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.

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.

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.

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.

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.

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.

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.

Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1α axis in db/db mice.

AIMS/HYPOTHESIS: Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes. METHODS: Four groups of male C57BLKS/J db/m and db/db mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks. RESULTS: The db/db mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1-PGC-1α signalling and of the key downstream effectors, the PPARα-oestrogen-related receptor (ERR)-1α-sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling and the downstream effectors, PPARα-ERR-1α-SREBP1. CONCLUSIONS/INTERPRETATION: The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.

Combined use of rituximab and plasmapheresis pre-transplant increases post-transplant infections in renal transplant recipients with basiliximab induction therapy.

INTRODUCTION: We investigated the effect of combined use of rituximab (RTX) and plasmapheresis (PP) pre-transplant on post-transplant infection. METHODS: A total of 196 patients undergoing living-donor kidney transplantation at Seoul St. Mary's Hospital, all of whom underwent basiliximab induction therapy, were included in the study. They were divided into 3 groups: RTX/PP/intravenous immune globulin (IVIG) (the RPI group; n = 53), RTX monotherapy (the RTX group; n = 14), and control (the CONT group; n = 129). We compared the post-transplant infections in the 3 groups. RESULTS: The overall prevalence of infection was significantly higher, and the infection-free survival rate was lower, in the RPI group compared with the RTX or CONT groups (P < 0.05). A trend toward more severe bacterial infections was seen in the RPI group compared with the other groups, and fungal infections developed only in the RPI group. After anti-rejection therapy, a significantly higher rate of infection developed in the RPI group than in the other groups (P < 0.05). In addition, the RPI group was an independent risk factor for the development of infection. CONCLUSION: Our results show that in the setting of basiliximab induction, the use of combined RTX and PP therapy pre-transplant significantly increases the risk for post-transplant infection.

Expression of CCL1 and CCL18 in atopic dermatitis and psoriasis.

BACKGROUND: Recent studies have shown that chemoattractive proteins play an important role in the organization of the innate and adaptive immune responses. There are some reports that chemokine (C-C motif) ligand (CCL)1 and CCL18, members of a family of chemoattractive proteins, have increased expression in atopic dermatitis (AD). AIM: To evaluate the quantity and pattern of CCL1 and CCL18 expression in lesions and blood of patients with AD, and compare them with those of patients with psoriasis. METHODS: Biopsy specimens were taken from atopic skin and normal-appearing skin of patients with AD and from the psoriatic skin only of patients with psoriasis. Quantitative real-time PCR analysis and immunohistochemistry of CCL1 and CCL18 expression were performed, and the quantities of expressed CCL1 and CCL18 in acute AD were compared with those of normal-appearing atopic skin and psoriatic skin. The serum level of CCL1 and CCL18 was assessed by ELISA. RESULTS: Expression of CCL1 mRNA and protein was significantly higher in the acute lesional skin of patients with AD than in their nonlesional skin or in the lesional skin of patients with psoriasis. Both CCL18 mRNA and protein were abundant in acute AD lesions and in psoriatic lesions, but were lower in the nonlesional skin of patients with AD. The serum levels of CCL1 and CCL18 were not different in patients with AD and patients with psoriasis. CONCLUSIONS: CCL1 is a chemokine that is associated with AD. Both CCL1 and CCL18 may play important roles in the initiation and progression of atopic skin inflammation.

Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein.

von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome that is characterized by the development of multiple vascular tumors and is caused by inactivation of the von Hippel-Lindau protein (pVHL). Here we show that pVHL, through its beta-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an alpha-domain-dependent manner. This is the first function to be ascribed to the pVHL beta-domain. Furthermore, we provide the first direct evidence that pVHL has a function analogous to that of an F-box protein, namely, to recruit substrates to a ubiquitination machine. These results strengthen the link between overaccumulation of HIF and development of VHL disease.

Renal dysfunction and barttin expression in Bartter syndrome Type IV associated with a G47R mutation in BSND in a family.

