Slight Reversal Research Articles

Effects of phosphodiesterase 5 inhibitor (viagra) on biochemical parameters of l-name-induced testicular toxicity in adult male wistar rats

Testicular toxicity is a growing concern in today's world, with various factors contributing to its prevalence. Nitric oxide (NO) imbalance, often induced by N (gamma)-nitro-L-arginine methyl ester (L-NAME), is a significant factor associated with testicular dysfunction. Sildenafil (Viagra), a phosphodiesterase type 5 inhibitor, has shown promise in improving testicular function by modulating NO levels. This study aimed to investigate the role of Sildenafil (Viagra) on biochemical parameters of L-NAME-induced testicular toxicity in Wistar rats. Twenty-four adult male Wistar rats were divided into four groups: Control (physiological saline-treated), L-Name (L-Name-induced testicular toxicity), PDE (Sildenafil-treated), and L-Name + Sildenafil (co-treatment) and subjected to a 56-day treatment regimen. At the end of the administration, the animals were sacrificed, tissues collected and biochemical and histological assessments were performed. Findings revealed that L-Name administration led to a significant decreased in nitric oxide levels, follicle stimulating hormone, luteinizing hormone, testosterone and increase in oxidative stress when compared to the control group. Furthermore, histological analysis demonstrated structural alterations in the testes of L-NAME-treated rats, indicative of testicular toxicity. Rats treated with Sildenafil showed a slight reversal of these adverse effects. Also, slight reversals of impaired spermatogenesis were evident in the co-treatment group. This study provides compelling evidence for the potential therapeutic role of sildenafil in ameliorating L-NAME-induced testicular toxicity in adult male Wistar rats.

Tunability of magnetoelectric coupling in BiFeO3–PbZr0.52Ti0.48O3–CoFe2O4 tri-phase composites for ultra-fast switching applications

Magnetoelectric coupling an exquisite feature of multiferroics make them suitable for advanced technological applications like magnetic sensors, spintronic devices, and fast-switching devices, respectively. In the present work, a series of tri-phase composites (1-x)(0.7BiFeO3 +0.3PbZr0.52Ti0.48O3) + xCoFe2O4 (x = 0.00, 0.02, 0.04, 0.06, 0.08, 0.10) is synthesized through sol–gel auto-combustion method followed by the solid-state ball milling route. The analysis of X-ray diffraction patterns confirms the development of the rhombohedral perovskite phase of BiFeO3, the tetragonal phase of PbZr0.52Ti0.48O3, and the cubic spinel structure of CoFe2O4. The micrographs clearly show an increase in the average grain size by enhancing the CoFe2O4 contents having sharp and distinct grain boundaries. The energy-dispersive X-ray study assures the exact formation of a composite recipe through elemental mapping. The ferroelectric analysis comprising bipolar polarization versus electric field loops exhibits a significant decrease in maximum polarization with an increase in remanent polarization by enhancing the CoFe2O4 contents in the composite. The positive up and negative down sequence validates the presence of leakage current in all the samples with precise measurement of remanent polarization with and without switching polarization. The gradual increase of CoFe2O4 contents causes an increase in the magnetic response of the composites. Meanwhile, the magnetoelectric coupling phenomenon for all the composition shows a linear response whereas for x = 0.1 there is a slight reversibility observed, making this tri-phase composite a robust candidate for fast-switching devices.

Disaggregation of Asphaltene Aggregates in Solutions Depending upon Affinity Indices of the Hansen Solubility Parameter Using Ultrasmall-, Small-, and Wide-Angle X-ray Scattering

Disaggregation of asphaltene aggregate in solution is investigated using ultrasmall-, small-, and wide-angle scattering of X-rays up to 300 °C under isobaric conditions. Wide-angle scattering profiles indicate that the longer range structure of asphaltene aggregates in toluene collapses around 150 °C. A further increase in the temperature to 300 °C, however, leads to a slight reversion to the aggregated state. This specific behavior in solution is discussed in terms of the transition of asphaltene from a solid to a melted state around 200 °C and the corresponding change in affinity indices of the Hansen solubility parameter (HSP) at elevated temperatures. Ultrasmall- and small-angle scattering profiles of samples in solution clearly show the correlation of asphaltene aggregation with the HSP indices. To understand a deeper insight into key aspects of asphaltene aggregation behavior, small-angle scattering of model compounds in toluene is measured. The scattering intensities of model compounds are classified into two groups: suggesting and confirming molecular structures contributing to enhanced aggregation and heteroaromatics containing sulfur, peri-condensed aromatic rings, and porphyrin.

