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Dysregulation of protein homeostasis, proteostasis, is a distinctive hallmark of many neurodegenerative disorders and aging. Deleteriously, the accumulation of aberrant proteins in Alzheimer's disease (AD) is accompanied with a marked collapse in proteostasis network. The current study explored the potential therapeutic effect of vardenafil (VAR), a phosphodiesterase-5 inhibitor, in AlCl3/d-galactose (d-gal)-induced AD in rats and its possible underlying mechanisms. The impact of VAR treatment on neurobehavioral function, hippocampal tissue architecture, and the activity of the cholinergic system main enzymes were assessed utilizing VAR at doses of 0.3 mg/kg and 1 mg/kg. Additionally, the expression level of amyloid-beta and phosphorylated tau proteins in the hippocampus were figured out. Accordingly, VAR higher dose was selected to contemplate the possible underlying mechanisms. Intriguingly, VAR elevated the cyclic guanosine monophosphate level in the hippocampus and averted the repressed proteasome activity by AlCl3/d-gal; hence, VAR might alleviate the burden of toxic protein aggregates in AD. In addition, a substantial reduction in the activating transcription factor 6-mediated endoplasmic reticulum stress was demonstrated with VAR treatment. Notably, VAR counteracted the AlCl3/d-gal-induced depletion of nuclear factor erythroid 2-related factor 2 level. Moreover, the anti-senescence activity of VAR was demonstrated via its ability to restore the balance of the redox circuit. The modulation of phosphatidylinositol-3-kinase/protein kinase B/p53 pathway and the reduction of nuclear factor kappa B level, the key regulator of senescence-associated secretory phenotype mediators release, with VAR treatment were also elucidated. Altogether, these findings insinuate the possible therapeutic benefits of VAR in AD management. [ABSTRACT FROM AUTHOR]

Matrix acidizing is vital to enhance the production of tight carbonate formations. In weak carbonate rocks or acid over-dissolution, the rock is prone to failure upon developing wormholes. Strengthening agents can play a significant role in mitigating failure and supporting more extended productivity. In this study, we tested 0.1 M and 0.2 M zinc sulfate (ZnSO4) and 0.5 M diammonium phosphate ((NH4)2HPO4) as strengthening agents, which change the dominant host mineral into harder ones. Both agents were tested on two different types of acidized (i.e., wormholed) carbonate rocks, specifically Austin chalk and Indiana limestone. The impulse hammer and acoustics measurements evaluated the carbonate rocks' mechanical properties before and after the treatment. In addition, scanning electron microscopy energy-dispersive X-ray spectroscopy (SEM–EDS) and scanning electron microscopy (SEM) were used to affirm the change of rock mineralogy into harder minerals after the treatment. The chemical treatment caused no noticeable change in the wormhole size and shape, as revealed by the scanned micro-computed tomography (micro-CT) images. The chemical treatment of the samples was conducted by core flooding the plugs at high pressure and temperature with 4–5 pore volumes of the chemicals and leaving them in the treatment solution for 72 h. As a result of the formation of harder minerals, the mechanical properties after the treatment showed improvement. Zinc sulfate raised the surface rock hardness of limestone by 16%, while diammonium phosphate showed a 30% increase when evaluated with the same technique. The most noticeable improvement happened to chalk after treatment with diammonium phosphate. Chalk impulse hammer hardness almost quadrupled with the diammonium phosphate. The acoustics measurements showed a similar result to the impulse hammer through an increase in the dynamic Young's modulus and a decrease in Poisson's ratio. [ABSTRACT FROM AUTHOR]

