The intention of our study was to establish the prevalence of low birth weight (LBW) as well as risk factors for LBW in infants born to a convenience sample of women enrolled in a home visitation maternal care program associated with the Center for Human Development in Southwest Trifinio, Guatemala.This is an observational study analyzing self-reported data from a quality improvement database. We recorded the distribution of birthweights of infants born to women enrolled in Madres Sanas that delivered between October 2018 and December 2019. We grouped women by LBW (<2500g ) and adequate birthweight (≥2500g) infants, and performed bivariate comparisons using sociodemographic, obstetric, and intrapartum data. Using the independent variables shown to have an association with LBW, we then performed a multivariable analysis.P=0.03). Women with LBW infants were also more likely to have fewer than 4 prenatal visits .There were 226 births among our program participants, 218 with recorded birthweights. The median birthweight was 3175g; 13.8% were LBW (<2500g), higher than Guatemala’s average of 10.9%. Through our bivariate analysis, we determined women with LBW infants were younger, with a median age of 20.8 (IQR [17.8-23.7]) compared to a median age of 23.2 (IQR [19.8-27.3]) among women with infants ≥2500g (Two significant findings emerged from our analysis: LBW infants were more commonly born to women who were younger in age and who had received fewer than 4 prenatal visits. These findings are consistent with existing literature on LBW in Latin America. Our study helps to strengthen the data around these associations and gives credence to programming and policy efforts in Latin America that support adequate prenatal care for all and youth education about reproductive health and contraceptive access. In 2015The intent in this study was to identify the prevalence of and risk factors associated with LBW in infants born to a convenience sample of women living in the lowlands of Southwestern Guatemala. Though this was a secondary analysis of a quality improvement database not designed to prospectively answer this question, we hypothesized that inadequate prenatal care, younger maternal age, and low levels of education would be associated with LBW in our convenience sample.2.2.1In 2011, a partnership between the University of Colorado and local agribusiness in the lowlands of Southwestern Guatemala resulted in the creation of the Center for Human Development (CHD) . This or2.2The population studied included a convenience sample of women enrolled in the Madres Sanas maternal health program. All enrolled women that delivered a live newborn between October 1, 2018 and December 3, 2019 were included in this study.2.3This is a secondary analysis of a quality improvement database that has ethical approval from the Colorado Multiple Institutional Review Board (COMIRB # 15-0909). Given the quality improvement nature, women are not individually consented for collection of their data, but the data was anonymized.2.4This secondary data analysis of a quality improvement database has the primary outcome of LBW. LBW was defined as <2500 grams; data is collected by mother self-report of what she was told at the facility where she delivered or by the traditional birth attendant, although women sometimes present written documentation of birthweight. We compared the population of women with a LBW infant to those with a normal birthweight infant (≥2500 grams). We aimed to be able to identify sociodemographic (collected at the enrollment visit), obstetric (collected at enrollment), and intrapartum characteristics (collected at < 72 hour visit) associated with LBW. This data was collected by the community health nurses as part of the Madres Sanas program and was collected prospectively. It included demographic, antepartum, obstetric, and delivery characteristics.2.5P<0.05 were considered statistically significant, and then analyzed in a multivariable logistic regression. STATA software version 15.2  was used for analysis.This analysis includes a description of the population of women observed during the study timeframe divided into the population of women who delivered a LBW infant compared to women with a normal weight infant. In bivariate comparisons we analyzed sociodemographic, antepartum, and intrapartum characteristics using Pearson’s chi-squared test for nominal categorical variables unless there was a low cell size, in which case Fisher’s exact test was used. The Kruskal-Wallis test was used for comparison of continuous variables. Variables with a 3.th grade); 12% of the population reported being illiterate. Most women were married (88.1%) with 1.9% of women reporting employment. The population included women from 12 communities in the area; 56% of women lived within close proximity to the CHD and 44% lived in areas considered to be far from the CHD. Communities designated as “far” are still reachable within 30 minutes on a motorcycle.Between October 1, 2018 and December 3, 2019 there were 226 live births in the Madres Sanas program. As shown in P=0.03). Women with LBW infants were also more likely to have fewer than 4 prenatal visits . The remaining sociodemographic and obstetric characteristics were not found to have a significant association with LBW in bivariate comparisons. After determining a significant association between both maternal age and number of prenatal visits and the outcome variable of LBW, we performed a logistic regression to examine the relationship further. In this multivariable analysis (P=0.03). Additionally, women with 4 or more prenatal visits were 60% less likely to have a LBW infant .Regarding antepartum and obstetric characteristics, most women were multiparous (56.9%). Prior to conception, 23.7% reported using contraception. 80.7% of the women were seen at least 4 times during their pregnancy for antenatal care. The cesarean birth rate was 48.6% of all births, and 65.1% of women had a history of at least one prior cesarean birth. Home births occurred in 30.9% of the population, 69.1% of deliveries were in a hospital or clinic setting, and 74% had a skilled attendant at the birth (nurse or physician). In the bivariate analysis, women with LBW infants were younger, with a median age of 20.8 (IQR [17.8-23.7]) compared to a median age of 23.2 (IQR [19.8-27.3]) among women with infants ≥2500g . We also found LBW infants were 60% less likely to be born to women that had received more than 4 prenatal visits. Significant findings in the analysis help to inform ways in which the LBW rates could be reduced. The correlation we found between younger age and LBW is not a novel finding, as many other studies have endorsed an association between adolescent mothers and LBW in Latin America [In this analysis we gained insight into the prevalence of and predictors associated with LBW in a convenience sample of women living in rural Southwest Guatemala. From our quality improvement database, we determined the prevalence of LBW infants born to women enrolled in the Center for Human Development’s Madres Sanas program was 13.8%, considerably higher than the national statistic of 10.9% reported by UNICEF in 2015 [Additionally, it supports the need for education about and access to contraception for adolescents. The Center for Human Development has another program, “Big Decisions,” an initiative focused on sexual education and knowledge about contraception for youth in the community, which is intended to prevent pregnancy and could have implications for LBW. A number of Latin American studies have identified access to adequate prenatal care as a key factor in improving birth outcomes and preventing LBW, as we found in our analysis , 4. TherThe limitations of this study include its small sample size, the use of self-reported data, the convenience sample study design, the secondary analysis study design, and the relatively short window of time in which data was collected. Additionally, several variables are notably absent from the analysis, namely validated measures of nutrition and gestateonal age. Maternal weight gain and anemia have been shown to be associated with LBW in prior research , and ges5.In conclusion, analysis of our quality improvement database utilizing data obtained through the Madres Sanas program revealed a higher prevalence of LBW 13.8%) than is typically seen in Latin American countries , 3, 5. L.8% than


A phase 2 study by Johnson et al. found that once-daily dosing of viloxazine ER in 200, 300, or 400 mg dosages in children with ADHD for eight weeks resulted in a statistically significant reduction of ADHD-RS-IV total score. A post hoc analysis of data from four phase 3, randomized, placebo-controlled, double-blind, three-arm, clinical trials by Faraone et al. found that early response to viloxazine treatment, defined as a change in ADHD-RS-5 total score at week 2, best predicted the treatment response at week 6 . Proper treatment of the symptoms and comorbidities associated with ADHD is crucial in improving a patient's quality of life, cognitive function, and overall therapeutic outcomes. Viloxazine's mechanism of action, clinical effects, and limited side effect profile point toward the drug's relevance in the treatment of ADHD.Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. Over the past twenty years, research on the disease and its characteristics and treatment options has grown exponentially. The first-line pharmacologic treatment of ADHD is stimulants, which have a response rate of ~70%. With the support of four phase 3 studies involving more than 1,000 pediatric patients 6–17 years old, the FDA has approved the non-stimulant, serotonin-norepinephrine modulating agent (SNMA) viloxazine in an extended-release capsule (viloxazine ER) for treatment of ADHD in children aged 6–17. Viloxazine modulates serotonergic activity as a selective 5-HT2 According to DSM-5, attention deficit hyperactivity disorder (ADHD) is a “chronic, neurologically-based illness characterized by a persistent pattern of inattention and/or hyperactivity and impulsivity that are more inappropriate or disruptive than those in other children of a comparable age resulting in functional impairment in multiple settings, and these behaviors have been present for at least six months .” The coADHD is the most common neurodevelopmental disorder in children . Over thIn 2013, the DSM-5 revised the criteria for diagnosis, including raising the age limit for onset of qualifying symptoms from before six years of age to before 12 years of age, requiring the presence of symptoms in at least two settings, and requiring five rather than six symptoms for diagnosis in patients age 17 and older  and norepinephrine (NE), resulting in inattention and hyperactivity. One leading theory specifies hypoactivity of NE and DA in the prefrontal cortex (PFC), which is involved in attention, formulating plans, organizing thoughts, and suppressing the processing of irrelevant and distracting stimuli, allowing a person to remain focused on a specific task . MagnetiThe caudate