Isolated CNS relapse of medullary aggressive high-grade B-cell lymphoma on 18F-FDG-PET/CT

This is a case of high-risk, aggressive, high-grade medullary B-cell lymphoma presenting with new onset of neurological dysfunction following initial complete response to the standard chemoimmunotherapy. A whole-body re-staging PET using fluorodeoxyglucose (18F-FDG) integrated with computed tomography (18FDG-PET/CT) performed with clinical suspicion of arachnoiditis, eloquently demonstrated unequivocal multifocal FDG uptake by the spinal cord without evidence of systemic recurrence, leading to a clinical diagnosis of secondary CNS lymphoma, which is a rare complication of DLBCL with ominous prognosis. Four cycles of Modified-MATRIX protocol resulted in a halt in fulminant course of the disease and the patient experienced slight reversal of the neurological deficits, although not deemed clinically fit for a repeat 18FDG-PET/CT due to his poor general well-being. Repeat MRI was suggestive of partial recovery, however. The clinical stability was proven short-lived, and the patient experienced progressive lower limb weakness only 3 weeks after discharge following his last cycle of treatment. Isolated CNS relapse of lymphoma is a rare occurrence in the literature. The CNS recurrence is more often leptomeningeal or confined to the brain parenchyma rather than the spinal cord. The role of 18FDG-PET/CT in the diagnostic algorithm of secondary CNS lymphoma is unclear and its significance in risk stratification and assessing the response to treatment has not been evaluated. This case report illustrates the imaging findings of a more unusual form of the disease with multifocal intramedullary involvement of the spinal cord, and highlights imaging features of this rare condition with 18FDG-PET/CT and MRI to support decision making in good clinical practice.

MicroRNA Regulates Early-Life Stress–Induced Depressive Behavior via Serotonin Signaling in a Sex-Dependent Manner in the Prefrontal Cortex of Rats

BackgroundThe underlying neurobiology of early-life stress (ELS)-induced major depressive disorder is not clearly understood. MethodsIn this study, we used maternal separation (MS) as a rodent model of ELS and tested whether microRNAs (miRNAs) target serotonin genes to regulate ELS-induced depression-like behavior and whether this effect is sex dependent. We also examined whether environmental enrichment prevents susceptibility to depression- and anxiety-like behavior following MS and whether enrichment effects are mediated through serotonin genes and their corresponding miRNAs. ResultsMS decreased sucrose preference, which was reversed by enrichment. Males also exhibited greater changes in forced swim climbing and escape latency tests only following enrichment. Slc6a4 and Htr1a were upregulated in the frontal cortex following MS. In male MS rats, enrichment slightly reversed Htr1a expression to levels similar to control rats. miR-200a-3p and miR-322-5p, which target SLC6A4, were decreased by MS, but not significantly. An HTR1A-targeting miRNA, miR-320-5p, was also downregulated by MS and showed slight reversal by enrichment in male animals. miR-320-5p targeting of Htr1a was validated in vitro using SHSY neuroblastoma cell lines. ConclusionsAltogether, this study implicates miRNA interaction with the serotonin pathway in ELS-induced susceptibility to depression-related reward deficits. Furthermore, because of its recovery by enrichment in males, miR-320 may represent a viable sex-specific target for reward-related deficits in major depressive disorder.

