Fine-tuning Fluorescence of Amlodipine Adopting on Blocking of Photoinduced Electron Transfer (PET): Application in Human Plasma.

Assessing medication adherence through the determination of antihypertensive drugs in biological matrices holds significant importance. Amlodipine (AP), a potent antihypertensive medication extensively prescribed for hypertensive patients, is particularly noteworthy in this context. This article aims to introduce a rapid, simple, improved sensitivity, and reproducibility in detecting AP in its pure form, tablet formulation, and spiked human plasma than the other reported methods. The proposed method utilizes a fluorescence approach, relying on the inhibition of the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom in the primary amino moiety of AP. This inhibition is achieved by acidifying the surrounding medium using 0.2 M acetic acid. By blocking PET, the target AP drug is sensitively detected, at [Formula: see text] 423 nm over a concentration range 25-500 ng mL- 1 showcasing an exceptionally low quantitation limit of 1.41 ng mL- 1. Notably, this innovative technique was successfully applied to detect AP in its solid dosage form and spiked human plasma. Remarkably, matrix interference was found to be insignificant, underscoring the robustness and applicability of the established approach. The combination of speed, sensitivity, and reproducibility makes this method particularly suitable for assessing medication adherence in patients prescribed AP for hypertension.

Efficacy of Repeated Low-Level Red Light (RLRL) therapy on myopia outcomes in children: a systematic review and meta-analysis.

BACKGROUND: Myopia is the most prevalent form of refractive error that has a major negative impact on visual function and causes blurring of vision. We aimed to determine if Repeated Low-Level Red Light (RLRL) treatment is beneficial in treating childhood myopia in terms of axial length (AL), spherical equivalent refraction (SER), and sub foveal choroidal thickness (SFCT). METHODS: This systematic review was performed on RLRL for treatment of myopia in children compared to single vision spectacles (SVS). We employed the search strategy with key terms myopia and low-level light therapy then we searched PubMed, Scopus, Cochrane, and Web of Science databases. The mean differences (MD) were used to evaluate the treatment effects. Heterogeneity was quantified using I2 statistics and explored by sensitivity analysis. RESULTS: Five randomized controlled trials (RCTs) were included in our meta-analysis with a total of 833 patients, 407 in treatment group and 426 in control group. At a 3 month follow up period, pooled studies show a statistical difference in AL between RLRL and SVS group (MD = -0.16; 95% CI [-0.19, -0.12], SER (MD = 0.33; 95% CI [0.27, 0.38]), and SFCT (MD = 43.65; 95% CI [23.72, 45.58]). At a 6 month follow up period, pooled studies show a statistical difference in AL between RLRL and SVS group (MD = -0.21; 95% CI [-0.28, -0.15]), SER (MD = 0.46; 95% CI [0.26, 0.65]), and SFCT (MD = 25.07; 95% CI [18.18, 31.95]). At a 12 month follow up period, pooled studies show a statistical difference in AL between RLRL and SVS group (MD = -0.31; 95% CI [-0.42, -0.19]) and SER (MD = 0.63; 95% CI [0.52, 0.73]). CONCLUSION: This is the first systematic review and meta-analysis investigating only RCTs evidence supporting the efficacy of 650 nm RLRL for myopia control in the short term of 3, 6, and 12 months follow up. The present review revealed the clinical significance of RLRL as a new alternative treatment for myopia control with good user acceptability and no documented functional or structural damage. However, the effect of long-term RLRL treatment and the rebound effect after cessation require further investigations.

Facile, eco-friendly and sensitive fluorimetric approach for detection of chlorpromazine: Application in biological fluids and tablet formulations as well as greenness evaluation of the analytical method.

