is an ideal region to explore the spatial heterogeneity of the dust fertilization effect. Here, the distribution and variation of dust deposition, high dust deposition events (HDDE) and Chlorophyll-a concentration (Chl-a, mg m-3) in the Northwestern Pacific during spring from 1998 to 2020 were investigated. The differences in the response of phytoplankton biomass (using Chl-a as a proxy) to HDDE in the YS, the ECS, the SNWP and the NWPSG were explored. Our results indicated that a large amount of dust was deposited into the Northwest Pacific during spring, resulting in numerous HDDE. The HDDE could stimulate the increase of phytoplankton biomass in the whole area of the Northwestern Pacific during spring. The response probabilities of Chl-a to HDDE were most significant (~80%) in the SNWP and the duration of response was the longest, even lasting for up to 40 days. While the response probabilities of Chl-a to HDDE were lowest in the YS and ECS (~65%), increasing from north to south, and most of the responses were less than 20 days. The response of Chl-a to HDDE was also detected in NWPSG, confirming the dust fertilization effect in oligotrophic waters, with response probabilities of 70% and duration less than 30 days. Overall, this study provides a more comprehensive understanding of the differences of phytoplankton response to dust deposition in varying trophic regions.


Radiation Oncology Emergencies.
This article reviews the most common oncologic emergencies encountered by the radiation oncologist, including malignant spinal cord compression, intramedullary spinal cord metastasis, superior vena cava syndrome, hemoptysis, and airway compromise caused by tumor. Important trials evaluating different treatments for these emergencies are reviewed. The role of corticosteroids, surgery, chemotherapy, and radiation therapy in these patients is discussed and patient-specific treatment guidelines are suggested.


Gender, Police Culture, and Structured Ambivalence: Navigating 'Fit' with the Brotherhood, Boys' Club, and Sisterhood.
Women are increasingly represented in policing; however, inclusion alone will not eradicate existing structural and cultural barriers to meaningful change. Insights from interviews with ninety-one Canadian women police of varied rank and tenure, demonstrate women's experiences of structured ambivalence as they strategically deploy and resist gendered policing narratives of the Brotherhood, Boys' Club, and Sisterhood to negotiate their own 'fit.' In this way, they both challenge and reinforce gendered boundaries that create barriers to meaningful transformation. These findings demonstrate the need for change initiatives to address the complex and ever-shifting role of gender in policing organizations.


The Influence of Piezoelectric Transducer Stimulating Sites on the Performance of Implantable Middle Ear Hearing Devices: A Numerical Analysis.
To overcome the inherent deficiencies of hearing aids, implantable middle ear hearing devices (IMEHDs) have emerged as a new treatment for hearing loss. However, clinical results show that the IMEHD performance varies with its transducer's stimulating site. To numerically analyze the influence of the piezoelectric transducer's stimulating sites on its hearing compensation performance, we constructed a human ear finite element model and confirmed its validity. Based on this finite element model, the displacement stimulation, which simulates the piezoelectric transducer's stimulation, was applied to the umbo, the incus long process, the incus body, the stapes, and the round window membrane, respectively. Then, the stimulating site's effect of the piezoelectric transducer was analyzed by comparing the corresponding displacements of the basilar membrane. Besides, the stimulating site's sensitivity to the direction of excitation was also studied. The result of the finite element analysis shows that stimulating the incus body is least efficient for the piezoelectric transducer. Meanwhile, stimulating the round window membrane or the stapes generates a higher basilar membrane displacement than stimulating the eardrum or the incus long process. However, the performance of these two ideal sites' stimulation is sensitive to the changes in the excitation's direction. Thus, the round window membrane and the stapes is the ideal stimulating sites for the piezoelectric transducer regarding the driving efficiency. The direction of the excitation should be guaranteed for these ideal sites.


