[Bullous autoimmune diseases of the oral mucosa].
Autoimmune bullous diseases (AIBD) are characterized by autoantibodies targeted against adhesion molecules, impairing their formation. According to localization criteria, pemphigus (intraepidermal blister and desmosomal involvement) and pemphigoid (subepidermal blister and dermoepidermal junction involvement) can be distinguished. In two-thirds of the cases, pemphigus vulgaris begins with oral lesions (mainly the buccal mucosa and palate, rarely the gingiva). Skin lesions are usual. Excepting paraneoplastic pemphigus (a recently individualized entity), oral lesions are uncommon in other types of pemphigus. Cicatricial pemphigoid mainly involves oral mucosa, frequently other mucous membranes, and rarely the skin. Gingival involvement is frequent. In case of desquamative gingivitis, the clip sign gives the diagnosis of cicatricial pemphigoid. Ocular involvement is frequent and causes blindness. Epidermolysis bullosa acquisita and IgA linear dermatosis are rare. Bullous pemphigoid and bullous lupus rarely involve the oral mucosa. Diagnosis of AIBD requires a biopsy within the mucosal membrane lesion for pathology examination and another biopsy in a lesion-free area for direct immunofluorescence detection of antibody fixation. Immunoelectron microscopy or immunoblast transfer may be needed for positive diagnosis. Corticosteroids are used to treat pemphigus and dapsone is used for cicatricial pemphigoid. Immunosuppressive therapy is rarely needed.


Urinary proteomics and drug discovery in chronic kidney disease: a new perspective.
Chronic kidney disease (CKD) is becoming a worldwide public health problem. The identification of a specific set of early biomarkers for CKD is extremely relevant to progress in disease knowledge, improving diagnosis, treatment, or development, and monitoring efficacy of new drugs. As kidney fibrosis can be considered the common pathological way to end stage renal failure, independent of the initial renal insult, these biomarkers are therefore biomarkers of early tubulo-interstitial fibrosis. The availability of a specific set of biomarkers for CKD is the mandatory condition to create new dedicated drugs and validate them in clinics without waiting years for a functional response in patients. We suggest here specific cohorts of patients where this early signature of fibrosis may be simpler to be identified.


Sister chromatid cohesion at the centromere: confrontation between kinases and phosphatases?
Accurate chromosome segregation in mitosis and meiosis requires that the cohesin complex be protected at the centromere by the Shugoshin/MEI-S332 protein family. Recent studies show that Sgo directly binds the phosphatase PP2A, tethering it to the centromere where it can protect cohesin subunits from phosphorylation, and that localization of Sgo/MEI-S332 itself is regulated by phosphorylation.


The impact of contingency management on quality of life among cocaine abusers with and without alcohol dependence.
The use of quality of life (QOL) measures in substance abuse treatment research is important because it may lead to a broader understanding of patients' health status and effects of interventions. Despite the high rates of comorbid cocaine and alcohol use disorders, little is known about the QOL of this population, and even less about the impact of an efficacious behavioral treatment, contingency management (CM), on QOL. In this study, data from three clinical trials were retrospectively analyzed to examine QOL in outpatient cocaine abusers with and without alcohol dependence (AD) and the impact of CM on QOL over time as a function of AD status. Patients were randomized to standard care (n = 115) or standard care plus CM (n = 278) for 12 weeks. QOL was assessed at baseline and Months 1, 3, 6, and 9. At treatment initiation, AD patients had lower QOL total scores and they scored lower on several subscale scores than those without AD. CM treatment was associated with improvement in QOL regardless of AD status. These data suggest that CM produces benefits that go beyond substance abuse outcomes, and they support the use of QOL indexes to capture information related to treatment outcomes.


[Efficacy analysis of endoscopic endonasal transsphenoidal surgery for recurrent or regrowing pituitary adenomas].
To analyze the safety and efficacy of surgical removal of recurrent or regrowing pituitary adenomas by endoscopic endonasal transsphenoidal approach. The clinical data were retrospectively reviewed for 28 patients undergoing endoscopic endonasal transsphenoidal surgery for recurrent or regrowing pituitary adenomas between April 2010 and December 2013. There were 9 males and 19 females with a mean age of 44. 2 (11 - 73) years. The maximal tumor diameter ranged from 2. 1 to 6.9 cm. The Knosp grades were 1 -2 (n = 11), 3 (n =8) and 4 (n =9). Fifteen tumors were endocrinically functional and the remainder endocrinically nonfunctional. All operations were performed with an assistance of intraoperative neuronavigation. Neuro-ophthalmological, neuroimaging and endocrinological results were followed up postoperatively. And surgical outcomes and risk factors were analyzed for incomplete tumor resection in previous operations. The mean follow-up period was 19. 1 (3 - 45) months. Gross total resection(n = 18, 64. 3%), subtotal resection(n = 6, 21. 4%) and partial resection(n = 4, 14. 3%) were achieved. Postoperatively, visual acuity improved in 11 patients (73. 3%) and 6 patients (40. 0%) showed endocrine remission. Qne patient had short-term postoperative leakage of cerebrospinal fluid (CSF). Endoscopic endonasal transsphenoidal surgery is both safe and effective for recurrent or regrowing pituitary adenomas.


[Campylobacter fetus endocarditis: a case report].
Campylobacter are known to be a cause of enteritidic infections but Campylobacter fetus is more often a cause of systemic infections, mainly in fragilized patients. We report a C. fetus endocarditis. The prognosis seemstobe improved by a prolonged betalactam antibiotic treatment.


Outcomes and general health-related quality of life among patients medically treated in general daily practice for lower urinary tract symptoms due to benign prostatic hyperplasia.
This study's aim was to describe and evaluate outcomes of medical strategies used for lower urinary tract symptoms (LUTS) treatment in general practice and to assess impact of LUTS on patients' general health-related quality of life (HRQoL). This cross-sectional observational study was conducted by French general practitioners. Eligible patients were males aged ≥50 years, diagnosed for at least one year and currently treated for LUTS due to benign prostatic hyperplasia (BPH). Several validated questionnaires were documented by patients to assess severity of LUTS (IPSS), specific quality of life (IPSS-Q8), impact of LUTS (BII), LUTS evolution (VNS) and general HRQoL (EQ-5D). Among 1,098 patients included, 82.7% were treated with monotherapies and 17.3% with combinations. Mean treatment duration was 5.2 ± 3.2 years, and 47.2% of patients had at least one treatment modification since initiation. Patients reported diminished quality of life (IPSS-Q8 ≥3) (42.3%), persisting symptoms (IPSS-score ≥12) (35.5%), symptoms worsening (VNS-score ≤-1) (18.8%) and high bother (BII-score ≥9) (2.6%). Globally, 52.8% had at least one of these unsatisfactory outcomes. Regarding general HRQoL, mean EQ-5D utility significantly decreased with LUTS severity (mild: 0.90 ± 0.12; moderate: 0.81 ± 0.21; and severe symptoms: 0.73 ± 0.25; P < 0.001). As well, all five-dimensions of EQ-5D were significantly altered in patients with moderate-to-severe LUTS (<0.001), especially 'Pain/Discomfort' and 'Anxiety/Depression'. In multivariate analyses including age and comorbidities, EQ-5D utility index remained negatively associated with each additional unit in the IPSS-score. This study shows that around half of BPH patients medically treated report unsatisfactory outcomes, suggesting consequential unmet medical needs in general practice. Also, moderate-to-severe LUTS significantly impact on general HRQoL.


Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer's Disease.
Alzheimer's disease (AD) is the most prevalent cause of dementia and is pathologically characterized by the presence of parenchymal senile plaques composed of amyloid β (Aβ) and intraneuronal neurofibrillary tangles of hyperphosphorylated tau protein. The accumulation of Aβ also occurs within the cerebral vasculature in over 80% of AD patients and in non-demented individuals, a condition called cerebral amyloid angiopathy (CAA). The development of CAA is associated with neurovascular dysfunction, blood-brain barrier (BBB) leakage, and persistent vascular- and neuro-inflammation, eventually leading to neurodegeneration. Although pathologically AD and CAA are well characterized diseases, the chronology of molecular changes that lead to their development is still unclear. Substantial evidence demonstrates defects in mitochondrial function in various cells of the neurovascular unit as well as in the brain parenchyma during the early stages of AD and CAA. Dysfunctional mitochondria release danger-associated molecular patterns (DAMPs) that activate a wide range of inflammatory pathways. In this review, we gather evidence to postulate a crucial role of the mitochondria, specifically of cerebral endothelial cells, as sensors and initiators of Aβ-induced vascular inflammation. The activated vasculature recruits circulating immune cells into the brain parenchyma, leading to the development of neuroinflammation and neurodegeneration in AD and CAA.


The metabolic responses of slideboard exercise in females.
Recently, slideboard exercise training has been introduced as a mode of aerobic training. The purpose of the investigation was to determine the acute cardiovascular and metabolic responses to slideboard exercise. Subjects consisted of 20 healthy females with a mean age of 26.5 +/- 7.9 years, and a VO2max of 40.8 +/- 5.6 ml.kg-1.min-1. The results of the investigation showed that 10 min of a commercially produced slideboard routine elicited mean heart rate (HR) responses ranging from 160 to 168 beats.min-1 and VO2 values of 27.5 to 33.5 ml.kg-1.min-1. A sub-group of 10 subjects was also evaluated while performing sliding exercise at different sliding rates (SR). Subjects performed the standard slide technique at metronome cadences of SR-40, SR-50, and SR-60 slide.min-1. As sliding rate increased so did HR and VO2. The subjects demonstrated mean responses of approximately 55 to 81% of VO2max for the slower to the most rapid sliding rates, respectively. Compared to treadmill exercise at the same oxygen consumption levels, the heart rates for sliding were approximately 15% higher. Slideboard exercise can be an alternative mode of aerobic training.