Monitoring antipsychotic drugs in biological fluids, such as human serum and urine, is important for ensuring the safety and efficacy of psychiatric treatments. This process helps maintain therapeutic drug levels, minimize side effects, and optimize patient well-being. Chlorpromazine (CZ) is a widely prescribed antipsychotic drug used for conditions like schizophrenia, bipolar disorder, and acute psychosis. Almost all existing sensing techniques for CZ are either insensitive spectrophotometric methods or involve long and complex chromatographic procedures, limiting their routine use. In this work, we introduce a facile, green, and sensitive fluorimetric strategy with high reproducibility for detecting CZ in its pure form, tablet formulation, and spiked human plasma and urine without the need for derivatization reactions. The proposed method relies on the inhibition of the intramolecular photoinduced electron transfer (PET) effect by using 2.0 M acetic acid. This approach enables the linear detection of CZ from 3.0 to 600 ng/mL with remarkably low quantitation and detection limits of 1.51 and 0.49 ng/mL, respectively. Moreover, the developed method's greenness was evaluated.

The feasibility and usability of mixed reality teaching in a hospital setting based on self-reported perceptions of medical students.

BACKGROUND: Clinical teaching during encounters with real patients lies at the heart of medical education. Mixed reality (MR) using a Microsoft HoloLens 2 (HL2) offers the potential to address several challenges: including enabling remote learning; decreasing infection control risks; facilitating greater access to medical specialties; and enhancing learning by vertical integration of basic principles to clinical application. We aimed to assess the feasibility and usability of MR using the HL2 for teaching in a busy, tertiary referral university hospital. METHODS: This prospective observational study examined the use of the HL2 to facilitate a live two-way broadcast of a clinician-patient encounter, to remotely situated third and fourth year medical students. System Usability Scale (SUS) Scores were elicited from participating medical students, clinician, and technician. Feedback was also elicited from participating patients. A modified Evaluation of Technology-Enhanced Learning Materials: Learner Perceptions Questionnaire (mETELM) was completed by medical students and patients. RESULTS: This was a mixed methods prospective, observational study, undertaken in the Day of Surgery Assessment Unit. Forty-seven medical students participated. The mean SUS score for medical students was 71.4 (SD 15.4), clinician (SUS = 75) and technician (SUS = 70) indicating good usability. The mETELM Questionnaire using a 7-point Likert Scale demonstrated MR was perceived to be more beneficial than a PowerPoint presentation (Median = 7, Range 6-7). Opinion amongst the student cohort was divided as to whether the MR tutorial was as beneficial for learning as a live patient encounter would have been (Median = 5, Range 3-6). Students were positive about the prospect of incorporating of MR in future tutorials (Median = 7, Range 5-7). The patients' mETELM results indicate the HL2 did not affect communication with the clinician (Median = 7, Range 7-7). The MR tutorial was preferred to a format based on small group teaching at the bedside (Median = 6, Range 4-7). CONCLUSIONS: Our study findings indicate that MR teaching using the HL2 demonstrates good usability characteristics for providing education to medical students at least in a clinical setting and under conditions similar to those of our study. Also, it is feasible to deliver to remotely located students, although certain practical constraints apply including Wi-Fi and audio quality.

Prognostic effects of cardiopulmonary resuscitation (CPR) start time and the interval between CPR to extracorporeal cardiopulmonary resuscitation (ECPR) on patient outcomes under extracorporeal membrane oxygenation (ECMO): a single-center, retrospective observational study.