Background: Anterior Cruciate ligament (ACL) reconstruction (ACLR) aims to restore the anatomy and function of the knee. Although stump preservation during ACLR could be technically challenging, it may improve the revascularization and proprioceptive function of the graft. In this study, we aimed to compare the functional outcome after ACLR with and without stump preservation.Methods: One hundred and twenty patients with acutely torn ACL and with intact tibial stump were included in this study. Half of them (60 cases) underwent ACLR with stump preservation. The other half (60 cases) had ACLR after total resection of the tibial stump. One hundred and nine out of 120 cases completed their 2 year-follow-up period. All patients were assessed by Tegner activity, Lysholm, and objective International Knee Documentation Committee (IKDC) scores. The side-to-side difference regarding stability was assessed by KT-1000 instrumented Lachman and proprioceptive function was measured by Passive angle reproduction test.Results: There was no statistically significant difference between both groups regarding Tegner activity, Lysholm, and IKDC scores. Knee stability measured by KT-1000 and complication rate also showed no significant difference. But there was a significant difference in proprioception favoring stump preservation. On the other hand, the operative time was significantly shorter with stump resection. There was no significant difference in the complications rate between both groups and there were no cases with stiffness in either group.Conclusion: Stump preservation ACLR is a safe technique that yields equivalent functional outcomes to standard ACLR. However; it provides better proprioception. It is more technically challenging, but in experienced hands; it is easily reproducible.Trial Registration: Registration number: NCT05364398 . 06/05/2022. [ABSTRACT FROM AUTHOR]

Perturbation of the protein homeostasis circuit is one of the principal attributes associated with many neurodegenerative disorders, such as Parkinson's disease (PD). This study aimed to explore the neuroprotective effect of roflumilast (ROF), a phosphodiesterase-4 inhibitor, in a rotenone-induced rat model of PD and investigate the potential underlying mechanisms. Interestingly, ROF (1 mg/kg, p.o.) attenuated motor impairment, prevented brain lesions, and rescued the dopaminergic neurons in rotenone-treated rats. Furthermore, it reduced misfolded α-synuclein burden. ROF also promoted the midbrain cyclic adenosine monophosphate level, which subsequently enhanced the 26S proteasome activity and the expression of the 20S proteasome. ROF counteracted rotenone-induced endoplasmic reticulum stress, which was demonstrated by its impact on activating transcription factor 6, glucose-regulated protein 78, and C/EBP homologous protein levels. Moreover, ROF averted rotenone-induced oxidative stress, as evidenced by its effects on the levels of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, reduced glutathione, and lipid peroxides with a significant anti-apoptotic activity. Collectively, this study implies repurposing of ROF as a novel neuroprotective drug owning to its ability to restore normal protein homeostasis. [Display omitted] • Treatment with Roflumilast (ROF) alleviated rotenone-induced motor impairment. • ROF reduced the burden α-Syn aggregates via boosting the 20S proteasome activity. • ROF abrogated the endoplasmic reticulum stress in rotenone-intoxicated rats. • ROF promoted the activity of Nrf2/HO-1 axis in rats. • ROF reversed rotenone-induced oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: This study aims to investigate the fate and histopathological effects of ethion on selected organs of the crayfish, Procamabrus clarkii. Crayfish were exposed to 1mgl−1 14C-ethion and the concentrations of ethion and its possible degradation products were measured in water and different organs of the crayfish over both the exposure and recovery periods. Chromatographic analysis revealed that ethion was degraded into ethion monooxon, ethion dioxon, O,O-diethyl phosphorothioate, O-ethyl phosphorothioate and one unknown compound. At the end of exposure period, ethion was accumulated in different organs of the crayfish especially in the hepatopancreas and gills. Following the transfer of crayfish to clean water for seven days, the concentration of insecticide residues were decreased in both the hepatopancreas and gills suggesting that these organs play an important role in elimination of ethion. On the other hand, the exposure of the crayfish to ¼ 96h-LC50 (0.36mgl−1) of ethion caused extensive ultrastructural alterations to both hepatopancreas and gill epithelial cells. In the hepatopancreas, the most notable pathological features included vacuolation, degradation and distinct cell lysis. In the gill epithelium, the histopathological alterations included infiltration of hemocytes, cytoplasmic vacuolation and a decrease in the number of basal plasma membrane infoldings. [Copyright &y& Elsevier]

