Erythema annulare centrifugum induced by COVID-19 vaccination.

With the expansion of the COVID-19 vaccination drive, an increasing number of adverse effects are surfacing. A 74-year-old woman presented with multiple erythematous and itchy patches on several sites. She had no relevant medical history, apart from the first AZD1222 vaccination 1 month previously. Microscopically, epidermal changes, including mild spongiosis and parakeratosis, were observed. Tight perivascular lymphocytic infiltration (coat-sleeve pattern) was also observed in the dermis. The final diagnosis was erythema annulare centrifugum (EAC) induced by SARS-CoV-2 vaccination. Based on this report, dermatologists should be aware of the possibility of EAC from the AZD1222 vaccination.

Ginseng berry concentrate prevents colon cancer via cell cycle, apoptosis regulation, and inflammation-linked Th17 cell differentiation.

The Asian ginseng root (Panax ginseng C.A. Meyer) is a very commonly used herbal medicine worldwide. Ginseng fruit, including the berry (or pulp) and seed, is also valuable for several health conditions including immunostimulation and cancer chemoprevention. In this study, the anticancer and anti-proliferative effects of the extracts of ginseng berry and seed were evaluated. The ginsenosides in the ginseng berry concentrate (GBC) and ginseng seed extract (GSE) were analyzed. We then evaluated their anti-colorectal cancer potentials, including antiproliferation, cell cycle arrest, and apoptotic induction. Further investigation consisted of the berry's adaptive immune responses, such as the actions on the differentiation of T helper cells Treg, Th1, and Th17. The major constituents in GBC were ginsenosides Re and Rd, which can be compared to those in the root. The GBC significantly inhibited colon cancer cell growth, and its anti-proliferative effect involved mechanisms including G2/M cell cycle arrest via upregulation of cyclin A and induction of apoptosis via regulation of apoptotic related gene expressions. GBC also downregulated the expressions of pro-inflammatory cytokine genes. For the adaptive immune responses, GBC did not influence Th1 and Treg cell differentiation but significantly inhibited Th17 cell differentiation and thus regulated the balance of Th17/Treg for adaptive immunity. Although no ginsenoside was detected in the GSE, interestingly, it obviously enhanced colon cancer cell proliferation with the underlined details to be determined. Our results suggested that GBC is a promising dietary supplement for cancer chemoprevention and immunomodulation.

Fracture recurrence in hip fracture with menopausal hormone therapy versus risedronate: a clinical trial.

OBJECTIVES: An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture. METHODS: Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD). RESULTS: Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group. CONCLUSIONS: MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.

The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study.

OBJECTIVE: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Korea. POPULATION: Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES: Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. CONCLUSIONS: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. TWEETABLE ABSTRACT: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.

Paternal age as an independent factor does not affect embryo quality and pregnancy outcomes of testicular sperm extraction-intracytoplasmic sperm injection in azoospermia.

This study was performed to evaluate the independent influence of paternal age affecting embryo development and pregnancy using testicular sperm extraction (TESE)-intracytoplasmic sperm injection (ICSI) in obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). Paternal patients were divided into the following groups: ≤30 years, 31-35 years, 36-40 years, 41-45 years and ≥46 years. There were no differences in the rates of fertilisation or embryo quality according to paternal and maternal age. However, clinical pregnancy and implantation rates were significantly lower between those ≥46 years of paternal age compared with other age groups. Fertilisation rate was higher in the OA than the NOA, while embryo quality, pregnancy and delivery results were similar. Clinical pregnancy and implantation rates were significantly lower for patients ≥46 years of paternal age compared with younger age groups. In conclusion, fertilisation using TESE in azoospermia was not affected by the independent influence of paternal age; however, as maternal age increased concomitantly with paternal age, rates of pregnancy and delivery differed between those with paternal age <41 years and ≥46 years. Therefore, paternal age ≥46 years old should be considered when applying TESE-ICSI in cases of azoospermia, and patients should be advised of the associated low pregnancy rates.

A study on setting of the fatigue limit of temporary dental implants.

