Protocol to encapsulate cerebral organoids with alginate hydrogel shell to induce volumetric compression.

In vitro organoids, including cerebral organoids, are usually developed without mechanical compression, which may contribute to a delay in maturation. Here, we present a protocol for encapsulating cerebral organoids with a thin shell of low-concentration alginate hydrogel. We describe steps for organoid generation, microfluidic chip culture, Matrigel coating, expansion culture, and alginate encapsulation. We then detail procedures for maturation culture and organoid characterization. The moderate compressive stimulation that the shell provides promotes cell proliferation and neuronal maturation. For complete details on the use and execution of this protocol, please refer to Tang et al.1.

Electrostatic potential difference between tumor and paratumor regulates cancer stem cell behavior and prognose tumor spread.

Tumor spread is responsible for most deaths related to cancer. Increasing the accuracy of cancer prognosis is critical to reducing the high mortality rates in cancer patients. Here, we report that the electrostatic potential difference (EPD) between tumor and its paratumor tissue is a prognostic marker for tumor spread. This finding is concluded from the patient-specific EPD values and clinical observation. The electrostatic potential values were measured on tissue cryosections from 51 patients using Kelvin probe force microscopy (KPFM). A total of ~44% (15/34) patients of Vtumor-paratumor > 0 were featured with tumor spread, whereas only ~18% (2/11) patients of Vtumor-paratumor < 0 had tumor spread. Next, we found the increased enrichment of cancer stem cells in paratumors with lower electrostatic potentials using immunofluorescence imaging, which suggested the attribution of tumor spread to the galvanotaxis of cancer stem cells (CSCs) toward lower potential. The findings were finally validated in breast and lung spheroid models composed of differentiated cancer cells and cancer stem cells at the ratio of 1:1 and embedded in Matrigel dopped with negative-, neutral- and positive-charged polymers and CSCs prefer to spread out of spheroids to lower electrostatic potential sites. This work may inspire the development of diagnostic and prognostic strategies targeting at tissue EPDs and CSCs for tumor therapy.

Vascularized Tumor Spheroid-on-a-Chip Model Verifies Synergistic Vasoprotective and Chemotherapeutic Effects.

Prolyl hydroxylases (PHD) inhibitors have been observed to improve drug distribution in mice tumors via blood vessel normalization, increasing the effectiveness of chemotherapy. These effects are yet to be demonstrated in human cell models. Tumor spheroids are three-dimensional cell clusters that have demonstrated great potential in drug evaluation for personalized medicine. Here, we used a perfusable vascularized tumor spheroid-on-a-chip to simulate the tumor microenvironment in vivo and demonstrated that the PHD inhibitor dimethylallyl glycine prevents the degradation of normal blood vessels while enhancing the efficacy of the anticancer drugs paclitaxel and cisplatin in human esophageal carcinoma (Eca-109) spheroids. Our results point to the potential of this model to evaluate anticancer drugs under more physiologically relevant conditions.

Polycythemia as a Complication of Long-acting Injectable Testosterone Undecanoate / 대한남성과학회지

Polycythemia is a condition in which the red blood cell count is increased due to an inherited or acquired mutation, a physiologic response to hypoxia, autonomous erythropoietin production, or deliberate erythropoietin administration. Higher testosterone levels appear to act as a stimulus for erythropoiesis and testosterone replacement therapies have rarely been reported as causes of polycythemia. We report here a case of a 51-year-old man with polycythemia that was caused by long-acting testosterone undecanoate (Nebido(R)).

Efficacy of Desmopressin in Treatment of Adult Nocturia / 대한비뇨기과학회지

PURPOSE: This study was performed to investigate the effect of desmopressin on nocturia in patients with irritative symptom who do not respond effectively to first line therapy, such as benign prostatic hyperplasia(BPH) medication(alpha-blocker and finasteride), antimuscarinics or calcium antagonist. MATERIALS AND METHODS: Patients had been treated for unresolved severe nocturia(<3 times per night) in spite of first-line therapy for more than 3 months. Additional medication of desmopressin was recommended to the patients with unresolved nocturia in spite of first line therapy. According to clinical diagnosis, the patients were classified into three groups: Group I of male with BPH, Group II of male without BPH and Group III of female. The response to each first-line therapy and desmopressin treatment was estimated by the number of nocturia and quality of life. Additionally, before and after desmopressin treatment, voiding diary and urodynamic study were evaluated, respectively. RESULTS: A total of 79 patients were enrolled in this study. Severe nocturia patients unresolved to 1st line therapy were improved after combination therapy of 1st line therapy with desmopressin. In 66(83.5%) of the total 78 patients, the number of nocturia was significantly reduced to less than 3 after combination therapy. According to groups, the number of nocturia was significantly reduced to less than 3 in 84.8% of Group I(n=46), 71.4% of Group II(n=21), and 100% of Group III(n=12), respectively. CONCLUSIONS: Combination therapy with desmopressin effectively reduced nocturia in patients with unresolved severe nocturia in spite of first line treatment. We recommend combination therapy of desmopressin with first line treatment for unresolved severe nocturia in adults. Long term efficacy and adverse effects should be assessed for the generalized use of desmopressin.