Bartter syndrome (BS) Type IV, associated with a G47R mutation in the BSND gene, is known to result in a mild renal phenotype. However, we report here on three brothers with varying degrees of renal dysfunction from mild to end-stage renal disease associated with renal barttin and ClC-K expression. The brothers had histories of polyhydramnios, prematurity, polyuria, deafness, and small body size. Laboratory findings showed hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and an increased urinary excretion of sodium, potassium and chloride, consistent with BS Type IV. Microscopic examination of renal tissue showed hyperplasia of cells at the juxtaglomerular apparatus with dilated atrophic tubules and tubulointerstitial fibrosis. A weak barttin signal related to CIC-K expression in the cytoplasm of tubule cells, but not the basement membrane, was noted. A sequence analysis of the BSND gene showed that the affected males were homozygous for a missense G47R mutation in exon 1 of BSND. These findings suggest that the G47R mutation results in a dramatic decrease in barttin expression, which appears to be related to the location of CIC-K being changed from the basement membrane to the cytoplasm in the tubule and might have varying effects on renal function associated with factors other than this gene.

Artificial neural network weights of residues for the serological specificities of HLA.

New human leucocyte antigen (HLA) alleles are assigned largely based on their sequence homologies due to lack of information on the serological reactivities. Artificial neural networks (ANNs) have been tested as a possible tool for helping to predict the serology of new alleles in the absence of serological information. However, an ANN analysis per se imparts no information regarding which residues are important in determining serological specificity. To address this issue, we extracted ANN weights of HLA residues. The ANN was trained using 139 HLA-A, 302 HLA-B and 136 HLA-DRB1 alleles, for which serological specificities were assigned in the 2004 Nomenclature Report. When the trained ANN was evaluated using alleles that were contained in the HLA Dictionary 2008 but had not been employed in the training set, the accuracy was 91% (29/32) for HLA-A, 91% (40/44) for HLA-B and 90% (9/10) for HLA-DR. Finally, ANN residue weights were extracted by summing the weights of directly connected ANN nodes. When we assessed the significance of the ANN residue weights by comparing our data with the results of epitope studies conducted by El-Awar and colleagues, we found that the ANN weights tended to be high at the epitopes described by El-Awar et al. Furthermore, the ANN weights extracted in this work could be used to explain ambiguous characteristics of serological specificities to some extent. Our data are thus considered to support the results of the epitope studies conducted by El-Awar and advance our understanding of the ambiguous serological specificities of some alleles.

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.

Measurement of fetal urine production to differentiate causes of increased amniotic fluid volume.

OBJECTIVES: In polyhydramnios, amniotic fluid (AF) volume can be increased not only as a result of increased fetal urine production, but also due to several other factors, including impairment of both fetal swallowing and gastrointestinal (GI) absorption of AF. Our aim was to evaluate whether measurement of the fetal urine production rate (UPR) can be used to differentiate the causes of increased AF volume. METHODS: This cross-sectional study included 54 pregnant women with an increased amniotic fluid index (AFI), defined as AFI > or = 18 cm, divided into two groups according to the presence of fetal anomalies that are associated with impairment of fetal swallowing or decreased GI absorption of AF (Group 1, n = 14) or the absence of fetal anomalies (Group 2, n = 40). The control group included 96 normal pregnancies with normal AFI (8 < or = AFI < 18 cm) (Group 3). Fetal UPR was obtained by serial bladder volume measurements (two to four times, with a median interval of 5 min between each) using the rotational method of Virtual Organ Computer-aided AnaLysis (VOCAL()) with three-dimensional ultrasound. To adjust for fetal weight (Wt) and gestational age (GA), UPR_Wt and UPR_SD were calculated using the following formulae: UPR_Wt = measured UPR/estimated fetal weight and UPR_SD = (measured UPR - mean UPR for each GA)/SD of UPR for each GA. RESULTS: The AFI was increased significantly in Groups 1 and 2 compared with Group 3. However, the median fetal UPR in Group 1 did not differ from that of Group 3, in contrast to the higher median fetal UPR in Group 2 compared with Groups 1 and 3; this difference remained significant after adjusting for GA and estimated fetal weight in terms of UPR_SD and UPR_Wt. In Groups 2 and 3, AFI and UPR had a positive correlation in terms of UPR, UPR_SD and UPR_Wt. CONCLUSIONS: Our findings that fetal UPR is significantly increased in cases with increased AFI without fetal anomalies, but not in those with increased AFI and fetal anomalies involving decreased GI absorption of AF, might be used to differentiate causes of increased AF volume. In the absence of fetal anomalies, AFI and fetal UPR correlate positively.