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To compare baseline mental health symptoms and gender affirmation between Black/Latine versus White transgender/nonbinary youth (BLTY vs. WTY) and examine relationships between gender affirmation and mental health symptoms, and whether associations differed by race/ethnicity subgroup. Baseline data were analyzed from the gender-affirming hormone cohort of the Trans Youth Care United States Study—a 4-clinic site, observational study. Mental health symptoms assessed included depression, suicidality, and anxiety. Gender affirmation measures included the parental acceptance subscale from the perceived Parental Attitudes of Gender Expansiveness Scale-Youth Report; non-affirmation, internalized transphobia, and community connectedness subscales from the Gender Minority Stress and Resilience Measure–Adolescent; and self-reported living full time in affirmed gender. Fisher exact tests and independent sample t tests compared mental health symptoms and gender affirmation between subgroups. Logistic regression analyses evaluated associations between gender affirmation and mental health symptoms. Interaction analyses assessed differences in associations between subgroups. The sample (mean age 16 years, range 12–20 years) included 92 BLTY (35%) and 170 WTY (65%). Subgroups had comparable prevalence of depression and anxiety symptoms. WTY had higher prevalence of lifetime suicidality (73% vs. 59%; p =.02). There were no differences in gender affirmation. Among the whole sample, higher parental acceptance decreased odds of depression symptoms. Not living in affirmed gender increased odds of depression symptoms. Higher non-affirmation and internalized transphobia increased odds of depression and anxiety symptoms and suicidality. Associations did not vary by subgroup. BLTY and WTY had comparable mental health symptoms. For both subgroups, gender affirmation decreased odds of those symptoms. [ABSTRACT FROM AUTHOR]

Prior studies have identified a significant relationship between internalized transphobia and poor mental health among transgender and gender-diverse (TGD) adults; however, this relationship has not been extensively examined among youth. Further, little research has sought to explore protective factors, such as identity pride, and their influence on this relationship. We examined the association between internalized transphobia and depression and anxiety symptoms among TGD youth and explored the moderating role of gender identity pride on these associations. Participants were 315 TGD youth ages 12–20 years (mean = 16; standard deviation = 1.89) seeking gender-affirming hormone treatment at one of four major pediatric hospitals across the United States. At the time of enrollment, participants were naïve to gender-affirming hormone treatment. Participants self-reported mental health, internalized transphobia, and identity pride. Multiple regression models were used with depression and anxiety symptoms as outcomes and age, designated sex at birth, and perceived parental support included as covariates. Greater internalized transphobia was associated with greater depressive symptoms, and gender identity pride moderated this relationship, such that greater gender identity pride was associated with fewer depressive symptoms. Greater internalized transphobia was significantly associated with greater anxiety symptoms; no moderation effect was observed for this relationship. Gender identity pride influenced mental health symptoms for youth experiencing internalized transphobia and represents a potential key protective factor. These results support efforts to further develop, test, and implement clinical inventions to bolster identity pride for TGD youth. [ABSTRACT FROM AUTHOR]

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Caregivers of female infants with congenital adrenal hyperplasia (CAH) often confront complex medical decision-making (e.g., early feminizing genitoplasty). This study aimed to evaluate the relevant medical decisions and subsequent decisional regret of caregivers following their child's genitoplasty. Caregivers (N = 55) were recruited from multidisciplinary treatment programs for participation in a longitudinal study. Qualitative data was collected at 6–12 months following feminizing genitoplasty to evaluate caregiver-reported decision points across their child's treatment. Quantitative exploratory analysis evaluated pre-operative predictors of subsequent decisional regret. When prompted about their decision-making and potential regret, most caregivers (n = 32, 80%) reported that their daughter's genital surgery was their primary medical decision. Specific themes regarding genital surgery included the timing and type of surgery. Most caregivers reported no decisional regret (62%), with 38% reporting some level of regret. Greater pre-operative illness uncertainty predicted heightened decisional regret at follow-up, p =.001. Two-thirds of caregivers of female infants with CAH reported not regretting their decision-making. Nevertheless, over one-third of caregivers reported some level of regret, suggesting the need for improvements in shared decision-making processes. Many, but not all, families reported that this regret was related to surgical decision-making. Reducing caregiver illness uncertainty (e.g., providing clear information to families) may increase their satisfaction with decision-making. Further research is needed to determine how the evolving care practices surrounding early genitoplasty will impact families. [Display omitted] [ABSTRACT FROM AUTHOR]