Purification of Antibodies Against Entamoeba histolytica MIF and Their Use in Analyzing Human and Mouse Samples.
Macrophage migration inhibitory factor (MIF) is a proinflammatory and proproliferative cytokine expressed in humans. MIF homologs also exist in many pathogenic protozoans, including Entamoeba, Plasmodium, Toxoplasma, and Leishmania. Production of antibodies against parasite proteins allows for the generation of assays to measure and visualize parasite infection within hosts. In this chapter, we describe how to specifically purify antibodies against Entamoeba histolytica MIF (EhMIF), and subsequently use anti-EhMIF antibodies for ELISA on mouse and human samples and for immunohistochemistry on human tissue. These methods can be applied to any protein for high-quality antibody purification.


A heuristic method for rapid and automatic radiofrequency ablation planning of liver tumors.
Preprocedural planning is a key step in radiofrequency ablation (RFA) treatment for liver tumors, which is a complex task with multiple constraints and relies heavily on the personal experience of interventional radiologists, and existing optimization-based automatic RFA planning methods are very time-consuming. In this paper, we aim to develop a heuristic RFA planning method to rapidly and automatically make a clinically acceptable RFA plan. First, the insertion direction is heuristically initialized based on tumor long axis. Then, the 3D RFA planning is divided into insertion path planning and ablation position planning, which are further simplified into 2D by projections along two orthogonal directions. Here, a heuristic algorithm based on regular arrangement and step-wise adjustment is proposed to implement the 2D planning tasks. Experiments are conducted on patients with liver tumors of different sizes and shapes from multicenter to evaluate the proposed method. The proposed method automatically generated clinically acceptable RFA plans within 3 min for all cases in the test set and the clinical validation set. All RFA plans of our method achieve 100% treatment zone coverage without damaging the vital organs. Compared with the optimization-based method, the proposed method reduces the planning time by dozens of times while generating RFA plans with similar ablation efficiency. The proposed method demonstrates a new way to rapidly and automatically generate clinically acceptable RFA plans with multiple clinical constraints. The plans of our method are consistent with the clinical actual plans on almost all cases, which demonstrates the effectiveness of the proposed method and can help reduce the burden on clinicians.


Decision making in urological surgery.
Non-technical skills are important behavioural aspects that a urologist must be fully competent at to minimise harm to patients. The majority of surgical errors are now known to be due to errors in judgment and decision making as opposed to the technical aspects of the craft. The authors reviewed the published literature regarding decision-making theory and in practice related to urology as well as the current tools available to assess decision-making skills. Limitations include limited number of studies, and the available studies are of low quality. Decision making is the psychological process of choosing between alternative courses of action. In the surgical environment, this can often be a complex balance of benefit and risk within a variable time frame and dynamic setting. In recent years, the emphasis of new surgical curriculums has shifted towards non-technical surgical skills; however, the assessment tools in place are far from objective, reliable and valid. Surgical simulators and video-assisted questionnaires are useful methods for appraisal of trainees. Well-designed, robust and validated tools need to be implemented in training and assessment of decision-making skills in urology. Patient safety can only be ensured when safe and effective decisions are made.


Renal cholesteatoma.
Renal cholesteatoma is being reported more frequently in the literature. A case with a twenty-year documented history is presented, together with observations on differential diagnosis.


Keeping older patients healthy and safe as they travel.
For older patients, the trip of a lifetime can be fraught with health hazards. There's much you can do to keep them harm free.


Deficient production of hexadecenoic acid in the skin is associated in part with the vulnerability of atopic dermatitis patients to colonization by Staphylococcus aureus.
As one of the major skin fatty acids, cis-6-hexadecenoic acid (C16:1Delta6) exhibits a specific antibacterial activity and might play a specific role in the defense mechanism against Staphylococcus aureus, in healthy subjects whereas S. aureus frequently colonizes the skin of patients with atopic dermatitis (AD). Fatty acid composition of sebum at the recovery level was analyzed by gas chromatography and S. aureus colonizing the skin was assessed by the 'cup-scrub' method (9 patients and 10 healthy controls). To evaluate in vivo effect of C16:1Delta6 on colonization, C16:1Delta6 was applied for 2 weeks on the upper arm skin of another group of AD patients (11 patients). Analysis of sebum lipids revealed that there is a significant lower free C16:1Delta6 content in nonlesional skin from AD patients compared with healthy controls. This lower content is also accompanied by a significantly lower level of C16:1Delta6 in the total fatty acid composition of sebum (analyzed following hydrolysis). The lower level of free C16:1Delta6 correlated significantly (R(2) = 0.41, p < 0.01) with the numbers of S. aureus colonizing nonlesional skin. Topical application of free C16:1Delta6 on the skin of AD patients for 2 weeks abolished the markedly increased bacterial count in 6 out of the 8 AD patients tested. Free C16:1Delta6 may be involved in the defense mechanism against S. aureus in healthy skin and this deficit triggers the susceptibility of the skin to colonization by S. aureus in AD.


