Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia.

Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)2 effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.

NPK in treated wastewater irrigation: Regional scale indices to minimize environmental pollution and optimize crop nutritional supply.

Treated wastewater (TWW) is increasingly used for agricultural irrigation, and often contains higher concentrations of the major plant nutrients N, P, and K than freshwater, reducing the need for agricultural fertilization. However, excessive inputs of nutrients to cropping systems can be harmful to crops and the environment. The present study developed and employed six novel indices to assess the sustainability of TWW-irrigation and spatio-temporal trends in NPK loads to TWW-irrigated fields. Three indices relate to regional analysis of TWW-irrigation sustainability: the 'Environmental sustainability' index measures the TWW compliance with environmental irrigation standards; a 'Nutritional sustainability' index assesses whether the TWW satisfy crop fertilization requirements; a 'Basin nutrient surplus' index measures deviations of N or P loads to river basins from allowed levels. Three additional indices assess the environmental impact, potential loss of nutrients and fit of a given TWW for fertilization recommendations. We employed these indices to analyze a decade-long high spatio-temporal resolution data of TWW quality from Israel on a basin scale, for six TWW-irrigated plantation crops. The results reveal that in high-sensitivity hydrological areas, TWW is generally above the environmental standard for N and P; the TWW with lowest nutrient content is irrigated in low-sensitivity areas, leading to a reduced potential for utilization of nutrients in TWW. While the N irrigation standard (25 mg L-1) does not exceed the nutritional requirements of most analyzed crops, the P standard (5 mg L-1) results in excess fertilization for all analyzed crops. Therefore, environmental and nutritional sustainability of TWW-irrigation can be increased by diverting high-quality TWW to high-sensitivity areas and vice versa. Furthermore, development of local environmental standards will allow maximizing TWW NPK utilization in low-sensitivity areas, increasing nutritional sustainability. The indices presented in this study provide a tool to help maximize the nutritional benefits of TWW while minimizing its environmental impact.

Anatomical review of the mandibular lingula for inferior alveolar nerve block.

The purpose of this study was to perform a review of the literature related to the anatomy of the mandibular lingula and to provide information to improve the execution of effective anaesthesia of the inferior alveolar nerve in clinical practices of the mandible. Prognathic mandibles have a lingula that is located more posterior and superior than non-prognathic mandibles. Most of the lingulae are located above the occlusal plane, but it is occasionally located at or below the occlusal plane. The lingula of the triangular shape was generally located slightly more superior and posterior than other shapes. The mandibular lingula is an important anatomical landmark, and accurate information for exact lingula features is required during inferior alveolar nerve block anaesthesia. Proper evaluation of the lingula is key to effective anaesthesia and decreases the failure rate of the inferior alveolar nerve in clinical practices of the mandible.

Reducing salinity of treated waste water with large scale desalination.

Agriculture, the largest global water consumer, accounts for ~70% of freshwater use thereby considerably influencing water availability. The use of treated wastewater [TWW] for agricultural irrigation has been suggested as a possible solution to help mitigate water scarcity without disrupting food production. However, despite the benefits of TWW irrigation, it is often characterized by high salinity that can reduce crop performance and damage soil structure. In Israel, over 50% of the water used for irrigation is TWW, and a third of the produced TWW undergoes soil aquifer treatment [SAT], i.e., infiltration and percolation to groundwater through the soil before utilization for irrigation. In parallel, seawater desalination provides about 80% of the urban and industrial sector water use. These developments in Israel's water economy during the last three decades, accompanied by extensive governmental monitoring, enabled us to harness high-resolution nation-wide datasets to study the effects of the large-scale introduction of desalination and SAT on TWW quality and salinity in particular. The analyses revealed that large-scale desalination considerably reduced the salinity of TWW to levels similar to freshwater (up to 70% and 60% for Cl and Na, respectively). However, sodium absorption ratio remained unchanged due to the concurrent reductions of Na, Ca and Mg. Mg was reduced to levels that can potentially harm both crops and human health, while B concentrations increased to levels of possible toxicity to crops, suggesting the need for stringent requirements in the post-treatment process. Salinity of groundwater was increased by SAT in the long-term, but was reduced after the introduction of desalination. The results, encompassing almost three decades of water monitoring, suggest that high-quality TWW with a significant portion of desalinated base-water can provide groundwater salinity remediation services.

