Human Papillomavirus E2 Regulates SRSF3 (SRp20) To Promote Capsid Protein Expression in Infected Differentiated Keratinocytes.

UNLABELLED: The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the infected epithelial cell, suggesting a sophisticated interplay between host cell metabolism and virus replication. Previously, we demonstrated in differentiated keratinocytes in vitro and in vivo that HPV type 16 (HPV16) infection caused increased levels of the cellular SR splicing factors (SRSFs) SRSF1 (ASF/SF2), SRSF2 (SC35), and SRSF3 (SRp20). Moreover, the viral E2 transcription and replication factor that is expressed at high levels in differentiating keratinocytes could bind and control activity of the SRSF1 gene promoter. Here, we show that the E2 proteins of HPV16 and HPV31 control the expression of SRSFs 1, 2, and 3 in a differentiation-dependent manner. E2 has the greatest transactivation effect on expression of SRSF3. Small interfering RNA depletion experiments in two different models of the HPV16 life cycle (W12E and NIKS16) and one model of the HPV31 life cycle (CIN612-9E) revealed that only SRSF3 contributed significantly to regulation of late events in the virus life cycle. Increased levels of SRSF3 are required for L1 mRNA and capsid protein expression. Capsid protein expression was regulated specifically by SRSF3 and appeared independent of other SRSFs. Taken together, these data suggest a significant role of the HPV E2 protein in regulating late events in the HPV life cycle through transcriptional regulation of SRSF3 expression. IMPORTANCE: Human papillomavirus replication is accomplished in concert with differentiation of the infected epithelium. Virus capsid protein expression is confined to the upper epithelial layers so as to avoid immune detection. In this study, we demonstrate that the viral E2 transcription factor activates the promoter of the cellular SRSF3 RNA processing factor. SRSF3 is required for expression of the E4(^)L1 mRNA and so controls expression of the HPV L1 capsid protein. Thus, we reveal a new dimension of virus-host interaction crucial for production of infectious virus. SRSF proteins are known drug targets. Therefore, this study provides an excellent basis for developing strategies to regulate capsid protein production in the infected epithelium and the production of new virions.

Survival of acral lentiginous melanoma in the National Cancer Institute of Colombia.

OBJECTIVE: To determine survival of a cohort of patients with acral lentiginous melanoma (ALM), treated at the National Cancer Institute of Colombia, the largest referral hospital of the country. METHODS: All patients diagnosed with an invasive ALM between 2003 and 2009 at the Colombian National Cancer Institute were included for analyses and followed for vital status and date of death. Using Kaplan-Meier methods, overall survival at 1, 3 and 5 years post diagnosis was determined, and Cox proportional hazards models were constructed for the variables showing a significant effect on survival in univariate analyses. RESULTS: Overall survival of this cohort of 90 patients was 77% at 1 year, 59% at 3 years and 54% at 5 years after diagnosis. Females had a better prognosis in univariate analyses but this advantage disappeared in multivariate models. Clinical stage was a strong predictor of survival, in univariate and multivariate models, particularly among elderly patients. CONCLUSIONS: Prognosis of ALM in Colombia is relatively poor, particularly for patients with higher clinical stage. The large proportions of ALM diagnosed in stage III and IV explain the relatively poor survival, and illustrate the importance of improving prognosis by lowering stage at diagnosis through better education and early detection programmes.

Effects of dietary supplementation with a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) on joint mobility, comfort, and functional capacity in healthy overweight subjects: a randomized placebo-controlled clinical trial.

