Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSION: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Stabilization of microbial network by co-digestion of swine manure and organic wastes.

The production of biogas from organic waste has attracted considerable interest as a solution to current energy and waste management challenges. This study explored the methane (CH4) production potential of swine manure (SM), food waste (FW), and tomato waste (TW) and the changes in the microbial community involved in the anaerobic digestion process. The results revealed that the CH4 production potentials of the four kinds of SM samples were influenced by the characteristics of SM (e.g., age and storage period). Among the four kinds of SM samples, the CH4 yield from the manure directly sampled from primiparous sows (SM3) was the highest. The CH4 yield was significantly improved when SM3 was co-digested with FW, but not with TW. The addition of SM fostered a stable CH4 production community by enhancing the interaction between methanogens and syntrophic bacteria. Furthermore, the addition of FW as a co-substrate may improve the functional redundancy structure of the methanogenesis-associated network. Overall, the characteristics of SM must be considered to achieve consistent CH4 yield efficiency from anaerobic digestion since CH4 production potentials of SM can be different. Also, the contribution of co-substrate to the synergistic relationship between methanogens and syntrophic bacteria can be considered when a co-substrate is selected in order to enhace CH4 yield from SM.

Robotic single-port hysterectomy versus robotic multisite hysterectomy in benign gynecologic diseases: A retrospective comparison of clinical and surgical outcomes.

BACKGROUND: This study aimed to compare clinical and surgical outcomes of robotic single-port hysterectomy (RSPH) using the da Vinci® SP surgical system and robotic multisite hysterectomy (RMSH) with the da Vinci Xi system in benign gynecologic disease. METHODS: The retrospective study included 134 patients who underwent RSPH or RMSH between November 2019 and December 2020. Total operation time, amount of blood loss, and the change in hemoglobin (Hb) after surgery and the weight of the removed uteri were also measured. Data on complications such as post-operative fever and length of hospitalization were also compared and analyzed. RESULTS: There was no significant difference in the total operation time between the two groups, although the operation time was slightly longer in the RSPH group. Results in the RSPH group were superior to the RMSH group in docking time and wound incision time (1.67 ± 0.79 vs. 5.46 ± 2.25 min, p-value <0.01; 6.48 ± 4.29 vs. 9.10 ± 4.64 min, p-value <0.01, respectively). On the other hand, wound suture time took longer in the RSPH group (18.12 ± 5.66 vs. 10.69 ± 3.18 min, p-value <0.01). The weights of the removed specimens were higher in the RMSH group (302.64 ± 190.56 vs. 369.24 ± 181.70 g, p-value <0.04). The amount of blood loss during surgery and the difference in hemoglobin (Hb) before and after surgery were less in the RSPH group (97.39 ± 113.79 vs. 224.93 ± 152.29 mL, p-value <0.01, 1.51 ± 1.08 vs. 2.54 ± 1.08 g/dL, p-value <0.01). When considering the weight difference as a correction between the two surgical groups (because there were many heavier samples in the RMSH group), the blood loss of the RSPH group was also less than that of the RMSH group by 115.95 ± 23.78 mL (p-value <0.01). CONCLUSIONS: On the basis of our data, the robotic hysterectomy using the da Vinci SP surgical system might be feasible and safe, even if the hysterectomy is complex, and comparable to robotic multisite surgery by the da Vinci Xi system.

Robotic single-port myomectomy using the da Vinci SP surgical system: A pilot study.