“Stealth” dendrimers with encapsulation of indocyanine green for photothermal and photodynamic therapy of cancer

Poly(amido amine) dendrimers and indocyanine green have inevitable interaction with proteins and cells, which induces biological toxicity and reduces therapeutic efficacy in vivo. To overcome these shortcomings, a new drug delivery system G5MEK7C(n)-ICG with a “stealth” layer was prepared. The surface of G5MEK7C(n)-ICG was modified with double-layer super hydrophilic zwitterionic materials. In the “stealth” double-layer structure, the outer layer was consisted of zwitterionic Glu-Lys-Glu-Lys-Glu-Lys-Cys (EK7) peptide, and the inner layer was composed of amino and carboxyl groups with a ratio of 1:1. DLS results showed that the average hydrodynamic size of G5MEK7C(n)-ICG was about 25–30 nm, and the zeta potential was proven to undergo a slight charge reversal with the increasing pH values of solutions. Furthermore, G5MEK7C(n)-ICG exhibited excellent biocompatibility to red blood cells and proteins resistance. Photothermal and photodynamic experiments demonstrated that G5MEK7C(n)-ICG had a good photothermal conversion effect and generated singlet oxygen (1O2) under laser irradiation. The MTT and hemolysis results showed that the toxicity of G5 PAMAM was significantly reduced after modification double-layer structure. Cytotoxicity studies and flow cytometry showed G5MEK7C(70)-ICG under laser irradiation had a good effect on killing A549 cells. More importantly, the tumor inhibition rate of mice treated with G5MEK7C(70)-ICG (under laser irradiation) was 78.2% in vivo, which was higher than that of mice treated with free ICG. Compared with free ICG, G5MEK7C(70)-ICG caused less damage to the liver according to the enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Therefore, dendrimers modified with a zwitterionic double layer will be a promising candidate as a drug delivery system.

Effect of cold-anesthetization rate on blood biochemical parameters and muscle composition during live channel catfish Ictalurus punctatus waterless preservation

Cold-anesthetization waterless live fish preservation is considered a promising alternative strategy. This work investigates the effects of temperature chilling rates of 2, 4, and 6 °C/h on serum biological parameters and muscular chemical composition of channel catfish Ictalurus punctatus and the influence of waterless preservation time (6, 9, 12, 15, and 18 h) on survival after subjection to three chilling rates. Fish subjected to increasing chilling rates showed lower survival and shorter preservation time. The research results revealed that a temperature gradient drop of 2 °C/h was conducive to maintaining the activity of creatinine (CREA), lactic dehydrogenase (LDH), and pyruvate kinase (PK). The serum aspartic transaminase (AST) and alanine transaminase (ALT) activity dramatically increased after anesthetization. Blood urea nitrogen (BUN) and CREA, whose activity is sensitive to hydropenic conditions, increased significantly after waterless preservation and showed a slight reversal after recovery. Anesthetization caused a significant decrease in protein and fat in muscle, while no obvious trend was observed among different chilling groups. Muscle glycogen (MG) and water-holding capacity (WHC) decreased after anesthetization, then increased after preservation for 12 h, and decreased again after recovery for 24 h. The muscle pH showed the opposite trend. It can be concluded that the whole process resulted in marked changes in the muscle chemical composition. The development of a new green method for anesthetization of live channel catfish for long-term waterless preservation in the present work helps to determine the physiological changes that occur during preservation, providing an effective reference for investigation in other freshwater fish.

The end of the EU affair: the UK general election of 2019

The UK election of 12th December 2019 – the third election in five years and the second snap election in a row – returned a Conservative majority government led by Boris Johnson and the lowest number of Labour MPs since 1935. Three-and-a-half years after the 2016 referendum, the government finally had sufficient parliamentary support for Brexit, and at the end of January 2020 the UK left the European Union. The result of the election can largely be explained by the continuing importance of Brexit. The previous election, held in 2017, had seen an increase in party sorting along Brexit lines – Leavers had shifted towards the Conservatives, whilst Remainers shifted towards Labour. The 2019 election saw a continuation of that process on the Leave side, as the Conservatives continued to win over Leavers, but a slight reversal on the Remain side, with some Remainers abandoning Labour for more avowedly pro-EU parties such as the Liberal Democrats.