A temporary dental implant is a medical device which is temporarily used to support a prosthesis such as an artificial tooth used for restoring patient's masticatory function during implant treatment. It is implanted in the oral cavity to substitute for the role of tooth. Due to the aging and westernization of current Korean society, the number of tooth extraction and implantation procedures is increasing, leading to an increase in the use and development of temporary dental implants. Because an implant performs a masticatory function in place of a tooth, a dynamic load is repeatedly put on the implant. Thus, the fatigue of implants is reported to be the most common causes of the fracture thereof. According to the investigation and analysis of the current domestic and international standards, the standard for fatigue of implant fixtures is not separately specified. Although a test method for measuring the fatigue is suggested in an ISO standard, it is a standard for permanent dental implants. Most of the test standards for Korean manufacturers and importers apply 250 N or more based on the guidance for the safety and performance evaluation of dental implants. Therefore, this study is intended to figure out the fatigue standard which can be applied to temporary dental implants when measuring the fatigue according to the test method suggested in the permanent dental implant standard. The results determined that suitable fatigue standards of temporary dental implants should be provided by each manufacturer rather than applying 250 N. This study will be useful for the establishment of the fatigue standards and fatigue test methods of the manufacturers and importers of temporary dental implants.

The effect of bleaching agents on the degradation of vitamins and carotenoids in spray-dried whey protein concentrate.

Previous research has shown that bleaching affects flavor and functionality of whey proteins. The role of different bleaching agents on vitamin and carotenoid degradation is unknown. The objective of this study was to determine the effects of bleaching whey with traditional annatto (norbixin) by hydrogen peroxide (HP), benzoyl peroxide (BP), or native lactoperoxidase (LP) on vitamin and carotenoid degradation in spray-dried whey protein concentrate 80% protein (WPC80). An alternative colorant was also evaluated. Cheddar whey colored with annatto (15 mL/454 L of milk) was manufactured, pasteurized, and fat separated and then assigned to bleaching treatments of 250 mg/kg HP, 50 mg/kg BP, or 20 mg/kg HP (LP system) at 50°C for 1 h. In addition to a control (whey with norbixin, whey from cheese milk with an alternative colorant (AltC) was evaluated. The control and AltC wheys were also heated to 50°C for 1 h. Wheys were concentrated to 80% protein by ultrafiltration and spray dried. The experiment was replicated in triplicate. Samples were taken after initial milk pasteurization, initial whey formation, after fat separation, after whey pasteurization, after bleaching, and after spray drying for vitamin and carotenoid analyses. Concentrations of retinol, a-tocopherol, water-soluble vitamins, norbixin, and other carotenoids were determined by HPLC, and volatile compounds were measured by gas chromatography-mass spectrometry. Sensory attributes of the rehydrated WPC80 were documented by a trained panel. After chemical or enzymatic bleaching, WPC80 displayed 7.0 to 33.3% reductions in retinol, ß-carotene, ascorbic acid, thiamin, α-carotene, and α-tocopherol. The WPC80 bleached with BP contained significantly less of these compounds than the HP- or LP-bleached WPC80. Riboflavin, pantothenic acid, pyridoxine, nicotinic acid, and cobalamin concentrations in fluid whey were not affected by bleaching. Fat-soluble vitamins were reduced in all wheys by more than 90% following curd formation and fat separation. With the exception of cobalamin and ascorbic acid, water-soluble vitamins were reduced by less than 20% throughout processing. Norbixin destruction, volatile compound, and sensory results were consistent with previous studies on bleached WPC80. The WPC80 colored with AltC had a similar sensory profile, volatile compound profile, and vitamin concentration as the control WPC80.

Short communication: Sensitive detection of norbixin in dried dairy ingredients at concentrations of less than 1 part per billion.