AbeM, an H+-coupled Acinetobacter baumannii multidrug efflux pump belonging to the MATE family of transporters.
We cloned a gene, abeM, for a multidrug efflux pump from Acinetobacter baumannii using Escherichia coli as the host. Sequence analysis revealed that AbeM is a member of the MATE family of pumps. AbeM was found to be an H(+)-coupled multidrug efflux pump and a unique member of the MATE family.


Intraspecific differences in cadmium tolerance of Nitzschia palea (Kützing) W. Smith: a biochemical approach.
Intraspecific variability occurs in all types of organisms and is a driving force to speciation, conferring genotypic and phenotypic differences that enable adaptive responses to sub-lethal stimuli such as exposure to pollutants (including cadmium, Cd). Thus, differences in biochemical parameters are expected among isolates of the same species. Studying the extent of these differences throughout a stress range, will provide information for the development of approaches to mitigate habitat contamination. This work was designed to identify possible differences in Cd tolerance of five isolates of the freshwater diatom Nitzschia palea from different sampling sites. Each isolate was exposed to five increasing Cd concentrations during 10 days. Growth inhibition was assessed and intracellular accumulation of Cd was quantified. Superoxide dismutase and catalase activities were determined. Glutathione as well as lipid peroxidation (LPO) and intracellular protein content were quantified. The results obtained identified intraspecific differences among isolates. These differences were associated with different approaches of coping with Cd stress. Higher intracellular Cd concentrations induced lower tolerance in isolates, since antioxidant mechanisms were unable to fight effectively against higher oxidative stress. Reversely, lower intracellular accumulation of Cd induced lower oxidative damage and allowed cells to better tolerate exposure to Cd. LPO emerged as an excellent marker of oxidative stress in N. palea and its use can differentiate isolates according to their tolerance.


Follicular lymphoma and diffuse large B-cell lymphoma with BCL2 and IRF4 rearrangements in adult patients.
Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) with concurrent BCL2 and IRF4 rearrangements are rare. It is unclear whether such cases should be classified as large B- cell lymphoma with IRF4 rearrangement or FL/DLBCL-not otherwise specified. We identified 5 adult patients (FL, N = 3 and FL/DLBCL, N = 2) with concurrent BCL2 and IRF4 rearrangements. The median age at presentation was 77 years, and three patients presented with advanced stage disease. Both nodal and extranodal sites were involved and involvement was not limited to head and neck region. With a median follow-up of 18 months, 1 patient died and 4 patients were alive, including 3 who received chemotherapy and 1 who was observed. The neoplasms were histologically heterogeneous, including grade 2 and 3 FL and DLBCL. Four cases coexpressed CD10, BCL6, BCL2 and MUM1/IRF4. The Ki67 labelling index ranged from 20% to 95%. In 4 patients, the percentage of cells with BCL2 rearrangement was equal to or slightly greater than the cells harboring IRF4 rearrangement. Two cases underwent next generation sequencing tailored for lymphoid neoplasms. Both lacked mutations involving IRF4 and NF-kB pathway genes that are frequently detected in large B-cell lymphoma with IRF4 rearrangement, and one case showed DLBCL-EZH2 type mutations, including KMT2D and BCL2 mutations, similar to 2 previously reported DLBCL with BCL2 and IRF4 rearrangements. Adults with FL and FL/DLBCL with BCL2 and IRF4 rearrangements display clinicopathologic and mutational features more akin to FL and DLBCL and should not be characterized as large B-cell lymphoma with IRF4 rearrangement.