nucleus, corpus callosum, and cerebellar vermis may also be decreased in volume in individuals with ADHD . DA is sADHD is treated with pharmacological and non-pharmacological interventions, including psychotherapeutic and dietary approaches. The two classes of psychostimulants, methylphenidate, and amphetamine, are the first-line pharmacological treatments for ADHD . Second-Amphetamines demonstrate three main mechanisms of action. First, they also bind to monoamine transporters, norepinephrine transporter (NET), and dopamine transporter (DAT) to prevent the reuptake of their respective neurotransmitters. Second, amphetamines allow trace-amine associated receptor 1 (TAAR1) to phosphorylate the DAT transporter, allowing for ceased transport or inversing the efflux of dopamine. Third, amphetamines may enter presynaptic monoamine vesicles, causing an efflux of neurotransmitters toward the synapse .Atomoxetine (otherwise known as Strattera®) is a non-stimulant that acts as a norepinephrine reuptake inhibitor, increasing the amount of norepinephrine available in the synapse . AtomoxeIn terms of non-pharmacologic interventions, therapy and cognitive training techniques also show promise in the treatment of ADHD symptoms.Behavioral and cognitive-behavioral therapies alter the child's behavior through social learning principles . CognitiWith the support of four phase 3 trials of more than 1,000 pediatric patients, the FDA has approved the SNMA viloxazine in an extended-release (ER) capsule for the treatment of ADHD in children aged 6–17 , 18. Tho2B receptor antagonist and 5-HT2C receptor agonist and moderately inhibits NET, thus blocking the reuptake of norepinephrine  is unique compared to those of other ADHD and depression pharmacotherapies . Viloxaznephrine . The 5-Hnephrine . The 5-Hnephrine .The only moderate inhibitory activity of viloxazine at NET is consistent with the observed low rate of cardiac effects, more typical of primary norepinephrine reuptake inhibitors (NRIs) . ViloxazViloxazine ER is available in 100, 150, and 200 mg capsules. In pediatric patients aged 6–11 years of age, the recommended starting dose is 100 mg orally once daily and can be titrated in increments of 100 mg weekly to the maximum recommended dosage of 400 mg once daily, depending upon patient response and medication tolerability (i) for viloxazine at the norepinephrine transporter (NET) is 0.63 μM, while the half-maximal inhibitory concentration (IC50) is 0.2 μM , and the mean half-life of the viloxazine ER is 7.02 ± 4.74 h. Viloxazine undergoes metabolism via the cytochrome-P450 enzyme CYP2D6 and the UDP-glucuronosyltransferase enzymes UGT1A9 and UGT2B15. The inhibitory constant  is contraindicated, as administration of these drugs together could precipitate a hypertensive crisis. Viloxazine is primarily excreted renally as the major plasma metabolite 5-hydroxy-viloxazine glucuronide, such that special dosing and titration are crucial in patients with renal impairment , 20. VilP = 0.0012) between the Δ QtcI and viloxazine Cp and between 5-OH-VLX-gluc Cp and ΔQTcI (P = 0.0007), and secondary time point analyses did not show an effect of viloxazine ER on QtcI. The authors found that viloxazine ER does not have an impact on cardiac repolarization and/or another electrocardiogram (ECG) parameters, such that it does not increase the risk for cardiac arrhythmias.A study by Nasser et al. on the effect of viloxazine ER on the QTc interval of healthy adults . This stP = 0.0004 and P = 0.0244, respectively). There were also improvements in the CGI-I scores (P = 0.0020 and P < 0.0001), Conners 3-PS composite T-score (P = 0.0003 and P = 0.0002), and WIFIRS-P Total average score (P = 0.0019 and P = 0.0002) compared to placebo. There were also improvements in the CGI-I scores (P = 0.0020 and P < 0.0001), Conners 3-PS composite T-score (P = 0.0003 and P = 0.0002), and WIFIRS-P Total average score (P = 0.0019 and P = 0.0002) when compared to placebo. The authors found that the drug significantly improved ADHD symptoms. Adverse events related to treatment were mild and included headache, somnolence, and decreased appetite.A phase 3 study by Nasser et al. measured the change in the ADHD-Rating Scale-5 (ADHD-RS-5) total scores in schoolchildren with ADHD prescribed viloxazine ER . This wap = 0.031, 0.027, and 0.021, respectively) compared to the placebo  mean CFB in ADHD-RS-IV was significant  + methylphenidate (36 mg). Active drug amount was measured using chromatographic tandem mass spectrometry. Safety assessments such as vitals, ECGs, AEs, and clinical lab evaluations were assessed. For viloxazine ER alone, the following results were obtained: insomnia .post hoc analysis of data from four phase 3, randomized, placebo-controlled, double-blind, three-arm clinical trials by Faraone et al. was performed. This hoc analysis of data from four phase 3, randomized, placebo-controlled, double-blind, 3-arm clinical trials examining how early response to viloxazine ER predicts efficacy in pediatric patients. Treatment response was defined as having a ≥50% reduction in ADHD-RS-5 total score at Week 6. The CGI-score at weeks 1–3 and target dose were also assessed. The change in ADHD-RS-5 total score at week 2 best predicted the treatment response at week 6 . Of the study sample of 774 treated subjects, 342 subjects (44%) were categorized as responders to the treatment. A patient's ADHD-RS-5 scores at week 2 can be used to make clinically useful predictions of response to viloxazine. The week 2 data show higher levels of PPP that do not decrease excessively as sensitivity increases  scores with CGI scores. CGI scales are more intuitive assessments that can more easily assess the clinical implications of treatment. For the “improved” and “very much improved” ratings on the CGI-I, there were score improvements on the ADHD-RS-5 of ~55 and 80%, respectively, and improvements on the WFIRS-P of ~40 and 70%, respectively  compared to the placebo. There was also a statistically significant improvement in CGI-score for both the 200 and 400 mg dose groups  compared to placebo. There were no significant changes found in the Conners 3-PS Composite T-score  or WFIRS-P total average score . The most common AEs included decreased appetite, fatigue, headache, somnolence, and nausea. The authors concluded that the drug to be well-tolerated and to significantly improve ADHD symptoms , thus blocking the reuptake of norepinephrine (Over the past twenty years, research on ADHD and its characteristics and treatment options has grown exponentially, resulting in new pharmacologic options, including viloxazine . Viloxaznephrine . Viloxaznephrine . This drAE, MB, LK, and SY are responsible for the writing of the manuscript. HA, JW, EN, EC, AG, ADK, and AMK are responsible for editing. AE was also responsible for the idea concept and design of manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


A total of 50 neonates  participated in this study. LBW-VLBW neonates were further stratified as those with  and without  structural MRI (sMRI) abnormalities. TRUST and PC MRI studies were undertaken to determine OEF, CBF, and CMRO2. Ultimately, CMRO2 proved significantly lower (p = 0.01) in LBW-VLBW (vs term) neonates, both LBW-VLBW-a and LBW-VLBW-n subsets showing significantly greater physiologic deficits than term controls . CMRO2 and CBF in LBW-VLBW-a and LBW-VLBW-n subsets did not differ significantly (p > 0.05), although OEF showed a tendency to diverge (p = 0.15). However, OEF values in the LBW-VLBW-n subset differed significantly from those of term controls (p = 0.02). Compared with brain volume or body weight, these physiologic parameters yield higher area-under-the-curve (AUC) values for distinguishing neonates of the LBW-VLBW-a subset. The latter displayed distinct cerebral metabolic and hemodynamic, whereas changes were marginal in the LBW-VLBW-n subset  by comparison. Physiologic imaging may therefore be useful in identifying LBW-VLBW newborns at high risk of irreversible brain damage.Low birth-weight (LBW) and very low birth-weight (VLBW) newborns have increased risks of brain injuries, growth failure, motor difficulties, developmental coordination disorders or delay, and adult-onset vascular diseases. However, relatively little is known of the neurobiologic underpinnings. To clarify the pathophysiologic vulnerabilities of such neonates, we applied several advanced techniques for assessing brain physiology, namely T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI) and phase-contrast (PC) MRI. This enabled quantification of oxygen extraction fraction (OEF), global cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO Preterm newborns of low birth weight  or very low birth weight  present a substantial public health problem. In 2015, the worldwide prevalence was 14.6%, with 91% confined to low- and middle-income countries [primarily Southern Asia (24%) and sub-Saharan Africa (48%)]. More than 80% of perinatal deaths occur in LBW neonates .Although most LBW and VLBW preterm infants show catch-up gains in height and weight, they are still at increased risk of brain injuries , growth 133Xenon clearance  technologies have allowed noninvasive and quantitative measurements of critical neurophysiologic parameters, without need of contrast agents. The oxygen extraction fraction (OEF) of the brain is assessable using T2-relaxation-under-spin-tagging (TRUST) MRI technique , and glo2 using T2 prepared tissue relaxation inversion recovery (T2-TRIR) pulse sequences and ASL (2 and CBF in asphyxiated newborns with severe HIE (r = 0.88)  is another valuable means of perfusion MRI for this purpose. However, its signal-to-noise ratio (SNR) tends to be lower, the scan times lengthier, and there is a potential for confounding factors . In an earlier effort, infants with hypoxic ischemic encephalopathy (HIE) showed lower CBF and CMRO and ASL . Newborn = 0.88) . Our pre = 0.88) . Tortora = 0.88) . There h2 in a mixed group of LBW and VLBW newborns, comparing outcomes with those of term neonates.In the present study, we used TRUST MRI and PC MRI to determine OEF, CBF, and CMROn = 41) at birth weights >1,000 g but <2,500 g. Term neonates serving as controls (n = 9) had birth weights ≥2,500 g, were ≥37 weeks at birth, and showed no sMRI abnormalities. Population characteristics and results of blood gas analysis were listed in Our investigational protocol received approval from the Ethics Committee at Shengjing Hospital of China Medical University. Between June 2016 and December 2018, a total of 50 newborns accrued for study. The structural MRI pulse sequences performed included axial and sagittal T1-weighted imaging (TIWI), axial T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI). Congenital malformations, severe infections, or unusable MRI studies were grounds for exclusion. Subjects qualified as LBW-VLBW  obtained from all infants (LBW-VLBW and term) were viewed as Picture Archiving and Communication Systems (PACS) files by two neuroradiologists (YQ and XYS) with 10 years of experience, each blinded