BACKGROUND: Joint and connective tissue integrity, comfort and function are paramount to optimal performance in exercise, recreational and occupational activities. The fruit of Terminalia chebula has been used extensively in various traditional health systems for different ailments, with additional preclinical and clinical data demonstrating antioxidant and anti-inflammatory potential. The aim of this study was to evaluate the effects of a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) dietary supplementation on joint mobility, comfort, and functional capacity in healthy overweight subjects. METHODS: One-hundred and five (105) overweight, apparently healthy male and female subjects (35-70 years of age) were pre-screened and randomized to one of three groups for 84 days: placebo, AyuFlex1 (250 mg twice daily) or AyuFlex2 (500 mg twice daily) in a randomized, double-blind, placebo-controlled design. A two-week placebo lead-in period was used to improve data quality/validity. All subjects had no knee joint discomfort at rest, but experienced knee joint discomfort only with activity/exercise of at least 30 on 100 mm Visual Analog Scale (VAS). Primary outcome measures included symptoms of joint health and function as measured by modified-Knee Injury & Osteoarthritis Outcomes Score (mKOOS) global & modified-Western Ontario and McMaster Universities Arthritis Index (mWOMAC) subscales (discomfort, stiffness and function). Secondary outcomes included VAS questionnaires on overall/whole-body joint health, low back health, knee mobility, willingness and ability to exercise, 6-min walk test for distance and range of motion (ROM) of pain-free knee flexion/extension. Tertiary outcome measures included inflammatory (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α) and extracellular matrix (ECM)/Connective Tissue (COMP) biomarkers, and safety (vital signs and blood markers) & tolerability (Adverse Event (AE)/ side effect profiles). RESULTS: Compared to placebo, at day 84 AyuFlex® treatment significantly: 1) improved mKOOS global scores in AyuFlex1 + AyuFlex2 (P = 0.023), and improved total and physical function subscale of mWOMAC relative to baseline, 2) improved VAS scores for Knee Discomfort with activity/exercise in AyuFlex1 + AyuFlex2 (P = 0.001) relative to baseline, 3) improved VAS scores for whole-body joint function in AyuFlex1 + AyuFlex2 (P < 0.029) relative to baseline, 4) improved VAS score for decreased knee joint soreness following leg extension challenge for AyuFlex1 (P = 0.022) and AyuFlex2 (P = 0.043) relative to baseline, 5) improved 6-min walk performance distance covered (P = 0.047) and VAS discomfort (P = 0.026) post-6 min walk in AyuFlex1 + AyuFlex2 relative to baseline, 6) and tended to decrease COMP levels in AyuFlex1 + AyuFLex2 (P = 0.104) relative to baseline. All biomarkers of safety remained within normative limits during the study. Low back health tended to improve in the AyuFlex1 and AyuFlex2 group, but failed to reach significance relative to placebo group. CONCLUSIONS: AyuFlex® improved mKOOS global scores, knee joint discomfort with activity/exercise, 6-min walk test distance covered and discomfort post-6 min walk test, overall whole-body joint function, knee soreness following leg extension resistance exercise in a healthy, overweight population, without AE. Differences between 250 mg/BID and 500 mg/BID were non-significant for most of the outcome measures, validating the efficacy of the lower dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02589249 ; October 26, 2015.

Pharmacologic interventions to treat renal colic pain in acute stone episodes: Systematic review and meta-analysis.

OBJECTIVE: To assess effectiveness of pharmacologic interventions to relieve pain in patients suffering an acute stone episode. METHODS: Relevant trials that included patients with acute renal colic and radiological findings of urinary stones were identified in four databases. The main outcome was pain relief evaluated by Visual Analogue Scale score (VAS). RESULTS: In overall, diclofenac was superior to other NSAIDs for pain relief (MD of -12.57 [95% CI: -19.26, -5.88]). Paracetamol was superior to morphine for pain reduction at 30minutes (MD of -3.92 [95% CI: -6.41, -1.43]) and also to placebo at 15minutes (MD of -24.77 [95% CI: -33.19, -16.35]) and at 30minutes (MD of -16 [95% CI:-29, -2.96]) after drug administration. Finally, diclofenac was superior to paracetamol for pain reduction at 60 (MD of 6.60 [95% CI: 4.37, 8.83]) and 90minutes (MD of 3.4 [95% CI: 2.01, 4.79]). CONCLUSIONS: Diclofenac was superior to other NSAIDs and paracetamol for diminishing pain in patients suffering an acute stone episode. Paracetamol was superior to morphine and placebo for short pain relief. Future trials should address the role of paracetamol in the management of pain in patients suffering an acute stone episode.

Antibacterial effect of roselle extracts (Hibiscus sabadariffa), sodium hypochlorite and acetic acid against multidrug-resistant Salmonella strains isolated from tomatoes.