N-Acetylglucosamine mitigates lung injury and pulmonary fibrosis induced by bleomycin.
Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date, efficient therapeutic approach for such lung diseases is lacking. N-Acetylglucosamine (NAG), an acetylated derivative of glucosamine, has been proposed as a potential protector of lung function in several types of lung diseases. The mechanism by which NAG protects against lung injury, however, remains unclear. Here, we show that NAG treatment improves pulmonary function in bleomycin (BLM)-induced lung injury model measured by flexiVent system. At early phase of lung injury, NAG treatment results in silenced immune response by targeting ARG1+ macrophages activation, and, consequently, blocks KRT8+ transitional stem cell in the alveolar region to stimulate PDGF Rβ+ fibroblasts hyperproliferation, thereby attenuating the pulmonary fibrosis. This combinational depression of immune response and extracellular matrix deposition within the lung mitigates lung injury and pulmonary fibrosis induced by BLM. Our findings provide novel insight into the protective role of NAG in lung injury.


Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey.
The number of individuals diagnosed with diabetes mellitus is increasing. The diabetic may present with complications involving all systems of the body. While onychomycosis is often observed in diabetics, there have been no large studies on the prevalence of the condition in this patient group. We examined the prevalence of onychomycosis in diabetics attending diabetes and dermatology clinics in London, Ontario, Canada and Boston, MA, U.S.A. Diabetic subjects seen in dermatology offices were for unrelated dermatoses; those referred specifically for the management of onychomycosis were excluded from the sample. A total of 550 diabetic subjects was evaluated (283 males and 267 females), age 56.1 +/- 0.7 years (mean +/- SEM). Patients with type I diabetes constituted 34% of the sample. The racial origin was: 531 Caucasians, 17 Asians, one African-American and one American-Indian. Abnormal-appearing nails and mycological evidence of onychomycosis (mostly due to dermatophytes) were present in 253 (46%) and 144 (26%), respectively, of 550 subjects. The development of onychomycosis was significantly correlated with age (P < 0.0001) and male gender (P < 0.0001). Males were 2.99 times more likely to have onychomycosis compared with females (95% confidence interval, CI 1.94-4 61). After controlling for age and sex, the risk odds ratio for diabetic subjects to have toenail onychomycosis was 2.77 times compared with normal individuals (95% CI 2.15-3.57). After controlling for age and sex, a stepwise logistic regression demonstrated that significant predictors for onychomycosis included a family history of onychomycosis (P = 0.0001), concurrent intake of immunosuppressive therapy (P = 0.035) and peripheral vascular disease (P = 0.023). Toenail onychomycosis was present in 26% of the sample and is projected to affect approximately one-third of subjects with diabetes. Predisposing factors include increasing age, male gender, family history of onychomycosis, concurrent intake of immunosuppressive agents and peripheral vascular disease.


The mutagenic activity of selected compounds at the TK locus: rodent vs. human cells.
The mutagenic (TFT resistance) and toxic responses of mouse lymphoma (MOLY) L5178Y cells and human lymphoblast (HULY) TK6 cells were compared for 13 chemicals. The mutagenic activities of 8 of the 13 chemicals (62%) examined in the HULY and MOLY assays are in agreement - the results being judged positive in both assays. However, a dramatic difference is observed when the two conditions of metabolic activation are considered separately; the overall concordance of 8/13 has been achieved by combining a 13/13 (100%) agreement in the absence of S9 with a 1/6 (17%) agreement in the presence of S9. In the absence of S9, the concentration ranges, lowest significant doses, and shapes of the concentration-response curves for both toxicity and mutagenicity were similar in spite of the differences in exposure times (4 h for MOLY, 20 for HULY) and expression times (2 days for MOLY, 3 days for HULY). The general agreement observed in the absence of S9 contrasted with the differences manifested in its presence. 6 compounds which were negative in the absence of S9 were tested in both the MOLY and HULY assays in the presence of S9. Of the 6 chemicals, only 1 was positive in both MOLY and HULY under the latter condition; 4 others were positive in MOLY and negative in HULY whereas 1 was positive in HULY and negative in MOLY.


"Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies".
γ-glutamyltranspeptidase (GGT) is a bi-substrate enzyme conserved in all three domains of life. It catalyzes the cleavage and transfer of γ-glutamyl moiety of glutathione to either water (hydrolysis) or substrates like peptides (transpeptidation). GGTs exhibit great variability in their enzyme kinetics although the mechanism of catalysis is conserved. Recently, GGT has been shown to be a virulence factor in microbes like Helicobacter pylori and Bacillus anthracis. In mammalian cells also, GGT inhibition prior to chemotherapy has been shown to sensitize tumors to the therapy. Therefore, lately both bacterial and eukaryotic GGTs have emerged as potential drug targets, but the efforts directed towards finding suitable inhibitors have not yielded any significant results yet. We propose that delineating the residues responsible for the functional diversity associated with these proteins could help in design of species/clade specific inhibitors. In the present study, we have carried out phylogenetic analysis on a set of 47 GGT-like proteins to address the functional diversity. These proteins segregate into various subfamilies, forming separate clades on the tree. Sequence conservation and motif prediction studies show that even though most of the highly conserved residues have been characterized biochemically in previous studies, a significant number of novel putative sites and motifs are discovered that vary in a clade specific manner. Many of the putative sites predicted during the functional divergence type I and type II analysis, lie close to the known catalytic residues and line the walls of the substrate binding cavity, reinforcing their role in modulating the substrate specificity, catalytic rates and stability of this protein. The study offers interesting insights into the evolution of GGT-like proteins in pathogenic vs. non-pathogenic bacteria, archaea and eukaryotes. Our analysis delineates residues that are highly specific to each GGT subfamily. We propose that these sites not only explain the differences in stability and catalytic variability of various GGTs but can also aid in design of specific inhibitors against particular GGTs. Thus, apart from the commonly used in-silico inhibitor screening approaches, evolutionary analysis identifying the functional divergence hotspots in GGT proteins could augment the structure based drug design approaches.


An uncertainty budget for trace analysis by isotope-dilution ICP-MS with proper consideration of correlation.
Isotope-dilution mass spectrometry (IDMS) is considered to be a method without significant correction factors. It is also believed that this method is well understood. But unfortunately a large number of different uncertainty budgets have been published that consider different correction factors. These differences lead to conflicting combined uncertainties especially in trace analysis. It is described how the known correction factors must be considered in the uncertainty budget of values determined by IDMS combined with ICP-MS (ICP-IDMS). The corrections applied are dead time, background, interference, mass discrimination, blank correction and air buoyancy.IDMS measurements consist always of a series of isotope abundance ratio measurements and can be done according to different measurement protocols. Because the measurement protocols of IDMS are often rather sophisticated, correlations of influence quantities are difficult to identify. Therefore the measurement protocol has to be carefully considered in the specification of the measurand and a strategy is presented to properly account for these correlations. This will be exemplified for the estimation of mass fractions of platinum group elements (PGEs) and Re in the geological reference material UB-N (from CRPG-CNRS, Nancy in France) with ICP-IDMS. The PGEs with more than one isotope and the element Re are measured with on-line cation-exchange chromatography coupled to a quadrupole ICP-MS. All contents are below 10 microg kg(-1). Only osmium is separated from the matrix by direct sparging of OsO(4) into the plasma. This leads to transient signals for all PGEs and Re. It is possible to estimate the combined uncertainties and keep them favourably small despite the low contents, the transient signals and the sophisticated correction model.


Fine-needle aspiration of a presacral myelolipoma: a case presentation with flow cytometry and immunohistochemical studies.
Myelolipomas are benign soft-tissue tumors predominantly found in the adrenal gland. Extra-adrenal myelolipomas are rare, with about 30 previous cases reported. Approximately half of the reported cases were located in the presacral region. These were usually found at autopsy or during the workup of vague abdominal symptoms. Histologically, these lesions show bone marrow elements, with adipose tissue and scattered lymphoid aggregates. Radiologically-guided fine-needle aspiration (FNA) is helpful in establishing the diagnosis, thus obviating resection in some patients. We report on a case of an incidental presacral myelolipoma that underwent examination by computer tomography, magnetic resonance imaging, FNA, and immunohistochemical staining. This lesion was also analyzed by flow cytometry. To our knowledge, the use of the latter technique in the characterization of such tumors has not been previously reported.


