Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion

Background and Objectives@#The colonic epithelial layer is a complex structure consisting of multiple cell types that regulate various aspects of colonic physiology, yet the mechanisms underlying epithelial cell differentiation during development remain unclear. Organoids have emerged as a promising model for investigating organogenesis, but achieving organ-like cell configurations within colonic organoids is challenging. Here, we investigated the biological significance of peripheral neurons in the formation of colonic organoids. @*Methods@#and Results: Colonic organoids were co-cultured with human embryonic stem cell (hESC)-derived peripheralneurons, resulting in the morphological maturation of columnar epithelial cells, as well as the presence of enterochromaffin cells. Substance P released from immature peripheral neurons played a critical role in the development of colonic epithelial cells. These findings highlight the vital role of inter-organ interactions in organoid development and provide insights into colonic epithelial cell differentiation mechanisms. @*Conclusions@#Our results suggest that the peripheral nervous system may have a significant role in the development ofcolonic epithelial cells, which could have important implications for future studies of organogenesis and disease modeling.

Direct Conversion to Achieve Glial Cell Fates: Oligodendrocytes and Schwann Cells

Glia have been known for its pivotal roles in physiological and pathological conditions in the nervous system. To study glial biology, multiple approaches have been applied to utilize glial cells for research, including stem cell-based technologies. Human glial cells differentiated from pluripotent stem cells are now available, allowing us to study the structural and functional roles of glia in the nervous system, although the efficiency is still low. Direct conversion is an advanced strategy governing fate conversion of diverse cell types directly into the desired lineage. This novel strategy stands as a promising approach for preliminary research and regenerative medicine. Direct conversion employs genetic and environmental cues to change cell fate to that with the required functional cell properties while retaining maturity-related molecular features. As an alternative method, it is now possible to obtain a variety of mature cell populations that could not be obtained using conventional differentiation methods. This review summarizes current achievements in obtaining glia, particularly oligodendrocytes and Schwann cells.

Application of digital implant system on implant treatment with “all-on-4” concept / 대한치과보철학회지

Recently, digital implant systems are expanding its influence in dental area. Due to technical improvement, they jumped over their limits nowadays. We can use these newest systems to treat edentulous patient, from implant surgery to fabrication of prosthesis. In this case, The patient was a fifty years old female. She had a full edentulous ridge on mandible and wanted to reconstruct occlusion with using implants. We planned to use digital implant system with “all-on-4” concept on mandible and produced surgical guide for flapless implant surgery. After the surgery, we tried to fabricate full arch prosthesis just using a digital devices and confirmed satisfying result.

A young couple's grave found in the Rakhigarhi cemetery of the Harappan Civilization / 대한해부학회지

The Harappan Civilization, one of the earliest complex societies in the world, flourished on the Indian subcontinent. Although many additional Harappan settlements and cemeteries have been discovered and investigated, no coupled burials at Harappan cemeteries have been reported to date. In 2013–2016, we excavated the cemetery of the Rakhigarhi site (Haryana), the largest city of the Harappan Civilization. At the site, we found a grave that turned out to be a coupled (joint) burial of the primary type. This report is the first anthropologically confirmed case of coupled burial from a Harappan cemetery.

Implant prosthesis for fully edentulous patients using intra-oral scanning and abutment merging technique: A case report / 대한치과보철학회지

In this case, the impression surface of the existing denture was scanned and was inverted three-dimensionally to express the residual ridge form. Implant planning was performed on the superimposed data of the CT with the scanned image of the denture with radiopaque markers attached. At the day of surgery, customized abutments fabricated in accordance with the form of the gingival margin were linked with fixtures and temporary restorations were set. In the process of fabricating the final prosthesis after the osseointegration of implant fixture, the intraoral scan images at abutment level were merged with images of the abutments scanned and stored before implant surgery. By fabricating the final prosthesis with the abutments obtained by merging can increase the marginal fitness of the final prosthesis and simplify the clinical process.