BACKGROUND: The impact of the chronological sequence of events, including cardiac arrest (CA), initial cardiopulmonary resuscitation (CPR), return of spontaneous circulation (ROSC), and extracorporeal cardiopulmonary resuscitation (ECPR) implementation, on clinical outcomes in patients with both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA), is still not clear. The aim of this study was to investigate the prognostic effects of the time interval from collapse to start of CPR (no-flow time, NFT) and the time interval from start of CPR to implementation of ECPR (low-flow time, LFT) on patient outcomes under Extracorporeal Membrane Oxygenation (ECMO). METHODS: This single-center, retrospective observational study was conducted on 48 patients with OHCA or IHCA who underwent ECMO at Hamad General Hospital (HGH), the tertiary governmental hospital of Qatar, between February 2016 and March 2020. We investigated the impact of prognostic factors such as NFT and LFT on various clinical outcomes following cardiac arrest, including 24-hour survival, 28-day survival, CPR duration, ECMO length of stay (LOS), ICU LOS, hospital LOS, disability (assessed using the modified Rankin Scale, mRS), and neurological status (evaluated based on the Cerebral Performance Category, CPC) at 28 days after the CA. RESULTS: The results of the adjusted logistic regression analysis showed that a longer NFT was associated with unfavorable clinical outcomes. These outcomes included longer CPR duration (OR: 1.779, 95%CI: 1.218-2.605, P = 0.034) and decreased survival rates for ECMO at 24 h (OR: 0.561, 95%CI: 0.183-0.903, P = 0.009) and 28 days (OR: 0.498, 95%CI: 0.106-0.802, P = 0.011). Additionally, a longer LFT was found to be associated only with a higher probability of prolonged CPR (OR: 1.818, 95%CI: 1.332-3.312, P = 0.006). However, there was no statistically significant connection between either the NFT or the LFT and the improvement of disability or neurologically favorable survival after 28 days of cardiac arrest. CONCLUSIONS: Based on our findings, it has been determined that the NFT is a more effective predictor than the LFT in assessing clinical outcomes for patients with OHCA or IHCA who underwent ECMO. This understanding of their distinct predictive abilities enables medical professionals to identify high-risk patients more accurately and customize their interventions accordingly.

UPLC/ESI/MS profiling of red algae Galaxaura rugosa extracts and its activity against malaria mosquito vector, Anopheles pharoensis, with reference to Danio rerio and Daphnia magna as bioindicators.

BACKGROUND: Anopheles pharoensis has a major role in transmitting several human diseases, especially malaria, in Egypt?. Controlling Anopheles is considered as an effective strategy to eliminate the spread of malaria worldwide. Galaxaura rugosa is a species of red algae found in tropical to subtropical marine environments. The presence of G. rugosa is indicative of the ecosystem's overall health. The current work aims to investigate UPLC/ESI/MS profile of G. rugosa methanol and petroleum ether extracts and its activity against An. pharoensis and non-target organisms, Danio rerio and Daphnia magna. METHODS: Galaxaura rugosa specimens have been identified using DNA barcoding for the COI gene and verified as G. rugosa. The UPLC/ESI/MS profiling of G. rugosa collected from Egypt was described. The larvicidal and repellent activities of G. rugosa methanol and petroleum ether extracts against An. pharoensis were evaluated, as well as the toxicity of tested extracts on non-target organisms, Dan. rerio and Dap. magna. RESULTS: The UPLC/ESI/MS analysis of methanol and petroleum ether extracts led to the tentative identification of 57 compounds belonging to different phytochemical classes, including flavonoids, tannins, phenolic acids, phenyl propanoids. Larval mortality was recorded at 93.33% and 90.67% at 80 and 35 ppm of methanol and petroleum ether extracts, respectively, while pupal mortality recorded 44.44 and 22.48% at 35 and 30 ppm, respectively. Larval duration was recorded at 5.31 and 5.64 days by methanol and petroleum ether extracts at 80 and 35 ppm, respectively. A decrease in acetylcholinesterase (AChE) level and a promotion in Glutathione-S-transferase (GST) level of An. pharoensis 3rd instar larvae were recorded by tested extracts. The petroleum ether extract was more effective against An. pharoensis starved females than methanol extract. Also, tested extracts recorded LC50 of 1988.8, 1365.1, and 11.65, 14.36 µg/mL against Dan. rerio, and Dap. magna, respectively. CONCLUSIONS: Using red algae derivatives in An. pharoensis control could reduce costs and environmental impact and be harmless to humans and other non-target organisms.

Limb loading enhances skill transfer between augmented and physical reality tasks during limb loss rehabilitation.