A survey of the effect of some drugs, chemicals, and enzymes on calcium oxalate precipitation in the rat kidney.
A single intraperitoneal injection of sodium oxalate was used to induce intrarenal tubular precipitation of calcium oxalate in rats. This experimental model was used to screen the efficacy of hydrochlorothiazide, orthophosphate, methylene blue, trypan blue, retinal folic acid, neuraminidase, and lysozyme in retarding intratubular calcium oxalate precipitation. Orthophosphate caused a 53 per cent reduction in calcium oxalate precipitation relative to the control animals.


[Radiology and pregnancy. Principles, general requirements and exposure].
In a radiology department there are frequently asked questions associated with pregnant and breast feeding women. These are related to either pregnant patients or staff members or the questions are centered on the fetus as a patient. For pregnant patients the potential exposure to the mother and the fetus related to the imaging modality selected as well as the effects of the necessary contrast media must be taken into account. Even for methods without ionizing radiation possible limitations in the use for pregnant women must be discussed. Finally, this medical check defines the imaging modality and the necessary protocol and contrast media. The present article describes the legal requirements in Germany, the technical exposure and pharmacological risks for the pregnant woman and the fetus regarding imaging modalities with and without ionizing radiation. The forthcoming second article will address the risk analysis for examinations with ionizing radiation and will present recommendations for typical clinical imaging problems.


How to differentiate retrieval from storage deficit: a stochastic approach to semantic memory modeling.
Some of the methods currently used to differentiate retrieval from storage deficits in brain damaged patients are revisited. Indices based on association or agreement measures among the responses given by the subject on repeated trials, as well as direct estimates of storage and retrieval abilities based on crude percentages, are open to criticism. A simple Markov chain stochastic approach, which is free of the drawbacks of the other methods and which distinguishes storage from retrieval deficits more reliably and powerfully, is proposed.


An association between Emergency Medicine residencies and improved trauma patient outcome.
A study was done to compare trauma patient outcome at American College of Surgeons (ACS) Level l Trauma Centers with Emergency Medicine residency programs (EMRP+) to those without (EMRP-). Ten Level l Trauma Centers were reviewed from the ACS National Trauma Database (5 centers with and 5 without EM residency programs). Of 18,591 trauma patient records, 8679 were identified as EMRP-, and 9912 as EMRP+. After deleting incomplete data sets, 6621 EMRP- and 6150 EMRP+ records remained. Comparisons between patient age, gender, TRISS, complications, deaths, hospital, ICU and ventilator days, and numbers of burns, penetrating and blunt trauma were performed using t-test and chi-square analysis. Despite having a statistically significant older patient population, with more burn and penetrating trauma patients requiring longer ICU stays and longer ventilatory support (p < 0.0001), Emergency Medicine Residency program hospitals had a significantly lower complication rate (5.14% vs. 11.04%, respectively, p < 0.0001), death rate (4.704% vs. 5.479%, respectively, p = 0.0013), and shorter overall hospital stays (Mean 4.94 days, SD +/- 8.74 vs. 6.35 days, SD +/- 11.22, respectively, p < 0.0001) than EMRP- hospitals. The presence of Emergency Medicine residency programs at ACS Level I Trauma Centers is associated with improved trauma patient outcomes.


Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscle.
Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease (COPD) an inflammatory condition characterised by neutrophilic inflammation and release of proinflammatory mediators such as interleukin-8 (IL-8). Human airway smooth muscle cells (HASMC) are a source of proinflammatory cytokines and chemokines. We investigated whether cigarette smoke could directly induce the release of chemokines from HASMC. HASMC in primary culture were exposed to cigarette smoke extract (CSE) with or without TNFalpha. Chemokines were measured by enzyme-linked immunosorbent assay (ELISA) and gene expression by real time polymerase chain reaction (PCR). Data were analysed using one-way analysis of variance (ANOVA) followed by Bonferroni's t test CSE (5, 10 and 15%) induced IL-8 release and expression without effect on eotaxin or RANTES release. At 20%, there was less IL-8 release. TNFalpha enhanced CSE-induced IL-8 release and expression. However, CSE (5-30%) inhibited TNFalpha-induced eotaxin and RANTES production. The effects of CSE on IL-8 release were inhibited by glutathione (GSH) and associated with the induction of the oxidant sensing protein, heme oxygenase-1. Cigarette smoke may directly cause the release of IL-8 from HASMC, an effect enhanced by TNF-alpha which is overexpressed in COPD. Inhibition of eotaxin and RANTES by cigarette smoke is consistent with the predominant neutrophilic but not eosinophilic inflammation found in COPD.


Study of equid herpesviruses 2 and 5 in Iceland with a type-specific polymerase chain reaction.
The horse population in Iceland is a special breed, isolated from other horses for at least 1000 years. This provides an exceptional opportunity to investigate old and new pathogens in an inbred herd with few infectious diseases. We have developed a high sensitivity semi-nested PCR to study equid gammaherpesviruses 2 and 5 (EHV-2 and 5) in Iceland. The first PCR is group specific, the second type-specific, targeting a 113bp sequence in the glyB gene. DNA isolated from white blood cells and 18 different organs was tested for the presence of EHV-2 and 5. This was done in adult horses and foals, healthy and with various enteric infections. Both virus types were easily detected in all types of organs tested or EHV-2 in 79% cases and EHV-5 in 63%. In DNA from PBMC or buffy-coat EHV-2 was found in 20% cases and EHV-5 in 10%, all except one positive were foals. Co-culture of PBMC on fetal horse kidney cells was efficient for detecting EHV-2 but not for EHV-5. We verify here for the first time infections with EHV-2 and 5 in horses in Iceland and show that both viruses are common.


Heart transplant recipient patient with COVID-19 treated with tocilizumab.
A heart transplant 62-year-old patient referred for coronavirus-19 disease (COVID-19) pneumonia. At admission, he was febrile, tachypnoeic, and mild hypoxic with dry cough; during hospitalization, a diffuse morbilliform skin rash appeared. He was treated with tocilizumab with symptoms improvement, without a complete pulmonary function recovery. Skin rash, highly suggestive for COVID-19 cutaneous involvement, persisted for ten days despite tocilizumab administration.


Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression.
Diabetes has been reported to increase the expression of cytochrome P450 (CYP) 2E1 messenger RNA (mRNA) and protein several-fold, and enhanced expression has been associated with elevated ketone bodies. Primary cultured rat hepatocytes were used to explore ketone body and insulin regulation of CYP2E1 expression. Hydroxybutyrate and acetoacetate (AC), alone or in combination, either failed to affect or decreased CYP2E1 mRNA levels by up to 90% relative to untreated hepatocytes. Insulin produced a concentration-dependent decrease in CYP2E1 mRNA levels, and insulin receptor immunoprecipitation showed a correspondence between receptor phosphorylation and the decrease in CYP2E1 mRNA levels at physiologic levels of insulin. Phosphatase inhibitors decreased CYP2E1 mRNA levels by greater than 95%. The phosphatidylinositol 3-kinase (PI3-kinase) inhibitors wortmannin or LY294002 and rapamycin, an inhibitor of p70 S6 kinase phosphorylation, ameliorated the insulin-mediated decrease in CYP2E1 mRNA levels. Geldanamycin, which inhibits Src kinase, also abrogated the insulin-mediated decrease in CYP2E1 mRNA levels. In contrast, the protein kinase C (PKC) inhibitor bisindolylmaleimide, the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, and the p38 mitogen-activated protein (MAP) kinase inhibitor SB202190 did not affect the insulin-mediated decrease in CYP2E1. CYP2E1 mRNA half-life decreased from approximately 48 hours in the absence of insulin to approximately 15 hours at 10 nmol/L insulin, and this decrease was prevented by wortmannin. The half-life of CYP2B mRNA was increased by insulin, whereas that of CYP3A was unaffected. Analysis of CYP2E1 gene transcription using heterogeneous nuclear RNA (hnRNA) showed that insulin suppressed CYP2E1 transcription. In conclusion, these data show involvement of transcriptional and posttranscriptional mechanisms in the insulin-mediated regulation of CYP2E1 and implicate PI3-kinase, p70 S6 kinase, and Src kinase in mediating these effects.


Boosting Solid-State Reconversion Reactivity to Mitigate Lithium Trapping for High Initial Coulombic Efficiency.
An initial Coulombic efficiency (ICE) higher than 90% is crucial for industrial lithium-ion batteries, but numerous electrode materials are not standards compliant. Lithium trapping, due to i) incomplete solid-state reaction of Li+ generation and ii) sluggish Li+ diffusion, undermines ICE in high-capacity electrodes (e.g., conversion-type electrodes). Current approaches mitigating lithium trapping emphasize ii) nanoscaling (<50 nm) to minimize Li+ diffusion distance, followed by severe solid electrolyte interphase formation and inferior volumetric energy density. Herein, this work accentuates i) instead, to demonstrate that the lithium trapping can be mitigated by boosting the solid-state reaction reactivity. As a proof-of-concept, ternary LiFeO2 anodes, whose discharged products contain highly reactive vacancy-rich Fe nanoparticles, can alleviate lithium trapping and enable a remarkable average ICE of ≈92.77%, much higher than binary Fe2 O3 anodes (≈75.19%). Synchrotron-based techniques and theoretical simulations reveal that the solid-state reconversion reaction for Li+ generation between Fe and Li2 O can be effectively promoted by the Fe-vacancy-rich local chemical environment. The superior ICE is further demonstrated by assembled pouch cells. This work proposes a novel paradigm of regulating intrinsic solid-state chemistry to ameliorate electrochemical performance and facilitate industrial applications of various advanced electrode materials.


Preprocessing Sequence Coverage Data for More Precise Detection of Copy Number Variations.
Copy number variation (CNV) is a type of genomic/genetic variation that plays an important role in phenotypic diversity, evolution, and disease susceptibility. Next generation sequencing (NGS) technologies have created an opportunity for more accurate detection of CNVs with higher resolution. However, efficient and precise detection of CNVs remains challenging due to high levels of noise and biases, data heterogeneity, and the "big data" nature of NGS data. Sequence coverage (readcount) data are mostly used for detecting CNVs, specially for whole exome sequencing data. Readcount data are contaminated with several types of biases and noise that hinder accurate detection of CNVs. In this work, we introduce a novel preprocessing pipeline for reducing noise and biases to improve the detection accuracy of CNVs in heterogeneous NGS data, such as cancer whole exome sequencing data. We have employed several normalization methods to reduce readcount's biases that are due to GC content of reads, read alignment problems, and sample impurity. We have also developed a novel efficient and effective smoothing approach based on Taut String to reduce noise and increase CNV detection power. Using simulated and real data we showed that employing the proposed preprocessing pipeline significantly improves the accuracy of CNV detection.


Vitamin D metabolism in preterm infants: serum calcitriol values during the first five days of life.
To ascertain the activity of the vitamin D biosynthetic pathway, the serum concentration of 1,25-dihydroxyvitamin D (calcitriol) was measured in 16 preterm infants (32 to 37 weeks of gestation) at 1 to 2 and 120 hours of age. Half of the subjects received a daily oral supplement of 2,100 IU of vitamin D3 during the five-day study period. In the first two hours of life, all subjects were hypocalcemic (8.2 +/- 0.2 mg/dl) and 14 subjects had low concentrations of 25-hydroxyvitamin D (calcidiol, 8 +/- 1 ng/ml). The latter finding probably reflects a mild degree of vitamin D deficiency in the mothers of our subjects. Calcitriol concentrations (42 +/- 3 pg/ml) were comparable to those of older children. At 120 hours of age, the control group had no significant change in calcitriol values, whereas the group supplemented with D3 had a more than threefold increase. There was a positive correlation between the circulating concentrations of calcidiol and calcitriol over the period of the study. The data show that, after 32 weeks of gestation, renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity is present, with the rate of calcitriol synthesis being apparently substrate limited. Early neonatal hypocalcemia is therefore unlikely to be caused by an impairment of vitamin D activation.