Norbixin is the water-soluble carotenoid in annatto extracts used in the cheese industry to color Cheddar cheese. The purpose of norbixin is to provide cheese color, but norbixin is also present in the whey stream and contaminates dried dairy ingredients. Regulatory restrictions dictate that norbixin cannot be present in dairy ingredients destined for infant formula or ingredients entering different international markets. Thus, there is a need for the detection and quantification of norbixin at very low levels in dried dairy ingredients to confirm its absence. A rapid method for norbixin evaluation exists, but it does not have the sensitivity required to confirm norbixin absence at very low levels in compliance with existing regulations. The current method has a limit of detection of 2.7 µg/kg and a limit of quantification of 3.5 µg/kg. The purpose of this study was to develop a method to extract and concentrate norbixin for quantification in dried dairy ingredients below 1 µg/kg (1 ppb). A reverse-phase solid-phase extraction column step was applied in the new method to concentrate and quantify norbixin from liquid and dried WPC80 (whey protein concentrate with 80% protein), WPC34 (WPC, 34% protein), permeate, and lactose. Samples were evaluated by both methods for comparison. The established method was able to quantify norbixin in whey proteins and permeates (9.39 µg/kg to 2.35 mg/kg) but was unable to detect norbixin in suspect powdered lactose samples. The newly developed method had similar performance to the established method for whey proteins and permeates but was also able to detect norbixin in powdered lactose samples. The proposed method had a >90% recovery in lactose samples and a limit of detection of 28 ppt (ng/kg) and a limit of quantification of 94 ppt (ng/kg). The developed method provides detection and quantification of norbixin for dairy ingredients that have a concentration of <1 ppb.

Progression of Osteoporosis After Kidney Transplantation in Patients With End-Stage Renal Disease.

BACKGROUND: This study investigated the prevalence of osteoporosis and the risk factors for its progression in kidney transplant recipients (KTRs). METHODS: Dual energy X-ray absorptiometry was used to prospectively measure changes in bone mineral density (BMD) before kidney transplantation (KT) and 1 year after transplantation in 207 individuals. We also analyzed the risk factors of osteoporosis progression during this period. RESULTS: Prior to KT, the mean BMD score (T-score of the femur neck area) was -2.1 ± 1.2, and the prevalence of osteoporosis was 41.5% (86/207). At 1 year post-transplantation, the mean BMD score significantly decreased to -2.3 ± 1.1 (P < .001), and the prevalence of osteoporosis increased to 47.3% (98/207; P = .277). The BMD score worsened over the study period in 69.1% (143/207) of patients, improved in 24.1% (50/207), and showed no change in 6.8% (14/207). Minimal intact parathyroid hormone (iPTH) improvement after KT was found to be an independent risk factor of osteoporosis progression. CONCLUSIONS: This study demonstrates progressive loss of BMD after KT and sustained secondary hyperparathyroidism might influence the progression of osteoporosis.

Oncogenic BRAF fusions in mucosal melanomas activate the MAPK pathway and are sensitive to MEK/PI3K inhibition or MEK/CDK4/6 inhibition.

Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated. We biologically characterized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which cell line harboring ZNF767-BRAF fusion were established for further molecular analyses. In an independent data set, NFIC-BRAF fusion was identified in an oral PMM case and TMEM178B-BRAF fusion and DGKI-BRAF fusion were identified in two malignant melanomas with a low mutational burden (number of mutation per megabase, 0.8 and 4, respectively). Subsequent analyses revealed that the ZNF767-BRAF fusion protein promotes RAF dimerization and activation of the MAPK pathway. We next tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. In conclusion, BRAF fusions define a new molecular subset of PMM that can be targeted therapeutically by the combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.

Temperament and character traits in patients with tinnitus: a prospective case series with comparisons.