STABILISE; treatment of aortic dissection, a single Centre experience.
To outline the process of the STABILISE technique and its use; reporting patient outcomes and midterm follow up for complicated aortic dissection. Single centre retrospective analysis from January 2011 to January 2021 using the STABILISE technique which utilises balloon assistance to facilitate intimal disruption and promote aortic relamination. Sixteen patients underwent endovascular aortic repair with the STABILISE technique for aortic dissection over the study period. Fourteen patients (14/16; 88%) had acute dissection. Two of 16 (12%) were chronic. The median age of the patient cohort was 61 years (range 32-80 years) and consisted of a male majority (n = 11; 69%). The median time from diagnosis to intervention was 5 days (1-115 days; IQR 1-17.3). More than half (56%) had surgical repair of a acute type A aortic dissection prior to radiological intervention. The procedure was technically successful with no procedural mortality. Two patients were lost to follow up and two died in the post-operative period. Twelve patients had ongoing follow up with an average number of 2.9 ± 1.6 scans performed. Follow up was available in thirteen patients (81%) with a median follow up period of 1097 days (IQR 707-1657). The rate of re-intervention (n = 2/16; 13%) requiring additional stenting was in line with published re-intervention data (15%). Follow up showed a reduction in false lumen size following treatment with total luminal dimensions remaining stable over the follow-up period. The STABILISE technique as a procedure for complicated aortic dissection, either acute or chronic, appears safe with stable mid-term aortic remodelling and patient outcomes. Level 3, Retrospective cohort study.


Diffusion of Pneumocystis jirovecii in the surrounding air of patients with Pneumocystis colonization: frequency and putative risk factors.
In a prospective bicentric study, Pneumocystis jirovecii excretion and diffusion was explored in air samples collected in the rooms occupied by 17 Pneumocystis-colonized patients. P. jirovecii DNA was detected by real-time PCR in the air collected from 3 patients' rooms (17.6%), with identical genotypes in corresponding clinical and air samples. Pneumocystis DNA was detected for 2/3 patients with autoimmune disease treated with corticosteroids versus 1/6 patients with hematologic disease and 0/5 kidney transplant recipients. These data confirm the possible excretion of the fungus by Pneumocystis-colonized patients and thus bring additional arguments for the prevention of airborne transmission in hospital wards.


Ultrasound-Guided Genicular Nerve Thermal Radiofrequency Ablation for Chronic Knee Pain.
Osteoarthritis (OA) of the knee is one of the most common joint diseases affecting adults in the United States. For elderly patients with multiple medical comorbidities who do not wish to undergo total knee arthroplasty (TKA), lifestyle modification, pharmacologic management, and injections are the mainstay of therapy. Previously, pain management interventions were limited to intra-articular joint injections and viscosupplementation with hyaluronic acid. Fluoroscopic-guided techniques for radiofrequency ablation (RFA) of the genicular nerves have been previously described and a recent cadaveric study suggests that ultrasound-guided genicular nerve blocks can be performed accurately. We performed an ultrasound-guided radiofrequency ablation of the genicular nerves in 88-year-old woman who had deferred surgical management given her age. Following successful ultrasound guided diagnostic genicular nerve blocks, she proceeded to RFA using the same ultrasound guided technique. The procedure resulted in significant pain relief and improvement in overall function for greater than 6 months. The use of ultrasound provides a relatively rapid and noninvasive method to directly visualize genicular nerves and surrounding vasculature. Our case suggests that, for genicular nerve blockade and RFA, ultrasound may be a useful alternative to fluoroscopy. Not only did the procedure result in significant pain relief that has persisted for greater than 6 months but also more importantly her function status and quality of life were improved.


Optimizing blood pressure control in patients with chronic kidney disease.
The majority of patients with chronic kidney disease have hypertension, which is an independent risk factor for progression of kidney disease and cardiovascular disease. Therefore, hypertension should be stringently controlled to a blood pressure level of <130/80 mm Hg. Achieving this goal, which usually requires two or more antihypertensive agents, slows the progression of kidney disease and reduces the risk of cardiovascular disease. All antihypertensive treatments for patients with chronic kidney disease should include a renin-angiotensin-aldosterone system (RAAS) inhibitor (an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Initial therapy with fixed-dose RAAS inhibitor-based combinations should be considered, because this approach has been shown to bring significantly more patients to target blood pressure levels, compared with stepped-care treatment or sequential monotherapy. Fixed-dose combination therapy may also improve patient adherence to treatment by reducing the number of pills taken daily and the number of office visits for dosage adjustments. Recent clinical data suggest that the combination of a RAAS inhibitor and a dihydropyridine calcium channel blocker may provide more cardiovascular benefit than the generally recommended combination of a RAAS inhibitor and a diuretic in patients at high risk for cardiovascular events.


Robust object tracking with reacquisition ability using online learned detector.
Long term tracking is a challenging task for many applications. In this paper, we propose a novel tracking approach that can adapt various appearance changes such as illumination, motion, and occlusions, and owns the ability of robust reacquisition after drifting. We utilize a condensation-based method with an online support vector machine as a reliable observation model to realize adaptive tracking. To redetect the target when drifting, a cascade detector based on random ferns is proposed. It can detect the target robustly in real time. After redetection, we also come up with a new refinement strategy to improve the tracker's performance by removing the support vectors corresponding to possible wrong updates by a matching template. Extensive comparison experiments on typical and challenging benchmark dataset illustrate a robust and encouraging performance of the proposed approach.


High Level of Aristolochic Acid Detected With a Unique Genomic Landscape Predicts Early UTUC Onset After Renal Transplantation in Taiwan.
The unusual high dialysis prevalence and upper urinary tract urothelial carcinoma (UTUC) incidence in Taiwan may attribute to aristolochic acid (AA), which is nephrotoxic and carcinogenic, exposure. AA can cause a unique mutagenic pattern showing A:T to T:A transversions (mutational Signature 22) analyzed by whole exome sequencing (WES). However, a fast and cost-effective tool is still lacking for clinical practice. To address this issue, we developed an efficient and quantitative platform for the quantitation of AA and tried to link AA detection with clinical outcomes and decipher the genomic landscape of UTUC in Taiwan. We recruited 61 patients with de novo onset of UTUC after kidney transplantation who underwent radical nephroureterectomy. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was developed for the quantitation of AA. Pearson's chi-square test, Kaplan-Meier method, and Cox proportional hazard model were utilized to assess the correlations among AA detection, clinicopathological characteristics, and clinical outcomes. Seven tumors and seven paired normal tissues were sequenced using WES (approximately 800x sequencing depth) and analyzed by bioinformatic tool. We found that high level of 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AL-I) detected in paired normal tissues was significantly correlated with fast UTUC initiation times after renal transplantation (p = 0.035) and with no use of sirolimus (p = 0.046). Using WES analysis, we further observed that all tumor samples were featured by Signature 22 mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC)-associated gene mutations, p53 mutations, no fibroblast growth factor receptor 3 (FGFR3) mutation, and high tumor mutation burden (TMB). Especially, mammalian target of rapamycin (mTOR) activation predominated in dA-AL-I-detected samples compared with those without dA-AL-I detection and might be associated with UTUC initiation through cell proliferation and suppression of UTUC progression via autophagy inhibition. Accordingly, dA-AL-I detection can provide more direct evidence to AA exposure and serve as a more specific predictive and prognostic biomarker for patients with de novo onset of UTUC after kidney transplantation.


A Fast Color Image Encryption Algorithm Using 4-Pixel Feistel Structure.
Algorithms using 4-pixel Feistel structure and chaotic systems have been shown to resolve security problems caused by large data capacity and high correlation among pixels for color image encryption. In this paper, a fast color image encryption algorithm based on the modified 4-pixel Feistel structure and multiple chaotic maps is proposed to improve the efficiency of this type of algorithm. Two methods are used. First, a simple round function based on a piecewise linear function and tent map are used to reduce computational cost during each iteration. Second, the 4-pixel Feistel structure reduces round number by changing twist direction securely to help the algorithm proceed efficiently. While a large number of simulation experiments prove its security performance, additional special analysis and a corresponding speed simulation show that these two methods increase the speed of the proposed algorithm (0.15s for a 256*256 color image) to twice that of an algorithm with a similar structure (0.37s for the same size image). Additionally, the method is also faster than other recently proposed algorithms.


Propofol for sedation for direct current cardioversion.
Direct current cardioversion is a low-risk and standard procedure to restore normal sinus rhythm in patients with tachyarrhythmias. It requires sedation to facilitate the procedure, as it is painful and distressful. The preferred anesthetic drug must be short acting, producing conscious sedation, to enable rapid recovery after the procedure. In this sense, this narrative review focuses on the critical analysis of recent randomized studies and presents about the safety and effectiveness of propofol, comparing it with other established sedatives, mainly etomidate and midazolam. The research was performed on MEDLINE database with Propofol and Cardioversion keywords. In most cases, propofol comes to be the best option, with a quick recovery time and low rates of side effects. Different studies have demonstrated no inferiority when comparing to other drugs and, when these adverse events happened, they were easily and quickly handled. Exceptions in this scenario are those patients, particularly the elderly, with baseline important structural heart disease, in which etomidate with fentanyl has been pointed to lead to better hemodynamic stability.


[Evaluation of the immunoregulatory activity of neutrophilokine fractions in a macrophage model].
A procedure was proposed to evaluate the immunoregulatory activity of neutrophilokine fractions on a model of macrophages. It was established that all the fractions studied did not affect the absorptive capacity of these cells in both primary and secondary immune responses. At the same time, the majority of neutrophilokine fractions modulated the killer activity of macrophages: they potentiated or inhibited it. The proposed procedure for evaluating the regulatory effect of individual neutrophilokine fractions on a model of studying the killer activity makes it possible not only to characterize their activity, but also to identify helper and suppressor fractions, which discloses approaches to correcting an immune response by means of these fractions.


The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden.
CD20 monoclonal antibodies are widely used in clinical practice. Antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and direct cell death have been suggested to be important effector functions for CD20 antibodies. However, their specific contributions to the in vivo mechanism of action of CD20 immunotherapy have not been well defined. Here we studied the in vivo mechanism of action of type I (rituximab and ofatumumab) and type II (HuMab-11B8) CD20 antibodies in a peritoneal, syngeneic, mouse model with EL4-CD20 cells using low and high tumor burden. Interestingly, we observed striking differences in the in vivo mechanism of action of CD20 antibodies dependent on tumor load. In conditions of low tumor burden, complement was sufficient for tumor killing both for type I and type II CD20 antibodies. In contrast, in conditions of high tumor burden, activating FcγR (specifically FcγRIII), active complement and complement receptor 3 were all essential for tumor killing. Our data suggest that complement-enhanced antibody-dependent cellular cytotoxicity may critically affect tumor killing by CD20 antibodies in vivo. The type II CD20 antibody 11B8, which is a poor inducer of complement activation, was ineffective against high tumor burden. Tumor burden affects the in vivo mechanism of action of CD20 antibodies. Low tumor load can be eliminated by complement alone, whereas elimination of high tumor load requires multiple effector mechanisms.