Comparison between general, spinal, epidural, and combined spinal-epidural anesthesia for cesarean delivery: a network meta-analysis.

BACKGROUND: This study is a network meta-analysis to compare maternal and fetal outcomes associated with four different anesthetic techniques for cesarean delivery. METHODS: An arm-based, random-effects frequentist network meta-analysis was performed. A random effect model was selected considering deviance information criteria. Randomized trials reporting the following outcomes were included: Apgar score at 1- or 5-min; umbilical arterial and venous pH; umbilical arterial pH <7.2; and neonatal score at 2-4 hours. Loop-specific heterogeneity was evaluated by risk of odds ratio and τ2. Quality of evidence was assessed using the GRADE approach. RESULTS: Data from 46 randomized trials including 3689 women contributed to the study. There were significant differences in Apgar score ≤6 at 1 min between spinal versus general anesthesia (odds ratio 0.27, 95% confidence interval [CI] 0.13 to 0.55: moderate quality evidence) and Apgar scores at 1- and 5-min, favoring spinal anesthesia. Umbilical venous pH associated with epidural anesthesia was significantly higher than that with general anesthesia (mean difference 0.010, 95% CI 0.001 to 0.020: moderate quality evidence) or spinal anesthesia. Spinal anesthesia was ranked best for Apgar score ≤6 at 1-min (SUCRA=89.8), Apgar score at 1-min (SUCRA=80.4) and 5-min (SUCRA=90.5). Epidural anesthesia was ranked highest for umbilical venous pH (SUCRA=87.4) and neonatal score (SUCRA=79.3). CONCLUSIONS: Spinal and epidural anesthesia were ranked high regarding Apgar scores and epidural anesthesia was ranked high regarding umbilical venous pH, but the results were based on small heterogeneous studies with high or unclear risks of bias.

Effect of prolonged inspiratory time on gas exchange during robot-assisted laparoscopic urologic surgery.

BACKGROUND: Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia. METHODS: In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis. RESULTS: There was a significant decrease in partial pressure of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1 but in group B the PaO2 at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.

Pharmacological interventions for protecting renal function after cardiac surgery: a Bayesian network meta-analysis of comparative effectiveness.

Many drugs have been investigated as potentially protective of renal function after cardiac surgery. However, their comparative effectiveness has not been established. We performed an arm-based hierarchical Bayesian network meta-analysis including 95 randomised controlled trials with 28,833 participants, which allowed us to compare some agents not previously compared directly. Renal outcomes, including: the incidence of postoperative renal dysfunction and haemodialysis; serum creatinine level at 24 hours postoperatively; all-cause mortality; and length of hospital and ICU stay, were compared. Exploratory meta-regression was conducted for potential effect modifiers. A random effects model was selected according to the evaluation of model fit by deviance information criteria. Atrial natriuretic peptide (odds ratio (95%CrI) 0.28 (0.17-0.48); moderate-quality evidence), B-type natriuretic peptide, dexmedetomidine, levosimendan and N-acetyl cysteine significantly decreased the rate of postoperative renal dysfunction compared with placebo. Atrial natriuretic peptide (OR (95%CrI) 0.24 (0.10-0.58); low-quality evidence), B-type natriuretic peptide, and dexamethasone significantly decreased the need for haemodialysis. Levosimendan significantly decreased mortality, OR (95%CrI) 0.49 (0.27-0.91); low-quality evidence). The benefit of atrial natriuretic peptide was still apparent when baseline renal function was normal. None of the potential effect modifiers were significantly correlated with our renal outcomes. Atrial natriuretic peptide was ranked best regarding renal dysfunction, haemodialysis and length of hospital stay. Levosimendan was ranked best regarding mortality and ICU stay. However, our results should be interpreted cautiously given the assumptions made about transitivity and consistency.

Teratogenic and anticonvulsant effects of zinc and copper valproate complexes in zebrafish.

Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum across all types of seizures and epileptic syndromes. Unfortunately, approximately 30% of epileptic patients are refractory to the classical AED. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. In this preliminary study, we assess the embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, a derivative of valproic acid and the N-donor ligand in an adult zebrafish epileptic seizure model induced by pentylenetetrazole. The most toxic complex was [Cu(Valp)2Bipy], in which the LC50 was 0.22 µM at 48 h post fertilization (HPF) and 0.12 µM at 96 HPF, followed by [Zn(Valp)2Bipy] (LC50 = 10 µM). These same metallodrugs ([Cu(Valp)2Bipy] 10 mM/kg and [Zn(Valp)2Bipy] 30 mM and 100 mM/kg) displayed superior activity, thus reducing the seizure intensity by approximately 20 times compared to sodium valproate (175 mM/kg). Overall, [Cu(Valp)2Bipy] showed the best anticonvulsant effects. However, because of the toxicity of copper, [Zn(Valp)2Bipy] is considered the most promising anticonvulsant for future studies.

Genomic characterization of the porcine CRTC3 and the effects of a non-synonymous mutation p.V515F on lean meat production and belly fat.

cAMP-responsive element-binding protein (CREB)-regulated transcriptional coactivator 3 (CRTC3) is well known to be related to obesity in humans and mice. However, the effects of CRTC3 have not been studied in pigs. Here, we characterized the structure of the porcine CRTC3 gene and identified single nucleotide polymorphisms (SNPs) in its coding region. Moreover, mRNA expression profiles of CRTC3 in muscle and fat tissues were examined. Of the 40 identified SNPs, the p.V515F mutation, located on exon 16, was genotyped in 368 Yorkshire pigs. The p.V515F mutation was significantly associated with lean meat production ability, including reduced back fat thickness (P=0.0317) and loin eye area (P=0.0174). Moreover, the SNP was significantly associated with differences in intermuscular fat (P=0.0092), total muscle area in the belly (P=0.0108), and total fat percentage in the belly (P=0.0298). Taken together, our results suggest that the p.V515F mutation affects to lean meat production ability and amount of belly fat.

Ex vivo magnetic resonance imaging using hyaluronic acid fillers: Differences between monophasic and biphasic fillers.

BACKGROUND/PURPOSE: Hyaluronic acid (HA) is an anionic, non-sulfated glycosaminoglycan distributed throughout the human skin and injectable HA fillers are the most commonly used in aesthetic field. This study aimed to determine if differences in physical characteristics of HA products (monophasic or biphasic fillers) affect the patterns of magnetic resonance imaging (MRI). METHODS: Twenty biphasic fillers and nine monophasic fillers were obtained from a commercial source, and examined with a 3.0 Tesla MRI scanner. Visual assessments and measurements of signal intensity for region of interest (ROI) were performed. A non-parametric Wilcoxon rank sum test was used to compare the ROI values. RESULTS: Visual assessments by a radiologist did not show significant differences between the two types of fillers. While the signal intensity between the two types of filler did not differ significantly for T1-weighted images, the signal intensity of the biphasic filler was lower than that of the monophasic filler for T2-weighted images (P<.01). CONCLUSION: Monophasic and biphasic HA fillers exhibited different MRI properties. Our findings may provide better insights into the use of in vivo MRI to evaluate aesthetic, procedure-related complications.

The incidence and characteristics of 3-month mortality after intraoperative cardiac arrest in adults.