OBJECTIVE: To describe the personality traits of temperament and character in patients with tinnitus and to identify differences in these traits associated with the severity of tinnitus. STUDY DESIGN: Case series with comparisons. SETTING: Tertiary referral centre. PARTICIPANTS: From January to December 2014, one hundred and thirty-four adult patients with chronic subjective tinnitus completed psychoacoustic measurements of tinnitus and the Temperament and Character Inventory (TCI). MEASUREMENTS: Personality traits were assessed by the TCI. The TCI assesses seven dimensions of personality traits and four temperaments 'novelty seeking, harm avoidance, reward dependence, persistence', as well as three characters 'self-directedness, cooperativeness, self-transcendence'. MAIN OUTCOME MEASURES: The values of the TCI parameters in the tinnitus patients were compared with reference data from a non-institutional adult population, and associations between TCI parameter values and tinnitus severity were evaluated. RESULTS: In terms of temperament, tinnitus patients had higher scores for 'harm avoidance', whereas scores for 'novelty seeking', 'reward dependence' and 'persistence' were significantly lower than the reference. In terms of character, lower 'cooperativeness' and 'self-transcendence' were identified in the subjects with tinnitus. The 'novelty seeking' score was inversely related to tinnitus severity (r = -0.285, P = 0.001), while other temperament and character traits did not show significant correlations. CONCLUSIONS: There may be a connection between tinnitus and personality traits, especially in the case of 'novelty seeking', which is relatively constant over a lifetime. The TCI questionnaire may be useful in facilitating the application of personality traits to tailored counselling for tinnitus.

Clinical Outcome of Simultaneous Native Nephrectomy and Kidney Transplantation in Patients With Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: End-stage renal disease patients with autosomal dominant polycystic kidney disease may require native nephrectomy for various indications. However, the appropriate timing for nephrectomy in kidney transplantation and its effect on allograft survival have not been fully investigated. METHODS: We retrospectively analyzed 41 kidney transplant recipients with autosomal dominant polycystic kidney disease in whom transplantation was done simultaneously, after, or without native nephrectomy at Seoul St. Mary's hospital between January 1987 and February 2014. We divided patients into 2 groups based on when native nephrectomy was performed: simultaneously (group A, n = 13) and after or without nephrectomy (group B, n = 28), and compared perioperative outcomes, posttransplantation complications, and allograft survival rates. RESULTS: The mean operative time was significantly longer in group A than in group B (6.48 ± 1.84 vs 5.27 ± 0.84 hours; P = .048). The mean numbers of units required for intraoperative blood transfusions were also significantly higher in group A than in group B (3.66 ± 3.43 vs 0.75 ± 0.26 units; P = .018). However, there were no differences between groups in the incidence of acute rejection and other complications such as postoperative bleeding and infectious complications (P > .05, for all). The allograft survival rate also did not differ between groups (P > .05). CONCLUSIONS: Our study showed that patients undergoing simultaneous nephrectomy and kidney transplantations had clinical outcomes, in terms of complications and allograft survival, that were comparable to those in patients undergoing kidney transplantations with or without previous nephrectomy.

NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer.

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme involved in NAD+ biosynthesis. Although NAMPT has emerged as a critical regulator of metabolic stress, the underlying mechanisms by which it regulates metabolic stress in cancer cells have not been completely elucidated. In this study, we determined that breast cancer cells expressing a high level of NAMPT were resistant to cell death induced by glucose depletion. Furthermore, NAMPT inhibition suppressed tumor growth in vivo in a xenograft model. Under glucose deprivation conditions, NAMPT inhibition was found to increase the mitochondrial reactive oxygen species (ROS) level, leading to cell death. This cell death was rescued by treatment with antioxidants or NAD+. Finally, we showed that NAMPT increased the pool of NAD+ that could be converted to NADPH through the pentose phosphate pathway and inhibited the depletion of reduced glutathione under glucose deprivation. Collectively, our results suggest a novel mechanism by which tumor cells protect themselves against glucose deprivation-induced oxidative stress by utilizing NAMPT to maintain NADPH levels.

Mid-trimester amniotic fluid pro-inflammatory biomarkers predict the risk of spontaneous preterm delivery in twins: a retrospective cohort study.