AIM: To report our initial experience with robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system and to evaluate the feasibility of the procedure. MATERIAL AND METHODS: This prospective observational study was performed at a university teaching hospital from January 2019 to December 2019. Sixty-one women with symptomatic fibroids received RSPM. RESULTS: Based on seven resected fibroids and a maximal diameter of resected fibroids <10 cm, the women were arbitrarily divided into two groups. The mean number and maximal diameter of the removed fibroids were 3.7 ± 3.8 (2.3 ± 1.8 in Group 1 vs. 7.2 ± 5.3 in Group 2) and 7.6 ± 2.9 cm (6.8 ± 1.6 in Group 1 vs. 9.5 ± 4.3 in Group 2), respectively. The mean operation time, hemoglobin change, and hospital stay were 149.9 ± 72.9 min (123.8 ± 43.8 in Group 1 vs. 217.6 ± 89.4 in Group 2), 2.3 ± 1.0 g/dL (2.1 ± 0.9 in Group 1 vs. 2.7 ± 1.2 in Group 2), and 4.5 ± 0.8 days (4.4 ± 0.8 in Group 1 vs. 4.7 ± 0.9 in Group 2). There was no conversion to multi-port laparoscopy or laparotomy nor were there any major complications. CONCLUSIONS: RSPM using the da Vinci SP surgical system is feasible surgical modality for women with symptomatic fibroid and is expected to increase indications of single-port myomectomy by solving many of the ergonomics problems inevitably accompanying single-port laparoscopic myomectomy.

The Association of Ovarian Reserve with Exposure to Bisphenol A and Phthalate in Reproductive-aged Women.

BACKGROUND: Exposure to endocrine disrupting chemicals (EDCs) that influence the hormonal and homeostatic systems is known to be associated with gynecologic health risks in many countries. In this study, we evaluated exposure to EDCs associated with diminished ovarian reserve (DOR) and gynecologic health risks. METHODS: This cross-sectional study was performed from September 2014 to November 2014 and included 307 Korean reproductive-aged women. Anthropometric measurements, laboratory tests with urine and blood sampling and pelvic ultrasound examinations were performed. RESULTS: Urinary bisphenol A (BLA) level was significantly higher in the DOR group with anti-Müllerian hormone lower than 25 percentile (1.89 ± 2.17 ug/g and 1.58 ± 1.08 ug/g, P < 0.05). Urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-N-butyl phthalate, and substrates of phthalate were evaluated and no significant difference was observed between the DOR group and non-DOR group. Logistic regression analysis suggested an increase in infertility in high BPA exposure group and the odds ratio (OR, 4.248) was statistically significant after adjustment for age, birth control pills, and the age of menarche, parity, and waist circumference. High phthalate exposure was associated with endometrial polyp after adjustment (OR, 2.742). CONCLUSION: BPA exposure might be associated with DOR and infertility. Meanwhile, endometrial polyp is increased in women with high phthalate exposure. Therefore, the risk of exposures to EDCs for reproduction should be a matter of concern in reproductive-aged women.

A case of inherited type 1 and type 2A von Willebrand disease confirmed by diagnostic exome sequencing.

A 10-year-old male and his family members visited a pediatric hematology clinic due to coagulopathy. Laboratory tests indicated von Willebrand disease (vWD) in all the family members. We conducted diagnostic exome sequencing for confirmation. The patient was confirmed to be a compound heterozygote for vWD: c.2574C > G (p.Cys858Trp) from his father (known variant of vWD type 1) and c.3390C > T (p.Pro1127_Gly1180delinsArg) from his mother (variant known to result in exon 26 skipping in vWD type 2A). He was managed with factor VIII and von Willebrand factor complex concentrate during palatoplasty due to bleeding despite pre-operative desmopressin injection. The operation was completed successfully.