Transgender/gender-diverse (TGD) youth are treated with gonadotropin-releasing hormone agonists (GnRHas) to halt endogenous puberty and prevent the development of secondary sex characteristics discordant with their gender identity. This treatment may have significant impact on growth and height velocity (HV). Participants were recruited prior to GnRHa initiation from four gender specialty clinics in the U.S. Anthropometric, laboratory, and Tanner-stage data were abstracted from medical records. Fifty-five TGD youth (47% designated male at birth) with a mean ± standard deviation age of 11.5 ± 1.2 years were included in the analysis. HV in the first year of GnRHa use was median (interquartile range) 5.1 (3.7–5.6) cm/year. Later Tanner stage at GnRHa initiation was associated with lower HV: 5.3 (4.4–5.6) cm/year for Tanner stage II, 4.4 (3.3–6.0) cm/year for Tanner stage III, and 1.6 (1.5–2.9) cm/year for Tanner stage IV (p =.001). When controlled for age, there was not a significant difference in mean HV between TGD youth and prepubertal youth; however, when stratified by Tanner stage individuals starting GnRHa at Tanner stage IV had an HV below that of prepubertal youth, 1.6 (1.5–2.9) versus 6.1 (4.3–6.5) cm/year, p =.006. Overall, TGD youth treated with GnRHa have HV similar to that of prepubertal children, but TGD youth who start GnRHa later in puberty have an HV below the prepubertal range. Ongoing follow-up of this cohort will determine the impact of GnRHa treatment on adult height. [ABSTRACT FROM AUTHOR]

• Men and women have different lipoprotein subclasses. • Men have lipoprotein subtype profiles that are more atherogenic than those of women. • Transmasculine adolescents have lipoprotein subtypes that are like cisgender males. Differences in lipoprotein-particle subclasses between men and women start in puberty and narrow after menopause, suggesting a role for sex steroids. In this cross-sectional cohort study, we examined lipoprotein subtype profiles in transmasculine adolescents treated with testosterone. Transmasculine adolescents (n = 17) had lipoprotein profiles that were similar to those of cisgender males (n = 33) and more atherogenic than those of cisgender females (n = 32), with higher concentrations of small low-density lipoprotein (LDL) particles (435 ± 222 nmol/L vs. 244 ± 163 nmol/L, p = 0.008) and lower concentrations of large high-density lipoprotein (HDL) particles (1.5 ± 1.3 μmol/L vs 2.7 ± 1.2 μmol/L, p = 0.003) when compared to cisgender females. Thus, testosterone appears to be a major contributor to differences in lipoprotein profiles, a surrogate for cardiovascular disease risk, between cisgender women and both transgender and cisgender men. [ABSTRACT FROM AUTHOR]

Experiments performed by various groups confirm the validity of the proteolysis model of Notch signaling as well as the roles of proteolysis and trafficking of Notch during receptor maturation. In these studies, two molecules that undergo similar patterns of proteolysis were examined. These included the beta-amyloid precursor protein and the sterol regulatory element binding protein.

This study aimed to characterize two developmental cohorts of transgender and nonbinary youth enrolled in the Trans Youth Care Network Study and describe their gender identity–related milestones and baseline mental health and psychosocial functioning. Trans Youth Care participants were recruited from four pediatric academic medical centers in the U.S. before initiating medical treatment for gender dysphoria either with gonadotropin-releasing hormone agonists (GnRHa) or gender-affirming hormones (GAH). GnRHa cohort data were collected from youth and a parent; GAH cohort data were collected from youth only. A total of 95 youth were enrolled in the GnRHa cohort. Mean age was 11.22 years (standard deviation = 1.46), and the majority were white (52.6%) and designated male at birth (51.6%). Elevated depression symptoms were endorsed by 28.6% of GnRHa cohort youth, and 22.1% endorsed clinically significant anxiety. Approximately one fourth (23.6%) endorsed lifetime suicidal ideation, with 7.9% reporting a past suicide attempt. A total of 316 youth were enrolled in the GAH cohort. The mean age was 16.0 years (standard deviation = 1.88), and the majority were white (62%) and designated female at birth (64.9%). Elevated depression symptoms were endorsed by 51.3% of the GAH cohort, and 57.3% endorsed clinically significant anxiety. Two-thirds (66.6%) endorsed lifetime suicidal ideation, with 24.6% reporting a past suicide attempt. Life satisfaction was lower among both cohorts compared with population-based norms. GnRHa cohort youth appear to be functioning better from a psychosocial standpoint than GAH cohort youth, pointing to possible benefits of accessing gender-affirming treatment earlier in life. [ABSTRACT FROM AUTHOR]

