Endocan as a Potential Marker for Predicting All-Cause Mortality in Hemodialysis Patients.

Endocan, a pro-inflammatory cytokine and pro-angiogenic factor, is a marker of endothelial dysfunction and has been proven to correlate with cardiovascular disease. In hemodialysis (HD) patients, cardiovascular disease is the major cause of mortality. Our study aimed to investigate the relationship between serum endocan and all causes of mortality in HD patients. A total of 103 patients, aged over 20 years old and undergoing HD for more than 3 months, were included and followed for 36 months. Mortality events, serum endocan, biochemical data, body mass index, systolic and diastolic blood pressure, baseline characteristics, and the use of antihypertensive and lipid-lowering drugs were recorded. In our study, a total of 26 deaths (25.2%) occurred. Hemodialysis patients with diabetes mellitus, older age, higher serum endocan, and lower creatinine and albumin levels had a higher risk of mortality. Adjusting for prognostic variables, HD patients with higher serum endocan (p = 0.010) and lower serum creatinine (p = 0.034) demonstrated significantly higher all-cause mortality. In our study, increased endocan and lower creatinine are associated with all-cause mortality in HD patients. Serum endocan levels could serve as a biomarker for a high mortality risk in HD patients.

Finite Element Analysis Model for Assessing Expansion Patterns from Surgically Assisted Rapid Palatal Expansion.

Surgically assisted rapid palatal expansion (SARPE) was introduced to release bony resistance to facilitate skeletal expansion in skeletally mature patients. However, asymmetric expansion between the left and right sides has been reported in 7.52% of all SARPE patients, of which 12.90% had to undergo a second surgery for correction. The etiologies leading to asymmetric expansion remain unclear. Finite element analysis has been used to evaluate the stress associated with SARPE in the maxillofacial structures. However, as a collision of the bone at the LeFort I osteotomy sites occurs only after a certain amount of expansion, most of the existing models do not truly represent the force distribution, given that the expansion amount of these existing models rarely exceeds 1 mm. Therefore, there is a need to create a novel finite element model of SARPE that could perform a clinically required amount of expander activation for further analysis of the expansion patterns of the hemimaxillae in all three dimensions. A three-dimensional (3D) skull model from cone beam computed tomography (CBCT) was imported into Mimics and converted into mathematical entities to segment the maxillary complex, maxillary first premolars, and maxillary first molars. These structures were transferred into Geomagic for surface smoothing and cancellous bone and periodontal ligament creation. The right half of the maxillary complex was then retained and mirrored to create a perfectly symmetrical model in SolidWorks. A Haas expander was constructed and banded to the maxillary first premolars and first molars. Finite element analysis of various combinations of buccal osteotomies at different angles with 1 mm clearance was performed in Ansys. A convergence test was conducted until the desired amount of expansion on both sides (at least 6 mm in total) was achieved. This study lays the foundation for evaluating how buccal osteotomy angulation influences the expansion patterns of SARPE.

The skeletal and dental age advancements of children and adolescents with overweight and obesity: A systematic review and meta-analysis.

INTRODUCTION: Over the past decades, a trend of increasing obesity among children has emerged. This study aimed to evaluate and summarize the impacts of overweight and obesity on children's and adolescents' skeletal and dental developmental advancement that may influence orthodontic management. METHODS: Registered with the Prospective Register of Systematic Reviews (registration no. CRD42022347488), this study complies with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Particularly, relevant original studies on skeletal or dental age evaluation were screened from accessible electronic databases and supplemented by hand-searching. Meta-analysis was recruited to calculate differences (and their 95% confidence interval [CI]) between subjects with overweight or obese and normal-weight counterparts. RESULTS: After applying the inclusion and exclusion criteria, 17 articles were selected for the final review. Two of the 17 selected studies were found to have a high risk of bias and moderate the other 15. A meta-analysis detected no statistically significant difference in skeletal age between children and adolescents with overweight and normal-weight counterparts (P = 0.24). However, the dental age of children and adolescents with overweight was found to be 0.49 years (95% CI, 0.29-0.70) advanced in comparison with normal-weight counterparts (P <0.00001). In contrast, children and adolescents with obesity were found to have advanced skeletal age by 1.17 (95% CI, 0.48-1.86) years (P = 0.0009) and dental age by 0.56 (95% CI, 0.37-0.76) years (P <0.00001) compared with their normal-weight counterparts. CONCLUSION: Because the orthopedic outcomes of the orthodontic intervention are closely tied to the skeletal age of the patients, these results suggest that the orthodontic evaluation and treatment of children and adolescents with obesity might occur earlier than that of the normal-weight population.