to group data. They independently scored MRI abnormalities for each infant, using a method similar to one already described  that focA 3T MRI system equipped with a phased-array head coil  was used for all MR scans. Prior to imaging procedures, a pediatrician sedated infants through nasal feedings of chloral hydrate (50 mg/kg). This is standard clinical practice at our institution. All newborns were well fed, visually monitored, and hearing protected during scans.2; and scan time, 30 s.Axial T1-weighted spin-echo images were acquired at the following settings: repetition time/echo time (TR/TE), 200 ms/2.3 ms; section thickness, 5 mm; field of view (FOV), 180 mm × 150 mm × 89 mm; matrix size, 224 × 162; and scan time, 34.4 s. For sagittal T1-weighted spin-echo images, the following settings were used: TR/TE, 250 ms/2.3 ms; section thickness, 5 mm; FOV, 230 mm × 230 mm × 107 mm; matrix size, 256 × 250; and scan time, 33.0 s. Axial T2WI used the following settings: TR/TE, 5,000 ms/80 ms; section thickness, 5 mm; FOV, 180 mm × 150 mm × 90 mm; matrix size, 112 × 112; and scan time, 40.9 s. Axial echo-planar imaging (EPI) DWI was performed as follows: TR/TE, 3,500 ms/63 ms; section thickness, 5 mm; FOV, 180 mm × 180 mm × 89 mm; b values, 0 and 1,000 s/mmOxygen extraction fraction was calculated as follows:where Ya and Yv signify arterial and venous oxygenation, respectively. Ya was measured peripherally, via pulse oximeter applied to neonatal toes. Yv was measured by TRUST MRI technique, given that blood T2 has a calibrationable relation with oxygenation level. This sequence utilizes a spin-labeling module to isolate pure venous blood signals, thereafter applying a series of T2-preparation pulses to modulate the MRI signal, the monoexponential fitting of which yields blood T2 . A T2-YvFor measuring CBF, PC MRI employed bipolar gradients to encode flow velocities of blood supplying major feeding arteries of the brain, specifically left and right internal carotid arteries (LICA and RICA) and left and right vertebral arteries (LVA and RVA), allowing quantitation of total blood flow to the brain. Flow values were then normalized to brain volume, expressing CBF in units of mL/100 g/min. Time-of-flight MR angiograms (TOF-MRAs) were first performed to allow visualization of above-referenced feeding arteries. Imaging slabs were positioned at center of epistropheus, with 60-mm saturation slabs placed above to suppress venous signals. Settings of TOF MRA were as follows: TR/TE, 20 ms/3.45 ms; flip angle, 18°; FOV, 90 mm × 90 mm × 20 mm; voxel size, 0.8 mm × 0.8 mm × 2 mm; and scan duration, 23.7 s.Based on MRA images, four PC MRI scans were performed by orienting imaging slices perpendicular to and centered on respective target arteries, as previously described . Scans oProcessing of PC MRI data again followed existing procedures . Manual 2 was calculated according to Fick’s principle  on scan age, sex, and diagnostic group (independent variables). In regression analyses, paired groups were encoded as follows: LBW-VLBW (0) vs term (1) neonates; LBW-VLBW-a (1) vs LBW-VLBW-n (0) subsets; LBW-VLBW-a neonates (1) vs term controls (0); and LBW-VLBW-n neonates (0) vs term controls (1). LBW-VLBW newborns underwent MRI scans once their vital signs had stabilized, and ventilators were no longer required (3 weeks old on average). Term infants had good vital signs and were amenable to scanning at any time (1 week old on average). There were distinct chronologic differences in scan ages of these pairings. Due to remarkable disparities , it was 1 and b2 were based on results of an age- and sex-adjusted regression model similarly reported  and term neonates (n = 9), LBW-VLBW-a (n = 24) and LBW-VLBW-n (n = 17) subsets, LBW-VLBW-a neonates (n = 24) and term controls (n = 24), and LBW-VLBW-n neonates (n = 17) and term controls (n = 24). We also analyzed birth weight, brain volume, and cerebral physiologic parameters independently, generating receiver operating characteristic (ROC) curves to distinguish the LBW-VLBW-a subset from all other neonates and from the LBW-VLBW group overall. Inter-rater variations in MRI scores determined by YQ and XYS were assessed via intraclass correlation coefficient (ICC), rated as follows: 1.0–0.81, excellent; 0.80–0.61, very good; 0.60–0.41, good; 0.40–0.21, reasonable; and 0.20–0.00, poor. All computations were driven by standard software , setting significance at p < 0.05.where coefficients breported . Correctp = 0.89); CMRO2, 29.9 ± 11.4 μmol/100 g/min vs 48.9 ± 12.4 μmol/100 g/min (p < 0.001); CBF, 13.6 ± 5.0 mL/100 g/min vs 19.5 ± 3.8 mL/100 g/min (p = 0.002); and brain volume, 265.2 ± 74.5 mL vs 354.1 ± 52.0 mL (p = 0.001). Only OEF proved similar, the other parameters differing significantly by group.In LBW-VLBW and term neonates, measured parameters were as follows: OEF, 31.3 ± 10.5% vs 30.8 ± 6.2% (n = 41), including both LBW-VLBW-a and LBW-VLBW-n subsets, are detailed in p > 0.05). Fifteen LBW-VLBW newborns had required mechanical ventilation.Population characteristics and diagnostic outcomes  of the LBW-VLBW group (2 was significantly lower (p = 0.01) in LBW-VLBW (vs term) newborns, CBF (p = 0.06) and OEF (p = 0.67) did not differ significantly. Furthermore, CMRO2 (p = 0.48) and CBF (p = 0.63) failed to show scan age-related increases during this period of early development; and despite significant differences in birth weight, LBW-VLBW and term neonates did not differ significantly in brain volume.We first compared physiologic measures of LBW-VLBW and term neonates . Althoug2 rates relative to controls . Contrary to expectations, no significant differences in CMRO2 (p = 0.30), CBF (p = 0.50), or OEF (p = 0.15) recordings were evident across subsets upon linear regression analysis. Relative to term neonates, OEF was significantly lower (p = 0.02) in the LBW-VLBW-n subset.Next, we compared the two subsets of LBW-VLBW neonates (LBW-VLBW-a and LBW-VLBW-n) with term newborns, both displaying lower CMRO1, scan age; b2, sex), with 95% confidence interval (CI) of coefficients and respective p-values. Once corrected for scan age and sex, group comparisons of birth weight, CMRO2, CBF, OEF and brain volume produced similar results , the LBW-VLBW-a subset vs term controls , and the LBW-VLBW-n subset vs term controls . This suggests that observed differences in physiologic parameters (CMRO2 and CBF) of the LBW-VLBW-a subset and term controls stemmed from brain injuries and did not reflect scan age or sex. Corrected OEF values in the LBW-VLBW-n subset did differ significantly (p < 0.001) from those of term controls. There were no significant differences in corrected values of LBW-VLBW-a and LBW-VLBW-n subsets (p > 0.05). results . Correctp = 0.25], OEF , CMRO2 , CBF , and brain volume  in distinguishing the LBW-VLBW-a subset from term and LBW-VLBW neonates are shown in 2 demonstrated fair diagnostic performance in this regard.Receiver operating characteristic curves for birth weight . Some term neonates were also discounted due to abnormal laboratory results or MRI findings. Presently, the potential for neurocognitive deficits in these infants and the relevance of CMRO2 reductions on neurocognitive deficits. We will also bolster subject recruitment, further stratifying by birth weight  and sex, and foster a multicenter approach to ascertain neurocognitive thresholds for reductions in CMRO2. Owing to brain immaturity, especially in VLBW infants, there is exceptional vulnerability to injuries undermining the microstructural integrity and tract connectivity of periventricular white matter (a vascular watershed territory)  . Knut harritory) . We must2 at brain level. Finally, the image quality in It is unclear at this point whether administering an anesthetic, such as chloral hydrate, has any cerebrovascular hemodynamic ramifications. There is no direct evidence in studies of humans and animals that it increases CBF or lowers glucose metabolism . However2, and higher OEF tended to show minimal structural abnormalities. Physiologic imaging may be a useful means of identifying those LBW-VLBW newborns at high risk of developing irreversible brain damage.In the present study, we have demonstrated that structural damage in LBW-VLBW-a neonates is associated with metabolic and hemodynamic deficits of the brain. LBW-VLBW-n neonates with lower CBF and CMROThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study protocol had ethical approval from the Ethics Committee of Shengjing Hospital of China Medical University (IRB2015PS28K). Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.YQ contributed study concepts and design, and providing post-processing assistance. Both authors participated in analysis of experiment results, drafting and editing of the manuscript, and have read and approved the final manuscript for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The research was conducted on the effect of bird broilers fed with different hybrid rye doses on the fatty acids profile in muscle. The first experiment was performed on 3 geese broilers groups fed with hybrid rye, oats or hybrid rye and oats mix in proportion 1:1. No effect of the hybrid rye feeding of geese on the SFA level in meat was observed, but the MUFA level was significantly higher and PUFA level and n-6/n-3 PUFA ratio were significantly lower than in geese fed with oats. The second experiment was performed on 3 chicken broiler groups fed with mix of corn, wheat, soybean meal and rapeseed oil (control group), and fed with an addition of 10% or 20% hybrid rye in diet . No effect of hybrid rye feeding of chicken broilers on the meat quality and SFA level was observed. However, the MUFA level was higher and the PUFA level and n-6/n-3 PUFA ratio were lower in meat of chicken broilers fed with hybrid rye. In conclusion hybrid rye is a healthy ingredient in the diet of studied birds and may be used up to 20% in chicken broilers and 50% in the diets of geese. A 100% hybrid rye in geese diet caused lower final body weight. The feeding level and chemical content of feed mixtures affect animals’ growth and hormone’s metabolism, as well as the quantity and quality of fat deposited during the daily gain . One of The fatty acid profile in food plays an important role in human health. The higher share of unsaturated fatty acids in the diet reduces the risk of heart diseases, diminishes the risk of some types of cancer, asthma, and diabetes . There iFeed for poultry produced in Poland is based on cereals with high C 18:2 n-6 acid content and low C 18:3 n-3 acid content. However, the fatty acids profile varies significantly depending on the cereal type. For example, the C 18:2 n-6 and C 18:3 n-3 ratio, according to research, was for rye varieties 6.0–7.2:1, for the hybrid rye Fernando variety it was 6.4:1, for oats it was 12.4–22.7:1, for winter wheat it was 10.9:1, for winter barley it was 9.7:1, and for corn it was 33.7–43.8:1 . New hybDespite the growing interest in feeding poultry with hybrid rye, the knowledge of the effect of this feed on the fatty acids profile has not