OBJECTIVE: To evaluate the association between the concentrations of immune-related proteins in mid-trimester amniotic fluid (AF) and the subsequent risk of spontaneous preterm delivery in twins. STUDY DESIGN: The study population consisted of consecutive women with a twin pregnancy who underwent clinically indicated genetic amniocentesis at 15 to 20 weeks, and had a subsequent spontaneous delivery in the early preterm period (<32 weeks (cases)) or at term (37 to 42 weeks (controls)). AF was analyzed for cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13 and IL-15, interferon-γ, tumor necrosis factor-α), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-12), and chemokines (complement factor-D/Adipsin, Serpin E1/PAI-1, Adiponectin/Acrp30, C-Reactive Protein, CCL2/MCP-1, Leptin, Resistin) using multiplex immunoassay kits. The association between AF protein levels and subsequent early preterm birth were examined. RESULT: A total of 96 sets of twins were enrolled, including 17 early preterm birth cases and 79 term controls. AF concentrations of IL-6, IL-8, MMP-3, MMP-8 and MMP-9, and CCL2/MCP-1 were significantly higher in cases than controls. Among these analytes, the combination of AF IL-8 and MMP-9 values had the highest predictive value for early preterm birth. The risk was 8% (10/132) for IL-8<1200 pg ml(-1) and MMP-9<1000 pg ml(-1), 30% (15/50) for IL-8>1200 pg ml(-1) or MMP-9>1000 pg ml(-1), and 90% (9/10) for IL-8>1200 pg ml(-1) and MMP-9>1000 pg ml(-1) (P<0.001). CONCLUSION: High concentrations of IL-8 and MMP-9 in mid-trimester AF in twins predicted well the risk of early preterm birth.

Food hypersensitivity in adult patients with atopic dermatitis in Korea.

BACKGROUND: It is known that atopic dermatitis (AD) is associated with food or environmental allergens and increased levels of serum IgE. However, the role of hypersensitivity to food antigens in adult patients remains controversial. AIM: To evaluate the association between food hypersensitivity and AD in 126 adult Korean participants. METHODS: Patients with AD were assessed for a previous history of food hypersensitivity that aggravated the symptoms of AD. Blood samples were taken from the patients to measure food allergen-specific IgE. Based on history and laboratory results, open oral food challenge (OFC) tests were performed. RESULTS: Of 126 participants, 33 (26.2%) claimed to have experienced previous food hypersensitivity. Both pork and wheat (n = 5 each) were the main foods mentioned, followed by beef (n = 4) and shellfish (n = 3). We found that 20 participants (15.9%) had raised levels of food-specific IgE, with beef (n = 7), pork (n = 6), milk (n = 5) and wheat (n = 5) being the most common (some patients had more than one). However, when the open OFC tests were conducted in 48 participants with self-reported food hypersensitivity or raised levels of food-specific IgE, only one showed a positive reaction; this participant had a previous history of pork consumption exacerbating AD. CONCLUSIONS: Although some participants claimed to have a history of AD aggravation related to food intake, when an open OFC test was conducted, few of them had positive results. Our study result indicates that there is a positive reaction rate of only 0.79% for adults. We therefore conclude that adults are less sensitive than children with regard to the association between AD and food hypersensitivity.

Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation.

Emerging molecular studies have identified a subgroup of patients with unfavorable core-binding factor-positive (CBF)-AML who should be treated by intensified post-remission treatments. We analyzed 264 adults with CBF-AML from 2002 to 2011, and focused on 206 patients who achieved CR after standard '3+7' induction chemotherapy. Patients who achieved CR with an available donor were treated with allogeneic hematopoietic SCT (allo-HSCT, n=115) and the rest were treated with autologous (auto) HSCT (n=72) or chemotherapy alone (n=19). OS was not significantly different between CBFß/MYH11 (n=62) and RUNX1/RUNX1T1 (n=144), and auto-HSCT showed favorable OS compared with allo-HSCT or chemotherapy alone. Cytogenetic analysis identified that inv(16) without trisomy had a favorable OS and t(8;21) with additional chromosomes had an unfavorable OS, but multivariate analysis revealed those were NS. Patients with c-kit mutation showed inferior OS. For transplanted patients, residual post-transplant CBF-minimal residual disease quantitative PCR with higher WT1 expression at D+60 showed the worst OS with a higher incidence of relapse. Conclusively, we found that unfavorable CBF-AML can be defined with risk stratification using cytogenetic and molecular studies, and a careful risk-adapted treatment approach using frontline transplantation with novel therapies should be evaluated for this particular risk subgroup.