Sagittal and Vertical Changes of the Maxilla after Surgically Assisted Rapid Palatal Expansion: A Systematic Review and Meta-Analysis.

Surgically assisted rapid palatal expansion (SARPE) is often performed to correct the transverse deficiency in the maxilla for skeletally mature patients. However, there is little consensus on the sagittal and vertical displacement of the maxilla after SARPE. This systematic review aims to analyze the position changes of the maxilla in the sagittal and vertical dimensions after the completion of SARPE. Registered with PROSPERO (registration number: CRD42022312103), this study complied with the 2020 PRISMA guideline and was conducted on 21 January 2023. Original studies were screened from MEDLINE (PubMed), Elsevier (SCOPUS), and Cochrane, and supplemented by hand-searching. Cephalometric changes of skeletal vertical and sagittal measurements were the focus. A fixed-effects model was applied in R for meta-analysis. After applying inclusion and exclusion criteria, seven articles were included in the final review. Four studies had a high risk of bias, and the other three had a medium risk of bias. Meta-analysis revealed that the SNA angle increased by 0.50° ± 0.08° (95% confidence interval, 0.33° to 0.66°), and the SN-PP angle increased by 0.60° ± 0.09° (95% confidence interval, 0.41° to 0.79°) after SARPE. In summary, the maxilla displayed statistically significant forward and clockwise downward movement after SARPE. However, the amounts were small and might not be clinically significant. Due to the high risk of bias of included studies, our results must be taken cautiously. Future studies are needed to discern the effects of direction and angulation of the osteotomies of SARPE on the displacement of the maxilla.

New triazole-attached quinoxalines selectively recognize the telomeric multimeric G-quadruplexes and inhibit breast cancer cell growth.

The telomeric 3'-overhang had potential to form into higher-order structures termed multimeric G-quadruplexes (G4s), which may mainly exist in telomeres, representing an attractive drug target for development of anticancer agents with few side effects. However, only a few molecules that selectively bind to multimeric G4s have been found by random screening, which means a lot of room for improvement. In this study, we raised a feasible strategy to design small-molecule ligands with possible selectivity to multimeric G4s, and then synthesized a focused library of multi-aryl compounds by attaching triazole rings to the quinoxaline skeleton. Among them, QTR-3 was identified as the most promising selective ligand that may bind at the G4-G4 interface, which accordingly stabilized multimeric G4s and induced DNA damage in telomeric region, thereby leading to cell cycle arrest and apoptosis. Notably, QTR-3 showed more significant inhibition on breast cancer cells against normal mammary cells.

Neuroprotective effect of astragalin via activating PI3K/Akt-mTOR-mediated autophagy on APP/PS1 mice.

As a small molecule flavonoid, astragalin (AST) has anti-inflammatory, anti-cancer, and anti-oxidation effects. However, the impact and molecular mechanism of AST in Alzheimer's disease (AD) are still not clear. This study aims to investigate the neuroprotective effect and mechanism of AST on APP/PS1 mice and Aß25-35-injured HT22 cells. In this study, we found that AST ameliorated cognitive dysfunction, reduced hippocampal neuronal damage and loss, and Aß pathology in APP/PS1 mice. Subsequently, AST activated autophagy and up-regulated the levels of autophagic flux-related protein in APP/PS1 mice and Aß25-35-induced injury in HT22 cells. Interestingly, AST down-regulated the phosphorylation level of PI3K/Akt-mTOR pathway-related proteins, which was reversed by autophagy inhibitors 3-Methyladenine (3-MA) or Bafilomycin A1 (Baf A1). At the same time, consistent with the impacts of Akt inhibitor MK2206 and mTOR inhibitor rapamycin, inhibited levels of autophagy in Aß25-35-injured HT22 cells were activated by the administration of AST. Taken together, these results suggested that AST played key neuroprotective roles on AD via stimulating PI3K/Akt-mTOR pathway-mediated autophagy and autophagic flux. This study revealed a new mechanism of autophagy regulation behind the neuroprotection impact of AST for AD treatment.