Human Skeletal Remains from Ancient Burial Sites in India: With Special Reference to Harappan Civilization / 체질인류학회지

Harappan Civilization is well known for highly sophisticated urban society, having been flourished in extensive regions of northwestern part of Pakistan and northeastern part of Afghanistan as its heyday around 4500 years ago. Most archaeologists agree on the periodization of this civilization as three different phases (Early, Mature and Late), which represent its cultural process of origin, development and decline. From the Harappan sites, one can note that there were about more than fifty burial sites discovered so far related with the civilization. In this article, we are trying to introduce the brief picture of the Harappan burials from the archaeological as well as anthropological perspectives.

A Case of Condyloma Acuminata in a Virgin Systemic Lupus Erythematosus Patient

Anogenital infection with human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The majority of HPV infections are transient and subclinical, with subsequent clearance by the immune system. However, in some individuals, especially those with impaired immunity, HPV infection may persist and result in condyloma acuminatum, pre-cancerous cervical abnormalities, as well as cervical cancer. Because of the intrinsic immunological aberrations and immunosuppressive treatment, patients with systemic lupus erythematosus (SLE) have higher prevalence of anogenital HPV infection, and SLE itself appears to be a major risk factor for HPV infection. HPV infection is sexually transmitted via genital contact; autogenesis of condyloma acuminatum without sexual contact is rare. In this case, a 27-year old virgin female with SLE was admitted to our clinic, presenting anogenital condyloma acuminata. It report that SLE patient can have a disease of anogenital HPV infection, despite the lack of sexual contact. Therefore, we recommend that patients with SLE have regular gynecological evaluations, in addition to prophylactic HPV vaccinations.

A Case of Pheochromocytoma Misdiagnosed as Activation of Behcet's Disease / 대한내과학회지

A 30 year-old woman with a history of Behcet's disease was admitted to our clinic because of a paroxysmal attack of palpitations, headache, and ocular pain. Initially, we did not suspect a pheochromocytoma. We evaluated Behcet's disease activity because the cardiovascular and neurological symptoms mimicked those of Behcet's disease. Pheochromocytoma is often overlooked and can be fatal if not recognized and treated appropriately. In the present case, abdominal computerized tomography incidentally revealed a mass confirmed to be a pheochromocytoma in the left adrenal gland, and the tumor was successfully removed. This is the first Korean report of a pheochromocytoma in a patient with Behcet's disease. We suggest that pheochromocytoma should be included in the differential diagnosis of Behcet's disease if a patient presents with cardiovascular or neurological symptoms.

Relationships between serum vitamin D levels and clinical characteristics of drug reaction with eosinophilia and systemic symptoms syndrome

PURPOSE: Vitamin D deficiency (VDD) is widely spread and on the increase throughout the world. Although vitamin D is essential for skeletal mineralization, VDD or vitamin D insufficiency (VDI) has been associated with nonskeletal disorders including cardiovascular disease, cancer, allergic disease and skin disease. However, a few reports showed the association of vitamin D and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Thereafter, we evaluated the association between vitamin D and DRESS syndrome. METHODS: We conducted a retrospective study on 45 patients with DRESS syndrome. Four hundred and ninty-eight healthy people who visited the health screening center were enrolled in the study as a control group. We investigated the clinical characteristics, the causative drugs and treatments in the patients with DRESS syndrome, and also analyzed the associations with serum 25-hydroxyvitamin D (25(OH)D3). RESULTS: Forty-four patients (97.8%) had low serum vitamin D levels; 21 patients were VDD (serum 25(OH)D3 <10 ng/mL), and 23 patients were VDI (serum 25(OH)D3 10 to 30 ng/mL). There were no significant differences in clinical parameters between two groups. Serum 25(OH)D3 level of the study patients was significantly lower that of the controls (12.3+/-9.6 ng/mL vs. 17.3+/-5.5 ng/mL, P<0.001). Serum 25(OH)D3 level showed a significant negative correlation with admission days (r=-0.377, P=0.011). CONCLUSION: The majority of the patients with DRESS syndrome showed low vitamin D levels. Serum 25(OH)D3 was inversely correlated with admission days.