BACKGROUND: There is little information about clinical outcomes after intraoperative cardiac arrest (IOCA). We determined the incidence and characteristics of 3-month mortality after IOCA. METHODS: The electronic medical records of 238,648 adult surgical patients from January 2005 to December 2014 were reviewed retrospectively. Characteristics of IOCA were documented using the Utstein reporting template. RESULTS: IOCA occurred in 50 patients (21/100,000 surgeries). Nineteen patients died in the operating room, and further 12 patients died within 3 months post-arrest (total mortality: 62%). Three survivors at 3 months post-arrest had unfavourable neurological outcome. Finally, 34 patients showed unfavourable clinical outcomes at 3 months post-arrest. The incidences of non-cardiac surgery, emergency, pre-operative intubation state, non-shockable initial cardiac rhythm, hypovolaemic shock, pre-operative complications-induced cardiac arrest, non-anaesthetic cause of cardiac arrest, intra- and post-arrest transfusion, and continuous infusion of inotrope or vasopressor in intensive care unit (ICU) were significantly higher in non-survivors at 3 months post-arrest. Total epinephrine dose administrated during arrest was higher, and the duration of cardiac compressions was longer in non-survivors at 3 months post-arrest. CONCLUSIONS: In this study, the incidence of IOCA was 21/100,000 surgeries and the 3-month mortality rate after IOCA was 62%. Several factors including surgical emergency, non-shockable initial cardiac rhythm, pre-operative complications, surgical complications, long duration of cardiac compressions, high total epinephrine dose, transfusion, and continuous infusion of inotropes or vasopressors in ICU seemed to be risk factors for 3-month mortality after IOCA. These risk factors should be considered in the light of relatively small sample size of this study.

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding.

This corrects the article DOI: 10.1038/onc.2011.331.

An ultra-high gain and efficient amplifier based on Raman amplification in plasma.

Raman amplification arising from the excitation of a density echelon in plasma could lead to amplifiers that significantly exceed current power limits of conventional laser media. Here we show that 1-100 J pump pulses can amplify picojoule seed pulses to nearly joule level. The extremely high gain also leads to significant amplification of backscattered radiation from "noise", arising from stochastic plasma fluctuations that competes with externally injected seed pulses, which are amplified to similar levels at the highest pump energies. The pump energy is scattered into the seed at an oblique angle with 14 J sr-1, and net gains of more than eight orders of magnitude. The maximum gain coefficient, of 180 cm-1, exceeds high-power solid-state amplifying media by orders of magnitude. The observation of a minimum of 640 J sr-1 directly backscattered from noise, corresponding to ≈10% of the pump energy in the observation solid angle, implies potential overall efficiencies greater than 10%.

Increased impedance near cut-off in plasma-like media leading to emission of high-power, narrow-bandwidth radiation.

Ultra-intense, narrow-bandwidth, electromagnetic pulses have become important tools for exploring the characteristics of matter. Modern tuneable high-power light sources, such as free-electron lasers and vacuum tubes, rely on bunching of relativistic or near-relativistic electrons in vacuum. Here we present a fundamentally different method for producing narrow-bandwidth radiation from a broad spectral bandwidth current source, which takes advantage of the inflated radiation impedance close to cut-off in a medium with a plasma-like permittivity. We find that by embedding a current source in this cut-off region, more than an order of magnitude enhancement of the radiation intensity is obtained compared with emission directly into free space. The method suggests a simple and general way to flexibly use broadband current sources to produce broad or narrow bandwidth pulses. As an example, we demonstrate, using particle-in-cell simulations, enhanced monochromatic emission of terahertz radiation using a two-colour pumped current source enclosed by a tapered waveguide.

A preliminary study of new single polymorphisms in the T helper type 17 pathway for psoriasis in the Korean population.

Psoriasis is a polygenic and multi-factorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin (IL)-17A, IL-17 receptor (IL-17R) and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper type 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis. In 208 patients and 266 normal controls, we analysed 31 single nucleotide polymorphisms in 12 genes (CAMP, IL17A, IL17F, IL17RA, IL22, JAK1, JAK2, JAK3, STAT3, TLR7, TLR9 and TYK2; abbreviations: CAMP, human cathelicidin antimicrobial peptide; STAT-3, signal transducer and activator of transcription 3; TLR, Toll-like receptor; TYK2, tyrosine kinase 2). Patients with psoriasis showed a strong association for IL17F rs763780 [odds ratio (OR) = 3·27, P = 0·04], which results in a histidine-to-arginine substitution, and JAK2 rs2274471 (OR = 2·66, P = 0·02). In addition, JAK2 rs7849191 showed a protective pattern, met the significance threshold (OR = 0·77, P = 0·05) and showed a tendency for an inverse association with the frequency of early-onset psoriasis under age 40 years (P = 0·07). In haplotype analysis, JAK1 rs310241A/rs2780889T showed a protective effect (OR = 0·73, P = 0·03) in psoriasis. In conclusion, we report two new psoriasis-susceptibility loci, in IL17F and JAK2, as well as a newly identified late-onset associated protective JAK2 locus and a protective JAK1 haplotype in the Korean population.