BACKGROUND: Virtual and augmented reality (AR) have become popular modalities for training myoelectric prosthesis control with upper-limb amputees. While some systems have shown moderate success, it is unclear how well the complex motor skills learned in an AR simulation transfer to completing the same tasks in physical reality. Limb loading is a possible dimension of motor skill execution that is absent in current AR solutions that may help to increase skill transfer between the virtual and physical domains. METHODS: We implemented an immersive AR environment where individuals could operate a myoelectric virtual prosthesis to accomplish a variety of object relocation manipulations. Intact limb participants were separated into three groups, the load control (CGLD; [Formula: see text]), the AR control (CGAR; [Formula: see text]), and the experimental group (EG; [Formula: see text]). Both the CGAR and EG completed a 5-session prosthesis training protocol in AR while the CGLD performed simple muscle training. The EG attempted manipulations in AR while undergoing limb loading. The CGAR attempted the same manipulations without loading. All participants performed the same manipulations in physical reality while operating a real prosthesis pre- and post-training. The main outcome measure was the change in the number of manipulations completed during the physical reality assessments (i.e. completion rate). Secondary outcomes included movement kinematics and visuomotor behavior. RESULTS: The EG experienced a greater increase in completion rate post-training than both the CGAR and CGLD. This performance increase was accompanied by a shorter motor learning phase, the EG's performance saturating in less sessions of AR training than the CGAR. CONCLUSION: The results demonstrated that limb loading plays an important role in transferring complex motor skills learned in virtual spaces to their physical reality analogs. While participants who did not receive limb loading were able to receive some functional benefit from AR training, participants who received the loading experienced a greater positive change in motor performance with their performance saturating in fewer training sessions.

Hybrid Beamforming in Massive MIMO for Next-Generation Communication Technology.

Hybrid beamforming is a viable method for lowering the complexity and expense of massive multiple-input multiple-output systems while achieving high data rates on track with digital beamforming. To this end, the purpose of the research reported in this paper is to assess the effectiveness of the three architectural beamforming techniques (Analog, Digital, and Hybrid beamforming) in massive multiple-input multiple-output systems, especially hybrid beamforming. In hybrid beamforming, the antennas are connected to a single radio frequency chain, unlike digital beamforming, where each antenna has a separate radio frequency chain. The beam formation toward a particular angle depends on the channel state information. Further, massive multiple-input multiple-output is discussed in detail along with the performance parameters like bit error rate, signal-to-noise ratio, achievable sum rate, power consumption in massive multiple-input multiple-output, and energy efficiency. Finally, a comparison has been established between the three beamforming techniques.

Aspergillus flavus YRB2 from Thymelaea hirsuta (L.) Endl., a non-aflatoxigenic endophyte with ability to overexpress defense-related genes against Fusarium root rot of maize.

Fusarium root rot, caused by Fusarium solani (Mart.) Sacc., represents one of the most damaging diseases of maize affecting plant growth and yield. In this study, the antagonistic potential of a non-aflatoxigenic endophytic Aspergillus flavus YRB2, isolated from Thymelaea hirsuta (L.) Endl., was tested against F. solani in vitro. In addition, its biocontrol activity against Fusarium root rot of maize was evaluated under greenhouse conditions. Its impacts on plant molecular, pathological, physiological, and growth levels were also studied. Results obtained revealed a potent antagonistic behavior for A. flavus YRB2 against F. solani in vitro, recording 80% growth inhibition. Seventeen secondary metabolites were detected in the n-hexane extract of A. flavus YRB2 filtered culture broth using GC-MS analysis. Among them, various antifungal secondary metabolites were produced, namely palmitic acid, α-linolenic acid, stearic acid, 2, 4-di-tert-butylphenol, diisobutyl phthalate, and heneicosane. In contrast, HPLC analysis showed that no aflatoxins (B1, B2, G1, and G2) were detected. Under greenhouse conditions, colonization of maize plants with A. flavus YRB2 exhibited a potential biocontrol activity against Fusarium root rot, recording 73.4% reduction in the disease severity. Triggering of transcriptional expression level of the defense-related genes JERF3 (7.2-fold), CHI II (8-fold), and POD (9.1-fold) was reported, indicating the inducing effect on the plant immunity. In addition, an increment in the antioxidant enzymes POD and PPO, and the total phenolic content in maize roots was also observed in response to this treatment. Moreover, a growth-promoting effect was also observed for colonization of maize plants with A. flavus YRB2. Based on the obtained data, we can conclude that A. flavus YRB2 may represent a promising biocontrol and growth-promoting agent for maize plants against Fusarium root rot. Nevertheless, field evaluation is highly requested before the use recommendation.