Resistive index as a predictor of acute kidney injury caused by an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker in chronic kidney disease patients

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) may induce acutekidney injury (AKI).The aim of this study was to evaluate the role of the resistive index (RI), which reflects renal artery resistance on renal duplex ultrasonography, as a predictor of AKI in chronic kidney disease (CKD) patients who are prescribed an ACE inhibitor or ARB. METHODS: We screened 105 CKD patients evaluated with renal duplex ultrasonography from 2008 to 2012. We excluded patients not treated with ACE inhibitor or ARB and diagnosed with renal artery stenosis. Finally, we retrospectively analyzed the medical records of 54 patients. AKI was defined as increased serum creatinine by >30% compared with baseline after starting ACE inhibitor or ARB treatment. RESULTS: The mean age of the patients was 60.5+/-13.0 years, serum creatinine level was 1.85+/-0.85 mg/dL and 22.2% of the patients had AKI after the use of an ACE inhibitor or ARB. The RI (P=0.006) and the percentages of patients with diabetes (P=0.008)and using diuretics (P=0.046) were higher in the AKI group.The area under the receiver operating characteristics curve for the prediction of AKI was 0.736 (95% confidence interval=0.587-0.885, P=0.013),and RI> or =0.80 predicted AKI with 83.3% sensitivity and 61.9% specificity. In the multivariate analysis, RI> or =0.80 was an independent prognostic factor [Exp (B)=8.03, 95% confidence interval=1.14-56.74, P=0.037] for AKI. CONCLUSION: RI> or =0.80 on the renal duplex ultrasonography may be a helpful predictor for AKI in CKD patients who are prescribed an ACE inhibitor or ARB.

A Cases of Adult Onset Still's Disease with Hemolytic Anemia

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology. AOSD is characterized by fever, arthralgia, salmon-colored skin rash, hepatosplenomegaly and its laboratory abnormalities include leukocytosis, elevated liver enzyme, negative autoantibody, and hyperferritinemia. The clinical course varied and severe complicated conditions, such as hemophagocytic syndrome, and disseminated intravascular coagulation, occurred occasionally. Such a complication is accompanied with hemolytic anemia and lead to be a fatal course. We report the first case of AOSD with hemolytic anemia, which improved with high dose steroid therapy.

A Cases of Adult Onset Still's Disease with Hemolytic Anemia

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology. AOSD is characterized by fever, arthralgia, salmon-colored skin rash, hepatosplenomegaly and its laboratory abnormalities include leukocytosis, elevated liver enzyme, negative autoantibody, and hyperferritinemia. The clinical course varied and severe complicated conditions, such as hemophagocytic syndrome, and disseminated intravascular coagulation, occurred occasionally. Such a complication is accompanied with hemolytic anemia and lead to be a fatal course. We report the first case of AOSD with hemolytic anemia, which improved with high dose steroid therapy.

Residents' Expectation of Family Medicine-Specific Training Program and Its Current State / 가정의학회지