UNLABELLED: Antibiotic-resistant Salmonella strains were isolated from saladette and red round type tomatoes, and an analysis done of the antibacterial activity of roselle calyx extracts against any of the identified strains. One hundred saladette tomato samples and 100 red round tomato samples were collected from public markets. Each sample consisted of four whole tomatoes. Salmonella was isolated from the samples by conventional culture procedure. Susceptibility to 16 antibiotics was tested for the isolated Salmonella strains by standard test. The antibacterial effect of four roselle calyx extracts (water, methanol, acetone and ethyl acetate), sodium hypochlorite and acetic acid against antibiotic-resistant Salmonella isolates was evaluated on contaminated tomatoes. Twenty-four Salmonella strains were isolated from 12% of each tomato type. Identified Salmonella serotypes were Typhimurium and Typhi. All isolated strains exhibited resistance to at least three antibiotics and some to as many as 12. Over contaminated tomatoes, the roselle calyx extracts produced a greater reduction (2-2·6 log) in antibiotic-resistant Salmonella strain concentration than sodium hypochlorite and acetic acid. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of multidrug-resistant Salmonella in vegetables is a significant public health concern. Multidrug-resistant Salmonella strains were isolated from raw tomatoes purchased in public markets in Mexico and challenged with roselle Hibiscus sabdariffa calyx extracts, sodium hypochlorite and acetic acid. On tomatoes, the extracts caused a greater reduction in the concentration of antibiotic-resistant Salmonella strains than sodium hypochlorite and acetic acid. Roselle calyx extracts are a potentially useful addition to disinfection procedures of raw tomatoes in the field, processing plants, restaurants and homes.

Real-time data acquisition and alerts may reduce reaction time and improve perfusionist performance during cardiopulmonary bypass.

Delayed perfusionist identification and reaction to abnormal clinical situations has been reported to contribute to increased mortality and morbidity. The use of automated data acquisition and compliance safety alerts has been widely accepted in many industries and its use may improve operator performance. A study was conducted to evaluate the reaction time of perfusionists with and without the use of compliance alert. A compliance alert is a computer-generated pop-up banner on a pump-mounted computer screen to notify the user of clinical parameters outside of a predetermined range. A proctor monitored and recorded the time from an alert until the perfusionist recognized the parameter was outside the desired range. Group one included 10 cases utilizing compliance alerts. Group 2 included 10 cases with the primary perfusionist blinded to the compliance alerts. In Group 1, 97 compliance alerts were identified and, in group two, 86 alerts were identified. The average reaction time in the group using compliance alerts was 3.6 seconds. The average reaction time in the group not using the alerts was nearly ten times longer than the group using computer-assisted, real-time data feedback. Some believe that real-time computer data acquisition and feedback improves perfusionist performance and may allow clinicians to identify and rectify potentially dangerous situations.

Theoretical consideration of the effect of drug holidays on BMD and tissue age.

UNLABELLED: It has been suggested that some patients undergoing prolonged treatment for osteoporosis with anti-resorptive agents may benefit from discontinuing treatment. Here we use a computer simulation of bone cell activity to estimate changes in bone mineral density (BMD) and tissue age when treatment is discontinued. INTRODUCTION: Although anti-resorptive agents are effective at reducing fracture risk, questions remain regarding how long patients should continue treatment and how long treatment should be discontinued. Suspending treatment as part of a drug holiday may reduce the risk of adverse effects, but may also lead to reduced BMD. METHODS: We use a computer simulation of the bone remodeling process to estimate how BMD and mean tissue age are changed after treatment is suspended. Mean tissue age is studied because increased tissue age has been associated with impaired bone quality and has been linked to the risk of adverse effects. RESULTS: Our simulations suggest that BMD gains from anti-resorptive therapy can be lost over time, especially with anti-resorptive agents that have little residual effects. With regard to mean tissue age, the simulations suggest that increases in tissue age from anti-resorptive treatment are long lasting; increases in mean tissue age caused by treatment may remain for as long as 15 years after treatment is suspended. After stopping treatment, reductions in BMD are expected to occur long before mean tissue age returns to normal. CONCLUSIONS: Our simulations suggest that, when using a long-lasting anti-resorptive agent, 1- to 5-year drug holidays may have little effect on BMD in most patients but that drug holiday intervals that maintain BMD are unlikely to reverse alterations in tissue age caused by treatment. Our analysis echoes recent reviews suggesting patient selection and monitoring when anti-resorptive treatment is discontinued.