Comparison of white blood cell counts by WNR, WDF, and WPC channels in Sysmex XN hematology analyzer.

INTRODUCTION: The Sysmex XN modular system (Sysmex, Kobe, Japan) uses a novel technology for white blood cell (WBC) count and differential, using separate channels: white cell nucleated (WNR), WBC differential (WDF), and white progenitor cell (WPC) channels. We questioned how concordant WBC counts would be between them. METHODS: In a total of 6327 consecutive specimens, WBC counts were compared between WNR and WDF channels. They were also compared in three groups of WBC counts and two groups of chemotherapy status. In 508 specimens from the 4361 specimens that were run on the XN-20 module, the WPC channel was used for reflex test. Data were compared using Pearson's correlation, absolute difference, and percent difference (%D). RESULTS: WBC counts between WNR and WDF channels showed very high correlations in total specimens (r = 0.9976) and in the groups of WBC counts and chemotherapy. As WBC count increased, absolute difference increased, while %D decreased (P < 0.0001, both). Percent difference was 1.55% in total specimens and showed the highest value in the severe leukopenia group (<1.0 × 10(9)/L, 6.18%). CONCLUSIONS: This is the first large-scale study on novel channel technology for WBC counts in the Sysmex XN. WBC counts by WNR, WDF, and WPC channels are highly correlated, and they are overall interchangeable and reliable.

Chirped pulse Raman amplification in warm plasma: towards controlling saturation.

Stimulated Raman backscattering in plasma is potentially an efficient method of amplifying laser pulses to reach exawatt powers because plasma is fully broken down and withstands extremely high electric fields. Plasma also has unique nonlinear optical properties that allow simultaneous compression of optical pulses to ultra-short durations. However, current measured efficiencies are limited to several percent. Here we investigate Raman amplification of short duration seed pulses with different chirp rates using a chirped pump pulse in a preformed plasma waveguide. We identify electron trapping and wavebreaking as the main saturation mechanisms, which lead to spectral broadening and gain saturation when the seed reaches several millijoules for durations of 10's - 100's fs for 250 ps, 800 nm chirped pump pulses. We show that this prevents access to the nonlinear regime and limits the efficiency, and interpret the experimental results using slowly-varying-amplitude, current-averaged particle-in-cell simulations. We also propose methods for achieving higher efficiencies.

Evaluation of zinc effect on cadmium action in lipid peroxidation and metallothionein levels in the brain.

Cadmium (Cd) is a known hepato- and nephrotoxic pollutant and zinc (Zn) metalloproteins are important targets of Cd. Hence, the administration of Zn may mitigate Cd toxic effects. However, the interaction of Cd and Zn has been little investigated in the brain. Previously, we reported a protective effect of Zn on mortality caused by Cd in rats. Here, we tested whether the protective effect of Zn could be related to changes in brain Zn-proteins, metallothionein (MT) and δ-aminolevulinate dehydratse (δ-ALA-D). Male adult rats were daily administered for 10 days with Zn (2 mg kg-1), Cd (0.25 and 1 mg kg-1) and 0.25 mg kg-1 of Cd plus Zn and 1 mg kg-1 of Cd plus Zn. The body weight loss, food intake deprivation, and mortality occurred in 1 mg kg-1 of Cd, but Zn co-administration did mitigate these effects. The brain Zn content was not modified by treatment with Cd, whereas cerebral Cd levels increased in animals exposed to Cd. The administration of 0.25 mg kg-1 of Cd (with or without Zn) induced lipid peroxidation and decreased MT concentration, but 2 mg kg-1 of Zn and 1 mg kg-1 of Cd did not change these parameters. Brain δ-ALA-D was not modified by Cd and/or Zn treatments. Since the co-administration of Zn did not attenuate the changes induced by Cd in the brain, our results suggest that the protective effect of Zn on impairments caused by Cd in animal status is weakly related to a cerebral interaction of these metals.