Abstract: The present study was undertaken to elucidate the cellular mechanisms, which govern metal sequestration and detoxification in gastropods. For this purpose the pond snail, Lymnaea stagnalis was exposed to environmentally relevant concentrations of three species of metals (Al, Zn and Cd) for 30 days and the localization and fate of these metals were followed in different tissues of the snails. The measurement of relative distribution of metals between tissues revealed that the digestive gland and kidney account for most of the accumulated metals. Al and Cd (non-essential metals) were redistributed to the digestive gland, possibly because of the presence of specific binding entities in the digestive glands of the herein species. This study focuses on the role of intracellular metal-containing granules on metal sequestration. Three main types of granules were identified in the digestive gland cells namely small, green and yellow granules. The morphological examination and the progressive accumulation of elements within these granules revealed that they are developmental stages with the yellow granule being the mature one. The total number of these granules was found to be significantly increased upon exposure of the snails to Al only. This increase may be a response to the large amount of Al that is accumulated through feeding route of this grazing snail. X-ray microanalysis (XRMA) revealed that metals were localized in all three types of digestive gland granules. The increased amount of ligands (P and S) in the granules may give evidence for their role in metal sequestration. Levels of Al and P were positively correlated in the digestive gland granules. It is possible that aluminium is bound to phosphorus to render it insoluble and so to both immobilize it within the lysosome and to be excreted in a highly insoluble form. On the other hand, both Zn and Cd induced marked upregulation of S in mature (yellow) granules by 26- and 11-folds, respectively. The lysosomal codeposition of S and either Cd or Zn in the lysosomal granules in addition to the increase in RER cisternae may indicate that the exposure to these metals could induce metallothionein synthesis in the cells. The microscopical examinations in the present study revealed that metal detoxification from the digestive gland cells may occur via faeces or via basal exocytosis towards hemocytes dispersed by the connective tissue in the visceral mass. In the kidney, one type of granules, the excretory concretions, was identified in the nephrocytes. The significant increase in the number of these concretions in the snail L. stagnalis upon exposure to metals may give further evidence for their role in metal excretion. [Copyright &y& Elsevier]

Silicon (Si) has a marked affinity for aluminium (Al(III)), but not other trace metals such as cadmium (Cd(II)) and zinc (Zn(II)). Exogenous orthosilicic acid (Si(OH)4) ameliorates the toxicity of Al(III) to the pond snail Lymnaea stagnalis, but its mechanism of action is unclear. Here, studies were conducted to ascertain whether interaction between orthosilicic acid and Al(III) occurs in the water column to prevent Al(III) uptake, or in the tissues to reduce the toxicity of accumulated metal. Silicon did not reduce the accumulation of Al(III) by the digestive gland (the main ‘sink’ for trace metals in L. stagnalis) following exposure of the snail for 30 days to 500 μg l−1 added Al(III) and 13-fold molar excess of orthosilicic acid. However, Si concentrations correlated well with Al(III) levels in the digestive gland (R2=0.77), giving a ratio of 2.5:1 (Al(III):Si). Exposure to Zn(II) or Cd(II) and 13-fold molar excess of orthosilicic acid did not prevent uptake of these metals, or result in a correlation between metal and Si concentrations of the snail digestive gland. These data show that aquated orthosilicic acid does not prevent Al(III) accumulation by L. stagnalis. However, following exposure, the ratio of Al(III) to Si in the digestive gland is suggestive of the early formation of hydroxyaluminosilicates, probably proto-imogolites (2–3:1 Al(III):Si). Whether hydroxyaluminates are formed ex vivo in the water column and taken up by snails into the digestive gland, or formed in situ within the digestive gland remains to be established. Either way, orthosilicic acid clearly prevents the in vivo toxicity of Al(III) rather than reducing its uptake. Silicon appears to have an important role in the handling Al(III) by the pond snail which may also have wider relevance in understanding the role of Si in ameliorating Al(III) toxicity. [Copyright &y& Elsevier]

Examines the mechanism of aluminum-dependent regulation of intracellular silicon in freshwater snails (Lymnaea stagnalis). Use of X-ray microanalysis; Effect of aluminum exposure on the accumulation of lysosomal granules; Liability of aluminum in a ligand competition assay.

