Endoplasmic reticulum aminopeptidase 1 polymorphism Ile276Met is associated with atopic dermatitis and affects the generation of an HLA-C associated antigenic epitope in vitro.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease of complex aetiology, with interactions between susceptibility genes and environmental factors. We have previously described a protective effect of the KIR2DS1 gene encoding the natural killer cell receptor, whose ligands are HLA-C molecules. Here, we found an association of HLA-C*05:01 allele with AD. KIR-HLA-C interactions are affected by peptides presented by HLA-C. The generation of these peptides is strongly influenced by endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2). Expression and activity of ERAP molecules depend on the polymorphisms of their genes. OBJECTIVE: Possible associations of several single nucleotide polymorphisms (SNPs) in the ERAP1 and ERAP2 genes with susceptibility to AD. METHODS: Peripheral blood DNA isolation from 318 patients and 549 controls. PCR-SSO or PCR-SSP for HLA-C typing; TaqMan Genotyping Assay for ERAP typing. RESULTS: Only one SNP in the ERAP1 gene, rs26618T>C, causing the amino acid change Ile276Met, had an association with AD. To gain insight on the functional role of this SNP, we produced recombinant variants differing only at position 276 (Ile or Met) and tested their aminopeptidase activity against a N-terminally extended precursor LIVDRPVTLV of the HLA-C*05:01 epitope IVDRPVTLV. Both ERAP1 variants were able to efficiently generate the epitope, although the 276Ile allotype was able to do this about 50% faster. Furthermore, both variants were quite inefficient in further degradation of the mature epitope. Finally, we found that the effect of 276Met on susceptibility to AD was seen only in KIR2DS1-negative individuals, not protected by this KIR. CONCLUSION: Associations of HLA-C*05:01 allele and rs26618T>C (Ile276Met) ERAP1 polymorphism with AD, and a significant difference between these two ERAP1 variants in their ability to generate an epitope for the HLA-C*05:01 molecule was found.

Genetic polymorphisms and expression of HLA-G and its receptors, KIR2DL4 and LILRB1, in non-small cell lung cancer.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule absent from most normal tissues but detected in many malignant tumors. It is recognized by cells of the immune system using LILRB1, KIR2DL4 and LILRB2 receptors. We attempted to find out whether some polymorphisms of HLA-G, LILRB1 and KIR2DL4 genes are associated with susceptibility to nonsmall cell lung cancer (NSCLC). Four polymorphisms in HLA-G, i.e. -964A>G (rs1632947), -725C>G>T (rs1233334), -716T>G (rs2249863) in the promoter, and a 14 base pair insertion/deletion (14 bp indel) in the 3'-untranslated region (3'UTR), and five in LILRB1 - 5651G>A (rs41308748) in intron 14, 5717C>T L622L (rs1061684), 5724G>A E625K (rs16985478), 5774 C>A P641P (rs41548213) in exon 15, and 5806C>T (rs8101240) in 3'UTR - as well as 9620 9A/10A (rs11410751) polymorphism in exon 7 of KIR2DL4 were typed using different laboratory techniques. Only one single nucleotide polymorphism (SNP) in HLA-G (-964A>G) and one in LILRB1 (5724G>A) were found to influence the risk of NSCLC. In addition, 5724G>A was associated with protection from tumor cell infiltration of regional lymph nodes. Most importantly, we detected HLA-G and LILRB1 expression in tumor specimens, but no correlation with genetic polymorphisms was observed. HLA-G and LILRB1 protein expression levels in tumor tissue were significantly correlated with tumor stage.

Parenting Children with Disorders of Sex Development (DSD): A Developmental Perspective Beyond Gender.

Advances in therapeutics for specific conditions have contributed to a categorical psychological approach to chronic diseases that affect children. Consensus statements and clinical guidelines recognize stress associated with disorders of sex development (DSD) for patients and their caregivers - yet much remains to be learned concerning the social adjustment, mental health, and quality of life of affected children and their families. We present preliminary data on the psychosocial comorbidities of caregivers of children with DSD, including stigma, isolation, stress, anxiety, and depressive symptomatology. Evidence is offered in support of individualized psychological approaches for families according to such variables as: 1) gender of the caregiver, 2) gender of the affected child and 3) presence of genital ambiguity at birth. Development of feasible, targeted interventions to ameliorate psychosocial comorbidities among caregivers is needed to optimize social adjustment, mental health, and health-related quality of life (HRQoL) for children with DSD.