been widely investigated. Therefore, this research aimed to examine the effect of the hybrid rye variety on chicken broilers and geese fatty acids profile in poultry breast meat.Two separate experiments were performed on the influence of the hybrid rye Brasetto variety in feed on the fatty acids content in geese and chicken broilers meat. A different experimental pattern was applied for each poultry species.An experiment was performed on young geese of the Polish Zatorska rare breed, a meat type that is a part of the genetic resource protection program. The experimental plan is presented in There were 300 goslings in the flock (150 young ganders and 150 young geese) that were moved after hatching and sexing, to the rearing building with 7 birds per sq m in the bedding system on the straw, with natural light, and with a starting temperature of 28 °C lowered to 22 °C in the third week of life. The birds had access to feed and water. They were fed with compound feed no. 1—the feed content is presented in 3/1 kg of BWG/1 h and the concentrations of CO2 and NH3 were maintained below 2000 and 20 ppm, respectively. The chickens were weighed with BD3T electronic scales with an accuracy of 0.1 g  and randomly assigned to 1 of 3 treatments, each comprising 3 replicate cages, with 8 birds per cage . From 1 to 42 days of age, all the chickens were provided with water and feed ad libitum.A total of 72 1-day-old, male Rose 308 chickens were used. These were obtained from a commercial hatchery and had an average initial weight of 41 g. The birds were housed in wire-flooded cages, in an environmentally controlled room in the poultry house at the Experimental Station of the National Research Institute of Animal Production in Balice, Poland. During the study, the temperature in the experimental facility was maintained from 32 °C at 1 day of age to 21 °C at 21 days of age, and later, relative humidity cycled from 50 to 60%, air exchange was 1 mAll the birds were reared up to 42 days of age and fed with crumbled starter (1 to 21 days) and pelleted grower-finisher (22 to 42 days) isonitrogenous and isoenergetic diets , which wBroilers were slaughtered at 42 days of age in the commercial slaughterhouse conditions.M. pectorialis major) for lab tests.The geese carcasses after slaughter were chilled in the day-night cycle at 4 ºC. The carcasses for tests were randomly chosen in the scheme of 12 male and 12 female carcasses from each of the 3 experimental groups (24 samples per group). Next, 48 h after slaughter, the breast muscle was cut out .Water holding capacity (WHC) was measured with the Grau and Hamm method  modifiedp < 0.05). The results are presented as average values and standard error of the mean (SEM).The obtained data were subjected to the analysis of variance (ANOVA) using Statistica 6.0 software . Tukey’sAll experimental procedures performed on live animals followed the EU Directive 2010/63/EU for animal experiments  and the The studied groups of geese were obtained different final body weight at seventeen weeks of age .p < 0.05). It was connected with higher energy value and higher fat content of oat in comparison to hybrid rye  from those groups fed with the oat or rye-oat mixture, reaching 39.59% and 41.42% respectively. The oleic acid C 18:1 content in the trans spatial configuration was less favorable in those geese fed with hybrid rye than in the geese fed with oats or a rye-oat mixture (0.32% in group A and 0.27% in groups B and C).It is worth noticing that the highest level of C 18:1 oleic acid with a double bond in the cis spatial configuration was reported in the group of geese fed with hybrid rye (43.12%) that was significantly different . The trans C 18:1 acid positively decreased from 0.19% in the control group to 0.12% in group B, with 30% rye in the dose (p < 0.01). The addition of 10% rye in the dose did not have a significant influence on the C 18:1 trans acid in the meat of the chicken broilers.The obtained results indicate the significant effect of hybrid rye in the chicken broilers diet on the fatty acids profile in the breast muscle . The addp < 0.05), and a higher addition did not have such an effect. There were differences between the PUFA n-3 and PUFA n-6 levels that caused a profitable decrease in the n-6/n-3 ratio, with a higher rye share in the dose from 5.8 in the control group to approx. 4.6 in the group fed with a 20% hybrid rye share in the compound feed (p < 0.01). The addition of rye also had a significant effect on lowering the cholesterol level in the broilers breast muscle, from 72.5 to approximately 60–64.5 mg/100 g tissue in the experimental groups (p < 0.01).The results of the PUFA levels were inconclusive because the lower rye addition in the dose caused their decrease in the tested muscle (p < 0.05) and a reduction in yellowness (p < 0.01), as well as an improvement in WHC (p < 0.01). However, it had no effect on the sensory characteristics of meat.Physicochemical and sensory traits of the chicken breast muscles are presented in Present lifestyles and human eating habits make us prone to delivering surplus amounts of energy to our bodies with all the undesired health consequences. Dieticians recommend reducing fat consumption to the level when energy is delivered by fat in not more than 25–30% of daily intake . These recommendations are aimed at delivering optimal amounts of nutrients with the fat dose and zero or limited amounts of undesirable ingredients [This study showed that geese feeding with the hybrid rye caused the lowering of final body weight in comparison to feeding with oat. However, rye addition in mixture with oat in proportion 1:1 levelled this negative effect on birds’ growth. On the contrary in the chicken broilers feeding rye addition up to 20% in diet had no effect on its growth, because final body weight in all studied groups caused about 3 kg, and there was no significant change between groups. A comparison of final body weight at 40 days of age was stated in the study of McCafferty et al. [Hybrid rye used in geese feeding did not affect the SFA level in the meat samples, whereas in chicken broilers feeding it caused it to be lower by the 3 pp level compared to the control group, but only when a higher rye dose was added to the diet . In chicken broilers fed with a higher rye dose a significantly lower cholesteroleic saturated fatty acids level was confirmed C 12:0; C 14:0 and C 16:0. A significantly lower level of only lauric acid (C 12:0) was also found in the group of geese fed with a rye-oat mixture, compared to the control group and the group fed with rye only.A similar saturated fatty acids profile was reported in Chech geese by Uhlirova et al. . Geese wp < 0.01), but in the case of geese fed with oats and mixture rye/oats lowered the MUFA level in comparison to the group fed with hybrid rye (p < 0.01). It was a very important observation because the anti-carcinogenic effect of these acids is well known [The atherogenic acids level (arachidic acid C20:0 and behenic acid C22:0) did not depend on hybrid rye feeding in all of the experimental birds. Meanwhile, the MUFA profile was dependent on the rye diet in the geese and chicken broilers. As a result, the rye dose in the diet effect on the higher the MUFA level in chicken groups with 10 and 20% grains  than in the oat group (about 22.5%), i.e., 3.4 pp less. A proportionally lower effect was observed in geese fed with a rye-oat mixture (approximately 1 pp lower).Confirmed differences in PUFA n-6 and n-3 levels caused that the n-6/n-3 ratio was more profitable in the case of hybrid rye feeding of all the experimental birds. In chicken broilers meat, this ratio decreased with a higher rye dose, starting from 5.8 in the control group to 5.2 with 10% rye in the diet and to 4.6 in the group with 20% rye in the diet. In the meat of geese fed with oats, this ratio was 17.1, whereas in geese fed with rye 13.5 and geese fed with a rye-oat mixture, it was 13.2. A less positive n-6/n-3 ratio than obtained within this research was reported by Disetihe et al. (2019), in the experiment on chicken broilers feeding with a commercial mixture with soy (12.56) and with corn (8.99). A better n-6/n-3 ratio was reported by Uhlirova et al. , i.e., 9en week of age was stated in Karwowska et al. [In generally, the positive effect was observed in fatty acids profile of geese fed only with hybrid rye or with the mixture hybrid rye and oats in proportion 1:1. However, diets with only hybrid rye caused smaller final body weight. For this reason, the diet with the above mixture is better for production targets and geese meat quality. Lower than in oats feeding, the final body weight of chicken broilers at 17a et al. ’s study,There was no effect of hybrid rye feeding on the total cholesterol level in geese muscles. In chicken broilers, all hybrid rye levels in the diet caused a significant decrease of cholesterol level in the breast muscle, from approximately 73 mg/100 g in the control group to approximately 60–65 mg/100 g in groups fed with 10% and 20% of hybrid rye in the diet. It is commonly known that cholesterol is present in all animal cell membranes. It is the simplest place for cholesterol to form, and that is why its amount is not correlated with fat content in meat. Chicken and turkey meat contains on average 65–73 mg/100 g of cholesterol ,27, i.e.Regardless of the above-established dependencies between the supplementation of hybrid rye in the diet of broilers and the fatty acid profile in meat, there are some changes in its qualitative characteristics. In their study, Lisiak et al.  determinOn the other hand, in our studies on the effect of hybrid rye in diet of the chicken broilers on the quality characteristics of meat, it was shown that its addition resulted in greater final acidification of the breast muscle, improvement in WHC, and lowering the b* parameter level. There was no effect of feeding with this rye on the sensory traits of the chicken meat.No effect of feeding hybrid rye to geese on the SFA level was confirmed. However, the addition of 10% and 20% of hybrid rye in the diet lowered the SFA level in chicken broiler meat. The MUFA level was significantly dependent on the rye diet in geese and chicken broilers. Moreover, the MUFA level was higher and more positive when the addition of hybrid rye was higher. A significantly lower PUFA level in the meat of birds fed with hybrid rye was observed in geese. The n-6/n-3 PUFA ratio was significantly lower in all experimental birds fed, with the addition of hybrid rye which confirmed the benefits of including hybrid rye in the diets of these animals. The diet with mixture hybrid rye and oats in proportion 1:1 is better for production target and geese meat quality, because it was stated as having a better fatty acids profile and does not negatively effect the growth of geese. Generally, the feeding of geese and chicken broilers by the addition hybrid rye in the diet caused good quality of the meat, and in some traits, also led to an improvement in the comparison to the control group.