Purpose: Two different locking plate designs are now being used for volar plating of the distal radius fractures based on the freedom of screw direction; the fixed-angle, and the variable-angle (polyaxial) plates. We investigated the clinical and radiographic outcomes of both designs.Methods: We reviewed 96 patients with 113 unstable distal radius fractures that were operated on with volar locking plates. The patients' mean age was 41 years. Fixed-angle volar locking plates were utilized in 65 fractures and variable-angle volar locking plates in 48 fractures through modified Henry approach or extended carpal tunnel approach. Full clinical and radiographic evaluation was done for all patients with a mean follow-up of 14 months.Results: All patients had acceptable clinical and radiographic parameters. The overall functional results (Mayo score, Quick Disability of Arm, Shoulder, and Hand (Q-DASH) score, Range of motion (ROM), and grip strength) were in favor of the variable-angle plate. The radiographic parameters were better with the variable-angle group. The variable-angle group recorded less operative time but more mean image intensifier exposure time. There were two cases of flexor tendon rupture with the fixed-angle group. Fixation with the fixed-angle system needed K-wire augmentation more than the variable-angle group. There was a positive correlation between hand dominance and the final score.Conclusion: Distal radius volar locking plates yield satisfactory results comparable among different designs. In our series, the variable-angle system showed slightly better function and radiographic outcomes. Supplementary K-wires were needed more frequently with the fixed-angle system. [ABSTRACT FROM AUTHOR]

Purpose: To compare the clinical results, complication rates, and radiographic outcome between both methods of fixation of lateral malleolar fractures: lateral neutralization plates and intramedullary fully threaded screws. Patients and methods: This prospective case series study involved 73 patients with fractured lateral malleolus of type A, B according to Weber classification, to whom internal fixation was performed by either lateral plate and screws construct (Group A) or intramedullary screw (Group B). All patients were followed up for 12 months at least, with an average follow-up time of 12.7 months. Results: There was no significant difference in the functional outcome score between both groups. The intramedullary screw group had a significantly shorter operative time and time to full union (P<0.001 and =0.006 respectively). There was a relatively higher accuracy of reduction with the plate fixation group, but it was statistically insignificant. There was a relatively fewer complication rate with the use of intramedullary screw fixation compared to plate fixation. Conclusion: The use of intramedullary fixation is a good alternative for plate fixation in low fibular fractures (Weber A and B). Although plate fixation provides an optimal anatomic reconstruction of the fractures, intramedullary fixation may have a lower risk of complications. [ABSTRACT FROM AUTHOR]

Fracture conductivity is a measure of the fracture ability to transfer fluids from a hydrocarbon-bearing zone to a well. Proppant embedment in soft formations and rock weakening due to the acid/rock reaction limit the stimulation success resulting in sharp fracture conductivity decline. The focus of this study is to increase the rock strength by mineralogical alteration aimed at sustaining long-term fracture conductivity. To achieve these, several standard cylindrical Indian limestone plugs with diameters of 1.5 and 2.5 in and length of 3 in were treated with different types of zinc solutions to substitute calcium with zinc in calcite crystals. The goal of these mineral alterations is to change the principal component of limestone rocks surface, calcite (CaCO 3), into smithsonite (ZnCO 3). Smithsonite is harder than calcite and its lattice system is similar to calcite. The treatment was carried out by full immersion of samples into zinc solutions at a predetermined time intervals. The rock strength was measured from samples surface (Young's modulus) before and after the treatment by a non-destructive technique using an impulse hammer. Zinc sulfate solution was found to enhance the rock hardness by values ranging from 25% to 35% via the formation of a layer of smithsonite on the sample's surface. SEM, XRF, XPS and FIB-SEM experiments were conducted to understand the exchange mechanism that eventually led to the hardening. Also, effective porosity and permeability were measured before and after the chemical treatment to investigate its impact. A field-scale modeling study of rock hardness impact on productivity is provided as a preliminary proof of concept. • Improving hydraulic fracture conductivity in carbonate minerals by forming harder ones was proved to be possible. • Rock surface Young's modulus improved significantly when calcite minerals were replaced with smithsonite. • Hi-Res XPS, XRF, SEM, and FIB-SEM experiments were conducted to understand the exchange mechanism. • Automated impulse hammer measurements were taken to prove the increase in rock hardness. • Numerical simulations proved that enhancing the rock hardness could improve the fractured well productivity. [ABSTRACT FROM AUTHOR]