Disorders of Sex Development (DSD): Networking and Standardization Considerations.

Syndromes resulting in Disorders of Sex Development (DSD) are individually rare. Historically, this fact has hindered both clinical research and the delivery of evidence-based care. Recognizing the need for advancement, members of European and North American medical societies produced policy statements, notably the Consensus Statement on Management of Intersex Disorders, which recognize that optimal healthcare in DSD requires multidisciplinary teams in conjunction with networking of treatment centers and continued development of patient registries. This paper summarizes efforts in Europe and the U.S. toward creating networks focused on expanding discovery and improving healthcare and quality of life outcomes in DSD. The objectives and function of registry-based networks (EuroDSD/I-DSD), learning collaboratives (DSD-net), clinical outcomes research (DSD-Life), and networking hybrids (DSD-TRN) are reviewed. Opportunities for, and barriers to standardization in research and care are highlighted in light of practical considerations, for example, limitations in reliably classifying anatomic phenotypes and gaps in behavioral health staffing resources. The role of patient-reported outcomes is considered, with emphasis on integrating patient perspectives, given findings of limited agreement in outcome ratings by healthcare providers and patients. Finally, the characteristics of clinical centers likely to deliver the highest quality outcomes are discussed.

Application of termite nest for adsorption of Cr(VI).

This work proposes the use of tree termite nest as an adsorbent for the reduction/removal of Cr(VI) present in aqueous solution. In laboratory experiments, adsorption of Cr(VI) was sensitive to pH in the range investigated (2-5), with maximum adsorption capacity achieved at pH 2 (3.70 ± 0.04 mg g(-1), representing 93.2% removal of Cr). The termite nest was characterized by off-line pyrolysis GC/MS (py-GC/MS), infrared spectroscopy (FTIR), and electron paramagnetic resonance spectroscopy (EPR). Pyrolysis of the adsorbent produced a complex mixture of aromatic compounds, including the guaiacyl and syringilic derivatives that are characteristic of lignocellulosic materials. Infrared spectroscopy revealed deprotonation of the carboxylic acid group of the biomass with increasing pH, which was associated with a decrease in the capacity for adsorption of Cr(VI). The EPR g-factor for the termite nest samples varied between 2.0037 and 2.0038, indicating the presence of organic free radicals that were responsible for the redox reaction. A second line with g-factor values of 1.9790, only observed for the samples after contact with Cr(VI) solutions at different pH values, was assigned to Cr(III)-Cr(III) exchange coupled pairs, which explained the capacity of the adsorbent to retain a large portion of the Cr(III) ions produced after reduction of Cr(VI) to Cr(III). Fixed-bed column experiments showed that the termite nest had a maximum adsorption capacity of 18.60 mg Cr g(-1), an adsorption efficiency varying between 60.8 and 97.4%, and a desorption efficiency varying between 54.5 and 91.4%, for three successive cycles. The adsorbent presented excellent performance in the removal of chromium under acidic conditions, with the advantage that it could be regenerated and reused.

The weight of communication: The Canadian Medical Association Journal's discourse on obesity.

In this exploratory analysis, I use a Burkean dramatist approach to investigate the relatively under-examined dynamics of how medical knowledge on obesity has changed outside of the American context. I examine how, over the past forty years, Canadian medical professionals have used the Canadian Medical Association Journal to generate a field of knowledge which organizes the ways in which obesity can be described, studied and treated. I argue that since the 1970s medical professionals have been increasingly interested in the relationship between obesity and a broadly defined social environment, and that this merger is rhetorically realized in the concept of the "obesogenic environment." I suggest that the process of engaging obesity has generated rhetoric that has often been resonant with the political ideologies expressed in health policy, but that can also create opportunities for the expression of alternative social goals.

Anomalous magnetic behavior of Sm0.8Ca0.2MnO3 nanoparticles.

Magnetic properties of compacted Sm0.8Ca0.2MnO3 (SCMO) particles with average particle size of 23-100 nm, prepared by the glycine-nitrate method, have been investigated. It was found that the relative volume of the ferromagnetic phase decreases with decreasing particle size. Curves of field cooled and zero filed cooled magnetization (M(ZFC)) exhibit a bifurcation just below the Curie temperature (T(c) approximately 55-64 K) for all particles studied. The field dependence of M(ZFC) peak follows de Almeida-Thouless line. Both features are characteristic of spin-glasses (SG). Measurements of ac-susceptibility in the temperature range 5-300 K and the frequency range f = 10 Hz-10 kHz show a sharp peak for both real and imaginary components in the vicinity of T(c), apparently attributed to the Hopkinson effect. A second small peak is seemingly associated with antiferromagnetic or ferrimagnetic ordering. Though, for smaller particles both peaks depend on frequency, no shift to higher temperatures with increasing f, characteristic for SG systems, was observed. The dissimilarity in magnetic properties and dynamic characteristics observed for SCMO and for La0.8Ca0.2MnO3 nanoparticles is discussed, taking into account a difference in the width of the band and the strength of double exchange and interparticle interactions.