Investigating Chaos on the Johannesburg Stock Exchange

This study investigates the existence of chaos on the Johannesburg Stock Exchange (JSE) and studies three indices namely the FTSE/JSE All Share, FTSE/JSE Top 40 and FTSE/JSE Small Cap. Building upon the Fractal Market Hypothesis to provide evidence on the behavior of returns time series of the above mentioned indices, the BDS test is applied to test for non-random chaotic dynamics and further applies the rescaled range analysis to ascertain randomness, persistence or mean reversion on the JSE. The BDS test shows that all the indices examined in this study do not exhibit randomness. The FTSE/JSE All Share Index and the FTSE/JSE Top 40 exhibit slight reversion to the mean whereas the FTSE/JSE Small Cap exhibits significant persistence and appears to be less risky relative to the FTSE/JSE All Share and FTSE/JSE Top 40contrary to the assertion that small cap indices are riskier than large cap indices.

Time-varying price shock transmission and volatility spillover in foreign exchange, bond, equity, and commodity markets: Evidence from the United States

We study the cross-market financial shocks transmission mechanism on the foreign exchange, equity, bond, and commodity markets in the United States using a time-varying structural vector autoregression model with stochastic volatility (TV-SVAR-SV). The price shocks are absorbed immediately in two or three days, suggesting that all markets are quite efficient. A slight mean reversion and an overshooting behavior are observed. Considering the volatility spillover effect, we highlight two properties of volatility shocks. First, the effects of the volatility shocks are released gradually. Reaching peak volatility spillover levels would require five to ten days. Second, the dynamics of volatility spillovers vary tremendously over time. Different types of markets respond to certain, but not all, extreme events. Our findings suggest the need to conduct investor monitoring of current events instead of using technical analysis based on historical data. Investors should also diversify their portfolios using assets that can respond to different and extreme shocks.

Wind‐modulated buoyancy circulation over the Texas‐Louisiana shelf

AbstractThis numerical investigation examines buoyancy‐driven circulation on the Texas‐Louisiana shelf modulated by seasonal winds. In wintertime, with downcoast (in the direction of Kelvin wave propagation) wind forcing, the Mississippi‐Atchafalaya River plume exhibits a bottom‐advected pattern. The plume is fairly wide and the horizontal density gradients span almost across the entire shelf inshore of 50 m. Within the plume, vertical shear of alongshore flow is in thermal wind balance with the cross‐shore density gradient, and the shear causes a slight reversal of alongshore flow near the bottom. An alongshore flow estimated by the thermal wind relation, along with an assumption of zero bottom velocity, generally well agrees with the actual flow near the surface in regions deeper than 20 m. In spring and summer, the thermal‐wind‐balance‐derived flow deviates from the actual alongshore flow, and an Ekman flow driven by strong onshore wind makes the major contribution to the deviation. Besides, the summertime upcoast wind component transforms the plume to a surface‐advected state, resulting in reduced cross‐shore density gradients and increasing the relative importance of wind‐driven, barotropic alongshore flow, which contributes to the remaining deviation.

Chlorpyrifos and cypermethrin induce apoptosis in human neuroblastoma cell line SH-SY5Y.

Our previous in vivo studies showed that chlorpyrifos (CPF) and cypermethrin (CM) in a mixture dermally administered, strongly inhibited cholinesterase activity in plasma and the brain and were very toxic to the rat central nervous system. In this work, the mechanisms of neurotoxicity have not been elucidated. We used human undifferentiated SH-SY5Y cells to study mechanisms of pesticide-induced neuronal cell death. It was found that chlorpyrifos (CPF) and its mixture with cypermethrin (CPF+CM) induced cell death of SH-SY5Y cells in a dose- and time-dependent manner, as shown by MTT assays. Pesticide-induced SH-SY5Y cell death was characterized by concentration-dependent down-regulation of Bcl-2 and Bcl-xL as well as an increase in the caspase 3 activation. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal effect of pesticide-induced toxicity indicating that the major caspase pathways are not integral to CPF- and CPF+CM-induced cell death. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 and mecamylamine failed to attenuate pesticides effect. Atropine exhibited minimal ability to reverse toxicity. Finally, it was shown that inhibition of TNF-α by pomalidomide attenuated CPF-/CPF+CM-induced apoptosis. Overall, our data suggest that FAS/TNF signalling pathways may participate in CPF and CPF+CM toxicity.