Real-world prescribing patterns of long-acting benzodiazepines for elderly Koreans in 2013
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OBJECTIVE: We aimed to estimate the prevalence of prescriptions to long-acting benzodiazepines (BZDs) among elderly outpatients in Korea in 2013 and analyze the factors that led to inappropriate prescription practices. METHODS: Using the Korea Health Insurance Review and Assessment Service-National Patients Sample database in 2013, we estimated the pattern of BZD prescription among elderly outpatients. BZDs were categorized as long-acting (half-life (T1/2) ≥ 20 hours) or short-acting (T1/2 < 20 hours). In addition, we investigated the pattern of BZD prescription for populations defined according to patient, healthcare provider, and geographic characteristics. Multivariate logistic regression analysis was performed to estimate odds ratios and 95% confidence intervals and identify predictors of long-acting BZD use. RESULTS: Overall, 58,056 elderly patients (38,910 females, 67%) received at least 1 BZD prescription. The total number of BZD prescriptions was 78,843, of which long-acting BZD prescriptions accounted for 44.7%. Diazepam was the most frequently prescribed BZD (39.7%). Long-acting BZDs were most frequently prescribed in the primary-care setting and were relatively frequently prescribed in rural areas. Of the patients prescribed long-acting BZDs, 435 (3.5%) had chronic obstructive pulmonary disease. Long-acting BZD use varied across different medical institutions (p < 0.05). CONCLUSIONS: A decrease in long-acting BZD use was identified relative to data from previous studies. However, BZDs continued to be used, and their use should be further limited in the primary-care setting and in rural areas. The results of this study may provide fundamental data for further review of BZD utilization.
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Differential gene expression patterns during embryonic development of sea urchin exposed to triclosan.

Triclosan (TCS; 2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antibacterial agent used in common industrial, personal care and household products which are eventually rinsed down the drain and discharged with wastewater effluent. It is therefore commonly found in the aquatic environment, leading to the continual exposure of aquatic organisms to TCS and the accumulation of the antimicrobial and its harmful degradation products in their bodies. Toxic effects of TCS on reproductive and developmental progression of some aquatic organisms have been suggested but the underlying molecular mechanisms have not been defined. We investigated the expression patterns of genes involved in the early development of TCS-treated sea urchin Strongylocentrotus nudus using cDNA microarrays. We observed that the predominant consequence of TCS treatment in this model system was the widespread repression of TCS-modulated genes. In particular, empty spiracles homeobox 1 (EMX-1), bone morphogenic protein, and chromosomal binding protein genes showed a significant decrease in expression in response to TCS. These results suggest that TCS can induce abnormal development of sea urchin embryos through the concomitant suppression of a number of genes that are necessary for embryonic differentiation in the blastula stage. Our data provide new insight into the crucial role of genes associated with embryonic development in response to TCS. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 426-433, 2017.

Comparison of ultrasound-guided endometrial polypectomy carried out on the oocyte retrieval day and the first day of ovarian stimulation in IVF-ICSI cycles.

In this retrospective cohort study, the effect of endometrial polypectomy carried out on the day of oocyte retrieval and on the first day of ovarian stimulation in patients with a large (≥10 mm) endometrial polyp undergoing IVF and intractyoplasmic sperm injection (ICSI) was investigated and compared. A total of 74 eligible IVF-ICSI cycles in 74 women who underwent endometrial polypectomy on either the day of oocyte pick-up (late polypectomy group, 39 cycles) or the first day of ovarian stimulation (early polypectomy group, 35 cycles) between January 2007 and July 2012 were included in this study. Patient characteristics between early and late polypectomy groups were similar. Total dose and days of recombinant human FSH administered, numbers of retrieved oocytes, mature oocytes, fertilized oocytes, grade 1 or 2 embryos and embryos transferred between the two groups were also similar, as was clinical pregnancy rate per cycle, embryo implantation rate and spontaneous abortion rate between the two groups. Therefore, endometrial polypectomy on the day of oocyte retrieval could be a more patient-friendly option for patients with a large endometrial polyp undergoing IVF-ICSI.

Black cohosh inhibits 17ß-estradiol-induced cell proliferation of endometrial adenocarcinoma cells.

This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 µM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17ß-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 µM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C δ in a mouse model of diabetic retinopathy.