Automated external defibrillators: defining optimum levels of accuracy based on the clinical practice of consultant cardiologists.
Several consultant cardiologists were invited to assess the accuracy of the Lifepak 200 automated external defibrillator (AED) (Fig. 1), from ECG records collected from pre-hospital cardiac arrest victims. They were asked to classify the ECG rhythms, and also give an opinion on whether or not a shock should have been given, and the potential harm of inappropriate treatment. As there was no absolute agreement between cardiologists in rhythm classification, sensitivity of the AED for ventricular fibrillation varied from 78% to 100%, and the specificity was between 92% and 100% according to each cardiologist. They agreed that all ventricular fibrillation should be shocked and failure to do so would reduce a patient's chances of survival; and that all other rhythms, and asystole, should not be shocked. Most experts believed shocking asystole would not be harmful, but opinions regarding the potential harm of administering shocks to patients with pulseless rhythm were mixed.


Maternal preeclampsia is associated with an increased risk of retinopathy of prematurity.
To determine the effect of maternal preeclampsia on development and severity of retinopathy of prematurity (ROP) in preterm infants. This prospective study consisted of two groups: the study group, which is composed of preterm infants (≤32 weeks) born to a mother with preeclampsia, and the comparison group, which is composed of preterm infants (≤32 gestational age) born to normotensive mothers. We used the International Classification of Retinopathy of Prematurity Revisited for classifying ROP. The first eye examination was performed at postnatal age of 4 weeks. A total of 385 infants were included in the study. ROP was diagnosed in 109 infants (28%). The incidence of ROP in infants born to preeclamptic mothers (40.5%) was significantly higher compared with those born to normotensive mothers (22.4%) (P<0.05). The number of infants with stage 1, 2, and 3 ROP was significantly higher in infants born to preeclamptic mothers compared with the control group (P<0.05). In multiple logistic regression model, preeclampsia was found to predict ROP (odds ratio 1.78, 95% confidence interval 0.66-1.90). Maternal preeclampsia was found to be associated with increased ROP development risk in premature infants. ROP was also more severe in infants born to pre-eclamptic mothers. The role of maternal preeclampsia in the occurrence and severity of ROP remains to be elucidated.


Codon optimization of Saccharomyces cerevisiae mating factor alpha prepro-leader to improve recombinant protein production in Pichia pastoris.
To evaluate different codon optimization parameters on the Saccharomyces cerevisiae-derived mating factor α prepro-leader sequence (MFLS) to improve Candida antarctica lipase B (CAL-B) secretory production in Pichia pastoris. Codon optimization based on the individual codon usage (ICU) and codon context (CC) design parameters enhanced secretory production of CAL-B to 7 U/ml and 12 U/ml, respectively. Only 3 U/ml was obtained with the wild type sequence while the sequence optimized using both ICU and CC objectives showed intermediate performance of 10 U/ml. These results clearly show that CC is the most relevant parameter for the codon optimization of MFLS in P. pastoris, and there is no synergistic effect achieved by considering both ICU and CC together. The CC optimized MFLS increased secretory protein production of CAL-B in P. pastoris by fourfold.


Large arteriovenous malformation associated with persistent primitive hypoglossal artery--case report.
A rare case of large arteriovenous malformation (AVM) with persistent primitive hypoglossal artery in a 43-year-old male was treated by staged embolization, followed by total removal. AVM associated with carotid-basilar anastomosis is quite rare, but the incidence of AVM in patients with carotid-basilar anastomosis is high. AVM associated with persistent carotid-basilar anastomosis has no distinguishing features compared with ordinary AVM, but participation of the posterior circulation as a feeder is characteristic.


Iodoacetic acid activates Nrf2-mediated antioxidant response in vitro and in vivo.
Iodoacetic acid (IAA) is an unregulated drinking-water disinfection byproduct with potent cytotoxicity, genotoxicity, and tumorigenicity in animals. Oxidative stress is thought to be essential for IAA toxicity, but the exact mechanism remains unknown. Here we evaluated the toxicity of IAA by examining nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response, luciferase antioxidant response element (ARE) activity, and intracellular glutathione (GSH) in HepG2 cells. IAA showed significant activation of ARE-luciferase reporter, mRNA, and protein expression of Nrf2 and its downstream genes (GCLC, NQO1, and HO-1). IAA also increased the intracellular GSH level in HepG2 cells in a time- and concentration-dependent manner. Moreover, we verified IAA induced Nrf2-mediated antioxidant response in rats. Subsequently, we confirmed the specific role of Nrf2 in IAA induced toxicity using NRF2-knockdown cells. Deficiency of NRF2 significantly enhanced sensitivity to IAA toxicity and led to an increase of IAA induced micronulei. We also examined the effects of antioxidant on Nrf2-mediated response in IAA treated cells. Pretreatment with curcumin markedly reduced cytotoxicity and genotoxicity (micronuclei formation) IAA in HepG2 cells. Our work here provides direct evidence that IAA activates Nrf2-mediated antioxidant response in vitro and in vivo and that oxidative stress plays a role in IAA toxicity.


[Familial chylomicronemia].
Familial chylomicronemia is a disease in which a genetic mutation affects the ability of the organism to metabolize triglycerides bound to lipoproteins, causing extremely high plasma triglycerides and associated consequences. The most frequent complication is acute pancreatitis, which may lead to multiorganic failure or pancreatic insufficiency. Familial chylomicronemia also exerts a profound negative impact on quality of life, social relationships and professional development. The gene most frequently affected is lipoprotein lipase-1 gene (LPL), the enzyme in charge of hydrolyzing circulating triglycerides for tissue uptake. Mutations in other genes regulating maturation, transport or polymerization (eg. APOC2, APOAV, LMF-1, GPIHBP-1) of lipoprotein lipase-1, may also be involved. However, in about 30% of patients the causal variant is not identified. Familial chylomicronemia should be suspected in patients with severe hypertriglyceridemia with poor response to conventional treatment, or accompanied by eruptive xanthomas, lipemia retinalis or abdominal pain. The availability of risk scores and genetic tests should facilitate its opportune detection and management. Nutritional therapy is based on a very-low-fat diet with adequate supply of lipid-soluble vitamins and essential fatty acids, plus avoidance of alcohol consumption. Current pharmacological treatment may include fibrates and omega-3 fatty acids but prioritizes biotechnological agents targeting the molecular disturbances of the disease. These include an antisense oligonucleotide against apoC-III (volanesorsen), a monoclonal antibody against angiopoietin-like protein-3 (evinacumab), and other agents currently in development.


Non-compressive myelopathy: clinical and radiological study.
Fifty seven patients (42 males and 15 females) with non-compressive myelopathy were studied from 1997 to 1999. Acute transverse myelitis (ATM) was the commonest (31) followed by Vit B12 deficiency myelopathy (8), primary progressive multiple sclerosis (5), hereditary spastic paraplegia (3), tropical spastic paraplegia (2), subacute necrotising myelitis (1), radiation myelitis (1), syphilitic myelitis (1) and herpes zoster myelitis (1). 4 cases remained unclassified. In the ATM group, mean age was 30.35 years, antecedent event was observed in 41.9% case, 25 cases had symmetrical involvement and most of the cases had severe deficit at onset. CSF study carried out in 23 patients of ATM revealed rise in proteins (mean 147.95mg%, range 20-1200 mg/dL) and pleocytosis (mean 20.78/cumm, range 0-200 mm3). Oligoclonal band (OCB) was present in 28% of cases of ATM. The most common abnormality detected was a multisegment hyperintense lesion on T2W images, that occupied the central area on cross section. In 6 patients hyperintense signal was eccentric in location. MRI was normal in 4 cases of ATM. Thus ATM is the leading cause of non-compressive myelopathy. Clinical features combined with MRI findings are helpful in defining the cause of ATM.


Assessment of Experimental Techniques That Facilitate Human Granuloma Formation in an In Vitro System: A Systematic Review.
The process of granuloma formation is complex, and due to species differences, the validity of animal studies is somewhat questioned. Moreover, the large number of animals needed to observe the different stages of development also raises ethical questions. Therefore, researchers have explored the use of human peripheral blood mononuclear cells (PBMCs), a heterogeneous population of immune cells, in an in vitro model. This review included in vitro studies that focused on exposing PBMCs-from healthy, sensitized, or diseased individuals-to antigens derived from infectious agents-such as mycobacteria or Schistosoma spp.-or inorganic antigens-such as beryllium. The reviewed studies mainly explored how human in vitro granuloma models can contribute towards understanding the pathogenesis of granulomatous diseases, especially during the early stages of granuloma formation. The feasibility of granuloma modelling was thus largely assessed via experimental techniques including (1) granuloma scoring indices (GI), (2) cell surface markers and (3) cytokine secretion profiling. While granuloma scoring showed some similarities between studies, a large variability of culture conditions and endpoints measured have been identified. The lack of any standardization currently impedes the success of a human in vitro granuloma model.


Stroke, angiogenesis and phytochemicals.
Stroke, or brain attack, is the third leading cause of death and the leading cause of adult disability worldwide. There is a great demand for intervention therapy. Unfortunately, although more than 700 drugs that target neuroprotection showed beneficial effects in preclinical animal studies, none of them proved efficacious in treating stroke patients. There is recent interest in understanding mechanism for post-ischemic angiogenesis in the penumbra area, and correlation of the extent of angiogenesis with survival in stroke patients. It is postulated that besides replenishing oxygen and nutrients to ischemic tissue, angiogenesis may play a crucial role in neural protection and tissue recovery. Consequently, therapeutic agents to promote angiogenesis and formation of new vessels after stroke can offer promising approach. Several large population epidemiological and clinical studies have revealed a reciprocal relationship between intake of phytochemicals and incidence of stroke. However, the detailed cellular and molecular mechanisms leading to these beneficial effects remain to be elucidated. In this article, we review the current knowledge on phytochemicals and post-ischemic angiogenesis, and discuss the possibility of a combinatorial treatment, including neuroprotection, angiogenesis, neurogenesis, and phytochemicals regimen for stroke.