Nanometer size effect on structural and magnetic properties of La0.2Ca0.8MnO3.

Structural and magnetic properties of La0.2Ca0.8MnO3 nanoparticles with average size of 15-37 nm, prepared by the glycine-nitrate method, have been studied. Synchrotron experiments performed in the temperature range of 80-300 K have shown that a structural transition from room temperature orthorhombic Pnma to monoclinic P2(1)/m space group, associated with orbital ordering, occurs below 200 K in the studied particles. This transition observed for the largest particles of 37 nm is very close to that of bulk, as seen by similar temperature variation of lattice parameters and orthorhombic strain. The transition is highly suppressed for smaller 15 nm particles. Horizontal and vertical shifts of magnetic hysteresis loops (M(Shift) and H(EB)), displayed in a field cooled process, indicate size dependent exchange bias effect. It is also shown that M(shift) and H(EB), as well as the remanent magnetization M(r) and coercive field H(c) at low temperatures, exhibit a non-monotonic size dependence for particles around 23 nm. These effects may be attributed to the changes in uncompensated spins at the surface, anisotropy or alternatively to a transition from a multi-domain to the single domain state.

Sedative effects of essential oils obtained from Baccharis uncinella.

CONTEXT: Essential oils (EOs) have been reported to possess pharmacological properties, of which those related to the central nervous system have been especially attributed to mono- and sesquiterpenes. Baccharis uncinella DC. (Asteraceae) is used by the Laklaño Indians (Santa Catarina, Brazil) for sedative purposes. Interestingly, the species does not seem to be used medicinally elsewhere in Brazil. OBJECTIVE: This study was designed to compare the composition and sedative properties of B. uncinella EOs obtained closer (BU-SC) and farther (BU-PR) to the Laklaño Indian Reserve. MATERIALS AND METHODS: BU-SC and BU-PR obtained by hydrodistillation were analyzed by CG-MS. Mice treated with BU-SC and BU-PR (50 and 100 mg/kg) were evaluated regarding pentobarbital-induced sleeping time, body temperature, and locomotion. RESULTS: BU-SC presents a higher monoterpene/sesquitherpene ratio (0.31); α-pinene (6.42%), limonene (7.21%), caryophyllene (26.13%), spathulenol (13.39%) and caryophyllene oxide (13.26%) were identified as major components. BU-PR presents a low monoterpene/sesquitepene ratio (0.004); spathulenol (32.93%), caryophyllene oxide (27.78%), viridiflorol (5.29%) and α-cadinol (2.42%) were identified as the main components. Both samples significantly (p < 0.05, ANOVA) decreased locomotion and body temperature, as well as increased sleeping time. The hypnotic activity was sensitive to the differences in monoterpene composition. CONCLUSIONS: In comparison with a sample collected in Paraná State, B. uncinella EO collected closer to the Laklaño Indians possess a composition that better justifies the claimed sedative properties. The study confirms the value of traditional information to guide bioactivity assessment in medicinal plants, and gives notice to the ecological factors that can interfere with the conclusions of such assessments.

Evaluation of clinically relevant operating conditions for left ventricular assist device investigations.

Standardized boundary conditions for flow rate and pressure difference are currently not available for the development and certification process of ventricular assist devices. Thus, interdisciplinary studies lack comparability and quantitative assessment. Universally valid boundary conditions could be used for the application of numerical and experimental investigations and the approval procedure of ventricular assist devices. In order to define such boundaries, physiological data from INCOR® patients were evaluated. A total of 599 out of possible 627 ventricular assist device patients were analyzed regarding their cardiac demands of flow rate and pressure head. An analysis of long-term data was performed, in order to provide respective, static mean values for benchmark testing. Furthermore, the short-term data of 188 patients delivered field data-based dynamic flow and pressure curves. The results of the study revealed physiologically reasonable boundary conditions, which can be applied in numerical or experimental investigations of ventricular assist devices. For steady flow analysis, single values for flow rate (4.46 L/min) and pressure head (62 mmHg) are suggested. For the support of pulsatile and unsteady flow studies, seven typical patients and one representative dynamic curve for flow rate and pressure head are proposed.The standardized results provided in this article, can be used in favor of interdisciplinary comparability of future numerical computations or in vitro ventricular assist device tests in research, development, and approval.