Glaucoma is the leading cause of irreversible blindness worldwide, and pathologically elevated intraocular pressure (IOP) is the major risk factor. Neuroprotection is one of the potential therapies for glaucomatous retinal damage. Intravitreal mesenchymal stem cell (MSC) transplantation provides a viable therapeutic option, and human umbilical cord- (hUC-) MSCs are attractive candidates for cell-based neuroprotection. Here, we investigated the ability of transplanted hUC-MSCs to survive and migrate within the vitreous cavity and their neuroprotective effects on chronic glaucomatous retina. For this, we developed a chronic ocular hypertension (COH) rat model through the intracameral injection of allogeneic Tenon's fibroblasts. Green fluorescent protein-transduced hUC-MSCs were then injected into the vitreous cavity one week after COH induction. Results showed that a moderate IOP elevation lasted for two months. Transplanted hUC-MSCs migrated toward the area of damaged retina, but did not penetrate into the retina. The hUC-MSCs survived for at least eight weeks in the vitreous cavity. Moreover, the hUC-MSCs were efficient at decreasing the loss of retinal ganglion cells; retinal damage was attenuated through the inhibition of apoptosis. In this study, we have developed a novel COH rat model and demonstrated the prolonged neuroprotective potential of intravitreal hUC-MSCs in chronic glaucoma. Glaucoma comprises a group of diseases causing irreversible blindness characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Elevated intraocular pressure (IOP) is one of the most important risk factors for glaucomatous optic neuropathy. However, the common pharmacological or surgical treatments to reduce IOP do not halt progressive visual loss ; therefoThe primary obstacle limiting stem cell therapy is the identification of an appropriate cell source. Mesenchymal stem cells (MSCs) of different origins have shown the greatest potential in the treatment of optical neuropathy –6. For eTo study the mechanisms of glaucomatous damage, the widely used experimental approach is to induce elevated IOP in animals –19. InduIn the present study, we developed a novel method for inducing elevated IOP and preliminarily evaluated the reliability of this rat model of chronic glaucoma. Then, hUC-MSCs marked with GFP were transplanted intravitreally, to investigate whether transplanted hUC-MSCs could survive and migrate in the vitreous cavity. We also demonstrated long-term neuroprotective efficacy of transplanted hUC-MSCs in the novel model, through the evaluation of RGC loss, retinal damage, and apoptosis in retinal cells caused by IOP elevations.The study strictly adhered to the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research. The experimental protocols were approved by the experimental animal ethics committee of Xiamen University. Adult (8-12 weeks old) wild-type Sprague-Dawley rats were used in this study. In addition, two transgenic GFP-expressing Sprague-Dawley rats were used as donors of Tenon's fibroblasts. All rats were housed in light- and temperature-controlled conditions.In all rats, the right eye was injected intracamerally with allogeneic Tenon's fibroblasts (suspended in PBS) and used as the experimental COH eye, and the contralateral eye was injected intracamerally with PBS and served as the control group. One week after the induction of IOP elevation, all the IOP-induced rats were randomly divided into 2 groups as follows: hUC-MSCs were washed with phosphate buffer saline (PBS) and resuspended in PBS and intravitreally transplanted to the right eyes of 24 rats (COH+hUC-MSC group). PBS was intravitreally injected to the right eyes in another 18 rats that served as the COH group. All of the rats were sacrificed after 8 weeks.The GFP-Tenon's fibroblasts were isolated from the eyes of transgenic rat that ubiquitously expressed GFP. Briefly, the superficial layer of Tenon's capsule, attached to the sclera, in the eyes of the GFP-rat was isolated under an operating microscope, washed with Ca2+- and Mg2+-free Hank's solution  and digested by 0.2% dispase II . The isolated cells were incubated in humidified 95% air/5% CO2, detached with trypsin/EDTA solution and diluted 1 : 3 upon reaching 80% confluence. Cell culture was performed in Dulbecco's modified Eagle's medium , supplemented with 10% FBS and 1% penicillin/streptomycin.μL) was injected into the anterior chamber using a 30-gauge needle. Care was taken to avoid any injury to tissues inside the eye.GFP-labeled fibroblasts from passage 2 were used for cell injection. After general anesthesia, pupillary dilation of the right eye was achieved with 0.5% tropicamide. A suspension of Tenon's fibroblasts  in awake rats without anesthesia. Six measurements were consecutively performed according to instrument requirements, and the mean of the second through sixth readings was automatically calculated and then recorded. Such measurements were repeated five times on each eye at each time point. On each occasion, the IOP for each given rat was measured at the same time of day.High IOP of rats was maintained for 8 weeks, and the optic nerve of the eyeball was completely removed under anesthesia. The frozen section of optic nerve was stained with 2% toluidine blue. Optic nerve morphology changes were assessed under a bright-field microscope. For TEM, following 12 weeks of elevated IOP, optic nerve tissues were sectioned and counterstained with uranyl acetate and lead citrate. Images were acquired on a JEM-2100 electron microscope  operated at an accelerating voltage of 120 kV for morphology analysis.The use of the human umbilical cords for research was approved by the local ethics committee, and informed consent was obtained from all donors, following explanation of the research. The donors were pregnant women with no congenital diseases, hepatitis, syphilis, AIDS, or other infectious diseases, and the gestational ages were 37–40 weeks. The hUC-MSCs were isolated as previously described . BrieflyThe cells were labeled with antibodies against CD29-phycoerythrin (PE), CD44-fluorescein isothiocyanate (FITC), CD105-FITC, CD34-FITC, CD45-FITC, HLA-DR-PE, CD80-FITC, CD86-FITC, and CD31-FITC. Flow cytometry was performed using a FACS Calibur , and the data were analyzed with the Cell Quest software (BD Biosciences).μl DMEM-F12 (10% FBS) for 12 h. The GFP-gene-expressing lentiviral vectors  were added to the medium supplemented with 8 μg/ml of polybrene. Viral particles were removed after 24 h exposure. Two days later, hUC-MSCs were assessed under an inverted fluorescent microscope .To label hUC-MSCs, cells were placed in 12-well plates at a density of 105 cells per well in 500 μl, 20,000 cells/μl) was gently injected into the vitreous cavity with a 30-gauge Hamilton needle through the pars plana of the globe. The pinhole was covered up with erythromycin ointment [One week after COH induction, GFP-labeled hUC-MSCs were transplanted intravitreally into the COH eyes. After general and topical anesthesia, as described above, the hUC-MSC suspension (5 ointment .μm thickness) along the vertical meridian of the eyeballs through the optic nerve head. Tissue preparations were processed for either hematoxylin and eosin or toluidine blue or were examined under fluorescence microscope .The rats were sacrificed 60 days after hUC-MSC transplantation. The eyes were enucleated and fixed in 4% paraformaldehyde for 50 minutes at room temperature and then infiltrated with 30% sucrose/PBS for 24 h at 4°C. The whole-eye tissues were embedded in optimal cutting temperature compound. The frozen specimens were sectioned (7 μL each) into the superior colliculus at a point 6.0 mm caudal to the bregma and 1.0 mm lateral to the midline on both sides to a depth of 5.0 mm from the surface of the skull.The retrograde labeling of RGCs with Fluorogold was performed as previously described . RGCs ofSeven days after Fluorogold retrograde labeling, rats were sacrificed and the eyes were enucleated and fixed in 4% paraformaldehyde in PBS for 1 hour in the dark at 4°C. The retinas were dissected free, flat-mounted on a glass slide, and observed under the Leica fluorescence microscope. Manual RGC counting, by an investigator masked to the experimental procedures, was conducted in the superior, inferior, temporal, and nasal quadrants at distances of 1, 2, and 3 mm radially away from the optic nerve. Cells with intense dye staining and smaller or larger size than normal were considered to be microglia or macrophages and were excluded from the analysis .μm sections along the vertical meridian of the eye through the optic nerve head and stained with hematoxylin and eosin. Sections were examined under a light microscope [The cornea, lens, and vitreous of the rat were carefully removed, and the posterior eyecups were embedded in optimal cutting temperature compound. The frozen specimens of rat retinas were cut into 7 croscope .μg of total protein was dissolved in 12%-SDS gels, transferred to polyvinylidene fluoride membranes , and incubated overnight at 4°C with primary antibodies against caspase-8  and β-actin . Protein bands were detected with horseradish peroxidase-conjugated goat anti-rabbit IgG  and visualized by enhanced chemiluminescence reagents and quantified with the Quantity One software (Bio-Rad).Protein extraction and Western blots were performed as reported previously . In briep < 0.05.Data were expressed as mean ± standard deviation. All statistical analyses were performed using SPSS . One-way analysis of variance (ANOVA) was performed followed by the Student–Newman–Keuls test for multiple comparisons. Statistical significance was set at We first developed a rat COH model based on an intracameral injection of allogenic Tenon's capsule fibroblasts . To miniNext, the GFP-Tenon's fibroblasts were intracamerally injected. These cells were visible in the anterior chamber angle and the pupil at 3 and 7 days postinjection, under a Nikon AZ100 motorized zoom fluorescence microscope. Compared with the normal left eye, the iris at the edge of the pupil of the treated right eye was attached to the lens, resulting in pupil atresia, which may have further led to aqueous humor gathering in the posterior chamber. There was a very pronounced iris-bulge formation under ophthalmic operating microscope at 7 days . Two weeTo assess the reliability of the rat model, the induced elevation of IOP and the optic nerve injury were investigated. The injection of GFP-Tenon's fibroblasts into the anterior chamber (COH group) induced a prolonged and significant rise in IOP relative to the contralateral (left) eye. The increase in IOP was maintained throughout the duration of the experiment. Across animals, the mean IOP, averaged over the length of the experiment, for Tenon's fibroblast-injected eyes was 24.9 ± 6.1 mmHg, compared with 11.4 ± 0.9 mmHg for the control eyes. The peak of IOP for the injected eyes increased from 11.1 ± 1.4 mmHg to 30.9 ± 11.8 mmHg one week after the injection of Tenon's fibroblasts into the COH eyes.p < 0.05) higher mean IOPs than in the contralateral (left) eyes (control group), results showed that there was no significant difference in IOP profile, across the duration of the study, between ocular hypertensive eyes that received intravitreal hUC-MSC transplantation (COH+MSC group) and COH group that did not . At passage 2 (P2), the cells displayed a parallel or whirlpool-like arrangement when they reached 80% confluence . Flow cyGFP labeling, a simple and efficient technique, was applied to track the hUC-MSCs in the vitreous cavity. The efficiency of lentiviral transduction for labeling hUC-MSCs was about 85%, as observed under an inverted fluorescent microscope. The morphologic and biologic characterizations of the infected hUC-MSCs did not change, and the cells were in good condition after transduction .To perform an in vivo