A quantitative study on the trachea of the dog.
This study was carried out to record the detailed morphometric structure of the trachea in dogs using 15 female and four male healthy adult mongrel dogs. The diameter and thickness of each tracheal ring were measured, the number of tracheal rings varying from 36 to 45. All data were subjected to statistical analysis which was carried out on individual sections of the trachea, i.e. the cranial cervical, middle cervical, thoracic inlet and the intrathoracic tracheal regions, which consisted of 12, 12, nine and 12 tracheal rings, respectively. Fusion of the tracheal rings was especially obvious in the cranial cervical and thoracic inlet regions as a result of neck movements. The diameter and thickness of the tracheal rings are smallest at the thoracic inlet level because the direction of the trachea changes at this point where the thoracic inlet is relatively small and surrounded by bone. The ratios of inner transverse to inner vertical and outer transverse to outer vertical diameters were almost the same, between 1.14 and 1.25 in all regions, which indicated that the trachea is near-circular in shape in the dog. At the thoracic inlet level cross-sectional lumen areas are 7 and 6% smaller than those in the middle cervical and intrathoracic regions, respectively. The thinnest cartilage was seen at the thoracic inlet level where there is a risk of tracheal collapse.


Effector cell-derived lymphotoxin alpha and Fas ligand, but not perforin, promote Tc1 and Tc2 effector cell-mediated tumor therapy in established pulmonary metastases.
Cytolytic CD8(+) effector cells fall into two subpopulations based on cytokine secretion. Type 1 CD8(+) T cells (Tc1) secrete IFN-gamma, whereas type 2 CD8(+) T cells (Tc2) secrete interleukin (IL)-4 and IL-5. Although both effector cell subpopulations display Fas ligand (FasL) and tumor necrosis factor (TNF), tumor lysis is predominantly perforin dependent in vitro. Using an ovalbumin-transfected B16 lung metastasis model, we show that heightened numbers of adoptively transferred ovalbumin-specific Tc1 and Tc2 cells accumulated at the tumor site by day 2 after therapy and induced tumor regression that enhanced survival in mice with pulmonary metastases. Transfer of either TNF-alpha- or perforin-deficient Tc1 or Tc2 effector cells generated from specified gene-deficient mice showed no differences in therapeutic efficiency when compared with corresponding wild-type cells. In contrast, both Tc1 and Tc2 cells, derived from either FasL or TNF-alpha/lymphotoxin (LT) alpha double knockout mice, showed that therapeutic effects were dependent, in part, on effector cell-derived FasL or LTalpha. Six days after effector cell therapy, elevated levels of activated endogenous CD8/CD44(High) and CD4/CD44(High) T cells localized and persisted at sites of tumor growth, whereas donor cell numbers concomitantly decreased. Both Tc1 and Tc2 effector cell subpopulations induced endogenous antitumor responses that were dependent, in part, on recipient-derived IFN-gamma and TNF-alpha. However, neither effector cell-mediated therapy was dependent on recipient-derived perforin, IL-4, IL-5, or nitric oxide. Collectively, tumor antigen-specific Tc1 and Tc2 effector cell-mediated therapy is initially dependent, in part, on effector cell-derived FasL or LTalpha that may subsequently potentiate endogenous recipient-derived type 1 antitumor responses dependent on TNF-alpha and IFN-gamma.


Evidence for HCO(3) Transport by the Blue-Green Alga (Cyanobacterium) Coccochloris peniocystis.
The possibility of HCO(3) (-) transport in the blue-green alga (cyanobacterium) Coccochloris peniocystis has been investigated. Coccochloris photosynthesized most rapidly in the pH range 8 to 10, where most of the inorganic C exists as HCO(3) (-). If photosynthesis used only CO(2) from the external solution the rate of photosynthesis would be limited by the rate of HCO(3) (-) dehydration to CO(2). Observed rates of photosynthesis at alkaline pH were as much as 48-fold higher than could be supported by spontaneous dehydration of HCO(3) (-) in the external solution. Assays for extracellular carbonic anhydrase were negative. The evidence strongly suggests that HCO(3) (-) was a direct C source for photosynthesis.Weakly buffered solutions became alkaline during photosynthesis with a one-to-one stoichiometry between OH(-) appearance in the medium and HCO(3) (-) initially added. Alkalization occurred only during photosynthesis and was blocked by 3-(3,4-dichlorophenyl)-1, 1-dimethylurea, diuron. It is suggested that HCO(3) (-) was transported into cells of Coccochloris in exchange for OH(-) produced as a result of HCO(3) (-) fixation in photosynthesis.The inorganic C concentration required to support a rate of photosynthesis of half the maximum rate (K(m)) was 6 micromolar at pH 8.0 or, in terms of available CO(2), a K(m) of 0.16 micromolar. This value is two orders of magnitude lower than reported K(m) values for the d-ribulose-1,5-bisphosphate carboxylase for blue-green algae. It is suggested that the putative HCO(3) (-) transport by Coccochloris serves to raise the CO(2) concentration around the carboxylase to levels high enough for effective fixation.


Psychometric Properties of the Persian Version of the Love of Life Scale.
A love of life is defined as an overall positive attitude toward life and a liking for life. The present study was designed to evaluate the psychometric characteristics of a Persian version of the Love of Life Scale using a convenience sample of 145 Iranian female volunteer college students (M age = 23.0 years, SD = 3.4). The mean score on the Love of Life Scale was 61.08 (SD = 11.40). A principal component analysis with a Varimax rotation yielded two factors labeled (a) Positive Attitude Towards Life and Happy Consequences of Love of Life and (b) Meaningfulness of Life. Cronbach's alpha was .94 and the one-week test-retest reliability was .85. Love of Life Scale scores had significant positive correlations with scores on the Oxford Happiness Questionnaire, the Satisfaction with Life Scale, the General Self-Efficacy Scale, and the Adult Hope Scale. The scale displayed negative correlations with the Kessler Psychological Distress Scale and the Wish to be Dead Scale. It was concluded that the Persian form of the Love of Life Scale can be recommended for future research on positive psychology.


[Total knee replacement without patellar resurfacing: about 60 cases].
During total knee replacement, one of the main problems of surgeon is to choose between preservation of the patella or resurfacing with prosthetic replacement of patellar cartilage. This issue continues to be a subject of controversy within the orthopaedic community. There is no clear consensus on the optimal approach to the patella during total knee arthroplasty (TKA). We conducted a retrospective study of 60 patients undergoing total knee replacement without resurfacing of the patella. These procedures were performed in the Department of Orthopedics and Trauma-Surgery (B) at the University Hospital Hassan II, Fez, since January 2009 to December 2015. The average age of patients was 58 years, ranging between 20 years and 80 years. Female prevalence was clear (41 women, 72% and 16 men, 28%). Clinically, the majority of patients had mechanical pain and all patients underwent clinical and radiological examination. The IKS score was used to assess knee condition before and after surgery. The surgical procedure was based on total knee arthroplasty without patellar resurfacing. Post-operative complications included 7 cases of anterior knee pain, 2 cases of infection of superficial skin treated with appropriate antibiotic therapy and 3 cases of stiffness. No cases of hematoma, phlebitis or sepsis were reported. Clinical results after a follow-up period of 18 months were satisfactory. Given these results, the preservation of the patella allowed for very satisfactory middle term results regarding pain relief and restoration of function. In addition, potential complications of patella prosthesis were avoided. One limitation of these replacements without resurfacing is the occurrence, or sometimes the persistence, of anterior knee pain; hence the need for secondary resurfacing. Current data from the literature show that there is no consensus on the approach to the patella during total knee replacement. Finally, patella resurfacing is an approach that the surgeon should choose on the basis of current data. This said, the debate can continue focusing on a single issue: which approach should be used to the patella.


Enantiomer migration order in chiral capillary electrophoresis.
Enantiomer migration order (EMO) in chiral capillary electrophoresis (CE) represents a challenging issue, referred to in less than 20% of the articles on CE enantioseparations. This review article will (i) illustrate the actuality of the topic, (ii) discuss some technical problems related to EMO in CE enantioseparations, (iii) examine the principal differences between CE and other separation techniques from the viewpoint of enantiomer elution order, (iv) demonstrate the potential for a designed reversal of EMO in CE, and (v) emphasize the importance of studying EMO for better understanding of chiral CE as well as its more effective application. Along with CE, the results obtained by other instrumental techniques such as nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), X-ray crystallography, as well as molecular modeling calculations will be shortly discussed. Rather than referring to all published examples of the opposite migration order of enantiomers in CE, the emphasis will be on general aspects. Recently, the reversal of the EMO was described in detail in a book chapter (Chankvetadze, B., Capillary Electrophoresis in Chiral Analysis, Wiley & Sons, Chichester, UK 1997, Chapter 12) as well as in three review articles.


The Potential Role of Smart Infusion Devices in Preventing or Contributing to Medication Administration Errors: A Descriptive Study of 2 Data Sets.
Errors in medication administration are common, with many interventions suggested to reduce them. For intravenous infusion-related errors, "smart infusion devices" incorporating dose error reduction software are widely advocated. Our aim was to explore the role of smart infusion devices in preventing or contributing to medication administration errors using retrospective review of 2 complementary data sets that collectively included a wide range of errors with different levels of actual or potential harm. We reviewed 216 medication administration errors identified from an observational study in clinical practice and 123 medication incidents involving infusion devices reported to a national reporting system. The impact of smart infusion devices in preventing or contributing to these errors was assessed by the research team and an expert panel. The data suggest that use of any infusion device rather than gravitational administration may have prevented 13% of observed errors and 8% of reported incidents; additional reductions may be possible with standalone smart infusion devices, and further potential reductions with smart infusion devices integrated with electronic prescribing and barcode administration systems. An estimated 52% to 73% of errors that occurred with traditional infusion pumps could be prevented with such integrated smart infusion devices. In the few cases where smart infusion devices were used, these contributed to errors in 2 of 58 observed errors and 7 of 8 reported incidents. Smart infusion devices not only prevent some medication administration errors but can also contribute to them. Further evaluation of such systems is required to make recommendations for policy and practice.