BACKGROUND: The family medicine residency program consists mainly of clinical rotations in other specialties and the family medicine-specific training. We conducted this study to investigate how family medicine residents evaluated their training program that include family-oriented medicine, clinical preventive medicine, behavioral science and research in primary care. METHODS: In 2009, third-year residents of 129 training hospitals in Korea were surveyed to investigate the current state and their expectation of the residency program. The contents of questionnaires included training periods, conferences, procedures, interview techniques, outpatient and inpatient consultations, and written thesis. RESULTS: Total 133 out of 142 residents (93.7%) responded that 3 years of training is ideal or pertinent. Residents responded that the types of conference that they need most are journal review (81%), staff lecture (73.2%), and clinical topic review (73.2%), in that order. Procedures and interview techniques that the residents want to learn most were gastroscopy (72.5%), abdominal ultrasonography (65.2%), and pain management (46.4%). Hospitals where family medicine residents do not see hospitalized patients or patients in the outpatient clinic were 7.9% and 6.5%, respectively, whereas hospitals that maintain continuous family medicine outpatient clinics were only 40.8%. Education in outpatient clinic and articlewriting seminars was done less frequently in the secondary hospitals than in the tertiary hospitals. CONCLUSION: Evaluation and quality improvement of family medicine training program as well as specialty rotations should be considered in order to foster better family physicians. The efforts have to be made to minimize the difference in quality of each family medicine residency program.

A Case of Rituximab Treatment for Interstitial Lung Disease in a Patient with Antisynthetase Syndrome / 대한류마티스학회지

The clinical manifestations of antisynthetase syndrome are severe interstitial pneumonitis, mild polyarthritis, and myositis. This disease is accompanied by anti-Jo-1 antibodies and anti-Ro/SSA antibodies and occasionally by the concurrence of anti-Jo-1 and anti-Ro/SSA antibodies, which leads to a more severe form of interstitial lung disease. In this case, the patient was transferred to our hospital because of pulmonary fibrosis with myositis and diagnosed with antisynthetase syndrome and the concurrence of anti-Jo-1 with anti-Ro/SSA antibodies. He was refractory to glucocorticoids, and developed leucopenia and thrombocytopenia. He was treated with rituximab infusions, but the interstitial pneumonitis progressed very rapidly and he died.

A comparative study of Sephadex, glass wool and Percoll separation techniques on sperm quality and IVF results for cryopreserved bovine semen

The aim of this study was to compare the effects of spermatozoa separation techniques on sperm quality and in-vitro fertilization (IVF) results for cryopreserved bovine semen. Sephadex, glass wool and Percoll gradient separation techniques were used for sperm separation and sperm motility, morphology and membrane integrity were evaluated before and after separation. Also, cleavage and blastocyst developmental rate were investigated after IVF with sperm recovered by each separation technique. The motility of samples obtained by the three separation techniques were greater compared to the control samples (p < 0.05). The percentage of spermatozoa with intact plasma-membrane integrity, identified by 6-carboxyfluoresceindiacetate/propidium iodide fluorescent staining and the hypo-osmotic swelling test, was highest in the glass wool filtration samples (p < 0.05). The cleavage and blastocyst rate of total oocytes produced from glass wool filtration samples were also higher than the control and Sephadex filtration samples (p < 0.05), but were not significantly different from Percoll separation samples. However, a significantly greater number of cleaved embryos produced by glass wool filtration developed to blastocyst stage than those produced by Percoll separation (p < 0.05). These results indicate that spermatozoa with good quality can be achieved by these three separation techniques and can be used for bovine IVF. In particular, it suggests that glass wool filtration would be the most effective method of the three for improving sperm quality and embryo production for cryopreserved bovine spermatozoa.

Patient's Perspective of Common Cold and Health Care Utilization / 가정의학회지

BACKGROUND: Common cold is the most frequently seen ambulatory disease in primary care clinic of Korea. This study investigated the perspectives and expected pattern of health care utilization of patients who visit a primary care clinic in order to understand patients' health care behavior for treating common cold and to consider how to educate them effectively. METHODS: We surveyed 570 patients and their accompanying people who visited family medicine clinic and the health promotion center of a university hospital by questionnaire, in which we asked the patients what they think of the cause, symptom, and treatment of common cold and their pattern of health care utilization. RESULTS: The respondents replied that the cause of common cold was a virus (446, 85.3%), a bacteria (58, 11.3%) or others (18, 3.4%). Among the total, 475 respondents (88.6%) replied that they had taken cold medicine before and 264 respondents (55.7%) reported that the symptoms took 1-2 weeks to recover. A total of 285 respondents (58.3%) replied that they prefer red to go to the doctor and 198 (40.5%) replied that they prefer to go to a pharmacy. The respondents who thought that symptoms of common cold takes longer than one week tended to choose to visit a doctor. Patients thought that antibiotics (54.4%) and those that relieved common cold symptoms earlier (30.1%) were 'strong' cold medicine. CONCLUSION: The results of this survey showed that the difference in patients' perspectives made an effect on the patients' treatment seeking behavior. Even though medicine did not take effect to relieve symptoms, most patients wanted to continue to visit physicians. The family physician should not give only the prescription, but also make an effort to provide pertinent information to patients and educate them to acquire appropriate perspectives.