Association of the HLA-G gene polymorphism with multiple sclerosis in a Polish population.

Summary In this study, three polymorphic sites in the HLA-G gene: -725C>G>T, -716T>G and 14bp(indel) were genotyped. Significant differences were found between patients and controls in the alleles and genotypes for -725C>G>T and in three-point haplotypes. We observed also a significant difference in the age of disease onset between patients positive and negative for 14bp(ins). The results suggest that single nucleotide polymorphisms in the promoter of the HLA-G gene (mainly -725C>G>T), and 14bp(indel), or some genetic marker in tight linkage disequilibrium with them are associated with multiple sclerosis.

Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women.

CONTEXT: Recent interventional studies indicate that post-menopausal hormone replacement therapy is associated with an increased risk of cardiovascular mortality and breast cancer. Isoflavones, a class of plant estrogens, have structural similarities to estradiol. Hence, isoflavones may exert beneficial estrogenic health effects in postmenopausal women with fewer adverse effects. OBJECTIVE: To evaluate the effect of high-dose isoflavones on self-reported quality of life (QOL), cognition, lipoproteins and androgen status in post-menopausal women. DESIGN AND SUBJECTS: Double-blind, randomized, placebo-controlled, 12-week trial of 93 healthy, ambulatory, post-menopausal women (mean age 56 yr). The study was conducted at a tertiary care center in the United States. INTERVENTION: Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). Both soy and the placebo were provided in the form of a powder to be mixed with beverages. MAIN OUTCOME MEASURES: QOL was judged by the Menopause-specific Quality of Life (MENQOL) questionnaire while cognitive function was assessed with standard instruments. Total, free, and bioavailable testosterone, gonadotropins, SHBG, and fasting lipids were measured. RESULTS: Eighty-four women (90%) completed the study (active=38, placebo=46). There was a significant improvement in all 4 QOL subscales (vasomotor, psychosexual, physical, and sexual) among the women taking isoflavones, while no changes were seen in the placebo group. No significant changes in cognition, serum androgens or plasma lipids were seen within any of the groups. However, at the end of the study, a group-by-time interaction was observed such that total testosterone and HDL levels were significantly lower in the isoflavones compared to placebo groups. CONCLUSION: High-dose isoflavones is associated with improved QOL among women who have become menopausal recently. Hence, the timing of isoflavone supplementation with regards to the onset of menopause appears to be important. The use of isoflavones, as an alternative to estrogen therapy, may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms.

Frequencies of killer immunoglobulin-like receptor genotypes influence susceptibility to spontaneous abortion.

Natural killer (NK) cells are the most abundant lymphocyte population in the decidua. These cells express killer immunoglobulin-like receptors (KIRs), which upon recognition of HLA class I molecules on trophoblasts may either stimulate NK cells (activating KIRs) or inhibit them (inhibitory KIRs) to produce soluble factors necessary for the maintenance of pregnancy. KIR genes exhibit extensive haplotype polymorphism; individuals differ in both the number and kind (activating vs. inhibitory) of KIR genes. This polymorphism affects NK cell reactivity and susceptibility to diseases, including gynecological disorders. Therefore we KIR-genotyped 149 spontaneously aborting women and 117 control multiparae (at least 2 healthy-born children). Several genotypes (i.e. combinations of various KIR genes) were differently distributed among the patients and control subjects. Differences were observed in the numbers and the ratios of activating to inhibitory KIRs between patients and healthy women: (i) genotypes containing 6 activating KIR genes were less frequent and those containing 6 inhibitory KIR genes were more frequent in patients than in control subjects, and (ii) an excess of inhibitory KIRs (activating-to-inhibitory KIR gene ratios of 0.33 to 0.83) was associated with miscarriage, whereas ratios close to equilibrium (0.86-1.25) seemed to be protective. In addition, the results suggest for the first time that sporadic and recurrent spontaneous abortions as well as miscarriage in the presence or absence of autoantibodies may have different KIR genotypic backgrounds.

Distribution of killer cell immunoglobulin-like receptor genes in Poles.