assessment of the long-term survival of hUC-MSCs in the vitreous chamber after cell grafting, hUC-MSCs were labeled with the GFP-encoding lentiviral vector and monitored using a Nikon AZ100 motorized zoom microscope . Fluores2, whereas 8 weeks after induction of high IOP, RGC numbers were reduced to 1187 ± 44 cells/mm2. In eyes that received hUC-MSC transplantation, the RGC density was 1926 ± 81 cells/mm2, significantly higher than those without hUC-MSC transplantation , the inner plexiform layer (IPL), and the outer nuclear layer (ONL), and the number of RGCs had decreased by approximately 40%. In addition, the structures of the IPL and ONL were damaged by intraocular hypertension at 8 weeks in the COH model group. In contrast, the number of RGCs was significantly higher in the COH+hUC-MSC group than in the COH group. However, no differences were observed in the IPL and the ONL between the COH+hUC-MSC and COH groups, and the thicknesses of the IPL and ONL were consistent with that in the COH model group Figures . The GCLNext, to investigate whether hUC-MSCs could improve the survival of RGCs and alleviate the damage to the retinal cells, by inhibiting apoptosis signaling in the COH model, and to explore the involved mechanisms, the level of active caspase-8 in retinas was analyzed. As shown in In the present study, to test the neuroprotective effect of hUC-MSC transplantation, we first developed a rat model of COH/glaucoma by injecting cultured Tenon's fibroblasts into the anterior chamber of the eye. The results revealed that hUC-MSCs survived for at least 8 weeks that they had the ability to migrate preferentially toward the damaged site of the host retina in the vitreous cavity, and that they significantly reduced retinal damage and RGC loss. These findings suggest that there is a neuroprotective effect of hUC-MSCs in an animal model of glaucoma.Animal models are among the most useful tools for understanding disease pathology and for developing interventions against disease. To date, many rodent models have been reported to mimic the natural cause of glaucoma. In our study, rats were chosen as the animal model, in part because rats have similarities with humans in the anatomical features of the ocular anterior segment, aqueous fluid circulation, and optic nerve damage with elevated IOP . The resOur findings point to a plausible explanation for the elevated IOP in this novel model. The initial IOP elevation in this model may be the consequence of the aqueous humor drainage obstruction, due to the accumulation of fibroblasts in the anterior segment of the eye. One week after intracameral injection of fibroblasts, pupil atresia occurred, which might be the primary cause of the elevated IOP that lasted for approximately 2 months. In contrast with other methods to maintain elevated IOP , 28, 29,With the COH model established, we transplanted hUC-MSCs into the eyes and evaluated the changes in retinal morphology, RGC loss, and caspase-8 expression. Fluorescence from GFP-labeled hUC-MSCs could be detected inside the eye even 8 weeks after cell transplantation, indicating the survival of hUC-MSCs in the vitreous cavity. This result was similar to other reports showing that MSCs could survive for 5 weeks in the vitreous cavity in a glaucoma model , and thaHowever, although 2-month persistence was observed for hUC-MSCs in the vitreous, it is noteworthy that the Tenon's fibroblasts injected in the anterior ocular chamber persisted for less than 2 weeks, which is in line with other findings that transplanted MSCs persisted in the anterior chamber for only a few days . This maAnother finding in this study is the fluorescence evidence that some of the cells migrated to the retina as clusters 1-week posttransplantation, indicating that the injected hUC-MSCs had the ability to migrate preferentially toward the damaged site of the host retina, that is, in addition to the finding that the hUC-MSCs can survive a sufficiently long time within the vitreous cavity to generate a physiological effect by secreting neurotrophic factors. Together, these results imply that hUC-MSC transplantation through the vitreous cavity is feasible. This may have important implications for the development of cell-based neuroprotective therapies.Although our results demonstrated the migration of GFP-hUC-MSCs to the surface of the retina in the COH eyes, integration of hUC-MSCs with the retinal tissue could not be confirmed. In contrast to our results, a previous study reported that a limited number of transplanted adipose tissue and bone marrow-derived MSCs  did inteIntravitreally transplanted MSCs have been shown to provide a neuroprotective effect in different animal models of glaucoma. Adult bone marrow MSC transplantation increased RGC survival by about 25% at 4 weeks in a rat model of ischemia-reperfusion injury . In a COAccumulating evidence has shown that caspase signaling-dependent apoptosis plays a key role in the development and progression of glaucoma , 36. TheNevertheless, other mechanisms likely also contributed to the neuroprotective effect of hUC-MSCs. For example, the cytokines and neurotrophic factors secreted from MSCs, such as brain neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor, have been shown to provide neuroprotective effects in experimental models of glaucoma , 32. TheThe eye is considered a site with relative immune privilege , and hUCOur study showed that a single injection of allogeneic cultured Tenon's fibroblasts into the anterior chamber of the eye resulted in a moderate and sustained elevation of IOP, damaged the optic nerve, and caused characteristic glaucomatous RGC loss in the rat retina. This seems consistent with some features of chronic glaucoma and may be useful for exploring the pathogenesis of chronic glaucoma. Intravitreally injected hUC-MSCs survived for a prolonged period and migrated toward the injured site of the retina in the vitreous cavity, without penetrating the inner limiting membrane into the retina. The hUC-MSC injections improved RGC survival, as well as ameliorating retinal damage, by inhibiting apoptosis caused by high IOP in this COH rat model. Further investigations are needed to enhance the ability of hUC-MSCs to integrate into the damaged retina and to understand the mechanisms underlying the neuroprotective effect of hUC-MSC transplantation.


N = 42) versus matched healthy controls (N = 59). We investigated the relationship of resting gamma activity (30–48 Hz) with age in four right hemispheric electrode clusters where diminished gamma power in ADHD had previously been demonstrated by our group. We found significant non-linear association between resting gamma power and age in the lower frequency gamma1 range (30–39 Hz) in ADHD as compared to controls in all investigated locations. Resting gamma1 increased with age and was significantly lower in ADHD than in control subjects from early adulthood. We found no significant association between gamma activity and age in the gamma2 range (39–48 Hz). Alterations of gamma band activity might reflect altered cortical network functioning in adult ADHD relative to controls. Our results reveal that abnormal gamma power is present at all ages, highlighting the lifelong nature of ADHD. Nonetheless, longitudinal studies are needed to confirm our results.Decreased gamma activity has been reported both in children and adults with attention deficit/hyperactivity disorder (ADHD). However, while ADHD is a lifelong neurodevelopmental disorder, our insight into the associations of spontaneous gamma band activity with age is limited, especially in adults. Therefore, we conducted an explorative study to investigate trajectories of resting gamma activity in adult ADHD patients ( ADHD is the most prevalent childhood mental disorder, and is characterized by inappropriate inattention, hyperactivity and impulsivity compared to healthy peers. ADHD persists into adulthood with full diagnostic criteria, or with a partial remission and concomitant impairment in circa 50% of cases  which does not allow for an investigation of the EEG trajectories throughout the entire adult lifespan. Specifically, prior investigations were based on non-overlapping age cohorts, and the adult cohort was not sub-divided into adult age groups, which precludes conclusions about fine-grained changes in adulthood. Thus, our insight into the underlying electrophysiological changes in adulthood is still limited.Abnormalities of resting EEG activity in Attention Deficit/Hyperactivity Disorder (ADHD) have been reported in several previous publications , a right central (Cluster B) and an extended right centro–parieto–occipital (Cluster C) distribution in the gamma1 band (30–39 Hz) and a smaller, right centroparietal (Cluster D) localization in the gamma2 band (39–48 Hz). Resting gamma power was inversely associated with ADHD symptom severity in both frequency ranges.  treatment. At the time of the study, only methylphenidate was available for adults with ADHD. Adult ADHD participants were recruited from the Adult ADHD Outpatient Clinic of the Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary. Controls were recruited from the local community, clinical staff and their relatives.The inclusion criterion for the patient group was the diagnosis of ADHD based on a detailed clinical interview conducted in three steps as described by our group earlier  in a sound-attenuated room. Participants were not allowed to take caffeine or to smoke two hours prior to EEG-recording. Participants were instructed to sit calmly with eyes open during the four minutes long resting-state EEG-recording. Electrooculogram (EOG) was recorded using two electrodes placed over and below the outer canthi. EEG was digitized with a sampling rate of 1024 Hz. Preprocessing was performed using EMSE Suite . Data were band-pass filtered between 0.5 and 70 Hz and notch filtered at 50 Hz. For the ocular artifact removal, we used a spatial filtering approach, the Thin Plate Spline interpolation method described by Bookstein et al.  and gamma2 (39–48 Hz) power were applied as dependent variables in separate analyses. Study group  served as independent variable. Age was used as a continuous regressor. To investigate potential non-linear changes, age was included in the analysis both as a linear and a quadratic term. Interactions between study group and age (both in linear and quadratic terms) were also included in the analysis. Gender, treatment with MPH and overall symptom severity  served as covariates.We used ANCOVA as principal statistical model for this investigation, as it represents a combination of the methods of regression and the analyses of variance, unifying the advantages of the two approaches in the context of a single general linear model as described in prior literature  estimates of gamma activity at every five year in the age range from 18 to 58 years for the purpose of visualization of the gamma trajectories separately in each study group for each electrode cluster. For the purpose of the computation of the LS-mean estimates and their standard errors, we used the linear and quadratic coefficients of age regression that reached significance in the statistical model.To correct for multiple testing, in post-hoc comparisons performed with pairwise t-tests alpha was adjusted using Hochberg’s method Hochberg . All stadf = 2, p = 0.89). Furthermore, the results showed that approximately 28.6% and 26.2% of the ADHD subjects fell, respectively, in the younger and older age groups . The analogous numbers for the control subjects were 30.5% for the younger (< 25 years) and 22.0% for the older (> 35 years) subjects (with 52.5% being outside the intermediate age range).The summary of basic demographic and symptom severity characteristics is provided in Table ADHD showed significantly higher overall symptom severity measured by the Core Symptom