Recent studies revealed that Tonicity-responsive enhancer binding protein (TonEBP) directly regulates the transcription of aldose reductase (AR), which catalyzes the first step of the polyol pathway of glucose metabolism. Activation of protein kinase C δ (PKCδ) is dependent on AR and it has been linked to diabetic complications. However, whether TonEBP affects expressions of AR and PKCδ in diabetic retinopathy was not clearly shown. In this study, we used TonEBP heterozygote mice to study the role of TonEBP in streptozotocin (STZ)-induced diabetic retinopathy. We performed immunofluorescence staining and found that retinal expressions of AR and PKCδ were significantly reduced in the heterozygotes compared to wild type littermates, particularly in ganglion cell layer. To examine further the effect of TonEBP reduction in retinal tissues, we performed intravitreal injection of TonEBP siRNA and confirmed the decrease in AR and PKCδ levels. In addition, we found that a proapoptotic factor, Bax level was reduced and a survival factor, Bcl2 level was increased after injection of TonEBP siRNA, indicating that TonEBP mediates apoptotic cell death. In parallel, TonEBP siRNA was applied to the in vitro human retinal pigment epithelial (ARPE-19) cells cultured in high glucose media. We have consistently found the decrease in AR and PKCδ levels and changes in apoptotic factors for survival. Together, these results clearly demonstrated that hyperglycemia-induced TonEBP plays a crucial role in increasing AR and PKCδ levels and leading to apoptotic death. Our findings suggest that TonEBP reduction is an effective therapeutic strategy for diabetic retinopathy.

Hypoxia-modulated gene expression profiling in sea urchin (Strongylocentrotus nudus) immune cells.

Hypoxia is an issue that affects ocean coastal waters worldwide. It has severe consequences for marine organisms, including death and rapid adaptive changes in metabolic organization. Although some aquatic animals are routinely exposed and resistant to severe environmental hypoxia, others such as sea urchins (Strongylocentrotus nudus) have a limited capacity to withstand this stress. In this study, hypoxia induced a significant increase in the number of red spherule cells among coelomocytes, which function as immune cells. This suggests that sea urchin immune cells could be used as a biological indicator of hypoxic stress. In the current study, we used cDNA microarrays to investigate the differential expression patterns of hypoxia-regulated genes to better understand the molecular mechanisms underlying the response of immune cells to hypoxia. Surprisingly, the predominant major effect of hypoxia was the widespread suppression of gene expression. In particular, the expression of RNA helicase and GATA-4/5/6 was decreased significantly in response to hypoxia, even in field conditions, suggesting that they could be utilized as sensitive bioindicators of hypoxic stress in the sea urchin.

Dietary Poly-ß-Hydroxybutyrate Improved the Growth, Non-specific Immunity, Digestive Enzyme Activity, Intestinal Morphology, Phagocytic Activity, and Disease Resistance Against Vibrio parahaemolyticus of Pacific White Shrimp, Penaeus vannamei.

This study assessed the effects of dietary supplementation of poly-ß-hydroxybutyrate (PHB) on growth performance, feed efficiency, non-specific immunity, digestive enzyme capacity, phagocytic activity, hemocyte count, intestinal morphology, and disease resistance against Vibrio parahaemolyticus of Pacific white shrimp (Penaeus vannamei). Six diets were prepared by supplementing graded levels of PHB at 0.00, 0.25, 0.50, 1.00, 2.00, and 4.00% (Con, P0.25, P0.5, P1.0, P2.0, and P4.0, respectively). Triplicate groups of 90 shrimps (initial body weight 0.25 ± 0.01 g) per treatment were randomly assigned and fed an experimental diet for 56 days. The growth performance of shrimp was significantly improved by 1% dietary PHB supplementation. PHB-included diets fed shrimp showed significantly improved hepatopancreatic trypsin, chymotrypsin, and pepsin activities. Villus height was significantly increased with dietary PHB supplementation, and villus width was increased at a 1% inclusion level. P0.25, P0.5, and P4.0 groups significantly increased phenoloxidase activity, and the P2.0 group significantly increased anti-protease activity compared to the Con group. The survival of shrimp challenged against V. parahaemolyticus was higher in P0.5, P1.0, and P2.0 groups than in the Con diet. Dietary PHB supplementation improved weight gain, digestive enzyme activity, intestinal morphology, non-specific immunity, and disease resistance against V. parahaemolyticus of shrimp. According to the above observations, the optimal dietary PHB supplementation level for maximum weight gain would be 1% for Pacific white shrimp.