Continuous and discontinuous dynamic unbinding transitions in drawn film flow.

When a plate is withdrawn from a liquid bath a coating layer is deposited whose thickness and homogeneity depend on the velocity and the wetting properties of the plate. Using a long-wave mesoscopic hydrodynamic description that incorporates wettability via a Derjaguin (disjoining) pressure we identify four qualitatively different dynamic transitions between microscopic and macroscopic coatings that are out-of-equilibrium equivalents of known equilibrium unbinding transitions. Namely, these are continuous and discontinuous dynamic wetting and emptying transitions. Several of their features have no equivalent at equilibrium.

Overexpression of peroxiredoxin 2 in pterygium. A proteomic approach.

Pterygium is one of the most frequent pathologies in ophthalmology, and is a benign, fibrovascular lesion originating from the bulbar conjunctiva. It is composed of an epithelium and highly vascular, subepithelial, loose connective tissue. The etiology of pterygium is not clearly understood; the most widely recognized originating factor is ultraviolet radiation. It has been proposed that pterygium and neoplasia have common features, raising the possibility that pterygium is a neoplastic-like growth disorder. In this study, proteomic analysis was performed to show that peroxiredoxin 2 is overexpressed in pterygia compared to healthy conjunctivas. Twelve pterygium specimens were obtained together with healthy conjunctival tissue from the same eyes. Total proteins of pterygia and healthy conjunctivas were analyzed in SDS-PAGE. This analysis showed protein bands expressed exclusively in pterygium samples at the range of 20-25 kDa. After this, 2D electrophoresis was performed for the separation of total proteins; differential spots expressed in pterygium were excised and sequenced. Mass spectrometry (MS) data were searched in the NCBInr and EST databases using the MASCOT program. The spot was identified as peroxiredoxin 2. Real-time PCR, western blot and immunohistochemistry showed that peroxiredoxin 2 was increased in pterygium compared to healthy conjunctiva. Although, these results suggest that overexpression of peroxiredoxin 2 in pterygium could protect the cell against oxidative stress-induced apoptosis, further studies are required to establish the functional role of peroxiredoxin 2 in pterygium to determine its role in peroxidation and apoptosis in this pathology.

Case report: Remote monitoring using Spectrum Medical Live Vue allows improved response time and improved quality of care for patients on cardiopulmonary support.

Clinician rounding on bedside extracorporeal membrane oxygenation (ECMO) is a common coverage practice at many centers across the USA. Occasionally, clinical issues or concerns may go unnoticed for a considerable period of time during the intervals of clinician rounds. We report a case utilizing the LiveVue (Spectrum Medical, Fort Mill, SC) remote monitoring for care of a patient on ECMO. A patient was placed on veno-arterial (VA) ECMO in our intensive care unit, using a Rotaflow centrifugal pump and a Quadrox D polymethylpentene (PMP) fiber oxygenator (both Maquet, Fairfield, NJ). Following ECMO initiation and stabilization, a two-hour rounding schedule was established for the covering perfusionist. On day two, shortly after the perfusionist had rounded, the ECMO flow began fluctuating between 0.1 and 2.1 L/min. A compliance alert (i.e. red flashing notification) was recognized by the perfusion team on a large screen monitor installed in the perfusion pump room. Immediate response from the perfusion team identified venous inflow obstruction due to cannula malposition. The pump revolutions per minute (rpm) and, thus, the resulting flow were temporarily reduced to prevent vessel intimal damage and the surgical team was summoned to reposition the venous cannula. Later in that ECMO run, a steady rise in pre-oxygenator pressure was noted by the perfusionist. This increasingly concerning event was able to be trended and monitored with the LiveVue from a remote location. After a few hours, a compliance alert was noticed again on the LiveVue screen in the pump room. The pre-oxygenator pressure increased by 150 mmHg and the circuit flow decreased by half. Again, the perfusionist response was immediate and an oxygenator change-out ensued. Once more, a potentially dangerous clinical scenario was avoided with continuous critical parameter remote monitoring using the LiveVue system.