Total Score compared to controls. All four CAARS symptom factors were significantly higher in the ADHD group as compared to healthy controls Table .1 band (30–39 Hz), the analysis adjusted for symptom severity and treatment indicated a main effect of group , interactions of linear and quadratic age effect with group  in the right antero-frontal cluster (Cluster A). MPH treatment status, used as covariate in the analysis, also obtained significance . Both groups exhibited curvilinear developmental trajectories of gamma1 activity. First, gamma activity decreased until around 40 years, followed by a plateau and then by an increase until the late fifties. This increment resulted in higher gamma1 power in the oldest ages of the sample. The initial reduction of absolute gamma power was more pronounced in patients than in controls. Except for the youngest and oldest ages, ADHD had significantly lower resting gamma activity throughout the investigated age range  = 43.28, p < 0.0001, respectively) as well as interactions for study group with age for both the linear and the quadratic functions . MPH treatment status also obtained significance for both Cluster B [F(treatment) = 13.12 p = 0.0003] and Cluster C [F(treatment) = 127.67 p < 0001], with a 7% and 26% relative increase of gamma power for Cluster B and C, respectively, in the MHP treated subjects). At the earliest adult ages (< 20 years), ADHD had slightly higher right central and right centroparietal gamma1 power than controls. The developmental curves of gamma1 in these regions exhibited a curvilinear increase in both study groups. Gamma1 power in older ages was higher than in younger ages in both areas. In the right central region (Cluster B) gamma1 activity reached a plateau during the late thirties and early forties in ADHD, unlike in controls where a similar plateauing was observed slightly later. Gamma1 power decreased in both study groups in the upper limits of the investigated age range. A curvilinear increase of gamma1 power was found in both study groups over time in the right centroparietal region with a plateauing trend more apparently in controls. Except for the youngest ages, gamma1 power was significantly lower in ADHD then in controls over time in both scalp regions.In the right central and extended right centroparietal clusters  after adjustment for symptom severity and treatment we found significant main effects for study group , or the interaction effect of study group with age with respect to the linear  or quadratic functions . MPH treatment status, applied as covariate, obtained significance in the analysis . The developmental path of gamma2 power is depicted in Figure S1 in Supplementary material S1. Both study groups had a reduction of gamma2 power over time with a slight acceleration of the decrease in controls during the mid-fifties. There were no group differences detected in any age.In the gamma1 (30–39 Hz) power in adult ADHD compared to healthy controls. The course of the gamma1 trajectory curves was a curvilinear decrease in both study groups in the antero-frontal brain areas. Patients with ADHD had a more pronounced decline in early adulthood, and except for the lowest and highest ages, they also had significantly lower gamma1 power then control subjects at all ages. Furthermore, both ADHD and control subjects had a curvilinear developmental path with an increasing gamma activity in the right central and right centroparietal regions. In the right central region, there was a modest gamma1 power increase in early adulthood, with a slightly earlier plateauing in the patients. Except for the youngest ages (< 20 years of age), ADHD patients had significantly lower gamma1 power than controls over time. The aforementioned results were statistically significant after adjusting for treatment status with MPH and symptom severity. In case of the gamma2 (39–48 Hz) absolute power, no significant association with age was found. Gamma2 decreased over time in both ADHD and controls.The main finding that we report in this paper is a different developmental path of resting gammaWe note that our results showed no difference at early adulthood between the ADHD and healthy control subjects. Decreased gamma activity in child and adult ADHD has been reported in previous literature as an overall group effect, usually by averaging measurement data from subjects of an age range. The analyses typically did not include group with age interaction effects. Furthermore, it should be kept in mind that the most relevant resting EEG literature on gamma activity in ADHD so far was based on groups of children at a relatively young age  until early adulthood, but often fail to confirm disease-specific alterations during electrophysiologic maturarion  be present in the central and extended right centroparietal regions.Early signs of cortical thinning, characteristic for the normal cortical aging, are already present in middle-aged healthy individuals in the prefrontal, frontal and, to a lesser extent, in the parietal heteromodal association cortices . Acute administration of amphetamine salts induced an increase of spontaneous MEG gamma activity (30–106 Hz)  and higher age (> 35 years) ranges were included in our sample, we think that future studies should use a more targeted sampling design to assure a uniform age distribution. Third, major developmental changes occur from childhood through adolescence to early adulthood both in healthy controls and in ADHD. Since our study focused on adults, it is not possible to draw conclusions about the developmental path of gamma power in the earliest years of adulthood (< 20 years) where partially different trends were observed than in other age groups  than controls across most of the age range in our sample. The maximum of the differences in the antero-frontal region was observed during the middle-age with a diminution of differences in later ages. In case of the central and centroparietal regions, gamma activity differences increased with time. The results suggest that diminished resting gamma activity is stable over time in adult ADHD, and that different developmental paths might be present over the frontal and centroparietal cortices. In the framework of the dysfunctional network hypothesis, these results might reflect alterations of cortical organization, neural network structure and dynamics during late neurodevelopment and early aging in ADHD, as it is considered both a neurodevelopmental and a lifelong disorder. Our results contribute to the literature on the lifespan course of adult ADHD, underline its lifelong nature and might help to gain insight into the age-related changes of potential biomarkers for use in clinical practice.There was a curvilinear/non-linear association between resting gamma power and age in adult ADHD. Resting gamma power increased over time in both study groups. The course of trajectory curves is similar in patients than in controls, and ADHD patients had significantly lower resting gamma


Ceramics are advanced engineering materials in which have been broadly used in numerous industries due to their superior mechanical and physical properties. For application, the industries require that the ceramic products have high-quality surface finishes, high dimensional accuracy, and clean surfaces to prevent and minimize thermal contact, adhesion, friction, and wear. Ceramics have been classified as difficult-to-machine materials owing to their high hardness, and brittleness. Thus, it is extremely difficult to process them with conventional finishing processes. In this review, trends in the development of non-conventional finishing processes for the surface finishing of difficult-to-machine ceramics are discussed and compared to better comprehend the key finishing capabilities and limitations of each process on improvements in terms of surface roughness. In addition, the future direction of non-conventional finishing processes is introduced. This review will be helpful to many researchers and academicians for carrying out additional research related to the surface finishing techniques of ceramics for applications in various fields. A (Si3N4) ,13,14,15g et al. . SiC is g et al. . It suppg et al. ,19. Its g et al. . SiC hasg et al. ,22. Si3Ns, etc.) ,24. The However, before they are employed in such applications, the products or components made using the ceramics must be manufactured with both high quality and efficiency with attributes such as high-quality surface finish, clean surfaces, dimensional conformity, and high accuracy of shape, in order to prevent and minimize thermal contact, adhesion, friction, and wear ,39. The The conventional finishing processes include processes such as grinding , turning2O3 fine ceramic round bar (Ø 3 mm × 60 mm) [2 ceramic cylindrical bar (Ø 0.8 mm × 50 mm) [2O3 ceramic plate (100 mm × 100 mm × 2.5 mm) [2O3 ceramic tube (Ø 50 mm × 100 mm) [To overcome these problems, many researchers have adopted various non-conventional finishing processes , magnetorheological finishing (MRF), and clustered magnetorheological finishing (CMF)) to achieve smooth surface of advanced ceramics. The MAF process is a non-conventional finishing technique that was invented to produce a highly smooth surface and high workpiece form ultra-precision on round bar and inner surface materials using magnetic fields to govern a flexible magnetic abrasive brush during the finishing process ,51,52. T× 60 mm) , a ZrO2 × 50 mm) , an Al2O 2.5 mm) , and an  100 mm) . The mag 100 mm) . The MRF 100 mm) ,58,59 an 100 mm)  proposed 100 mm) , glass [ 100 mm) , and cry 100 mm) . The CMR 100 mm) .In this review paper, the finishing principles, finishing characteristics, current limitations, capabilities, and influence of these non-conventional finishing processes are discussed in detail and compared with regard to their ability to enhance the surface roughness and surface topography of difficult-to-machine ceramics. Finally, the future development of a new finishing procedure using a multi-axis/multi-faceted finishing technique for the surface finishing of materials of complex shapes, such as artificial hip joint ceramic components, is introduced.In recent years, there has been active development of novel non-conventional finishing processes and improvement of conventional processes to achieve the high-quality surface finish of difficult-to-machine materials such as ceramics, titanium alloys, tungsten, cobalt, and inconel 718 ,67,68,69Unlike conventional processes, the non-conventional finishing processes have major advantages in that they use the extremely low normal force with small cuts produced by micro abrasive tools, which enables the production of a superior surface finish and a damage-free surface . AdditioRa value of 0.21 μm after finishing by this process. Mun et al. [A cylindrical MAF is a non-conventional finishing process which is used to produce a high-level surface quality on the object with a mirror surface level ,78,79. Cn et al.  also ach2 ceramic cylindrical bar via different magnetic pole designs such as a magnetic pole with a sharp edge, a 2-mm square edge, and a 5-mm round edge.According to their study, the cylindrical MAF process is able to obtain smooth surface finishes on various cylindrical workpiece materials of various sizes. Due to the numerous potential advantages of this process, Heng et al.  chose it2 ceramic by Heng et al. [2 in a chuck and rotating it at 35,000 rpm inside the vibrating magnetic abrasive tools, a mixture of Fe powder (200 μm), diamond abrasives (1 μm), carbon nanotube (CNT) particles (0.04 μm), and light oil (0.2 mL). A ZrO2 ceramic (dimension: 0.8 mm × 50 mm) used in his study is shown in Ra) of ZrO2 was significantly decreased from 0.18 μm to 0.02 μm by the cylindrical MAF process under optimal conditions . AFM surface topography images of the ZrO2 ceramic are shown in 2 was