Asymmetric Maxillary Expansion Introduced by Surgically Assisted Rapid Palatal Expansion: A Systematic Review.

PURPOSE: A commonly reported complication of surgically assisted rapid palatal expansion (SARPE) that has not been explored extensively is uneven expansion between left and right sides, which requires secondary surgery for correction. This systematic review aims to analyze the prevalence and potential causes of asymmetric expansion in the transverse dimension after SARPE to guide the clinical practice. METHODS: Electronic databases and manual search were used to search for original articles published on SARPE on March 11, 2022. Original human studies that recorded the number and percentage of asymmetric expansion after two-piece SARPE were included. The 2020 Preferred Reporting Items for Systemic Reviews and Meta-Analyses guideline was implemented for the quality assessment and data analysis of the included articles. The study was registered at the International Prospective Register of Systematic Reviews under the number CRD42022300782. RESULTS: After applying inclusion and exclusion criteria, 13 articles were included in the final review. The risk of bias was high in 8 studies and medium in the other 5 studies. Overall, the prevalence of asymmetric expansion in the transverse dimension (different amount of expansion between left and right sides) was 7.52%, with 12.90% of patients involved receiving a second surgery for correction. Expander design did not significantly affect the rate of asymmetry expansion. Pterygomaxillary fissure release significantly increased the rate of asymmetry expansion (11.02% vs 5.08%, P < .001). In comparison, lateral nasal wall osteotomy (4.26% vs 14.77%, P < .001) and release of the nasal septum (5.22% vs 17.15%, P < .001) significantly lowered the rate of asymmetry expansion, respectively. CONCLUSIONS: Asymmetric dentoskeletal expansion between left and right sides is a common complication of SARPE procedures, mostly caused by variations in surgical cuts. However, the risk of bias in currently available publications is high. Further studies are warranted to fully understand the causes of asymmetric expansion.

Discovery of a fluorescent, long chain-bridged bispurine that selectively targets the c-MYC G-quadruplex.

G-quadruplexes (G4s) are special nucleic acid structures which are involved in the regulation of some key biological events like transcription and translation, which are now treated as promising therapeutic targets for cancers. Stabilizing the promoter G4 by small-molecule ligands can suppress the c-MYC oncogene transcription, thus inhibiting cancer cell proliferation. So far, targeting the very structure, a number of ligands have been reported. However, most of them showed unsatisfactory specificity to the c-MYC G4 over other G4s, resulting in uncertain side effects. In this contribution, we discovered a new class of bispurines bridged with flexible hydrocarbon chains, which presented somewhat selectivity to the c-MYC G4 possibly by adaptive binding, which then showed clear inhibition on the c-MYC expression rather than other G4-driven oncogenes. Moreover, these novel molecules had the potential to fluorescently label G4s. We believed that this study may shed light on the discovery of new functional small molecules targeting a specific G4 structure.

Success of infrazygomatic crest bone screws: patient age, insertion angle, sinus penetration, and terminal insertion torque.

INTRODUCTION: The aim of this study was to assess the 6-month survival (success) rate for infrazygomatic crest (IZC) bone screws relative to patient age, insertion angle, sinus penetration, and terminal insertion torque. METHODS: One hundred consecutive patients (27 males, 73 females; mean age 25.8 years; age range, 11.0-53.8 years) received IZC temporary anchorage devices (TADs) bilaterally (n = 200). Each TAD was routinely loaded with up to 14 oz (397 g or 389 cN), reactivated monthly, and followed for 6 months. Terminal insertion torque was measured, and radiographs were assessed to determine the length of the TAD engaged in bone and depth of penetration into the maxillary sinus. RESULTS: Compared with nonpenetrating IZC TADs, the mean results for the 96 (48%) TADs that did penetrate the sinus were: 3.23 mm of sinus penetration, 21.3% decrease in terminal insertion torque, and 31.5% less bone contact at the TAD osseous interface. Perforation prevalence increased with age from 35.7% (11-19 years) to 62.5% (>30 years) (P <0.01). Terminal insertion torque increased from 11-19 years to 20-29 years because of increasing bone density with age but then decreased at >30 years because of increased incidence of sinus penetration (P <0.05). Sinus penetration had no significant effect on IZC TAD survival. About 5% of the devices did fail when the final insertion torque was significantly (P <0.05) decreased to 7.37 N-cm compared with the mean torque of 11.63 N-cm for successful TADs. CONCLUSIONS: Both sinus perforation and IZC bone quality increased with age. Sinus penetration did not significantly affect the 6 month survival rate of IZC TADs because the loss of bone quantity at the interface was offset by the age-related increase in bone quality at the IZC site.