Preliminary Evaluation of the Effect of Mechanotactile Feedback Location on Myoelectric Prosthesis Performance Using a Sensorized Prosthetic Hand.

A commonly cited reason for the high abandonment rate of myoelectric prostheses is a lack of grip force sensory feedback. Researchers have attempted to restore grip force sensory feedback by stimulating the residual limb's skin surface in response to the prosthetic hand's measured grip force. Recent work has focused on restoring natural feedback to the missing digits directly through invasive surgical procedures. However, the functional benefit of utilizing somatotopically matching feedback has not been evaluated. In this paper, we propose an experimental protocol centered on a fragile object grasp and lift task using a sensorized myoelectric prosthesis to evaluate sensory feedback techniques. We formalized a suite of outcome measures related to task success, timing, and strategy. A pilot study (n = 3) evaluating the effect of utilizing a somatotopically accurate feedback stimulation location in able-bodied participants was conducted to evaluate the feasibility of the standardized platform, and to inform future studies on the role of feedback stimulation location in prosthesis use. Large between-participant effect sizes were observed in all outcome measures, indicating that the feedback location likely plays a role in myoelectric prosthesis performance. The success rate decreased, and task timing and task focus metrics increased, when using somatotopically-matched feedback compared to non-somatotopically-matched feedback. These results were used to conduct a power analysis, revealing that a sample size of n = 8 would be sufficient to achieve significance in all outcome measures.

Fabric phase sorptive extraction coupled with UPLC-ESI-MS/MS method for fast and sensitive quantitation of tadalafil in a bioequivalence study.

The current study coupled fabric phase sorptive extraction (FPSE) with ultraperformance liquid chromatography method with electrospray ionization and tandem mass detection (UPLC-ESI-MS/MS) for fast and sensitive determination of tadalafil (TAD) in a bioequivalence study. Fabric phase sorptive extraction allowed direct extraction of TAD from the sample matrix with improved selectivity, repeatability, and recoveries. A sol-gel Carbowax 20 M (CX-20 M) coated FPSE membrane revealed the best extraction efficiency for TAD because of its strong affinity for analytes via intermolecular interactions, high mass transfer rate to FPSE membrane, and high permeability. An automated multiple reaction monitoring (MRM) optimizer was employed for the best selection of the precursor and product ions, ion breakdown profile, the fine adjustment of the fragmentor voltages for each precursor ions, and the collision energies for the product ions. The chromatographic separation was conducted using a mobile phase A: 5.0 mM ammonium acetate with 0.1 % formic acid in water and mobile phase B: formic acid (0.1%) in acetonitrile in ratio (55:45, v/v) through isocratic elution mode on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 µm) column and the flow rate was adjusted at 0.4 mL min-1. The total run time per sample was 1.0 min. The method was validated by FDA standards for bioanalytical method validation over a concentration range of 0.1-100 ng mL-1 with a correlation coefficient of 0.9993 and the lower limit of quantitation (LLOQ) was 0.1 ng mL-1 in rat plasma. Intra- and inter-assay precision (%RSD) were lower than 4.1% and accuracy (%RE) was within 2.4%. The developed FPSE-UPLC-ESI-MS/MS method was effectively used in a randomized, two-way, single-dose, crossover study to compare the bioequivalence of two TAD formulations from different companies in male rats and verified to be bioequivalent.

The potential toxic effects of magnesium oxide nanoparticles and valproate on liver tissue.