Monensin supplementation during late gestation of beef cows alters maternal plasma concentrations of insulin-like growth factors 1 and 2 and enhances offspring preweaning growth.
This study evaluated the effects of maternal prepartum supplementation of dried distillers grains (DDG), with or without monensin addition, on maternal performance and physiology and offspring preweaning growth. On day 0 (approximately 197 ± 4 d prepartum), 150 multiparous, Brangus crossbred beef cows were ranked by their initial body weight (BW; 524 ± 51 kg) and body condition score (BCS; 5.0 ± 0.63), and then randomly assigned into one of 15 bahiagrass (Paspalum notatum) pastures (10 cows and 8.1 ha/pasture). Maternal treatments were randomly assigned to pastures (5 pastures/treatment) and consisted of no prepartum supplementation of DDG (NOSUP) or supplementation of DDG at 1 kg/cow/d (dry matter basis; DM) added with 0 mg (SUP) or 200 mg/d of monensin (SUPMO) from days 0 to 77. Effects of maternal treatment and maternal treatment × day of the study were not detected (P ≥ 0.63) for any forage data. Cow BCS on day 35 and near calving (day 77) did not differ (P ≥ 0.19) between SUP and SUPMO cows but both groups had greater (P ≤ 0.001) BCS compared with NOSUP cows. Cow BCS at the start of the breeding season (day 142) and on day 168 were the greatest (P < 0.0001) for SUPMO cows, least for NOSUP cows, and intermediate (P ≤ 0.02) for SUP cows. Maternal plasma concentrations of glucose did not differ (P ≥ 0.25) among treatments. Plasma concentrations of insulin-like growth factor 1 (IGF-1) on day 77 were the least for NOSUP cows (P ≤ 0.05) and did not differ (P = 0.66) between SUP and SUPMO cows, whereas plasma concentrations of IGF-2 on days 35 and 77 were greatest (P ≤ 0.05) for SUPMO cows and did not differ (P ≥ 0.60) between NOSUP and SUP cows. Birth BW of first offspring did not differ (P = 0.77) between SUP and SUPMO calves but NOSUP calves were lighter at birth (P ≤ 0.05) compared with SUP and SUPMO calves. Percentage of cows pregnant with a second offspring did not differ (P = 0.72) between SUP and SUPMO cows and were the least for NOSUP cows (P ≤ 0.05). First offspring BW at weaning (day 325) was greatest (P ≤ 0.05) for SUPMO calves, least for NOSUP calves, and intermediate for SUP calves. Therefore, adding monensin into prepartum DDG supplements for Bos indicus-influenced beef cows did not increase cow prepartum BCS but led to greatest offspring preweaning growth, likely by modulating maternal plasma concentrations of IGF-1 and IGF-2 during gestation.


Exploring the possibilities of some selected flour blends for the development of bakery products: Comparison with some physicochemical and functional properties of wheat flour.
This study explored the possibilities of some selected flour blends vis-a-vis the physicochemical and functional properties of wheat flour. Ten flour blends from potato starch, cassava, maize and soybean flours and wheat flour were made and evaluated for physicochemical, functional and anti-nutritional properties. The range of proximate values were for moisture (3.76%-6.67%), protein (4.33-8.96%), ash (1.35-1.96%), fat (3.37-4.88%), fibre (1.22-1.89%) and carbohydrate (78.35-84.94%), whereas wheat flour had moisture (9.45%), protein (11.31%), ash (2.54%), fat (3.78%), fibre (1.31%) and carbohydrate (73.90%). Cyanogenic glucoside, saponion and tannin contents increased with increase substitution of cassava and soybean flours. Pasting temperatures of flour blends ranged from 69.03 °C to 78.83 °C, while wheat flour had 78.05 °C. Peak, hot paste, breakdown, setback and cold paste viscosities were 1514-2822, 1036-1597, 487-1225, 580-884 and 1616-2461 cp in flour blends compared to 2361, 1360, 1001, 1079 and 2439 cp of wheat flour. Substitutions with soy flour decreased the peak, hot paste, breakdown and cold paste viscosities but increased the pasting temperatures. L*, a* and b* values ranged from 78.56 to 87.65, -0.34 to 0.71 and 10. 95 to 13.50 in flour blends while the wheat flour varied significantly at 2361.00, 1360.00 and 1001.00. The nutritional and pasting properties of some of flour blends were closely related to wheat flour and may be used for bakery requirements.


Differential Impact of Depressive and Manic Mood States on Alcohol Craving in Comorbid Bipolar Alcoholism: Preliminary Findings.
To examine the differential impact of depressive and manic mood states on alcohol craving in patients with bipolar disorder and comorbid alcoholism. Forty-four men and women, ages 18-65, with DSM-IV-TR comorbid diagnoses of bipolar I disorder and alcohol dependence were assessed over a three-month period to examine the extent to which their depressive and manic symptoms were associated with alcohol cravings (i.e., desire to use and not to use alcohol) at each assessment point, controlling for age, ethnicity, socio-economic status, baseline alcohol use, and number of assessments. Both manic and depressive symptoms were associated with greater desire to use alcohol. Only depressive symptomatology was associated with reduced desire not to use alcohol, and desire not to use alcohol declined over the course of the three-month treatment period. Whereas enhanced desire to drink alcohol may be a conditioned reaction to both manic and depressed mood states, desire not to drink alcohol may be more of an indicator of treatment motivation, which is negatively affected by depressed mood. Depressive symptoms may warrant prioritization and aggressive targeting early in treatment given that desire to refrain from alcohol use was only influenced by depressive symptoms and declined over the course of treatment.


Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure.
Although both asymptomatic ventricular arrhythmias and sudden death are common in patients with chronic heart failure, there is little evidence that patients who have frequent or complex ventricular arrhythmias are at increased risk of sudden death. Two hypotheses may explain the lack of an arrhythmia-sudden death relation in this disorder. First, complex ventricular arrhythmias may be a nonspecific manifestation of a dying left ventricle rather than an indication of a specific arrhythmogenic substrate. In fact, during long-term follow-up, patients with mild heart failure who have nonsustained ventricular tachycardia are more likely to develop clinical progression of the disease rather than sudden death. Second, sudden death may be related to events other than a malignant ventricular arrhythmia. The most common myocardial ischemia, whereas the terminal event in patients with an idiopathic dilated cardiomyopathy is commonly a severe bradyarrhythmia or electromechanical dissociation. Neither outcome can be predicted by a prior history of ventricular arrhythmias on ambulatory electrocardiographic monitoring. If asymptomatic ventricular arrhythmias do not lead to sudden death, then there would appear to be little reason to expect that antiarrhythmic drugs could prevent cardiac arrest in patients with chronic heart failure. This may explain why drugs that suppress ambulatory arrhythmias do not prevent sudden death in these patients, whereas interventions may reduce the risk of unexpected circulatory collapse in this disorder without suppressing ventricular ectopic activity. To make matters more complicated, the desirable actions of antiarrhythmic drugs are attenuated and their negative inotropic and proarrhythmic actions are enhanced in patients with severe cardiac dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)


[An epidemiologic analysis of brucellosis in Liaoning province].
In order to understand the increasing incidence rate of Brucellosis, the relationship between the epidemic trend and physical conditions of humans, data regarding Brucellosis in Liaoning province, in 1990-1996 was analysed. Results showed that the major cause which led to the Brucellosis recurrence was the importation of sheep named short-tail cold-resistant. The distribution of disease was widely spread. However, most endemic foci were being expanded. The spots in Tieling and Fushun area were merged and became one endemic area. Brucellosis maily involved in the farmer's family that raise sheep while pregnancy make women at reprodactive age susceptible to the disease. The incidence rate in city and rural areas were significantly different despite that they had the same environment that bacteria-carrier sheep were raised.


[Detection of chromosome aberrations in brain gliomas by primed in situ labelling].
To investigate the possibility of applying the primed in situ labelling (PRINS) method to detect chromosome aberrations in brain gliomas and eventually for pathological diagnosis, PRINS with chromosome 10 and 12 centromere specific primers as well as chromosome 1 telomere specific primer was carried out on tissues from 5 brain glioma cases, of which 4 cases were found to have monosomy 10 or loss of one copy of chromosome 10. The remaining case was found to have trisomy 12 and multi-copies of chromosome 1. It is suggested that PRINS is a new molecular cytological bio-technique which is faster, simpler and more efficient than conventional fluorescence in situ hybridization, and which may be clinically applied to detect chromosome aberrations in brain gliomas in the future.


Reductions in neuronal density in elderly depressed are region specific.
Frontal regions, including the orbitofrontal cortex (ORB) and dorsolateral prefrontal cortex (dlPFC) have been implicated in the neuropathology of geriatric depression. Prominent reductions in pyramidal neuron density have been recently reported in the ORB of older depressed subjects. However, the cellular pathology of the dlPFC has not yet been examined in these subjects. Postmortem tissue from the dlPFC (Brodmann's area 9, BA9) was collected from 10 older (>60 years old) subjects diagnosed with major depression and 10 age-matched non-psychiatric controls (CTRL). The majority of the subjects were the same as those used for our previous study on neuronal reductions in the ORB in older depressed. Overall (all six layers combined), and laminar density of pyramidal (presumably glutamatergic), and non-pyramidal (GABAergic) neurons as well as cortical and laminar width were measured using linear optical disector of Stereoinvestigator software. Neither the overall nor laminar density of pyramidal or non-pyramidal neurons was significantly different between groups. The cortical and laminar widths were also not affected. These results suggest that neuronal prefrontal pathology in elderly depressed is region specific. No significant changes were detected in the density of any type of neurons in the dlPFC of elderly depressed subjects (present study) whereas, prominent reductions in the density of pyramidal glutamatergic neurons were observed previously in the ORB.


ROS Induce β-Carotene Biosynthesis Caused by Changes of Photosynthesis Efficiency and Energy Metabolism in Dunaliella salina Under Stress Conditions.
The unicellular alga Dunaliella salina is regarded as a promising cell factory for the commercial production of β-carotene due to its high yield of carotenoids. However, the underlying mechanism of β-carotene accumulation is still unclear. In this study, the regulatory mechanism of β-carotene accumulation in D. salina under stress conditions was investigated. Our results indicated that there is a significant positive correlation between the cellular ROS level and β-carotene content, and the maximum quantum efficiency (F v /F m ) of PSII is negatively correlated with β-carotene content under stress conditions. The increase of ROS was found to be coupled with the inhibition of F v /F m of PSII in D. salina under stress conditions. Furthermore, transcriptomic analysis of the cells cultivated with H2O2 supplementation showed that the major differentially expressed genes involved in β-carotene metabolism were upregulated, whereas the genes involved in photosynthesis were downregulated. These results indicated that ROS induce β-carotene accumulation in D. salina through fine-tuning genes which were involved in photosynthesis and β-carotene biosynthesis. Our study provided a better understanding of the regulatory mechanism involved in β-carotene accumulation in D. salina, which might be useful for overaccumulation of carotenoids and other valuable compounds in other microalgae.