Disorders/differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. While there remains controversy around the traditionally binary concept of sex, most patients with DSD are reared either male or female depending on their genetic sex, gonadal sex, genital phenotype and status of their internal genital tract. This study uses prospective data from 12 institutions across the United States that specialize in DSD care. We focused on patients raised female. Eligible patients had moderate to severe genital atypia (defined as Prader score >2), were ≤2 years of age at entry, and had no prior genitoplasty. The aim of this study is to describe early post operative complications for young patients undergoing modern approaches to feminizing genitoplasty. Of the 91 participants in the cohort, 57 (62%) were reared female. The majority had congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (n = 52), 1 had ovo-testicular syndrome, 2 had mixed gonadal dysgenesis and 2 had partial androgen insensitivity syndrome (PAIS). Of the 50 participants who received early genitoplasty, 43 (86%) had follow-up at 6–12 months post-surgery. Thirty-two participants (64%) received a clitoroplasty, 31 (62%) partial urogenital mobilization and 4 (8%) total urogenital sinus mobilization. Eighteen percent (9/50) experienced post-surgical complications with 7 (14%) being rated as Clavien-Dindo grade III. Both parents and surgeons reported improved satisfaction with genital appearance of participants following surgery compared to baseline. This information on post-operative complications associated with contemporary approaches to feminizing genitoplasty performed in young children will help guide families when making decisions about whether or not to proceed with surgery for female patients with moderate to severe genital atypia. Summary Figure River diagram of mother's cosemsis rating over time in DSD patients undergoing early feminizing genitoplasty Summary Figure [ABSTRACT FROM AUTHOR]

The purpose of this study was to describe baseline physical and laboratory characteristics of participants in the largest prospective study of transgender and gender-diverse (TGD) youth in the United States. Participants were recruited from four clinics which specialize in the care of TGD youth before starting either GnRH analogs for pubertal suppression or gender-affirming hormone treatment. Anthropometric and laboratory measurements were abstracted from the medical chart. Baseline characteristics including height, weight, body mass index, blood pressure, and laboratory measurements were compared with those of age-matched National Health and Nutritional Examination Survey comparison group. Seventy-eight TGD youth with a median age of 11 years (range 8–14 years) were recruited before pubertal suppression, of whom 41 (53%) were designated male at birth, and 296 participants with a median age of 16 years (range 12–20 years) were recruited before beginning gender-affirming hormones, of whom 99 (33%) were designated male at birth. The mean high-density lipoprotein cholesterol was lower in the study participants when compared with that of National Health and Nutritional Examination Survey participants (50.6 ± 12.3 mg/dL vs. 53.3 ± 13.3 mg/dL, p =.001). Otherwise, the study cohorts were similar in terms of body mass index, proportion of overweight and obesity, blood pressure, and baseline laboratory variables. Before starting gender-affirming treatment, TGD youth are physiologically similar to the general population of children and adolescents in the United States, with the exception of slightly lower high-density lipoprotein cholesterol. Evaluation of this cohort over time will define the physiological effects of pubertal blockade and gender-affirming hormone treatment. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence has suggested a relationship between post-traumatic stress disorder (PTSD) and neurodegenerative disorder, such as Alzheimer disease. The association between PTSD and Parkinson disease (PD), however, remains unclear.Method: Using the Taiwan National Health Insurance Research Database, 7,280 subjects (1,456 patients aged ≥45 years with PTSD and 5,824 age-/sex-matched individuals without PTSD) were enrolled between 2002 and 2009 and followed to the end of 2011. Subjects who developed PD during the follow-up period were identified.Results: An increased risk of developing PD was found in patients with PTSD (Wald χ2 = 12.061, hazard ratio [HR]: 3.46, 95% confidence interval [CI]: 1.72-6.96) compared with individuals without PTSD, after adjusting for demographic data and medical and psychiatric comorbidities. The sensitivity tests after excluding the first year observation (Wald χ2 = 7.948, HR: 3.01, 95% CI: 1.40-6.46) and the first 3-year observation (Wald χ2 = 5.099, HR: 3.07, 95% CI: 1.16-8.15) were consistent.Conclusions: Patients with PTSD had an elevated risk of developing PD in later life. Further studies would be required to clarify the exact pathophysiology between PTSD and PD and to investigate whether the prompt intervention for PTSD may reduce this risk. [ABSTRACT FROM AUTHOR]