Do “Hot Hands” Exist in Funds of Hedge Funds?

One of the most important news events for the U.S. stock markets is certainly the election of the President. This study seeks to determine whether market reactions to elections are a valuable source of information for investors. Using data for the years 1896–2001, a momentum effect appears during the remainder of the election year, a slight reversal effect appears across the president’s term, and a strong reversal effect appears during the President’s second year in office. The difference in campaign information during the election and actual subsequent economic policy implementations may explain why the market’s vote does count. <b>TOPICS:</b>Real assets/alternative investments/private equity, security analysis and valuation, analysis of individual factors/risk premia

Does the Market’s Vote Count? The InformationalContent of Post-Presidential Election Returns

One of the most important news events for the U.S. stock markets is certainly the election of the President. This study seeks to determine whether market reactions to elections are a valuable source of information for investors. Using data for the years 1896–2001, a momentum effect appears during the remainder of the election year, a slight reversal effect appears across the president’s term, and a strong reversal effect appears during the President’s second year in office. The difference in campaign information during the election and actual subsequent economic policy implementations may explain why the market’s vote does count.

Fatty Infiltration and Rotator Cuff Atrophy

Moderate to severe fatty infiltration and rotator cuff atrophy are commonly associated with poor clinical outcomes and failed rotator cuff repair. Numerous animal and human studies have attempted to elucidate the etiology of fatty infiltration and rotator cuff atrophy. Mechanical detachment of the tendon in rotator cuff tears is primarily responsible. Suprascapular nerve injury may also play a role. CT, MRI, and ultrasonography are used to evaluate severity. The Goutallier staging system is most commonly used to evaluate fatty infiltration, and rotator cuff atrophy is measured using multiple techniques. The presence and severity of fatty infiltration have been associated with increasing age, tear size, degree of tendon retraction, number of tendons involved (ie, massive tears), suprascapular neuropathy, and traumatic tears. Fatty infiltration is irreversible and progressive if left untreated. Slight reversal of muscle atrophy has been noted after repair in some studies. Novel therapies are currently being evaluated that may eventually allow clinicians to alter the natural history and improve patient outcomes.

Restoring long-term potentiation impaired by amyloid-beta oligomers: Comparison of an acetylcholinesterase inhibitior and selective neuronal nicotinic receptor agonists

As nicotinic acetylcholine receptor (nAChR) agonists directly address cholinergic neurotransmission with potential impact on glutamatergic function, they are considered as potential new symptomatic treatment options for Alzheimer's disease compared to the indirectly operating acetylcholinesterase inhibitors such as the current gold standard donepezil. In order to evaluate the therapeutic value of nAChR activation to ameliorate cognitive dysfunction, a direct comparison between α4β2, α7 nAChR agonists, and donepezil was performed on the level of an ex vivo experimental model of impaired memory formation. First, we demonstrated that amyloid beta (Aβ)42 oligomers, which are believed to be the synaptotoxic Aβ-species causally involved in the pathophysiology of Alzheimer's disease, have a detrimental effect on long-term potentiation (LTP) in the CA1 region of rat hippocampal slices, a widely used cellular model of learning and memory. Second, we investigated the potential of donepezil, the α4β2 nAChR agonist TC-1827 and the α7 nAChR partial agonist SSR180711 to reverse Aβ42 oligomer induced LTP impairment. Donepezil showed only a slight reversal of Aβ42 oligomer induced impairment of early LTP, and had no effect on Aβ42 oligomer induced impairment of late LTP. The same was demonstrated for the α4β2 nAChR agonist TC-1827. In contrast, the α7 nAChR partial agonist SSR180711 completely rescued early as well as late LTP impaired by Aβ42 oligomers. As activating α7 nAChRs was found to be most efficacious in restoring Aβ42 oligomer induced LTP deficits, targeting α7 nAChRs might represent a powerful alternative approach for symptomatic treatment of AD.