A probiotic amylase blend reduces gastrointestinal symptoms in a randomised clinical study.

A randomised, placebo-controlled, double-blind, parallel clinical study was performed to examine the effects of a probiotic- amylase (PRO) blend on gastrointestinal (GI) symptoms. Sixty men and women (44.4 ± 8.9 yr; 82.0 ± 18.4 kg; 170.3 ± 11.5 cm; 28.1 ± 4.6 kg/m2) were randomised into PRO (n = 29) or placebo (PLA: n = 31) groups. Participants exhibited mild to moderate GI symptoms and severity [via Gastrointestinal Symptom Rating Scale (GSRS)] to be eligible for participation. Participants were tested before (Baseline) and after (POST) 6 weeks of supplementation on various gastrointestinal indices, the GSRS (to assess GI symptoms, frequency, and severity), an anxiety questionnaire (GAD-7), and an overall well-being questionnaire (SF-36). Two (PRO vs PLA) × 2 (Baseline vs POST) mixed factorial ANOVAs were completed to assess group, time, and (group × time) interaction effects. Fifty-two subjects who completed the entire study were analysed (PRO: n = 25, PLA: n = 27). There were statistically significant (P≤0.05) interactions for bloating, GSRS score, and abdominal discomfort but time effects for flatulence, constipation, stool regularity, and GAD-7 total score. PRO significantly reduced GSRS score (∼60 vs 25%, d = 0.72), bloating (∼49% vs 25%, d = -0.63) and abdominal discomfort (59% vs 32%, d = -0.66) to a greater degree than PLA. PRO significantly reduced subjective feelings of irritability, pain, and overall health interference. Oral supplementation of the probiotic-amylase blend was very well tolerated. Our study showed that the probiotic-amylase blend reduced the GSRS score and other GI symptoms to a greater degree than PLA. Clinical trial registration: clinicaltrials.gov #NCT05614726.

Comparison of the use of blood pressure telemonitoring versus standard medical care in the achievement of short-term therapeutic goals in blood pressure in patients with uncontrolled hypertension: An open-label clinical trial.

Background: In Mexico less than half of the treated hypertensive patients reach blood pressure (BP) targets. Most hypertensive individuals rely on the standard medical care (SMC) to achieve the BP control goals; however, the efficacy of BP telemonitoring (BPT) to achieve BP targets has been poorly studied. Aim: To compare the efficacy of BPT versus SMC to achieve BP goals in patients with uncontrolled hypertension. Methods: A two-arm, open-label clinical trial was conducted in patients ≥18 years with uncontrolled hypertension. The participants were randomized to 2 arms (BPT vs SMC) and followed for 12 weeks. For the statistical analysis, the chi-squared test and covariance were used. Results: One hundred and seventy-eight participants were included, BPT (n = 94) and SMC (n = 84), after 12 weeks of follow up, we observed a baseline-adjusted reduction in systolic BP with both BPT (-13.5 [1.3] mmHg) and the SMC (-5.9 [1.4] mmHg; p < 0.001) but a greater decrease with BPT (p < 0.001). Likewise, we found a baseline-adjusted reduction of diastolic BP with BPT (-6.9 [0.9] mmHg) and SMC (-2.7 [0.9] mmHg) (p = 0.007) with a more significant percentage change from baseline with BPT (-6.8% [1.0] vs 2.5% [1.1]; p = 0.007). In the BPT arm, a larger proportion of patients achieved the BP target versus SMC (30.5% vs 12.8%; p = 0.005). Conclusion: BPT showed a greater proportion of patients achieving office BP control goals (<140/90 mmHg), compared to standard medical care.

Atrial fibrillation: epidemiology, prognosis and therapy.

Atrial fibrillation is the most common cardiac tachyarrhythmia encountered in clinical practice affecting 1% of the population. It is characterized by uncoordinated atrial activation that can lead to embolic complications and reduction in cardiac output resulting in significant morbidity, mortality and a reduction in quality of life. The three major goals in the management of atrial fibrillation are rate control, prevention of thromboembolism and correction of rhythm disturbance. This article will review up-to-date thinking about strategies for achieving each of these fundamental goals of AF care, with an emphasis on new drugs such as dabigatran and dronedarone and emerging non-pharmacologic therapies such as catheter ablation and left atrial appendage exclusion. After many years with relatively few new treatments, the past few years have seen a number of exciting developments which will hopefully improve clinician's ability to improve the outcomes of patients with this chronic and troublesome condition.