Influence of blood group and von Willebrand factor on population pharmacokinetics and dose individualization of recombinant factor VIII in Taiwanese patients with haemophilia A.

INTRODUCTION: The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost-beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment. AIM: This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment. METHODS: A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed-effects modelling (NONMEM® ) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens. RESULTS: A two-compartment model with first-order elimination best described the rFVIII data. Weight-based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15-40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62-62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL. CONCLUSION: The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered.

New Dibenzoquinoxalines Inhibit Triple-Negative Breast Cancer Growth by Dual Targeting of Topoisomerase 1 and the c-MYC G-Quadruplex.

As c-MYC is one of the central players in triple-negative breast cancer (TNBC) oncogenesis, inhibiting c-MYC expression would be an effective anticancer strategy. Transcription-induced negative supercoiling is crucial in the regulation of c-MYC transcription, which facilitates the formation of a G4 structure in NHE III1 that can silence the transcription. However, topoisomerase 1 (Topo1) can dissipate this negative supercoiling, leading to continuous activation of c-MYC transcription. Thus, dual ligands targeting both Topo1 and c-MYC G4 appear to be significant in cancer therapy. In this study, a series of new dibenzoquinoxaline derivatives were designed, synthesized, and evaluated for both Topo1 and c-MYC inhibition. Among them, 5 was identified as the most promising dual ligand, which could effectively inhibit Topo1 activity and strongly stabilize c-MYC G4, thereby inhibiting cancer cell growth. Accordingly, this work suggests that this dual-targeting strategy may be effective in cancer therapy.

Effects of Hsian-tsao (Mesona procumbens Hemsl.) extracts and its polysaccharides on the promotion of wound healing under diabetes-like conditions.

The aim of the study was to evaluate the effects of Hsian-tsao (Mesona procumbens Hemsl.) and its polysaccharides on impaired wound healing in diabetes. The results indicate that ethanol extracts of Hsian-tsao (EE) and crude polysaccharides from water extracts of Hsian-tsao (WEP) had strong inhibitory effects on methylglyoxal (MG)-induced glycation and reactive oxygen species (ROS) production. EE and WEP also decreased MG-induced inflammation-related factors in RAW 264.7 macrophages and restored MG-impaired wound-healing factors in 3T3-L1 fibroblasts. Furthermore, EE and WEP were found to dose-dependently enhance the MG-impaired phagocytosis of Staphylococcus aureus and Pseudomonas aeruginosa by macrophages. Excitingly, EE and WEP significantly enhanced wound healing on the dorsal skin through regulation of macrophage inflammatory protein-2 (MIP-2), metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein expressions in diabetic mice, as evidenced by the percentage reduction in wound surface area and the results of histopathologic scoring analysis. In conclusion, these results suggest that Hsian-tsao extract and its polysaccharides might be utilized in alternative natural therapy to promote wound healing in diabetic individuals.

The voiding efficiency in rat models with dopaminergic brain lesions induced through unilateral and bilateral intrastriatal injections.