The Clinicopathologic Correlations of Histologic Tumor Necrosis for the Patients with Renal Cell Carcinom / 대한비뇨기과학회지

PURPOSE: The authors investigated the relation of histologic tumor necrosis to the other clinicopathologic factors that are known to be important prognostic indicators for the patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: The records of 89 patients who were surgically treated for RCC between June 2003 and July 2005 were evaluated for their basic clinical, laboratory and pathologic information, including the TNM classification, the nuclear grade and the Ki-67 expression. The association of the presence and extent of histologic tumor necrosis with the clinical, laboratory and pathologic features, and the Ki-67 labeling index were examined with chi-square tests, Fisher's exact test, Pearson's correlation analysis, Spearman correlation analysis and multivariate logistic regression analysis. RESULTS: Histologic tumor necrosis was present in 34 of the 89 (38.2%) total RCCs, 24 of 73 (32.9%) conventional RCCs, 9 of 13 (69.2%) papillary RCCs and 1 of 3 (33.3%) chromophobe RCCs. The presence of histologic necrosis in the primary tumor of the patients with RCC compared to the patients with RCC without necrosis was associated with higher levels of anemia, hypercalcemia, hyperalkaline phosphatemia, a higher TNM stage and grade, more perirenal fat invasion, lymphovascular invasion, sarcomatoid change and renal vein thrombosis, a higher Ki-67 labeling index and a larger tumor size. When classifying the RCC according to the histologic subtype, for the conventional RCC, histologic tumor necrosis was associated with the same clinical, laboratory and pathologic features, and the same Ki-67 labelling index as that of the other types of RCCs. The extent of necrosis in the conventional RCC was associated with the TNM stage (r=0.44, p=0.033). Multivariate analysis demonstrated that a higher TNM stage (odd ratio: 5.667; p=0.036; 95% confidence interval: 2.125-63.120) was an independent predictor of histologic tumor necrosis for conventional RCC. CONCLUSIONS: The presence of histologic necrosis was a predictor of the outcome for conventional RCC, and it should be routinely reported and used in clinical assessment.

Clinical Significance of a Single-Core Positive Prostate Cancers Detected on Extended Prostate Needle Biopsy / 대한비뇨기과학회지

PURPOSE: The widespread use of serum prostate specific antigen and extended needle biopsy of the prostate as screening procedures for prostate cancer has not only led to an increase of detecting prostate cancer as a whole, but also to an increase of detecting small low grade tumors. Still, the clinical significance of small, low grade, single-core positivity on prostate biopsy hasn't yet been determined. So, we tried to investigate the clinicopathological features of prostate cancers that showed only single- core positivity on extended prostate needle biopsy. MATERIALS AND METHODS: 144 patients were managed with radical prostatectomy during 2003-2005 at our institution. Insignificant prostate cancer on biopsy specimens was defined as a single-core positive biopsy containing a focus of 3mm or less of moderately differentiated prostate cancer (Gleason score< or=6) and clinical insignificant cancer in the radical specimens was defined as a low volume (<0.5cc) of moderately differentiated organ- confined prostate cancer. We analyzed the clinicopathological features and the clinical significance in regards to the number of positive cores and the biopsy significance. RESULTS: Of 144 patients, 46 (31.9%) patients were diagnosed on the basis on single-core positive prostate cancer. Of these 114 patients, 32 (69.6%) patients had insignificance prostate cancer on biopsy. Although the single core positive group had more favorable pathologic features than the multiple core positive group, only 5 (10.9%) were found to have clinically insignificant cancer at radical prostatectomy. Also, in the biopsy insignificant group, only 5 patients (15.6%) were found to have clinically insignificant cancer. However, there were no features that could accurately predict insignificant prostate cancer preoperatively. CONCLUSIONS: Although the clinicopathological features of the prostate cancers that were detected in only a single-core on prostate needle biopsy were observed to be suggestive of less advanced disease, most of such single-core positive cancers may be clinically significant disease.