Self-concept, Anxiety, Depression Scales and Behavior Estimation in Primary Nocturnal Enuresis / 대한비뇨기과학회지

Purpose: Nocturnal enuresis has been regarded as one of the most prevalent problems of childhood. Nocturnal enuresis may lead to a distressing and perplexing problem for children, resulting in social withdrawal, guilty feelings, and a sense of loneliness. In this study, we investigated changes in self-awareness, anxiety, depression, and behavior estimation before and after treatment in children with primary nocturnal enuresis. MATERIALS AND METHODS: Psychologic inventories were evaluated in 48 primary nocturnal enuretic patients who had been successfully treated for their nocturnal enuresis from April 2001 to March 2002. Before and after treatment, self-administered questionnaires, such as Kovac's Children's Depression Inventory, Piers-Harris Children Self-Concept scale, and State-Trait Anxiety Inventory for Children, were evaluated by the enuretics. Their parents were also evaluated by the Child Behavior Check list. RESULTS: In Kovac's Children's Depression Inventory and Piers-Harris Children Self-Concept scale, there were no signs of psychologic abnormality before and after treatment of nocturnal enuresis in terms of self-awareness and depression. Compared with the pre-treatment scores, there was significant improvement in trait anxiety after treatment of nocturnal enuresis (p<0.05). In the Child Behavior Check list, the parents thought that enuresis did not lead to abnormal behavior in their children. CONCLUSIONS: These results suggest no serious psychopathologic abnormalities before and after treatment of primary nocturnal enuresis. The enuretic patients may suffer from trait anxiety. Consequently, the successful treatment of nocturnal enuresis may alleviate a child's anxiety and prevent secondary psychopathologic abnormalities.

Effective Intervals of Serum Prostate Specific Antigen (PSA) Test for Screening of Prostate Cancer in Men with Initial Serum PSA Level below 2ng/ml / 대한비뇨기과학회지

PURPOSE: The aim of this study was to estimate the effective intervals of the serum prostate specific antigen (PSA) test in men aged over 50 years, with an initial PSA value below 2ng/ml, no palpable nodule at digital rectal examination (DRE) and no abnormal findings on transrectal ultrasonography (TRUS). MATERIALS AND METHODS: 209 men, with initial serum PSA levels below 4ng/ml, who had checked their PSA more than twice, with a minimal interval of 4 months, taking no BPH medication and with no lesion suspicious of malignancy on DRE and TRUS, were enrolled. The factors influencing the changes in the PSA were analyzed, and the rate of conversion of PSA over the cut-off level of 4ng/ml, or age specific reference level of PSA, calculated. Another group of 24 patients, with initial PSA levels below 4ng/ml, but showing no lesion suspicious of malignancy on DRE or TRUS, underwent transrectal biopsies, and their PSA velocities (PSAV) calculated. RESULTS: Of the 209 patients, a PSA conversion, over the age specific reference level of PSA, was not observed over a 4 years period in the group with an initial PSA below 1ng/ml. In the group with initial PSA levels between 1 and 2ng/ml, a PSA conversion of over 4ng/ml was observed in only 3.4% of patients over a 2 year period. Among 24 biopsies, 5 prostate cancers and one high grade PIN were detected, with the calculated PSAV from these patients being 0.75ng/ml/year. When this PSAV was applied as a cut-off value, the sensitivity and specificity were 33.3 and 11.1%, respectively. CONCLUSIONS: The PSAV did not effectively predict the presence of prostate cancer in men with an initial PSA below 4ng/ml. Therefore, in men over 50, and without a lesion suspicious of malignancy on DRE and TRUS, the suggested effective intervals for screening of prostate cancer, for men with an initial PSA below 1ng/ml and between 1 and 2ng/ml, should be 4 and 2 years, respectively.