Fe-Doped LiNbO(3) for Read-Write Applications.
High erase sensitivity is observed in heavily reduced crystals of Fe-doped LiNbO(3). Only 12 mJ/cm(2) of incident 4880-A radiation erases a hologram, nearly 3 orders of magnitude less energy than previously required. However, the maximum diffraction efficiency that can be reached in these crystals is substantially reduced. These results are shown to be consistent with an extremely low density of Fe(3+) ions. The crystals are resistant to optical scattering effects usually observed in Fe-doped LiNbO(3).


Assessing the localization of centrosomal proteins by PALM/STORM nanoscopy.
The structure of the centrosome was resolved by EM many years ago to reveal a pair of centrioles embedded in a dense network of proteins. More recently, the molecular composition of the centrosome was catalogued by mass spectroscopy and many novel components were identified. Determining precisely where a novel component localizes to within the centrosome remains a challenge, and until now it has required the use of immuno-EM. This technique is both time-consuming and unreliable, as it often fails due to problems with antigen accessibility. We have investigated the use of two nanoscopic techniques, photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), as alternative techniques for localizing centrosomal proteins. The localization of a known centrosomal component, the distal appendage protein Cep164 was investigated by direct STORM (dSTORM) and resolved with a high spatial resolution. We further validated the use of nanoscopic PALM imaging by showing that the previously uncharacterized centrosomal protein CCDC123 (Cep123) localizes to the distal appendages, forming ring-like structures with a diameter of 500 nm. Our results demonstrate that both PALM and STORM imaging have great potential as alternatives to immuno-EM.


Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension.
Endothelin-1 (ET-1) is known to have potent contractile and proliferative effects on vascular smooth muscle cells and is known to induce myocardial cell hypertrophy. We studied the pathophysiological role of endogenous ET-1 in rats with monocrotaline-induced pulmonary hypertension. Four-week-old rats were given a single subcutaneous injection of 60 mg/kg monocrotaline (MCT rats) or saline (control rats) and were killed after 6, 10, 14, 18, and 25 days. In the MCT rats, right ventricular systolic pressure progressively increased and right ventricular hypertrophy developed in a parallel fashion. The venous plasma ET-1 concentration also progressively increased, and this increase preceded the development of pulmonary hypertension. The isolated pulmonary artery exhibited a significantly weaker response to ET-1 in the MCT rats on day 25 but not on days 6 and 14. In the MCT rats, the expression of prepro ET-1 mRNA as measured by Northern blot analysis significantly increased in the heart on days 18 and 25, whereas it gradually decreased in the lungs. The peptide level of ET-1 in the lungs also significantly decreased in the pulmonary hypertensive stage. The expression of prepro ET-1 mRNA had increased by day 6 only in the kidneys. Continuous infusion of BQ-123, a selective ETA receptor antagonist, by an osmotic minipump (14.3 mg per day per rat for 18 days) significantly inhibited the progression of both pulmonary hypertension (right ventricular systolic pressure, 77.8 +/- 4.2 [mean +/- SEM] mm Hg [n = 10] versus 52.3 +/- 2.4 mm Hg [n = 7]; P < .01) and right ventricular hypertrophy (right ventricle/[left ventricle +/- septum], 0.56 +/- 0.03 [n = 10] versus 0.41 +/- 0.02 [n = 7]; P < .01). Histological examination revealed that BQ-123 also effectively prevented pulmonary arterial medial thickening. The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension. The present findings suggest that endogenous ET-1 contributes to the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension.


Portal and umbilical venous blood supply to the liver in the human fetus near term.
To determine the contribution of the umbilical (UV) and portal (PV) veins to blood supply to the human fetal liver in a low-risk population near term, and to assess the distribution between the left and right lobes. In 91 low-risk pregnancies with normally grown fetuses at 36 weeks of gestation we measured the distribution of blood in the UV and PV to the right and left hepatic lobes using ultrasound imaging and Doppler techniques. The median (10(th), 90(th) centile) total UV return was 205 (127, 294) mL/min, of which 25% (13, 47%) was shunted through the ductus venosus, 55% (35, 66%) was distributed to the left hepatic lobe, and 20% (11, 30%) was distributed to the right hepatic lobe. While the left lobe was supplied exclusively by the UV, the right lobe received 50% (20, 70%; 37 (16, 65) mL/min) of its venous blood supply from the PV. The total venous blood supply to the liver parenchyma was 185 (114, 277) mL/min; 21% (8, 34%) came from the PV supply to the right lobe and the remainder came from the UV supply to both lobes. The venous supply to the left lobe is from nutrient-rich UV blood; for the right lobe, half is from UV blood and half from nutrient-poor PV blood. This watershed between the portal and umbilical venous flows to the fetal liver suggests a corresponding functional dichotomy; this may be modified by hemodynamic influences, with long-term consequences.


[Occupational medicine physicians: acceptance of the professional role and motives for the choice of specialization].
The professional role of the physician embraces a relatively permanent and internally coherent system of behaviors perceived as the reaction of other people to expectations and actions related to health problems. Performing this role is the main source of income, social status and prestige. It should be stressed that the role of specialist in occupational medicine differs from that of specialists in other disciplines. Its distinctive feature is that it is not oriented towards treatment, but towards prevention. The study was carried out in 2006, using a questionnaire mailed to a random sample of 820 specialists in occupational medicine or industrial medicine (response rate, 35%) and conducting free interviews with 15 experts. The positive response to the question whether he or she would choose again the specialization in occupational medicine was an indicator of the acceptance of the assumed professional role. The results of the survey showed that 76% of respondents were positive and only 19% would have chosen another specialization. The responses to this question were diversified by the socio-demographic factors. On the basis of this diversification two profiles were constructed, favorable and unfavorable for the acceptance of the choice made in the past. Lack of work satisfaction, poor opportunities for professional advancement, and limited financial profits were reported as the major reasons for choosing other specialization than occupational medicine. The most frequently reported motives for choosing specialization in occupational medicine were the need to meet the requirements of the occupied position, the interest in this branch of knowledge and professional skills. It was also indicated that the acceptance of the role performed by the occupational medicine physician was strongly associated with the above mentioned motives and the expected financial profits. The majority of specialists in occupational medicine are satisfied with the choice of their specialization. Their choice was mostly inspired by autotelic (interests) and instrumental (financial profits and meeting the job requirements) motives.


Predictors of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators.
To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification. Cohort study of patients assigned to placebo in a randomized clinical trial. Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. M-mode and two-dimensional (2-D) echocardiograms performed at study entry and interpreted by local cardiologists. The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis. Left ventricular dysfunction from 2-D echocardiograms (P = 0.003) and the size of the left atrium from M-mode echocardiograms (P = 0.02) were the strongest independent predictors of later thromboembolism. Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism (history of hypertension, recent congestive heart failure, previous thromboembolism) identified 26% of the cohort with a low risk for thromboembolism (1.0% per year; 95% Cl, 0.2% to 4.0%). Compared with risk stratification using clinical variables alone, echocardiographic results altered thromboembolic risk stratification in 18% of the entire cohort and in 38% of those without clinical risk factors. Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation. Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that standard echocardiography contributes to risk stratification, differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis.


In search of health: quality of life among postpartum Palestinian women.
The postpartum period is a very important period for the health of the mother and the newborn. Despite its importance, research on this period is limited and tends to be more focused on biomedical aspects of the postpartum period. In the Occupied Palestinian Territory, little is known regarding women's postpartum wellbeing. This study utilizes the Maternal Postpartum Quality-of-Life instrument to assess Palestinian women's postpartum quality of life and the factors associated with variations in their quality-of-life scores. A cross-sectional survey utilizing the adapted Maternal Postpartum Quality-of-Life Questionnaire was completed in the Occupied Palestinian Territory with a final sample size of 1020 women. The mean overall quality-of-life score for the sample was 21.53 (maximum = 30), suggesting that women are slightly satisfied with their lives in the postpartum period. Main variations in quality-of-life scores were associated with regional district, refugee status, the loss of a relative due to Israeli occupation violence, standard of living and pregnancy wantedness. The results of this study highlight the diversity and complexity of the social context, in particular the region where women live, and the issue of pregnancy wantedness in postpartum quality of life. They also call into question the services currently offered to postpartum women.


Molecular and cytogenetic characterization of two patients with recurrent miscarriages and X-autosome translocation.
To report two patients with recurrent miscarriages and unique reciprocal X-autosomal translocation. Cytogenetic analysis was performed using G-banding and Molecular cytogenetic analysis by Fluorescence in situ hybridization to confirm the breakpoint regions. The chromosomal analysis of the two cases revealed a karyotype of 46,X,t(X;22)(p11.21;q13.3) in the first patient and 46,X,t(X;2)(q22;q13) in second patient. Both the cases were confirmed by using whole chromosome paint probes. This is the rare report of X-autosomal translocations with unique breakpoint regions and their association with recurrent miscarriages. The translocation breakpoint in case 2 on Xq22 and on Xp11.21 in case 1 might be a risk factor for recurrent miscarriages. Here the impact of the X-autosomal translocations is discussed.


Familial renal amyloidosis in Chinese Shar Pei dogs.
Renal amyloidosis was diagnosed in 14 young Chinese Shar Pei dogs, all of which were related. Clinical signs were those of renal failure and included vomiting, anorexia, lethargy, polydipsia, polyuria, weight loss, and dehydration. Some dogs had a history of intermittent fever and joint swelling. Laboratory findings also were compatible with renal failure and included azotemia, hyperphosphatemia, low total CO2 content in serum, isosthenuria, proteinuria, and hypercholesterolemia. All dogs had medullary deposition of amyloid, and 9 of 14 (64%) had glomerular involvement. The remaining renal lesions were typical of end-stage renal disease. In some dogs, amyloid deposits were found in other tissues (eg, liver, spleen, stomach, small intestine, myocardium, lymph node, prostate gland, thyroid gland, and pancreas). Amyloid deposits were sensitive to potassium permanganate oxidation, suggesting the presence of amyloid protein AA.


Assessment of the course of acute pancreatitis in the light of aetiology: a systematic review and meta-analysis.
The main causes of acute pancreatitis (AP) are biliary disease, alcohol consumption, hypertriglyceridaemia (HTG) and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this meta-analysis was to evaluate the effects of these aetiological factors on the severity and outcome of AP. Pubmed and Embase were searched between 01/01/2012 and 31/05/2020. Included articles involved adult alcoholic, biliary, HTG- or post-ERCP AP (PAP) patients. Primary outcome was severity, secondary outcomes were organ failures, intensive care unit admission, recurrence rate, pancreatic necrosis, mortality, length of hospital stay, pseudocyst, fluid collection and systematic inflammatory response syndrome. Data were analysed from 127 eligible studies. The risk for non-mild (moderately severe and severe) condition was the highest in HTG-induced AP (HTG-AP) followed by alcoholic AP (AAP), biliary AP (BAP) and PAP. Recurrence rate was significantly lower among BAP vs. HTG-AP or AAP patients (OR = 2.69 and 2.98, 95% CI 1.55-4.65 and 2.22-4.01, respectively). Mortality rate was significantly greater in HTG-AP vs. AAP or BAP (OR = 1.72 and 1.50, 95% CI 1.04-2.84 and 0.96-2.35, respectively), pancreatic necrosis occurred more frequently in AAP than BAP patients (OR = 1.58, 95% CI 1.08-2.30). Overall, there is a potential association between aetiology and the development and course of AP. HTG-AP is associated with the highest number of complications. Furthermore, AAP is likely to be more severe than BAP or PAP. Greater emphasis should be placed on determining aetiology on admission.


Coronavirus disease 2019 and the liver.
The objective of this review is to examine the epidemiology and pathogenesis of liver injury in coronavirus disease 2019 (COVID-19) and the impact of COVID-19 on patients with chronic liver disease (CLD) and liver transplant recipients. Abnormal liver chemistries occur in up to 60% of COVID-19 patients and are typically mild. COVID-19- associated liver injury may be because of direct viral cytopathic effect, immune-mediated damage, hypoxia, drug-induced liver injury (DILI), or exacerbation of CLD. COVID-19 patients with CLD and who are liver transplant recipients are at risk for severe disease and mortality. COVID-19 precipitated hepatic decompensation in 20-46% of cirrhotic patients. Alcohol consumption and cases of acute alcohol- associated hepatitis increased during the COVID-19 pandemic. Corticosteroids and calcineurin inhibitors are well tolerated to use during COVID-19 but immunomodulators have been associated with mortality. Less than 50% of transplant recipients produce adequate antibody titers after COVID-19 vaccination. COVID-19 patients with CLD should be monitored for liver injury and hepatic decompensation. Patients with CLD and liver transplant recipients should be considered for targeted COVID-19 pharmacotherapeutics and advised vaccination against COVID-19, including a third booster dose. CLD treatments and immunosuppression in liver transplant recipients could generally continue without interruption during COVID-19 infection, with the possible exception of immunomodulators.


The association of headache frequency with pain interference and the burden of disease is mediated by depression and sleep quality, but not anxiety, in chronic tension type headache.
A better understanding of potential relationship between mood disorders, sleep quality, pain, and headache frequency may assist clinicians in determining optimal therapeutic programs. The aim of the current study was to analyze the effects of sleep quality, anxiety, depression on potential relationships between headache intensity, burden of headache, and headache frequency in chronic tension type headache (CTTH). One hundred and ninety-three individuals with CTTH participated. Headache features were collected with a 4-weeks headache diary. The Hospital Anxiety and Depression Scale was used for assessing anxiety and depression. Headache Disability Inventory evaluated the burden of headache. Pain interference was determined with the bodily pain domain (SF-36 questionnaire). Sleep quality was assessed with Pittsburgh Sleep Quality Index. Path analyses with maximum likelihood estimations were conducted to determine the direct and indirect effects of depression, anxiety, and sleep quality on the frequency of headaches. Two paths were observed: the first with depression and the second with sleep quality as mediators. Direct effects were noted from sleep quality, emotional burden of disease and pain interference on depression, and from depression to headache frequency. The first path showed indirect effects of depression from emotional burden and from sleep quality to headache frequency (first model R 2 = 0.12). Direct effects from the second path were from depression and pain interference on sleep quality and from sleep quality on headache frequency. Sleep quality indirectly mediated the effects of depression, emotional burden and pain interference on headache frequency (second model R 2 = 0.18). Depression and sleep quality, but not anxiety, mediated the relationship between headache frequency and the emotional burden of disease and pain interference in CTTH.


Anthropometric and body frame size characteristics in relation to body mass index and percentage body fat among adult Bengalee male brick-kiln workers from Murshidabad, West Bengal, India.
Anthropometric and body frame size parameters (ABFSP) are used to interpret body mass and to evaluate nutritional status. Objective of the present study was to investigate the interrelationships between ABFSP, percentage body fat (BF%) and body mass index (BMI). The study was carried out in a sample of 141 adult Bengalee healthy male brick-kiln workers (age range 18-59 years) from Murshidabad district in West Bengal, India. Body weight was recorded; anthropometric measurements included height, breadth (elbow, wrist, hand, foot, ankle, knee), circumferences (mid-upper arm, chest, waist, hip, thigh, medial calf) and skinfolds (biceps, triceps, subscapular, suprailiac). Derived ABFSP included sum of breadth and circumferences, frame index, BMI, BF%, sum of skinfolds, ratio of central and peripheral skinfolds, arm muscle area, arm muscle circumference, arm fat area and brachial adipo-muscular ratio. Correlations (age-controlled) between ABFSP, BMI and BF% were highly significant (p < 0.001). The ABFSP and BF% varied significantly (p < 0.0001) in relation to BMI-based nutritional status (BNS). Multinomial logistic regression analysis (age-adjusted) showed ABFSP had statistically significant (p < 0.01) relationships with BNS. There were strong interrelationships between ABFSP, BMI and BF% independent of age. The ABFSP in individuals with normal BMI, suffering from undernutrition (low BMI) or overweight are different.


Plant omics: genome-wide analysis of ABA repressor1 (ABR1) related genes in rice during abiotic stress and development.
Rice is one of the world's most important food crops. Approximately 50% of rice production is affected by drought, an abiotic stress greatly impacting crop quality and yield. Agrigenomics research now offers the promise of understanding the drought stress impacts at a systems level. ABA repressor 1 (ABR1) is a member of the ethylene-responsive element-binding factor (ERF/AP2) superfamily of ERF transcription factors. We report here a global expression analysis of the rice ABR1-related genes where we identified the expression pattern of each Oryza sativa ERF (OsERF) during various developmental stages and abiotic stress treatments. The group X OsERFs, closely related genes orthologous to ABR1, exhibited significant differential expression profiles during certain stages of development and in response to abiotic stresses. We selected a subset of these genes and validated their observed expression profiles in response to abiotic stresses using quantitative RT-PCR. Moreover, we discovered that pairs of recently duplicated group X OsERFs display highly distinct expression profiles from one another. We determined the subcellular localization of two group X OsERF genes and observed localization to the nucleolus. To the best of our knowledge, this is the first report of localization of rice ERF protein to the nucleolus. This study also points out an overlap of expression under abiotic stress and reproductive developmental stages, indicating cross talk among different signaling pathways. This genome-wide expression analysis of rice ABR1 homologs paves the way for future functional analyses, with the goal to develop strategies to improve rice abiotic stress tolerance.


Awareness and Preventative Behaviours Regarding Toxoplasma, Listeria and Cytomegalovirus Among Pregnant Women
Aim Infection with toxoplasma, listeria and cytomegalovirus (CMV) infections can negatively affect pregnancy outcomes. Awareness of these infections, knowledge of preventive practices and pertinent behaviours was assessed. Methods A survey of patients at antenatal clinics in a Dublin maternity hospital was conducted over a six month period. Analysis was undertaken using SPSS. Results The response rate was 36% (287/800). One in two respondents were aware of toxoplasma, one in four of Listeria but only 1 in 10 of CMV. Overall, knowledge was highest among older, more educated pregnant women. Nativity had a significant effect on knowledge and behaviour, but increasing parity did not. However the majority practised key safe behaviours. Conclusion Information must be conveyed to pregnant women in a user friendly format and in a culturally sensitive way.


The labor force and urbanization in the Middle East: analysis and policy.
"The purpose of this paper is to describe and comment on the labor force movements in the Middle East with particular reference to the implications of these flows for the process of urbanization in the region. [The author deals] with both international transfers of labor and internal movements of labor to urban communities." The international flow of labor in the Middle East in general is first examined, and a classification scheme is outlined to identify the major differences that exist within the region. Internal labor force migration is then analyzed using data for Libya. The final sections of the paper deal with data collection and policy issues.


Ctenosciara alexanderkoenigi sp. n. (Diptera: Sciaridae), an exotic invader in Germany?
A new species of the genus Ctenosciara Tuomikoski, 1960 is here described based upon a single specimen, obtained from collectings in the garden at Museum Alexander Koenig in Bonn. Ctenosciara alexanderkoenigi sp. n. differs from all other congeneric European species by its striking coloration and distinct male genitalia. However, DNA barcoding reveals associations with two specimens from New Zealand. Therefore a recent migration of Ctenosciara species from the Australasian Region, the likely center of origin of the genus, is discussed. A key to the European species of Ctenosciara is provided. Barcoding results reveale that Ctenosciara exigua is not clearly distinguished from Ctenosciara hyalipennis by its COI sequence (both share the same BIN BOLD:AAH3983) and that its species status may be questionable.


Novel immunogenicity of Oka varicella vaccine vector expressing hepatitis B surface antigen.
Recombinant Oka (ROka) varicella vaccine expressing hepatitis B surface antigen (HBsAg) and subunit HBsAg vaccine (SHV) were used as primary and booster HBsAg vaccines in 3 combinations (SHV-SHV, SHV-ROka, and ROka-SHV) in guinea pigs. Immune responses to HBsAg and varicella-zoster virus gE:gI were evaluated. The 3 combinations induced similar levels of the lymphocyte proliferation response to HBsAg. Of the 3 combinations, SHV-SHV induced the strongest antibody response to an "a" loop of HBsAg and to the whole HBsAg. Its ratio of antibody titer to this loop versus HBsAg was significantly higher than that in SHV-ROka, suggesting the supplementary recognition of the conformational epitope of HBsAg in SHV-ROka. SHV-ROka induced delayed-type hypersensitivity (DTH) to the HBsAg and gE:gI produced in infected cells. Thus, ROka induced DTH to HBsAg and enhanced recognition of the conformational epitope. ROka varicella vaccine may serve as a novel vaccine vector to induce a Th1-type immune response.