uneven and had many peaks, with an average peak height of 0.18 μm  of the internal surface. To improve the high finishing efficiency for an alumina ceramic tube in the internal MAF process, the use of an ultrasonic vibration system was explored by Yun et al. [A schematic of the internal MAF process for the surface finishing of an alumina ceramic tube using the ultrasonic vibration L-shaped magnet is shown in n et al. . The processing procedure used in this study employs an L-shaped magnet and magnetic abrasive tools (mixture of iron powder and diamond abrasives) positioned inside the ceramic tube. Due to the strong magnetic field, the magnetic abrasive tools formed a flexible magnetic abrasive brush for acting against the rotating internal surface of the ceramic tube. During the finishing process, when the ceramic tube was rotated, the outside magnet was reciprocally moved along the ceramic tube axis, which drove movement of the internal magnet within the magnetic abrasive brush along the ceramic tube axis. At the same time, an L-shape magnet with a magnetic abrasive brush started to vibrate with a certain frequency via adherence to ultrasonic vibration. Using this procedure, the magnetic abrasive brush can effectively remove the unevenness from the internal surface of ceramic tube. Yun’s results showed that the Ra of an alumina ceramic tube was reduced from 1.1 µm to 0.03 µm by internal MAF accompanied with ultrasonic vibration under optimal conditions .2 ceramic plate. As ZrO2 is a difficult-to-machine material because of its high brittleness and high hardness, it could reduce the finishing efficiency of the general MRF process. To combat this potential problem, a permanent magnetic (PM) yoke excitation was added to the MRF process and the feasibility of this setup was examined [The MRF process is a non-conventional micro finishing technique which has been used to finish components without causing subsurface damage. In this process, a workpiece surface is finished in a magnetorheological finishing fluid which is composed of carbonyl iron power and magnetic abrasives suspended in a carrier liquid ,102. In examined .2 surfaces are shown in 2 workpiece. A ZrO2 workpiece is installed at a fixture that enables rotation along the B-axis. The finishing trough is fastened on the A-axis, which enables its rotation opposite to the B-axis. The PM yoke was installed below the ZrO2 workpiece, and it was used to enlarge the finishing area between the ZrO2 surface and the MR ribbon. During the finishing process, when the magnetorheological (MR) fluid passed over the magnetic field gradient, it stiffened to form a rectangular magnetorheological fluid ribbon within one millisecond. Due to the magnetic field gradient, the magnetic finishing abrasives float upward and congregate at the interface of the ZrO2 and the magnetorheological fluid ribbon. By the pressure of magnetorheological ribbon, the finishing abrasive acts strongly on the ZrO2 surface, resulting in high quality surface finishing. After the finishing process, the ZrO2 had a mirror surface with surface roughness values less than 1 nm. The evolution of the surface topography of a ZrO2 plate from before to after MRF is shown in 2, corresponding to a surface roughness of 71.976 nm (Ra) (see Ra) after finishing with a diamond abrasive within 30 min  see a. After  min see b. Figureectivity c, left. 3N4) ceramic balls.CMRF is a novel finishing process in which dynamic magnetic fields are formed via the synchronous eccentric rotation of numerous magnets . This pr3N4 balls is shown in 3N4 balls, and an MRF slurry . In the CMRF process, the ceramic balls are placed inside a groove of the lower finishing head, and they are surrounded by MRF slurry. The MRF slurry forms a magnetic chain shape because of the cluster magnetorheological effect caused by the N-pole and S-pole of the magnets [3N4 balls are eliminated by the abrasion between the spherical surfaces of the Si3N4 balls and the MRF abrasives. According to the results of Xiao et al. [3N4 balls is greatly improved, with the surface roughness value decreasing from 63 nm (Ra) to 4.35 nm (Ra) under optimal CMRF conditions.The CMRF process for Si magnets . During o et al. , after t3N4 balls before and after finishing by CMRF process are compared in 3N4 balls . To improve the finishing efficiency, researchers have applied critical parameters to their finishing processes, which have had major influence on improvement in surface roughness (Ra). In this study, a percentage of improvement in surface roughness equation was implemented in order to compare the finishing capabilities of each process on the improvements in surface roughness. Equation (1) expresses the percentage of improvement in the surface roughness (Ra) as a function of the non-conventional finishing processes. BFP is the value of (Ra) before the finishing process, AFP is the value of (Ra) after the finishing process, and PISR is the percentage improvement in surface roughness (Ra). According to Equation (1), it was found that the surface roughness improvement for each of these non-conventional finishing processes was greater than 56%. When cylindrical MAF, plane MAF, internal MAF, MRF, and CMRF process were used for finishing the surface of ceramics, they showed improvements of 88.88%, 56.54%, 97.27%, 99.02%, and 93.09%, respectively.From these studies, it is evident that all the discussed processes can successfully achieve the high-quality surface finish of difficult-to-machine ceramics with low values of surface roughness (Ra) obtained by these different non-conventional finishing processes. These data suggest that for achieving high surface quality of ceramic material bars, the cylindrical MAF process can be used because it can produce the best results within the short finishing time of only 40 s. A smooth surface on a ceramic plate can be achieved by different processes such as plane MAF and MRF process, with the best results found when the MRF process was used. The MRF process required only 30 min to obtain the optimal result, and the improvement in surface roughness by this process was 99.02%. In contrast, the plane MAF process required 80 min to obtain the optimal result, and the PISR of this process was only 56.54%. Therefore, it was found that MRF was best suited to finish the surface of plane ceramic material. As seen in The plane MAF and MRF process can be used in the optical industry for achieving the high-quality surface finish of transparent ceramic lenses, and these processes can be used in the semiconductor industry for achieving the high-quality surface finish of the electrostatic ceramic chuck component. The cylindrical MAF process can be used in the electronics industry for achieving the high-quality surface finish of a ceramic needle pin, and in the medical industry for items such as ceramic tooth screws. The internal MAF process can be used in the automotive industry for achieving the high-quality surface finish of ceramic nozzles, and for ceramic heat pipes used in heat transfer applications. With the CMRF process, it is possible to achieve high-quality surface finish of the ceramic bearing ball used in electric motors and in the aerospace applications.However, with these processes it is difficult to achieve the high-quality surface finish of the products with complex shapes which are currently used in the medical applications , and in gas turbine engine applications such as ceramic turbine rotors. This is due to the limitations of their experimental device that make it difficult to process complexly shaped surface ceramics.Therefore, in order to achieve the high-quality surface finish of the ceramic component with complex shapes, new developments and a new finishing procedure related to these non-conventional finishing processes are required.These non-conventional finishing processes have been shown to successfully finish the ceramic components of various shapes, including cylindrical bars, plates, tubes, and round balls. Despite the advantages of these processes, some limitations associated with these processes still remain.-The plane MAF, internal MAF, MRF, and CMRF processes are very slow because they require large finishing time for difficult-to-machine materials such as ceramics.-Products with freeform shapes, including elliptical, conical, wrinkle, and concave shapes are impossible to finish via these processes due to the variations in the finishing gap between the tools and the workpiece. Some limitations associated with recent non-conventional finishing processes are shown in The following limitations of these processes are listed below:Ceramics are advanced materials that are widely used in many high-tech industries. Ceramic components are highly priced when compared to other advanced materials such as cobalt chromium (Co-Cr) alloys, titanium alloys, and stainless steel. The challenges related to the surface finishing of ceramics include long finishing times, high energy consumption, high rate of tool wear, and poor surface finishes by conventional finishing processes. In spite of these difficulties, non-conventional finishing processes have been shown to successfully achieve the high-quality surface finish of advanced ceramics. However, most of these processes have major problems with finishing times, as they require long finishing times for hard materials such as advanced ceramics. In addition, these processes are not applicable for freeform surfaces.To overcome these problems, novel advanced research regarding finishing processes must be pursued. Novel advanced processes must go beyond the existing capabilities of the non-conventional finishing processes. To this end, future work could apply a multi-axis/multi-faceted surface finishing technique to the cylindrical MAF process for finishing ceramic components with spherical shapes, such as an artificial hip joint . The artUnlike the CMRF process, the rotational motions are applied in the X-, Y-, and Z-directions in the cylindrical MAF process. Rotational motion can be added to the spherical ball workpiece using a step motor, enabling workpiece rotation up to 10,000 rpm in the Y-direction. The rotational motions of both magnetic pole systems are generated by step motors, so they can simultaneously rotate in the X- and Z-directions. The addition of high rotational speed to the spherical ball workpiece can increase the relative action between the surface of spherical ball and the magnetic abrasive tools, resulted in the achievement of a high-quality surface finish on spherical ball workpiece within a short finishing time less than 10 min. The working principle of a cylindrical MAF process using a multi-axis/multi-faceted finishing technique for the surface finishing of ceramic components with spherical shapes such as artificial hip joints is shown in Ra). When the cylindrical MAF, plane MAF, internal MAF, MRF, and CMRF process were used for finishing the surface of ceramics, they showed surface roughness (Ra) improvements of 88.88%, 56.54%, 97.27%, 99.02%, and 93.09%, respectively.All the non-conventional finishing processes discussed in this review have been successful in achieving the high-quality surface finish of various difficult-to-machine ceramics with low values of surface roughness  inapplicability to finishing freeform surfaces, (2) lengthy finishing times, and (3) difficulty finishing the surface of ferromagnetic materials.In the future, a multi-axis/multi-faceted surface finishing technique can be added to the cylindrical MAF process for the surface finishing of difficult-to-machine ceramic components used in medical applications such as artificial hip joints. This process would have major advantages such as short processing times and the ability to process all common materials, including ceramics, metals, and polymers.According to the above papers, the conclusions of this study are as follows: