A Case of Anterior Communicating Artery Aneurysm Impending Rupture Presenting with Isolated Painful Adduction Palsy Mimicking Ischemic Internuclear Ophthalmoplegia

Anterior communicating artery (ACoA) aneurysms may rarely lead to oculomotor nerve palsy. We present here interesting cases in which isolated unilateral adduction paresis mimicking internuclear ophthalmoplegia (INO) was one of the symptoms of suspicious impending ruptured aneurysm of the ACoA. Careful neurologic examination is crucial for early discrimination with INO and oculomotor palsy.

Impact of Brain MRI Markers on Major and Mild Vascular Cognitive Impairment in CADASIL

Background@#Cognitive impairment is the second most common clinical manifestation in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, understanding of cognitive impairment in CADASIL has been hampered by lack of consensus on diagnosis of vascular cognitive impairment (VCI). We used vascular impairment of cognition classification consensus study principles (VICCCS-1) and protocols (VICCCS-2) to assess the cognitive impairment in CADASIL. We also evaluated the impact of MRI markers on major and mild VCI in CADASIL. @*Methods@#We prospectively recruited 64 patients who underwent standardized brain MRI and detailed neuropsychological test. MRI analysis included number of lacunes, number of cerebral microbleeds (CMB), normalized volume of white-matter hyperintensities (nWMH), and brain parenchymal fraction (BPF). BPF has been used to measure brain atrophy. The patients were divided into three groups: those with normal cognition (CADASIL-NC, n=14), those with mild VCI (CADASIL-mild VCI, n=38), and those with major VCI (CADASIL-major VCI, n=11). @*Results@#The three groups differed according to age, with the major VCI group being older. The major VCI group had more lacunes, more CMB, more extensive white matter lesions and lower BPF than NC group. There were no significant differences between NC and mild VCI groups in BPF. BPF and age were the independent predictors of major VCI. There was a tendency that women were at higher risk for mild VCI, though it did not reach statistical significance. Women were older than men, but had lower number of lacunes in mild VCI. @*Conclusions@#These findings suggest that brain atrophy and age are the main predictors of major VCI in CADASIL.

The Impact of Masticatory Function on Cognitive Impairment in Older Patients:A Population-Based Matched Case-Control Study

Purpose@#The aim of this study was to investigate the association between the changes in masticatory function and cognitive impairment by analyzing longitudinal data of older Korean patients. @*Materials and Methods@#Patients aged over 60 years with dental records between 2005 to 2010 (baseline; T1) and 2014 to 2020 (follow-up; T2) were selected in a single medical center. Based on the dementia diagnosis after T2, the cohort was classified into two groups, the dementia group (n=122) and the control group (n=366). Changes in masticatory function were calculated using the total functional tooth unit (T-FTU) in both groups. The incidence of tooth extraction (%) and the subsequent rehabilitation during the observation period were also evaluated. @*Results@#In the dementia group, T-FTU significantly decreased from T1 to T2 (9.81±2.78 to 9.11±3.16, respectively, p=0.008), while no significant change was observed in the control group. During the mean observation period of 9 years, significantly more teeth were extracted and neglected to be prosthetically restored in the dementia group than in the control group. Regression analysis revealed that the number of missing teeth neglected [odds ratio (OR)=1.195, 95% confidence interval (CI)=1.025–1.393, p=0.023] and previous alcohol consumption (OR=4.445, 95% CI=1.831–1.795, p=0.001) were the most significant risk factors of dementia. @*Conclusion@#There might be a causative relationship between the neglected missing dentition and the onset of dementia.

Degradation Properties of a Bi-layered Crosslinked Collagen Membrane for Localized Bone Regeneration: In Vitro and In Vivo Study

Purpose@#(i) To evaluate the biologic properties of a bi-layered 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-cross-linked collagen membrane (CCM) In Vitro. (ii) To assess the efficacy of CCM for localized bone regeneration In Vivo. @*Materials and Methods@#Biodegradation of CCM compared to a native collagen membrane (NCM) was assessed In Vitro. In Vivo, twelve male New Zealand White rabbits were used. Four calvarial, circular defects (diameter 8 mm) were created in each animal. The sites were randomly allocated to i) CCM+biphasic calcium phosphate (BCP) (CCM-BCP group), ii) CCM alone (CCM), iii) BCP alone (BCP) and, iv) negative control (control). Animals were sacrificed at 2 (n=6) and 8 weeks (n=6). Outcome measures included: micro-computed tomography (μCT) analysis (total augmented volume [TAV], new bone volume) and histomorphometry (total augmented area [TAA], newly formed bone, remaining membrane thickness [RMT]).Result: CCM was more resistant to degradation than NCM. μCT analysis showed CCM-BCP (196.43±25.30 mm 3 ) and BCP (206.23±39.13 mm 3 ) groups had significantly (P<0.01) larger TAV than the control (149.72±12.28 mm 3 ) after 8 weeks. Histomorphometrically, CCM-BCP group (17.75±5.97 mm 2 ) had significantly (P<0.01) greater TAA compared to the CCM group (7.74±2.25 mm 2 ) and the control (8.13±1.81 mm 2 ) after 8 weeks. After 8 weeks, RMT was reduced by 67%. @*Conclusion@#CCM can be a favorable choice of barrier membrane when performing guided bone regeneration (GBR) in localized bone defects. CCM has better resistance to degradation than the natural collagen membrane, In Vitro. In Vivo, CCM provides an advantageous integration of prolonged barrier function and biocompatibility for GBR.

Anti-LGI-1 Encephalitis with Worsening Symptoms Associated with Hyponatremia

Anti-leucine-rich glioma-inactivated 1 (LGI-1) encephalitis is clinically characterized by subacute cognitive decline and frequent seizures including fasciobrachial dystonic seizures. A 67-year-old man visited the emergency department due to the recurrent episodes of seizures of 4 days duration. At the time of the visit, he showed hyponatremia at Na 121 mg/dL. His symptoms were relieved by 3% sodium chloride and water restriction. Here we report a case of anti-LGI-1 encephalitis with worsening symptoms associated with hyponatremia.

Oculomotor Nerve Palsy that Developed after Endovascular Treatment in an Acute Stroke Patient with a Dissecting Occlusion of the Extracranial Internal Carotid Artery

Oculomotor nerve palsy is underrecognized clinical manifestation of extracranial internal carotid artery (ICA) dissection. Herein we report a case of complete oculomotor nerve palsy following endovascular revascularization, which developed in a patient with acute stroke due to extracranial ICA dissecting occlusion. We also discuss about the development mechanism of oculomotor nerve palsy, considering the vascular anatomy and the possibility of periprocedural complications during endovascular treatment.

Transcriptomic profiles and their correlations in saliva and gingival tissue biopsy samples from periodontitis and healthy patients

Purpose@#This study was conducted to analyze specific RNA expression profiles in gingival tissue and saliva samples in periodontitis patients and healthy individuals, and to determine their correlations in light of the potential use of microarray-based analyses of saliva samples as a periodontal monitoring tool. @*Methods@#Gingival tissue biopsies and saliva samples from 22 patients (12 with severe periodontitis and 10 with a healthy periodontium) were analyzed using transcriptomic microarray analysis. Differential gene expression was assessed, and pathway and clustering analyses were conducted for the samples. The correlations between the results for the gingival tissue and saliva samples were analyzed at both the gene and pathway levels. @*Results@#There were 621 differentially expressed genes (DEGs; 320 upregulated and 301 downregulated) in the gingival tissue samples of the periodontitis group, and 154 DEGs (44 upregulated and 110 downregulated) in the saliva samples. Nine of these genes overlapped between the sample types. The periodontitis patients formed a distinct cluster group based on gene expression profiles for both the tissue and saliva samples. Database for Annotation, Visualization and Integrated Discovery analysis revealed 159 enriched pathways from the tissue samples of the periodontitis patients, as well as 110 enriched pathways In the saliva samples. Thirty-four pathways overlapped between the sample types. @*Conclusions@#The present results indicate the possibility of using the salivary transcriptome to distinguish periodontitis patients from healthy individuals. Further work is required to enhance the extraction of available RNA from saliva samples.

Distinctive bone regeneration of calvarial defects using biphasic calcium phosphate supplemented ultraviolet-crosslinked collagen membrane

PURPOSE: To overcome several drawbacks of chemically-crosslinked collagen membranes, modification processes such as ultraviolet (UV) crosslinking and the addition of biphasic calcium phosphate (BCP) to collagen membranes have been introduced. This study evaluated the efficacy and biocompatibility of BCP-supplemented UV-crosslinked collagen membrane for guided bone regeneration (GBR) in a rabbit calvarial model.METHODS: Four circular bone defects (diameter, 8 mm) were created in the calvarium of 10 rabbits. Each defect was randomly allocated to one of the following groups: 1) the sham control group (spontaneous healing); 2) the M group (defect coverage with a BCP-supplemented UV-crosslinked collagen membrane and no graft material); 3) the BG (defects filled with BCP particles without membrane coverage); and 4) the BG+M group (defects filled with BCP particles and covered with a BCP-supplemented UV-crosslinked collagen membrane in a conventional GBR procedure). At 2 and 8 weeks, rabbits were sacrificed, and experimental defects were investigated histologically and by micro-computed tomography (micro-CT).RESULTS: In both micro-CT and histometric analyses, the BG and BG+M groups at both 2 and 8 weeks showed significantly higher new bone formation than the control group. On micro-CT, the new bone volume of the BG+M group (48.39±5.47 mm3) was larger than that of the BG group (38.71±2.24 mm3, P=0.032) at 8 weeks. Histologically, greater new bone area was observed in the BG+M group than in the BG or M groups. BCP-supplemented UV-crosslinked collagen membrane did not cause an abnormal cellular reaction and was stable until 8 weeks.CONCLUSIONS: Enhanced new bone formation in GBR can be achieved by simultaneously using bone graft material and a BCP-supplemented UV-crosslinked collagen membrane, which showed high biocompatibility and resistance to degradation, making it a biocompatible alternative to chemically-crosslinked collagen membranes.

Transcriptomic profiles and their correlations in saliva and gingival tissue biopsy samples from periodontitis and healthy patients

Purpose@#This study was conducted to analyze specific RNA expression profiles in gingival tissue and saliva samples in periodontitis patients and healthy individuals, and to determine their correlations in light of the potential use of microarray-based analyses of saliva samples as a periodontal monitoring tool. @*Methods@#Gingival tissue biopsies and saliva samples from 22 patients (12 with severe periodontitis and 10 with a healthy periodontium) were analyzed using transcriptomic microarray analysis. Differential gene expression was assessed, and pathway and clustering analyses were conducted for the samples. The correlations between the results for the gingival tissue and saliva samples were analyzed at both the gene and pathway levels. @*Results@#There were 621 differentially expressed genes (DEGs; 320 upregulated and 301 downregulated) in the gingival tissue samples of the periodontitis group, and 154 DEGs (44 upregulated and 110 downregulated) in the saliva samples. Nine of these genes overlapped between the sample types. The periodontitis patients formed a distinct cluster group based on gene expression profiles for both the tissue and saliva samples. Database for Annotation, Visualization and Integrated Discovery analysis revealed 159 enriched pathways from the tissue samples of the periodontitis patients, as well as 110 enriched pathways In the saliva samples. Thirty-four pathways overlapped between the sample types. @*Conclusions@#The present results indicate the possibility of using the salivary transcriptome to distinguish periodontitis patients from healthy individuals. Further work is required to enhance the extraction of available RNA from saliva samples.

Periodontal healing using a collagen matrix with periodontal ligament progenitor cells in a dehiscence defect model in beagle dogs

PURPOSE: To histologically characterize periodontal healing at 8 weeks in surgically created dehiscence defects in beagle dogs that received a collagen matrix with periodontal ligament (PDL) progenitor cells. METHODS: The bilateral maxillary premolars and first molars in 6 animals were used. Standardized experimental dehiscence defects were made on the buccal side of 3 premolars, and primary culturing of PDL progenitor cells was performed on the molars. Collagen matrix was used as a scaffold and a delivery system for PDL progenitor cells. The experimental sites were grafted with collagen matrix (COL), PDL progenitor cells with collagen matrix (COL/CELL), or left without any material (CTL). Histologic and histomorphometric analyses were performed after 8 weeks. RESULTS: The defect height from the cementoenamel junction to the most apical point of cementum removal did not significantly differ across the CTL, COL, and COL/CELL groups, at 4.57±0.28, 4.56±0.41, and 4.64±0.27 mm (mean ± standard deviation), respectively; the corresponding values for epithelial adhesion were 1.41±0.51, 0.85±0.29, and 0.30±0.41 mm (P<0.05), the heights of new bone regeneration were 1.32±0.44, 1.65±0.52, and 1.93±0.61 mm (P<0.05), and the cementum regeneration values were 1.15±0.42, 1.81±0.46, and 2.57±0.56 mm (P<0.05). There was significantly more new bone formation in the COL/CELL group than in the CTL group, and new cementum length was also significantly higher in the COL/CELL group. However, there were no significant differences in the width of new cementum among the groups. CONCLUSIONS: PDL progenitor cells carried by a synthetic collagen matrix may enhance periodontal regeneration, including cementum and new bone formation.

Maxillary sinus augmentation using biphasic calcium phosphate: dimensional stability results after 3–6 years

PURPOSE: This study was designed to observe the resorption pattern of biphasic calcium phosphate (BCP) used for maxillary sinus augmentation over a 3- to 6-year healing period, and to investigate factors affecting the resorption of BCP. METHODS: A total of 47 implants placed in 27 sinuses of 22 patients were investigated. All patients had residual bone height less than 5 mm at baseline. The modified Caldwell-Luc approach was used to elevate the maxillary sinus membrane, and the sinus cavity was filled with BCP (70% hydroxyapatite and 30% β-tricalcium phosphate). Implant placement was done simultaneously or in a staged manner. Serial radiographic analysis was performed up to 6 years postoperatively. RESULTS: During the follow-up period, no implant loss was reported. The mean reduced height of the augmented sinus (RHO) was 0.27±1.08 mm at 36 months, and 0.89±1.39 mm at 72 months postoperatively. Large amounts of graft material (P=0.021) and a long healing period (P=0.035) significantly influenced the amount of RHO. In particular, there was a significant relationship between a healing period longer than 40 months and RHO. CONCLUSIONS: BCP can achieve proper dimensional stability with minimal reduction of the graft height in a 3- to 6-year healing period after maxillary sinus augmentation. The healing period and the amount of graft material influenced the resorption of BCP.

Glyphosate-Induced Encephalopathy: A Case Report

No abstract available.

Biomimetic characteristics of mussel adhesive protein-loaded collagen membrane in guided bone regeneration of rabbit calvarial defects

PURPOSE: The aim of the present study was to evaluate the biocompatibility and barrier function of mussel adhesive protein (MAP)-loaded collagen membranes in guided bone regeneration (GBR). METHODS: Eight male New Zealand white rabbits were used. Four circular defects (diameter: 8 mm) were created in the calvarium of each animal. The defects were randomly assigned to 1) a negative control group, 2) a cyanoacrylate (CA)-loaded collagen membrane group (the CA group), 3) a MAP-loaded collagen membrane group (the MAP group), and 4) a group that received a polycaprolactone block with MAP-loaded collagen membrane (the MAP-PCL group). Specimens were harvested at 2 weeks (n=4) and 8 weeks (n=4) postoperatively for observational histology and histometric analysis. RESULTS: In the histologic analysis, MAP was completely absorbed without any byproducts. In contrast, some of the CA adhesive remained, showing an inflammatory reaction, at 8 weeks. In the MAP-PCL group, the MAP-loaded collagen membranes served as a barrier membrane despite their fast degradation in GBR. No significant difference was found in the amount of new bone between the MAP-PCL and MAP groups (1.82±0.86 mm2 and 2.60±0.65 mm2, respectively). CONCLUSIONS: The MAP-loaded collagen membrane functioned efficiently in this rabbit calvarial GBR model, with excellent biocompatibility. Further research is needed to assess clinical applications in defect types that are more challenging for GBR than those used in the current model.

Venous Thromboembolism Following Acute Ischemic Stroke: A Prospective Incidence Study

BACKGROUND: Asians were known to have a relatively lower incidence of venous thromboembolism (VTE), and there is insufficient evidence to suggest a specific D-dimer threshold level for screening VTE in patients with acute stroke. METHODS: We prospectively enrolled patients with acute ischemic stroke admitted to Jeju National University Hospital. The inclusion criteria were: 1) aged ≥18 years, 2) admission within seven days of symptom onset, and 3) an initial National Institute of Health Stroke Scale (NIHSS) score >1 for the affected lower limb. Ultrasound scans of the lower limbs and plasma D-dimer assays were performed on days 7–14 and 15–28 after stroke onset. RESULTS: Of 285 patients admitted during the study period, 52 patients met inclusion criteria (mean age 74.5, male 40.4%, median initial NIHSS score 12, and unable to walk unassisted at discharge 76.9%). During 7–14 days, 23 of 52 patients (44.2%) had a D-dimer level above 1.57 mg/L, and 9.6% had a level above 5.50 mg/L. Proximal deep vein thrombosis (DVT) was detected in 3 patients (5.8%, 95% confidence Interval 1.2–16.0%) on ultrasound examination. All DVTs were found in elderly female patients with severe leg weakness. No patient was diagnosed with pulmonary embolism during the study period. CONCLUSION: The incidence of VTE seems to be very low among Korean patients with acute ischemic stroke. Advanced age, female sex, and severe leg weakness were important risk factors for developing DVT in this study.

Bone Regeneration Using Block-type Deproteinized Porcine Bone Mineral with Collagen Membrane Using 3,4-Dihydroxyphenylalanine as Bone Adhesive

PURPOSE: The purpose of this study was to assess the adhesiveness and cytotoxicity of 3, 4-dihydroxyphenylalanine (DOPA), and to evaluate the role of collagen membrane with DOPA in the guided bone regeneration. MATERIALS AND METHODS: Peel resistance and cell cytotoxicity test were performed. Four defect types in nine rabbit calvaria were randomly allocated: i) control, ii) membrane, iii) deproteinized porcine bone mineral (DPBM) covered by membrane with DOPA, and iv) DPBM covered by membrane with cyanoacrylate. Animals were sacrificed at 2 (n=4) and 8 weeks (n=5) for microcomputed tomography and histomorphometric analysis. DOPA showed low peel resistance but high cell viability. RESULT: Cyanoacrylate and DOPA groups showed significantly higher mineralized tissue volume (MTV) compared to control and membrane groups at 2 weeks (P < 0.05). At 8 weeks, DOPA group showed the highest MTV. Significantly higher new bone area was found in DOPA group at 8 weeks (P < 0.05). Bone formation increased from 2 to 8 weeks in DOPA group (P < 0.05). CONCLUSION: DOPA showed high cell viability and in vivo study revealed predictable performance in bone regeneration.

The Brain Donation Program in South Korea

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Comparisons of the diagnostic accuracies of optical coherence tomography, micro-computed tomography, and histology in periodontal disease: an ex vivo study

PURPOSE: Optical coherence tomography (OCT) is a noninvasive diagnostic technique that may be useful for both qualitative and quantitative analyses of the periodontium. Micro-computed tomography (micro-CT) is another noninvasive imaging technique capable of providing submicron spatial resolution. The purpose of this study was to present periodontal images obtained using ex vivo dental OCT and to compare OCT images with micro-CT images and histologic sections. METHODS: Images of ex vivo canine periodontal structures were obtained using OCT. Biologic depth measurements made using OCT were compared to measurements made on histologic sections prepared from the same sites. Visual comparisons were made among OCT, micro-CT, and histologic sections to evaluate whether anatomical details were accurately revealed by OCT. RESULTS: The periodontal tissue contour, gingival sulcus, and the presence of supragingival and subgingival calculus could be visualized using OCT. OCT was able to depict the surface topography of the dentogingival complex with higher resolution than micro-CT, but the imaging depth was typically limited to 1.2–1.5 mm. Biologic depth measurements made using OCT were a mean of 0.51 mm shallower than the histologic measurements. CONCLUSIONS: Dental OCT as used in this study was able to generate high-resolution, cross-sectional images of the superficial portions of periodontal structures. Improvements in imaging depth and the development of an intraoral sensor are likely to make OCT a useful technique for periodontal applications.

Phenotypic Features of Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Subjects with R544C Mutation

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most-common single gene disorder of cerebral small vessel disease. There is no definite evidence of genotype-phenotype correlation in CADASIL. However, recent studies have shown the unique phenotypic feature of NOTCH3 R544C mutation. METHODS: We investigated the phenotypic spectrum of NOTCH3 R544C mutation in 73 CADASIL patients in Jeju between April 2012 and January 2014. RESULTS: Of the 73 subjects from 60 unrelated families included in this study, 40 (55%) were men. The mean age of the subjects was 62.2±12.2 (range 34-86 years). Cerebral infarction was the most frequent manifestation (37%), followed by cognitive impairment (32%), headache (17%), psychiatric symptom (16%), intracerebral hemorrhage (12%), transient ischemic attack (7%), and seizure (1%). The mean age of the subjects with ischemic or hemorrhagic episodes was 64.9±10.9 (range 41-86 years). A diagnosis of dementia was made in 12 subjects (16%). The mean age of the subjects with dementia was 75.6±6.5 (range 62-86 years). About 3% of subjects were unable to walk without assistance at assessment. Only one subject had developed chronic headache before the 40s. CONCLUSIONS: Our data support the hypothesis that CADASIL patients with R544C mutation in Jeju have relatively late onset disease.

Increased osteoinductivity and mineralization by minimal concentration of bone morphogenetic protein-2 loaded onto biphasic calcium phosphate in a rabbit sinus

PURPOSE: The purpose of the present study was to evaluate the effectiveness of a minimal concentration of bone morphogenetic protein-2 (BMP-2) in terms of quantitative and qualitative analyses of newly formed bone in a rabbit maxillary sinus model. METHODS: In 7 rabbits, sinus windows were prepared bilaterally. Biphasic calcium phosphate (BCP) loaded with 0.05 mg/mL BMP-2 was grafted into one sinus (the BMP group) and saline-soaked BCP was placed into the other (the control group) in each animal. The animals were allowed an 8-week healing period before being sacrificed. Specimens including the augmented area and surrounding tissues were then removed and evaluated both radiographically and histologically. RESULTS: There was a difference in the mineralization of new bone between the groups. In the BMP group, the greater part of the new bone consisted of mature lamellar bone with an evident trabecular pattern, whereas the control group showed mostly woven bone, consisting only partially of lamellar bone. Histometrically, the area of new bone was significantly greater (4.55±1.35 mm2 vs. 2.99±0.86 mm2) in the BMP group than in the control group (P<0.05); however, the total augmentation volumes were not significantly different between the groups. CONCLUSIONS: Within the limitations of this study, it can be suggested that a minimal concentration of BMP-2 (0.05 mg/mL) had an osteoinductive effect with accelerated mineralization in a rabbit sinus model using a BCP carrier.

Erratum: Body text. Bone formation around rhBMP-2-coated implants in rabbit sinuses with or without absorbable collagen sponge grafting

The authors recently found a mistake in their previously published article and sincerely regret these errors.