Bladder dysfunction is a common phenomenon in Parkinson's disease (PD) patients. A research attempt was made to analyze the voiding efficiency (VE) and bladder functions in rats with PD induced by unilateral or bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. PD rats were divided into unilateral- and bilateral-injected groups and subjected to rotation and beam walking tests. Further, the experimental rats underwent cystometric measurements for analyses of bladder dysfunction and VE. Immunohistochemical analysis was performed to analyze the dopaminergic neuron depletion on the target area. Outcomes of the rotation and beam walking tests revealed the extent of parkinsonism in the experimental rats. Urodynamic observations denoted that rats with unilateral PD exhibited a significantly decreased VE (from 68.3±3.5% to 32.7±5.8%), while rats with bilateral PD displayed a much-reduced and substantially lower level of VE of 18.3±5.1% compared to the control value and to that of rats with unilateral PD. Rats with bilateral PD showed more-extensive behavioral deficits and urodynamic changes than did rats with unilateral PD. These significant changes in motor, behavioral, bladder function and VE were due to an extensive degeneration of dopaminergic neurons in the substantia nigra region on both sides of the brain. The obtained results were substantiated with appropriate immunohistochemical results.

Influence of Adjacent Teeth Absence or Extraction on the Outcome of Non-Surgical Periodontal Therapy.

Background: Extraction of periodontally compromised or strategically non-important teeth is often an integral part of non-surgical periodontal treatment (NSPT). This study evaluated the association between the status of adjacent teeth and the outcome of NSPT on molars. Methods: Charting data of patients with generalized chronic periodontitis receiving NSPT in 2012-2014 were included. The association between initial clinical parameters and significant clinical improvement, including the reductions of probing pocket depth (PPD) and clinical attachment loss (CAL), in molar teeth with severe periodontitis after NSPT was assessed by a generalized linear model and logistic regression. Results: ≥7 mm PPD and <2 mm gingival recession (REC) at the tooth level, and ≥7 mm PPD, ≥7 mm CAL and <2 mm REC at the site level, were associated with significant clinical improvement. Absence or extraction of an adjacent tooth achieved an additional 0.22-0.23 mm and 0.60-0.83 mm clinical improvement. Among the interproximal sites, ≥7 mm PPD, <2 mm REC, ≥7 mm CAL,

Effect of Phyllanthus emblica L. fruit on methionine and choline-deficiency diet-induced nonalcoholic steatohepatitis.

Phyllanthus emblica L. fruit contains abundant bioactive components and exhibits a variety of biological activities. In this study, the hepatoprotective effect of water extract of P. emblica (WEPE) on nonalcoholic steatohepatitis (NASH) was evaluated. C57BL/6 mice were fed methionine and choline-deficiency diet (MCD diet) for 4 or 8 weeks to induce NASH. Results showed that administration of WEPE could significantly reduce serum AST and ALT as compared to MCD diet-alone group. Administration of WEPE could significantly decrease lipid peroxidation and CYP2E1 mRNA expression, and elevate the antioxidant activities in mice livers. In addition, administration of WEPE after 8 weeks could significantly decrease the mRNA expressions of TNF-α and IL-1ß in mice livers, but have less improving effect of hepatic steatosis and mononuclear cell infiltration. Taken together, MCD diet might cause serious hepatic steatosis and mild inflammation in mice livers, but administration of WEPE could ameliorate the rapid progression of NASH.

Beneficial Properties of Phytochemicals on NLRP3 Inflammasome-Mediated Gout and Complication.

Gouty arthritis is characterized by the precipitation of monosodium urate (MSU) crystals in the joint. Pro-inflammatory cytokine IL-1ß is a critical manifestation in response to MSU crystals attack. IL-1ß secretion is dependent on the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Abnormal activation of the NLRP inflammasome is related to cellular oxidative stress. However, recent studies have illustrated that phytochemicals with potent antioxidant activity exert inhibitory effects on NLRP3 inflammasome-mediated diseases. This review focuses on the current findings of studies on the NLRP3 inflammasome and the proposed mechanisms that MSU crystals trigger inflammation via activation of the NLRP3 inflammasome. We also summarized the potential use of phytochemicals on NLRP3 inflammasome-mediated diseases, suggesting that phytochemicals can further prevent acute gout attack.

Hypouricemic effects of Mesona procumbens Hemsl. through modulating xanthine oxidase activity in vitro and in vivo.