Effects of 1-methylcyclopropene and hot water quarantine treatment on quality of "Keitt" mangos.
The optimal 1-methylcyclopropene (1-MCP) treatment to slow ripening of whole "Keitt" mangos, either alone or in combination with hot water treatment (HWT) (prior to or post 1-MCP) was identified. USDA-APHIS mandates that HWT can be used for control of fruit flies, but this may affect fruit response to 1-MCP. Mangos were evaluated by repeated measurement of nondestructive firmness, peel color, and ethylene production on the same mango fruits during 2 wk of ripening at 20 °C after treatment. The magnitude of ethylene production increased as a result of both 1-MCP and HWT. With softer mangos (65 N), treatment with 1-MCP alone delayed fruit softening and extended the number of days to full-ripeness (25 N) from 5 d in untreated fruit to 11 d. For these riper fruit, application of 1-MCP prior to HWT extended the days to full-ripeness to 9 d compared with 7 d when 1-MCP was applied after HWT. With firmer mangos (80 N), 1-MCP treatments alone prolonged the days to full-ripeness to 13 d as compared to 11 d for the untreated fruit. There was no significant concentration effect on firmness retention among 1-MCP treatments (0.5, 1.0, or 10.0 μL/L). HWT resulted in a faster rate of fruit softening, taking only 7 d to reach full-ripeness. Combining 1-MCP with HWT reduced the rate of softening compared to HWT alone, resulting in 9 to 11 d to full-ripeness. Application of 1-MCP before HWT showed a greater ability to reduce the rate of fruit softening compared with 1-MCP treatment after HWT.


Strategies for Nitrite Replacement in Fermented Sausages and Effect of High Pressure Processing against Salmonella spp. and Listeria innocua.
The development of nitrite-free meat products is a current industrial concern. Many efforts have been attempted to replace the nitrite effect in cured meats colour formation and pathogens control. Our previous work evidenced that lactic acid and a cold ripening were the best hurdle technologies for nitrite-free fermented sausages from metabolomics. In the first part of this work, we investigated the effect of lactic acid compared with both two alternative additives (glucono-D-lactone and a mix of sodium di-acetate/sodium lactate) and with low-nitrite sausages, all of them following either cold or traditional ripening. For this purpose, microbiological analysis, pH, water activity (aw), and a sensory study were performed. All nitrite-free sausages (cold or traditional ripened) showed quality and safety traits similar to low-nitrite traditionally ripened ones used as control. In addition, sensory study revealed that sausages with lactic acid were the most preferred cold ripened samples, supporting that this is an optimal strategy for the production of nitrite-free sausages. We selected this product for further studies. Indeed, in the second part, we evaluated the impact of ripening, and other hurdle technologies as High Pressure Processing (HPP) and under-vacuum storage against Listeria innocua and Salmonella spp. by a challenge test. Maximal declines were obtained for ripening along with HPP (i.e., 4.74 and 3.83 log CFU/g for L. innocua and Salmonella spp., respectively), suggesting that HPP might guarantee nitrite-free sausages safety. Although the quality of raw materials remains essential, these hurdle strategies largely contributed to nitrite-free sausages safety, offering a promising tool for the meat industry.


Mechanism of sulfide-quinone reductase investigated using site-directed mutagenesis and sulfur analysis.
Biological sulfide oxidation is a reaction occurring in all three domains of life. One enzyme responsible for this reaction in many bacteria has been identified as sulfide:quinone oxidoreductase (SQR). The enzyme from Rhodobacter capsulatus is a peripherally membrane-bound flavoprotein with a molecular mass of approximately 48 kDa, presumably acting as a homodimer. In this work, SQR from Rb. capsulatus has been modified with an N-terminal His tag and heterologously expressed in and purified from Escherichia coli. Three cysteine residues have been shown to be essential for the reductive half-reaction by site-directed mutagenesis. The catalytic activity has been nearly completely abolished after mutation of each of the cysteines to serine. A decrease in fluorescence on reduction by sulfide as observed for the wild-type enzyme has not been observed for any of the mutated enzymes. Mutation of a conserved valine residue to aspartate within the third flavin-binding domain led to a drastically reduced substrate affinity, for both sulfide and quinone. Two conserved histidine residues have been mutated individually to alanine. Both of the resulting enzymes exhibited a shift in the pH dependence of the SQR reaction. Polysulfide has been identified as a primary reaction product using spectroscopic and chromatographic methods. On the basis of these data, reaction mechanisms for sulfide-dependent reduction and quinone-dependent oxidation of the enzyme and for the formation of polysulfide are proposed.


Screening for modulators of neural network activity in 3D human iPSC-derived cortical spheroids.
Human induced Pluripotent Stem Cells (iPSCs) are a powerful tool to dissect the biology of complex human cell types such as those of the central nervous system (CNS). However, robust, high-throughput platforms for reliably measuring activity in human iPSC-derived neuronal cultures are lacking. Here, we assessed 3D cultures of cortical neurons and astrocytes displaying spontaneous, rhythmic, and highly synchronized neural activity that can be visualized as calcium oscillations on standard high-throughput fluorescent readers as a platform for CNS-based discovery efforts. Spontaneous activity and spheroid structure were highly consistent from well-to-well, reference compounds such as TTX, 4-AP, AP5, and NBQX, had expected effects on neural spontaneous activity, demonstrating the presence of functionally integrated neuronal circuitry. Neurospheroid biology was challenged by screening the LOPAC®1280 library, a collection of 1280 pharmacologically active small molecules. The primary screen identified 111 compounds (8.7%) that modulated neural network activity across a wide range of neural and cellular processes and 16 of 17 compounds chosen for follow-up confirmed the primary screen results. Together, these data demonstrate the suitability and utility of human iPSC-derived neurospheroids as a screening platform for CNS-based drug discovery.


Pre-birth selection of umbilical cord blood donors.
. The fact that only a small percentage of cord blood units (CBU) stored are actually used for transplantation contributes to raising the already high costs of their processing and cryopreservation. The identification of predictors allowing the early identification of suitable CBU would allow a reduction of costs for the collection, storage and characterisation of CBU with insufficient volume or cell numbers. In our bank we have adopted a cut-off value for using CBU of 8 x 10(8) nucleated cells and a volume >or= 60 mL. In 365 banked CBU, we evaluated the correlation between neonatal/gestational parameters and laboratory data used to assess their quality. Biparietal diameter (BPD) and abdominal circumference were significantly and positively correlated with CBU volume (r(2)=0.12, p=0.0011 and r(2)=0.092, p=0.0063, respectively). Receiver operating characteristic (ROC) analysis showed that both parameters can be used to identify CBU with insufficient volume (BPD: area under the curve 0.69, 95% CI=0.57-0.82, p=0.004; abdominal circumference: area under the curve 0.67, 95% CI=0.54-0.79, p<0.01). BPD and head circumference, but not abdominal circumference or femoral length, were positively correlated with white blood cell (WBC) count (r(2)=0.215, p=0.031, and r(2)=0.299, p=0.015, respectively). Abdominal circumference, but not BPD, head circumference or femoral length, was statistically significantly correlated with the number of CD34(+) cells in the CBU. Weight at birth and placental weight were positively correlated with WBC count, blood volume, CD34(+) cell count, total colony-forming units and burst-forming units. . Pre-birth assessment of BPD might allow the selection of donors who would yield CBU of sufficient volume and WBC count and avoid the costs of collecting, transferring, storing and analysing CBU with a high probability of resulting unsuitable for transplantation.


Dual laser interferometer for plasma density measurements on large tokamaks.
A two-wavelength plasma density interferometer utilizing a CO(2) laser and an HeNe laser is described. The interferometer is being designed for use on Doublet III, a large noncircular cross-section tokamak. The use of the two wavelengths allows the distinction between fringe shifts due to plasma density and fringe shifts due to mirror vibrations. Plasma density fringe shifts of 1/10 of a fringe shift can be measured in the presence of mirror vibrations which cause several fringe shifts. A simple digital phase comparing electronic system is used.


[Cervical intervertebral disc calcification in children: report of 10 patients].
Eleven cervical intervertebral space calcifications were studied in ten children (5 boys, 5 girls), with mean age of 9.4 years. The aetiology, symptoms, roentgenographic clinic features were analyzied. All ten patients showed evidence of calcification of the cervical intervertebral disc. One had calcification in two disc spaces of the cervical spine and associated with subluxation of C1,2. Two patients had calcification protruded into the spinal canal without symptoms of spinal cord compression. One had symptom of nerve root irritation. Eight of ten patients had symptoms which disappeared in two weeks after treatment. Eight patients had been followed over one year. The calcification disappeared from 2 to 8 months. The diagnostic criteria for the syndrome of this study are: (1) pediatric age group only; (2) local or referred pain; (3) limited cervical spine motiion; (4) evidence of inflammation; (5) visible calcification of the cervercal intervertebral disc on roentgenogram; (6) self-limited course; (7) good result after conservative treatment and good prognosis.


Estrogen receptors alpha and beta exhibit different estradiol and estrogen response element binding in the presence of nonspecific DNA.
Estrogen receptors (ER) alpha and beta bind estradiol (E(2)) and estrogen response element (ERE) DNA sequences with high affinities. The different migration of ER--ERE complexes in the presence or absence of nonspecific DNA suggests that DNA may affect ER conformation and function. We measured the rate of E(2)--ER association and specific ER--ERE binding capacity (ERE--SBC) in the presence or absence of nonspecific DNA. Whereas DNA did not alter the rate of E(2)--ER alpha association, both ERE-containing and plasmid DNA decreased the rate of E(2) association with ER beta. Poly(dI-dC) decreased ERE--SBC of ER alpha, but did not affect the ERE--SBC of ER beta. Salmon sperm genomic DNA decreased the ERE--SBC of ER alpha, but increased the ERE--SBC of ER beta. We speculate that interaction of ER with genomic DNA may contribute to ER activation and play a role in the observed differences in transcriptional activity of ER alpha and ER beta.