Fracture conductivity is a fracture's capacity to deliver fluids from the hydrocarbon reservoir to the wellbore. Sustaining long-term fracture conductivity results in better well productivity and reserve recovery. Harder rocks tend to sustain conductivity better than do weak and ductile rocks because they are less likely to suffer from proppant embedment and the crushing and creeping of asperities. This study shows that the hardness of carbonate rocks can be improved significantly when they are treated with carbonate-consolidating chemicals. Ideally, this should be done without damaging the matrix permeability. This research tested the capacity of microemulsion, calcium hydroxide (Ca(OH) 2) nanoparticles, and tetraethyl orthosilicate (TEOS) to consolidate carbonate rocks. These are all believed to improve rock hardness by enhancing carbonate grain attachment. The treatments were applied to cores and slabs of Mississippian Indiana limestone and permo-carboniferous Khuff carbonate rocks. These chemicals were tested by either impregnation or complete immersion of the rock sample in a solution. SEM, X-ray fluorescence, porosity, permeability, and rock hardness were all measured before after the treatment. It was observed that the rock surface Young's modulus could be improved by 10%–38%. Matrix permeability was reduced by 50% when Ca(OH) 2 nanoparticles were tested. Nevertheless, the TEOS improved the carbonate rock's hardness and permeability 18% and 44%, respectively. A modeling study has also been provided to explain the impact of fractured rock strengthening on productivity improvement. • TEOS is an efficient chemical for strengthening of carbonates. • Ca(OH) 2 nanocrystals consolidate carbonates. • Treatments lead to an increase in Youngs modulus of up to 38%. • Permeability is improved in the case of TEOS treatments. [ABSTRACT FROM AUTHOR]

Ankle range of motion abnormalities have been often linked with alteration in knee kinematics leading to the development of patellofemoral pain syndrome (PFPS). Literature exploring the relationship between ankle dorsiflexion range of motion (DF ROM) and knee kinematics during functional tasks is scanty. This study aims to assess the relation between ankle DF ROM and frontal plane projection angle (FPPA), one of the knee kinematic variables, in individuals with and without PFPS during a step-down test. This is a case-control study in which seventy PFPS patients and other 70 asymptomatic control subjects had their ankle DF ROM measured using an inclinometer with the knee flexed and extended. Their FPPA angles were measured using Kinovea software while doing the step-down test. When the two groups were compared, ankle DF ROM measured with the knee flexed was higher in the control group (33.15 ± 4.96) than in the PFPS group (30.20 ± 6.93) (p = 0.03). In both the PFPS group and the control group, the correlation between FPPA and ankle DF ROM with the knee flexed was statistically insignificant (p = 0.075 and 0.323 respectively). Decreased ankle DF ROM can be one of the contributing factors to the development of PFPS in the context of greater dynamic knee valgus. [ABSTRACT FROM AUTHOR]

Acid fracture is a widely applied stimulation technique in carbonate formations; however, it has yet to be fully engineered. A holistic approach was taken in this study to improve the general understating of acid fracture from the field, laboratory, and modeling perspectives. Fully integrating these three elements is imperative to enhancing the performance of acid-fractured wells. The comprehensive review provided in this study will reduce the gap between job execution outcomes and acid fracture model predictions, a goal that is unattainable without knowledge of acid fracture fluid properties, potentials, and limitations. Such an understanding can be obtained from laboratory studies, as well as from job execution results. Obtaining accurate descriptions of the fluid and rock properties encountered during operation is essential. For instance, an experimental approach is applied to obtain the reaction kinetics, diffusion coefficients, and acid fracture conductivity. These, along with the fluid loss coefficient and pressure data obtained from field operations, are valuable modeling inputs. This study sheds light on improvements in acid fracture modeling capabilities made during the past several decades, as well as limitations in terms of capturing some of the fundamental physical phenomena occurring during the process of acid fracture. Essentially, a model that can predict stimulation outcomes can be used to improve the design. • Review of the fluids used in acid fracturing. • Review of the laboratory experiments to evaluate acid fracturing. • Review of the simulation models. • Review of field techniques and practices. • Recent advances in acid fracturing were reviewed. [ABSTRACT FROM AUTHOR]