[Application of the « Junior Doctor ¼ status in Radiation Oncology]. / Guide du Docteur Junior en oncologie-radiothérapie.

Introduced in 2017, the reform of the 3rd cycle has modified the organization of the residency in all specialties, and in particular radiation oncology. The residency was thus divided into 3 phases with increasing knowledge and responsibilities. The latter, carried out under the status of "junior doctor", created and defined by decree n°2018-571 of July 3, 2018 and the decree of January 16, 2020, is a phase of supervised autonomy of the resident. Radiotherapy is a singular specialty, with multiple and complex activities, and requires multiple skills. A guide defining the status of the "Junior Doctor" in radiation oncology therefore appears necessary, defining each resident's role and obligations. This guide is of an advisory nature and must be adapted to the particularities of each department. This guide aims to help the implementation of the reform of the 3rd cycle in radiation oncology and especially the final year called the consolidation phase. It is destined to evolve, expanded by individual and collective feedback and the constant renewal of our speciality.

Heterotopia associated with hippocampal sclerosis: an under-recognized cause of early onset epilepsy in children operated on for temporal lobe epilepsy.

PURPOSE: The aim of this study is to report on 52 children operated on for pharmacoresistant temporal lobe epilepsy, with special emphasis on histopathology and correlation with clinical features. METHODS: Charts were retrospectively analyzed. All children underwent comprehensive clinical, electrophysiological and radiological investigations before surgery. Surgical procedures were tailored according to scalp, foramen ovale and eventually depth electrode recordings. Histopathology was compared with clinical variables (χ (2) and Fisher's exact tests). Outcome was evaluated using the Engel scale. RESULTS: Developmental tumor was found in 14 cases, malformation of cortical development (MCD) in 26, isolated hippocampal sclerosis (HS) in 5 and gliosis in 7. Dual pathology (DP) affected 18 patients and the main extrahippocampal lesion consisted of microscopic sub-cortical heterotopias (HS-HT) for 15 patients who shared a particular clinical pattern: a history of febrile seizures (FS) and/or brain injury, early onset of epilepsy without latent period from FS to the first temporal seizure, and a particularly good outcome following surgery. CONCLUSION: In our pediatric temporal lobe surgery series, the prevalence for MCD and for DP was higher than in adult series. Age at seizure onset depends on pathology, and is earlier when involving the neocortex rather than only the hippocampus. We identify the association HS-HT (the most frequent DP in this series), with particular clinical features.

Combining partial nitritation and heterotrophic denitritation for the treatment of landfill leachate previous to an anammox reactor.

Landfill leachate can present extremely elevated concentrations of ammonium (up to 6,000 mg N-NH(4) (+) L(-1)) and a low biodegradable organic matter fraction. As an alternative to conventional systems, this wastewater can be treated on a more sustainable way by a fully autotrophic partial nitritation-anammox system. The operation of the first step of this system, the partial nitritation, is critical since the elevated concentrations of ammonium and nitrite in the reactor can severely inhibit ammonium oxidizing bacteria (AOB) activity. In this way, the inclusion of anoxic phases during the feeding events to promote the denitrification via nitrite can be a good option for upgrading the process performance and increasing the stability of the system. This paper deals with the evaluation of an anoxic-aerobic step-feed strategy for the operation of a partial nitritation SBR. Results of this study have revealed a decrease on the total nitrogen inside the reactor of more than 200 mg N L(-1) without prejudice on the partial nitritation process. Furthermore, this study has also allowed detecting an AOB activity reduction at the end of aerobic phases due to bicarbonate limitation and/or free nitrous acid inhibition.

The effect of urban landfill leachate characteristics on the coexistence of anammox bacteria and heterotrophic denitrifiers.