MiR-200b targets GATA-4 during cell growth and differentiation

GATA-4 is an important transcription factor involved in several developmental processes of the heart, such as cardiac myocyte proliferation, differentiation and survival. The precise mechanisms underlying the regulation of GATA-4 remain unclear, this is especially true for the mechanisms that mediate the post-transcriptional regulation of GATA-4. Here, we demonstrate that miR-200b, a member of the miR-200 family, is a critical regulator of GATA-4. Overexpression of miR-200b leads to the downregulation of GATA-4 mRNA and a decrease in GATA-4 protein levels. Moreover, miR-200b not only inhibits cell growth and differentiation but also reverses the growth response mediated by GATA-4, whereas depletion of miR-200b leads to a slight reversal of the anti-growth response achieved by knocking down endogenous GATA-4. More importantly, the cell cycle-associated gene cyclin D1, which is a downstream target of GATA-4, is also regulated by miR-200b. Thus, miR-200b targets GATA-4 to downregulate the expression of cyclin D1 and myosin heavy chain (MHC), thereby regulating cell growth and differentiation.

FBG Sensor for Contact Level Monitoring and Prediction of Perforation in Cardiac Ablation

Atrial fibrillation (AF) is the most common type of arrhythmia, and is characterized by a disordered contractile activity of the atria (top chambers of the heart). A popular treatment for AF is radiofrequency (RF) ablation. In about 2.4% of cardiac RF ablation procedures, the catheter is accidently pushed through the heart wall due to the application of excessive force. Despite the various capabilities of currently available technology, there has yet to be any data establishing how cardiac perforation can be reliably predicted. Thus, two new FBG based sensor prototypes were developed to monitor contact levels and predict perforation. Two live sheep were utilized during the study. It was observed during operation that peaks appeared in rhythm with the heart rate whenever firm contact was made between the sensor and the endocardial wall. The magnitude of these peaks varied with pressure applied by the operator. Lastly, transmural perforation of the left atrial wall was characterized by a visible loading phase and a rapid signal drop-off correlating to perforation. A possible pre-perforation signal was observed for the epoxy-based sensor in the form of a slight signal reversal (12–26% of loading phase magnitude) prior to perforation (occurring over 8 s).

Review of Organic Farming Policy in Australia: Time to Wipe the Slate Clean?

Organic farming has risen in popularity with both farmers and consumers, with Australia having the largest area of certified organic land in the world. Australian governments have traditionally ignored the organic farming sector, while making policies that have hampered its further development. Although policies have become more favorable over time, recently, there has been a slight reversal in approach. Such a reversal in policy makes Australia unique when compared to the pro-organic policy developments in nearly all other developed countries. This article reviews Australian government organic farm policy and outlines key areas where policy changes are necessary in property rights, public extension, research, market based instruments and institutions.

Paleoenvironmental context of archaeological sites, implications for subsistence strategies under Holocene climate change, northern Kenya

AbstractThe Holocene was time of dramatic climate change in East Africa, shifting from wetter climate in the Early–Mid Holocene (∼10–5ka) to drier climates in the Late Holocene, followed by a slight reversal at &lt;1ka. The Holocene was a time of cultural change from hunter‐gatherer and fishing to pastoralism. Recent excavations along the eastern shores of Lake Turkana, Kenya (4°N) provide new archaeological materials, a high‐resolution stratigraphic and paleoenvironmental data set, OSL dates, and cultural records in the context of documented environmental change (falling lake levels). Archaeological site FwJj25 (4.20 ± 0.28ka), on the northeastern margin of Lake Turkana, provides one of the earliest records of pastoralism in the region. The palimpsest record of FwJj5 (0.90 ± 0.06ka) was in a small valley containing a groundwater seep located 5km from the lake. FwJj5 reflects occupation by people who may have covered great distances in accessing resources, but were likely drawn to an environmental refugia of freshwater springs during times of regional aridity. © 2011 Wiley Periodicals, Inc.