Concordance of Gleason Scores between Prostate Needle Biopsy and Radical Prostatectomy Specimens according to the Number of Biopsy Cores / 대한비뇨기과학회지

PURPOSE: Accurate grading of tumor is critical for administering the correct prostate cancer treatment. Meanwhile, the concordance of Gleason scores (GS) between sextant prostate needle biopsy and the radical prostatectomy (RP) specimen is known to be poor. We investigate if extended needle biopsy could improve the cancer detection rate and GS accuracy. MATERIALS AND METHODS: A total 826 consecutive patients each underwent 12 core prostate biopsies guided by TRUS. Of these patients, 136 consecutive patients underwent RP. Of the systemic 12 cores, we compared the subset of standard sextant cores, the set of lateral sextant cores and the 12 core set. RESULTS: The biopsy were positive in 218 cases (26.4%), 213 cases (25.7%) and 265 cases (32%) for the standard sextant, lateral sextant and twelve core biopsy, respectively. Concordance between prostate biopsy and prostatectomy GS was observed in 71 of 104 cases (68.3%), 80 of 110 cases (72.7%) and 98 of 136 cases (72.1%) for the standard sextant, lateral sextant and twelve core biopsy, respectively. Upgrading of 1 or more points was done in 26 of 104 cases (25.0%), 19 of 110 cases (17.3%) and 26 of 136 cases (19.1%), and downgrading 1 or more point was done in 7 of 104 cases (6.7%), 11 of 110 cases (10.0%) and 12 of 136 cases (8.8%) with the standard sextant, lateral sextant and twelve core biopsy, respectively. CONCLUSIONS: Twelve core needle biopsies lead to a higher cancer detection rate than do the sextant and lateral sextant needle biopsies. Twelve core and lateral sextant needle biopsies lead to higher concordance of the needle biopsy and surgical specimen GS compared with the standard sextant needle biopsy.

Clinicopathological Significance of the Lymphovascular Invasion Detected in Specimens from Radical Retropubic Prostatectomies / 대한비뇨기과학회지

PURPOSE: We tried to determine the clinicopathological significance of lymphovascular invasion (LVI) in patients who were treated for prostate cancer with radical retropubic prostatectomy. MATERIALS AND METHODS: From November 2003 to June 2005, 165 patients underwent radical retropubic prostatectomy for clinically-localized prostate cancer at our institution. The results of the final pathologic analyses were reviewed. RESULTS: Of the 165 total patients, foci of LVI were identified in 46 patients. LVI was associated with a higher preoperative serum level of prostate-specific antigen (p=0.006), the Gleason score (p<0.0001), a higher weight of tumor volume (p<0.0001), a higher rate of capsular penetration (p<0.0001), a higher rate of seminal vesicle involvement (p<0.0001), and a higher rate of a positive margin (p<0.0001). CONCLUSIONS: Since the pathological features of LVI appear to be associated with the other established features of more advanced prostate cancers, they may prove to be useful markers for predicting the prognosis of patients who undergo radical prostatectomy. Our findings support performing routine evaluation for LVI in radical prostatectomy specimens and its inclusion in the models for predicting the clinical outcome.