Killer cell immunoglobulin-like receptors (KIRs) present on natural killer cells and minor subpopulations of T cells recognize class I human leucocyte antigen (HLA) molecules on the surface of target cells. Humans differ by the presence or absence of some KIR genes on their chromosomes. As KIRs are important for the outcome of tissue transplantation (particularly for haematopoietic stem cell transplantation) and possibly for pregnancy and autoimmune diseases, knowledge of the KIR gene distribution in a given human population is of practical value. Therefore, we tested 363 healthy individuals from Western Poland for the presence or absence of KIR genes. Results are compared with those published for other human populations. KIR gene frequencies in Poles are close to these in other Caucasoids but different from those in Asian and African populations, and particularly distant from those in Australian Aborigines.

Distribution of the CTLA-4 single nucleotide polymorphisms CT60G>A and +49A>G in psoriasis vulgaris patients and control individuals from a Polish Caucasian population.

Psoriasis vulgaris is a multifactorial disease with an autoimmune component, and T lymphocytes seem to be involved in its aetiology. CTLA-4 molecule is an important down-regulator of T-lymphocyte activation, and several polymorphisms of the CTLA-4 gene were found to be associated with some autoimmune diseases. We examined whether single nucleotide polymorphisms (SNPs) in the CTLA-4 gene, CT60A>G and +49A>G, are associated with psoriasis vulgaris. Alleles of these two SNPs were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Both the CT60G>A and the +49A>G alleles and genotypes were distributed similarly in patients and controls. Although the two SNPs studied here in Poles were in linkage disequilibrium, all four possible two-locus haplotypes were found, one of them rare; of the remaining three, the haplotype +49G, CT60G was significantly (P = 0.019, OR = 0.58, 95%CI = 0.37-0.91) less frequent in the patient group with disease onset between the ages of 21 and 40 years than in controls and the other patient groups, whereas the frequencies of the other haplotypes were similar in patients and controls. To the authors' knowledge, this is the first study on CTLA-4 CT60 allele frequencies in psoriasis.

Preliminary report: Surgical outcomes following genitoplasty in children with moderate to severe genital atypia.

INTRODUCTION: Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. OBJECTIVE: The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. STUDY DESIGN: This 11-site, prospective study included children aged ≤2 years, with Prader 3-5 or Quigley 3-6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. RESULTS: Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) (Summary Figure). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. DISCUSSION: In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. CONCLUSION: In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management.

Local microscopic properties and annealing effect of Rb0.85Fe1.9Se2 single crystals.

Investigation of mesoscopically phase-separated Rb0.85Fe1.9Se2 single crystals has been performed and two iron sites: nonmagnetic and magnetic ones, were observed by Mössbauer spectroscopy. The softening of the nonmagnetic one, having clearly more soft dynamics, was found to be gained further by the annealing of the single crystals at phase separation temperature, T p, leading to the reduction of size of initially separated domains and their more homogenous distribution in the tetragonal matrix of the studied sample. The magnetic Fe sites of Rb0.85Fe1.9Se2 show strong magnetic texture, indicating the perpendicular to the ab-plane orientation of the iron magnetic moments. It was found that the annealing at T p causes a systematic decrease of the isomer shift of the doublet by 0.02(1) mm s-1.

Prospective assessment of cosmesis before and after genital surgery.

INTRODUCTION: Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center. OBJECTIVE: The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery. STUDY DESIGN: This prospective, observational study included children aged <2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty. RESULTS: Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P < 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings. DISCUSSION: This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life. CONCLUSION: In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.

Possible association of cytotoxic T-lymphocyte antigen 4 gene promoter single nucleotide polymorphism with acute rejection of allogeneic kidney transplant.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) molecule is an important inhibitor of T-lymphocyte response. Polymorphisms in the CTLA-4 gene have been described to be associated with numerous autoimmune diseases. However, similar studies in solid organ transplantation have been scarce. Therefore, we examined the distribution of three single nucleotide dimorphisms, namely, -1147T/C, -318C/T, and +49A/G, in two groups of allogeneic kidney graft recipients: (1) those with at least one acute rejection episode ("rejectors"; n = 38) and (2) those with no signs of acute rejection ("nonrejectors"; n = 53). Allele frequencies in both groups of patients were similar in two positions, -1147T/C and +49A/G. However, rejectors showed slight differences from nonrejectors for allele and genotype frequencies in position -318. The -318T allele was two times less frequent among rejectors than nonrejectors, a difference that was close to statistical significance (P = .039; P corrected = .0583), and may reach it when greater numbers of patients are tested.