The liver is the main organ responsible for drug and xenobiotic metabolism and detoxification in the body. There are many antiepileptic drugs and nanoparticles that have been reported to cause serious untoward biological responses and hepatotoxicity. The aim of this study is to investigate the potential toxic effect of aspartic acid-coated magnesium oxide nanoparticles (Mg nano) and valproate (valp) using an in vitro three-dimensional (3D) human liver organoid model and an in vivo pentylenetetrazole (PTZ)-induced convulsion model in rats. Here, 3D human liver organoids were treated with valp or valp + Mg nano for 24 h and then incubated with PTZ for an extra 24 h. As the in vivo model, rats were treated with valp, Mg nano, or valp + Mg nano for 4 weeks and then they were treated with PTZ for 24 h. Toxicity in the liver organoids was demonstrated by reduced cell viability, decreased ATP, and increased reactive oxygen species. In the rat convulsion model, results revealed elevated serum alanine aminotransferase and aspartate aminotransferase levels. Both the in vitro and in vivo data demonstrated the potential toxic effects of valp + Mg nano on the liver tissues.

A Cost-Effective Inertial Measurement System for Tracking Movement and Triggering Kinesthetic Feedback in Lower-Limb Prosthesis Users.

Advances in lower-limb prosthetic technologies have facilitated the restoration of ambulation; however, users of such technologies still experience reduced balance control, also due to the absence of proprioceptive feedback. Recent efforts have demonstrated the ability to restore kinesthetic feedback in upper-limb prosthesis applications; however, technical solutions to trigger the required muscle vibration and provide automated feedback have not been explored for lower-limb prostheses. The study's first objective was therefore to develop a feedback system capable of tracking lower-limb movement and automatically triggering a muscle vibrator to induce the kinesthetic illusion. The second objective was to investigate the developed system's ability to provide kinesthetic feedback in a case participant. A low-cost, wireless feedback system, incorporating two inertial measurement units to trigger a muscle vibrator, was developed and tested in an individual with limb loss above the knee. Our system had a maximum communication delay of 50 ms and showed good tracking of Gaussian and sinusoidal movement profiles for velocities below 180 degrees per second (error < 8 degrees), mimicking stepping and walking, respectively. We demonstrated in the case participant that the developed feedback system can successfully elicit the kinesthetic illusion. Our work contributes to the integration of sensory feedback in lower-limb prostheses, to increase their use and functionality.

Novel scaffold hopping of potent benzothiazole and isatin analogues linked to 1,2,3-triazole fragment that mimic quinazoline epidermal growth factor receptor inhibitors: Synthesis, antitumor and mechanistic analyses.

A series of benzothiazole/isatin linked to 1,2,3-triazole moiety and terminal sulpha drugs 5a-e and 6a-e were synthesized and evaluated for cytotoxic activity against a panel of cancer cell lines. The novel compounds showed variable IC50 range of activity and some of them were potent compared to reference drug. The promising compounds were subjected as postulated the mimicry proposal for quinazoline-based EGFR inhibitors for their inhibitory profile against EGFR TK enzyme. That data obtained revealed that most of these compounds were potent EGFR TK inhibitors at nanomolar concentrations. Among these, compounds 5a and 5b showed more potent activity on EGFR compared to erlotinib (IC50 103 and 104 versus 67.6 nM). Based upon the results, molecular docking analysis was performed on EGFR receptor and proved the strong contribution of fragments; benzothiazole, isatin, and triazole to the binding ATP pocket. When these selected compounds 5a and 5b were tested in an HepG2 model, they could effectively inhibited tumor growth, strongly induced cancer cell apoptosis, and suppressed cell cycle progression leading to DNA fragmentation. Well-DMET profile of the most active derivatives was presented and compared to the reference drugs. Taken together, we introduced novel triazole-sulpha drug hybrid for the first time as EGFR inhibitors and the results of our studies indicate that the newly discovered inhibitors have significant potential for anticancer treatment.

Impact of flow and angioarchitecture on brain arteriovenous malformation outcome after gamma knife radiosurgery: the role of hemodynamics and morphology in obliteration.