Uric acid is a metabolite obtained from purine by xanthine oxidase activity (XO) and high levels of serum uric acid leads to hyperuricemia and gout. Mesona procumbens Hemsl. has been used as a healthy beverage and a traditional remedy. In this study, the hypouricemic effects of M. procumbens extracts were evaluated in vitro and in vivo. The 50% ethanol extract of M. procumbens (EE50) showed the strongest inhibitory effect on monosodium urate (MSU)-induced XO activity in THP-1 cells. However, the phenolics and flavonoids in EE50 may not serve as inhibitors of XO. EE50 prevented an increase in the serum uric acid level in potassium oxonate (PO)-challenged ICR mice and streptozocin (STZ)-induced SD rats. EE50 down-regulated STZ-induced liver XO activity, and it restored renal OAT1 and urate transporter expression. STZ-induced renal interleukin-1ß (IL-1ß) and the tumor necrosis factor-α (TNF-α) level were inhibited by EE50 treatment. EE50 exhibits the hypouricemic effect via down-regulation of XO activity, suggesting that EE50 has potential to improve hyperuricemia and its complications.

Simultaneous Detection of 3-Nitrotyrosine and 3-Nitro-4-hydroxyphenylacetic Acid in Human Urine by Online SPE LC-MS/MS and Their Association with Oxidative and Methylated DNA Lesions.

Reactive nitrogen species (RNS) can modify proteins at tyrosine and tryptophan residues, and they are involved in the pathogenesis of various human diseases. In this study, we present the first liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method that enables the simultaneous measurement of urinary 3-nitrotyrosine (3-NTYR) and its metabolite 3-nitro-4-hydroxyphenylacetic acid (NHPA). After the addition of stable isotope-labeled internal standards, urine samples were purified and enriched using manual solid-phase extraction (SPE) and HPLC fractionation followed by online SPE LC-MS/MS analysis. The limits of quantification in urine were 3.1 and 2.5 pg/mL for 3-NTYR and NHPA, respectively. Inter- and intraday imprecision was <15%. The mean relative recoveries of 3-NTYR and NHPA in urine were 89-98% and 90-98%, respectively. We further applied this method to 65 urinary samples from healthy subjects. Urinary samples were also analyzed for N-nitrosodimethylamine (NDMA) as well as oxidative and methylated DNA lesions, namely, 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), N7-methylguanine (N7-MeG), and N3-methyladenine (N3-MeA), using reported LC-MS/MS methods. Urinary 3-NTYR and NHPA levels were measured at concentrations of 63.2 ± 51.5 and 77.4 ± 60.8 pg/mL, respectively. Urinary 3-NTYR and NHPA levels were highly correlated with each other and with 8-oxoGua and 8-oxodGuo. Our findings demonstrated that a relationship exists between oxidative and nitrative stress. However, 3-NTYR and NHPA were correlated with N7-MeG and N3-MeA but not with NDMA, suggesting that NDMA may not be a representative biomarker of N-nitroso compounds that are induced by RNS.

On optimal retreat distance for the equivalent source method-based nearfield acoustical holography.

As a basic form of the equivalent source method (ESM) that is used to nearfield acoustical holography (NAH) problems, discrete monopoles are utilized to represent the sound field of interest. When setting up the virtual source distribution, it is vital to maintain a "retreat distance" between the virtual sources and the actual source surface such that reconstruction would not suffer from singularity problems. However, one cannot increase the distance without bound because of the ill-posedness inherent in the reconstruction process with large distance. In prior research, 1-2 times lattice spacing, or the inter-element distance of microphones, is generally recommended as retreat distance in using the ESM-based NAH. While this rule has shown to yield good results in many cases, the optimal choice is a complicated issue that depends on frequency, geometry of the physical source, content of evanescent waves, distribution of sensors and virtual sources, etc. This paper deals about attaining the best compromise between the reconstruction errors induced by the point source singularity; the reconstruction ill-posedness is an interesting problem in its own right. The paper revisits this issue, with the aid of an optimization algorithm based on the golden section search and parabolic interpolation. Numerical simulations were conducted for a baffled planar piston source and a spherically baffled piston source. The results revealed that the retreat distance appropriate for the ESM ranged from 0.4 to 0.5 times the spacing for the planar piston, while from 0.8 to 1.7 times average spacing for the spherical piston. Experiments carried out for a vibrating aluminum plate also revealed that the retreat distance with 0.5 times the spacing yielded better reconstructed velocity than those with 1/20 and 1 times the spacing.