Development of delayed thyroid stimulating hormone elevation in small-for-gestational-age infants: is a second screening needed?

PURPOSE: Recent reports indicate that small for gestational age (SGA) could be a risk factor for delayed thyroid stimulating hormone (dTSH) elevation in preterm infants. The development of dTSH elevation in SGA late-preterm infants with a gestational age of 34-36 weeks has been investigated in only a few studies. METHODS: In the present retrospective study, 70 SGA infants and 86 sex- and gestational age-matched controls who presented with normal results on initial thyroid function testing were included. RESULTS: SGA infants had a significantly higher prevalence of dTSH elevation (15.7% vs. 3.5%, P=0.009) compared with appropriate-for-gestational age infants. In SGA infants, the mean age at the time of dTSH was 24 days. Development of dTSH was associated with SGA and medical treatment with dopamine or furosemide. After adjusting for confounding factors, multiple logistic regression analysis showed SGA was a significant risk factor for the development of dTSH elevation (odds ratio, 23.2; 95% confidence interval, 2.27-236.91; P=0.008). CONCLUSION: SGA infants may be at risk for dTSH and clinicians could consider a second thyroid screening test around the age of 1 month.

Short stature with low serum alkaline phosphatase activity: a case report of hypophosphatasia.

Hypophosphatasia (HPP) is a rare condition characterized by abnormal bone mineralization. The manifestations of HPP vary from no symptoms to intrauterine fetal death; short stature is another indication of HPP. A 3 ½-year-old boy presented with short stature, transient hypercalcemia, and mild gait disturbance without definite bony deformity. Laboratory examination revealed transient hypercalcemia, normal phosphorous and 25-hydroxy vitamin D levels, and mildly low alkaline phosphatase levels. A targeted next-generation sequencing panel associated with inborn errors of metabolism revealed a pathogenic heterozygous mutation in the ALPL gene, c.979T>C (p.Phe327Leu). When a child visits a hospital with short stature, decreased height velocity, and low alkaline phosphatase level, clinicians should consider the possibility of HPP even if definite skeletal dysplasia is not evident.

What is the role of robotic surgery in ovarian cystectomy with fertility preservation?

To investigate the role of robotic single-site (RSS) ovarian cystectomy in fertility preservation, which was compared with single-port laparoscopic (SPL) surgery based on AMH changes. We retrospectively analyzed medical records of total 156 patients who underwent SPL (n = 72) or RSS (n = 84) surgery with the da Vinci® Si or Xi system. The pre/post-operative AMH levels and total diameter of ovarian cysts were measured. In addition to the surgical method, AMH changes were compared according to the laterality, multiplicity, and pathology of ovarian cysts. A comparison of the characteristics of the SPL group and RSS group, revealed that there were no significant differences in the average age, the diameter of the ovarian cyst, and the number of locule. There were also no statistical differences between the pre-operative and post-operative AMH levels and the average surgical time including the docking time in robotic surgery. A comparison based on the surgical methods, revealed that the decrease in post-operative AMH was lower in the RSS group (24.2 ± 35.9%) than in the SPL group (34.9 ± 29.1%) significantly (p = 0.044). In patients with endometriosis, the decrease in AMH was greater, than that in patients without endometriosis. A longer operation time, larger ovarian cysts and multi-locular cysts were associated with lower AMH level in both the SPL and RSS groups (Pearson correlation coefficient: - 0.320, p = 0.0001, - 0.218, p = 0.007, - 0.236, p = 0.003, respectively). RSS ovarian cystectomy could be a promising new therapeutic option for fertility preservation in complex cases to avoid an additional side port.