BACKGROUND: Few studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR). METHODS: A prospectively enrolled single-center cohort of patients with bAVMs treated by GKSR has been studied to define independent predictors of obliteration with particular attention to angioarchitectural variables. Only patients older than 18 years old (y.o.), who underwent baseline digital subtraction angiography (DSA) and clinico-radiological follow-up of at least 36 months, were included in the study. RESULTS: Data of 191 patients were evaluated. After a mean follow-up of 80 months (range 37-173), total obliteration rate after first GKSR treatment was 66%. Mean dose higher than 22 Gy (P = .019, OR = 2.39, 95% CI 1.15-4.97) and flow rate dichotomized into high vs non-high (P < .001, OR = 0.23, 95% CI 0.11-0.51) resulted to be independent predictors of obliteration. Flow-surrogate angioarchitectural features did not emerge as independent outcome predictors. CONCLUSIONS: Flow rate seems to be associated in predicting outcome after GKSR conferring high-flow AVM a lower occlusion rate. Its role should be considered when planning radiosurgical treatment of bAVM, and it could be added to other parameters used in GKRS outcome predicting scales.

Conventional analysis of trial-by-trial adaptation is biased: Empirical and theoretical support using a Bayesian estimator.

Research on human motor adaptation has often focused on how people adapt to self-generated or externally-influenced errors. Trial-by-trial adaptation is a person's response to self-generated errors. Externally-influenced errors applied as catch-trial perturbations are used to calculate a person's perturbation adaptation rate. Although these adaptation rates are sometimes compared to one another, we show through simulation and empirical data that the two metrics are distinct. We demonstrate that the trial-by-trial adaptation rate, often calculated as a coefficient in a linear regression, is biased under typical conditions. We tested 12 able-bodied subjects moving a cursor on a screen using a computer mouse. Statistically different adaptation rates arise when sub-sets of trials from different phases of learning are analyzed from within a sequence of movement results. We propose a new approach to identify when a person's learning has stabilized in order to identify steady-state movement trials from which to calculate a more reliable trial-by-trial adaptation rate. Using a Bayesian model of human movement, we show that this analysis approach is more consistent and provides a more confident estimate than alternative approaches. Constraining analyses to steady-state conditions will allow researchers to better decouple the multiple concurrent learning processes that occur while a person makes goal-directed movements. Streamlining this analysis may help broaden the impact of motor adaptation studies, perhaps even enhancing their clinical usefulness.

Mechanistic effects of mesenchymal and hematopoietic stem cells: New therapeutic targets in myocardial infarction.

Myocardial infarction (MI) results in dysfunction and irreversible loss of cardiomyocytes and is of the most serious health threats today. Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) have been explored as promising cell therapy in MI and regenerative therapy. Recently, reports investigated the potential therapeutic effects of MSCs or HSCs transplantation after MI in numerous experimental and clinical studies; however, their results are controversy and needs more explorations. The current review is an attempt to clarify the therapeutic potentials of MSCs and HSCs in MI therapy, as well as their possible effects; especially the paracrine one and the exosome-derived stem cell among animal models as well as clinical trials conducted within the last 10 years. In this context, various sources of MSCs and HSCs have been addressed in helping cardiac regeneration by either revitalizing the cardiac stem cells niche or revascularizing the arteries and veins of the heart. In addition, both MSCs and HSCs could produce paracrine mediators and growth factors which led to cardiomyocytes protection, angiogenesis, immunemodulation, antioxidants, anti-apoptotic, anti-inflammatory, antifibrotic, as well as increasing cardiac contractility. Recently, microRNAs (miRNAs), post-transcriptional regulators of gene expression, and long non-coding RNA (lncRNA), a miRNA sponge, are recent stem cell-derived mediators can be promising targets of MSCs and HSCs through their paracrine effects. Although MSCs and HSCs have achieved considerable achievements, however, some challenges still remain that need to be overcome in order to establish it as a successful technique. The present review clarified the mechanistic potentials of MSCs and HSCs especially paracrine effects involved in MI including human and animal studies and the challenges challenges regarding type, differentiation, route, and number of injections.

Hydrogen peroxide modulates redox status, energy metabolism, and gene expression in a dose- and time-dependent manner in rat liver.