Heterotrophic denitrification coexists with the anammox process contributing to N removal owing to the biodegradable organic matter supply from urban landfill leachate and the decay of microorganisms. Both biomasses consumed nitrite increasing the nitrite requirements of the system. The aim of this paper is the study of the causes which induce the system to decrease nitrogen removal efficiency. In this study, urban landfill leachate has been treated in an anammox Sequencing Batch Reactor (SBR) for 360 days. The anammox reactor treated on average 0.24 kgN m(-3) d(-1) obtaining nitrogen removal efficiencies up to 89%. The results demonstrated that i) a suitable influent nitrite to ammonium molar ratio is a crucial factor to avoid troubles in the anammox reactor performance; ii) an excess of nitrite implied nitrite accumulation in the reactor; iii) a lower nitrite supply than the necessary for the system could force a loss of specific anammox activity due to nitrite competition with denitrifiers. These results pointed out the importance of the previous partial-nitritation process control in order to obtain a correct influent nitrite to ammonium molar ratio for the anammox reactor. In addition, sudden variation of the leachate characteristics must be avoided.

[Amphiphilic cyclodextrins and their applications. Preparation of nanoparticles based on amphiphilic cyclodextrins for biomedical applications]. / Les cyclodextrines amphiphiles et leurs applications. Elaboration de nanoparticules de cyclodextrines amphiphiles pour des applications biomédicales.

Solubilization of hydrophobic drugs at the molecular level as inclusion complexes inside cyclodextrins (CDs) offers a good alternative for improving their stability, solubility and bioavailability, and for preventing against their possible toxicity or controlling secondary effects. Therefore CDs are widely used as solubilizing excipients. However since dissociation takes place too readily upon dilution, inclusion complexes inside simple water-soluble CD appears ineffective for drug delivery applications. Chemical modifications of CDs allow them to self-organize as larger assemblies useful for resolving this lability issue. Depending on the position, the number and the nature of these groups, amphiphilic CDs can form assemblies such as vesicles, solid-lipid nanoparticles, nanospheres, liquid crystals, or micellar systems. This review deals with the synthesis of amphiphilic cyclodextrins leading to supramolecular assemblies and the physical properties of these assemblies. From the first sulfonated amphiphilic cyclodextrins isolated in our laboratory in 2003, to the latest ones being regioselectively functionalized by two or four fluoroalkyl chains, through the persubstituted fluorinated cyclodextrines, all these amphiphilic cyclodextrins have shown good abilities for encapsulation. Complexation of bioactive molecules (acyclovir) by these modified alpha-cyclodextrin derivatives, the encapsulation efficiency and release profile were measured as an assessment of the properties of such nanoparticles regarding drug delivery applications.

Fishes of southern South America: a story driven by temperature.

The latitudinal extension of southern South America imposes a thermal gradient that affects the structure of marine and freshwater fish assemblages and the biology of the species through direct exposure to the temperature gradients or by means of a web of historical and ecological relationships. We have reviewed biological and ecological data of marine and freshwater fishes from the southern Neotropics, including Patagonia, and report several examples of dependence on temperature, from glacial times to today's climate change. We were able to identify historic and present effects on the diversity of fish assemblages, isolation, southern limits for the distribution of species, and morphological variation among populations. There is a wide range of characteristics that exemplify an adaptation to low temperatures, including biochemical peculiarities, physiological adjustments, and alternative life history patterns, and these appear in both freshwater and marine, and native and exotic fishes. The consequences of stable temperature regimes in both the ocean and thermal streams deserve special mention as these shape specialists under conditions of low selective pressure. At present, habitat use and interactions among species are being subject to changes as consequences of water temperature, and some of these are already evident in the northern and southern hemispheres.

Mechanisms of NRF2 activation to mediate fetal hemoglobin induction and protection against oxidative stress in sickle cell disease.

IMPACT STATEMENT: Sickle cell disease (SCD) is a group of inherited blood disorders caused by mutations in the human ß-globin gene, leading to the synthesis of abnormal hemoglobin S, chronic hemolysis, and oxidative stress. Inhibition of hemoglobin S polymerization by fetal hemoglobin holds the greatest promise for treating SCD. The transcription factor NRF2, is the master regulator of the cellular oxidative stress response and activator of fetal hemoglobin expression. In animal models, various small chemical molecules activate NRF2 and ameliorate the pathophysiology of SCD. This review discusses the mechanisms of NRF2 regulation and therapeutic strategies of NRF2 activation to design the treatment options for individuals with SCD.