AIM: The aim of this study was to investigate the effect of three different hydrogen peroxide (H2 O2 ) levels on blood and liver oxidative status, energy metabolites, and gene expression in male albino rats at two time intervals (2 and 4 weeks). METHODS: A total of 32 rats were divided into four groups. The first group received tap water and served as control. The second group received low dose of hydrogen peroxide (H2 O2 ; 0.25%), The third group received medium dose of H2 O2 (0.5%) and the fourth group received high dose of H2 O2 (1%) in drinking water. RESULTS: Present data showed that medium and high dose increased oxidative stress markers, decreased cell energy, and decreased antioxidant enzyme gene expression (GPx and Nrf2) and its downstream in contrast low dose did not show significant effects. CONCLUSION: This study might indicate that hydrogen peroxide medium level is the best dose for redox model status.

Design, synthesis, molecular docking of new lipophilic acetamide derivatives affording potential anticancer and antimicrobial agents.

Fifteen new substituted N-2-(2-oxo-3-phenylquinoxalin-1(2H)-yl) acetamides 5a-f, 6a-f, and 8a-c were synthesized by reacting ethyl 2-(2-oxo-3-phenylquinoxalin-1(2H)-yl)acetate with various primary amines including benzylamines, sulfonamides, and amino acids. The in vitro antimicrobial screening of the target compounds was screened to assess their antibacterial and antifungal activity. As a result, seven compounds namely; 5a, 5c, 5d, 6a, 6c, 8b and 8c showed a promising broad spectrum antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the analogs 5c and 6d were nearly as equiactive as ciprofloxacin drug. Meanwhile, four compounds namely; 5c, 6a, 6f and 8c exhibited appreciable antifungal activity with MIC values range 33-40 mg/mL comparable with clotrimazole (MIC 25 mg/mL). In addition, the anticancer effects of the synthesized compounds were evaluated against three cancer lines. The data obtained revealed the benzylamines and sulpha derivatives were the most active compounds especially 5f and 6f ones. Further EGFR enzymatic investigation was carried out for these most active compounds 5f and 6f resulting in inhibitory activity by 1.89 and 2.05 µM respectively. Docking simulation was performed as a trial to study the mechanisms and binding modes of these compounds toward the enzyme target, EGFR protein kinase enzyme. The results revealed good compounds placement in the active sites and stable interactions similar to the co-crystallized reference ligand. Collectively, the analogs 5f and 6f could be further utilized and optimized as good cytotoxic agents.

Improving internal model strength and performance of prosthetic hands using augmented feedback.

BACKGROUND: The loss of an arm presents a substantial challenge for upper limb amputees when performing activities of daily living. Myoelectric prosthetic devices partially replace lost hand functions; however, lack of sensory feedback and strong understanding of the myoelectric control system prevent prosthesis users from interacting with their environment effectively. Although most research in augmented sensory feedback has focused on real-time regulation, sensory feedback is also essential for enabling the development and correction of internal models, which in turn are used for planning movements and reacting to control variability faster than otherwise possible in the presence of sensory delays. METHODS: Our recent work has demonstrated that audio-augmented feedback can improve both performance and internal model strength for an abstract target acquisition task. Here we use this concept in controlling a robotic hand, which has inherent dynamics and variability, and apply it to a more functional grasp-and-lift task. We assessed internal model strength using psychophysical tests and used an instrumented Virtual Egg to assess performance. RESULTS: Results obtained from 14 able-bodied subjects show that a classifier-based controller augmented with audio feedback enabled stronger internal model (p = 0.018) and better performance (p = 0.028) than a controller without this feedback. CONCLUSIONS: We extended our previous work and accomplished the first steps on a path towards bridging the gap between research and clinical usability of a hand prosthesis. The main goal was to assess whether the ability to decouple internal model strength and motion variability using the continuous audio-augmented feedback extended to real-world use, where the inherent mechanical variability and dynamics in the mechanisms may contribute to a more complicated interplay between internal model formation and motion variability. We concluded that benefits of using audio-augmented feedback for improving internal model strength of myoelectric controllers extend beyond a virtual target acquisition task to include control of a prosthetic hand.