Lipocalin-2 (Lcn2; also known as neutrophil gelatinase associated lipocalin, NGAL) levels are increased in obesity and diabetes and associate with insulin resistance. Correlations exist between Lcn2 levels and various forms or stages of heart failure. Insulin resistance and autophagy both play well-established roles in cardiomyopathy. However, little is known about the impact of Lcn2 on insulin signaling in cardiomyocytes. In this study, we treated H9c2 cells with recombinant Lcn2 for 1 h followed by dose- and time-dependent insulin treatment and found that Lcn2 attenuated insulin signaling assessed via phosphorylation of Akt and p70S6K. We used multiple assays to demonstrate that Lcn2 reduced autophagic flux. First, Lcn2 reduced pULK1 S555, increased pULK1 S757 and reduced LC3-II levels determined by Western blotting. We validated the use of DQ-BSA to assess autolysosomal protein degradation and this together with MagicRed cathepsin B assay indicated that Lcn2 reduced lysosomal degradative activity. Furthermore, we generated H9c2 cells stably expressing tandem fluorescent RFP/GFP-LC3 and this approach verified that Lcn2 decreased autophagic flux. We also created an autophagy-deficient H9c2 cell model by overexpressing a dominant-negative Atg5 mutant and found that reduced autophagy levels also induced insulin resistance. Adding rapamycin after Lcn2 could stimulate autophagy and recover insulin sensitivity. In conclusion, our study indicated that acute Lcn2 treatment caused insulin resistance and use of gain and loss of function approaches elucidated a causative link between autophagy inhibition and regulation of insulin sensitivity by Lcn2. [ABSTRACT FROM AUTHOR]

Purpose Cloacal exstrophy is associated with multiple comorbidities that affect growth. This report describes long-term growth outcomes in a large cohort of patients with cloacal exstrophy and explores associated comorbidities. Methods Records of 71 patients with cloacal exstrophy who were treated between 1974 and 2015 were reviewed, and 62 patients with growth data from 2 to 20 years of age were included. Genetic sex, gender of rearing, and all heights, weights, and comorbidities were noted for each patient. Height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, and BMIZ) were determined using US Centers for Disease Control 2000 growth data, and average patient z-scores were calculated. Results There were 904 height and 1301 weight measurements available for 62 patients. 31 were genetically 46,XY, 21 of whom underwent gonadectomy in infancy and were raised female. 46,XX patients, 46,XY male patients, and 46,XY female patients all had median HAZ and WAZ substantially lower than the general population, with median HAZ less than - 2, while maintaining normal BMIZ. Short bowel syndrome and enterocystoplasty with intestine were associated with lower z-scores for all parameters. Conclusions Patients with cloacal exstrophy have significant multifactorial long-term growth failure. These benchmark data can be used to further optimize management. Level of evidence: 2b [ABSTRACT FROM AUTHOR]

Surgical intervention in youth with differences of sex development (DSD) is a controversial topic. Historically, evidence suggests that genital surgery in DSD is associated with mixed patient satisfaction. However, less is known about surgical outcomes under therapeutic advancements in the past several decades. The purpose of the current study is to provide an updated and empirical qualitative examination of the surgical experiences and responses to care of adolescents and young adults (AYA) with DSD in order to fill this gap in the literature and inform patient care. Qualitative interviews were conducted with 37 AYA (ages 12–26) with DSD. Interviews were transcribed, coded, and analyzed thematically. Three major themes were identified: 1) knowledge related to surgery; 2) surgical and medical experience; and 3) psychosocial factors related to surgery. Results demonstrated that most AYA were not involved in the decision to pursue surgery and were observed to have varying levels of knowledge regarding their surgeries. Most participants in the current study had received a DSD-related surgery and the majority described having positive surgical experiences and few regrets. Nonetheless, AYA described both medical and psychosocial challenges related to their surgeries and recoveries and offered feedback on ways to improve the surgical process. The current study provides a qualitative examination of the surgical experiences of 37 AYA with DSD. Findings highlight the importance of regular and ongoing communication with providers to improve knowledge related to surgery during the decision-making process as well as after surgical intervention. Results underscore the benefits of multidisciplinary teams and the value of patient handouts and decision aids in assisting AYA in the decision to pursue surgical intervention. Other specific recommendations for providers include increased patient privacy during genital exams, greater emphasis on psychoeducation and pain management strategies, and the use of behavioral health services to assist with challenges and social support. The decision to pursue surgical intervention in youth with DSD remains a complex and controversial issue, and more information regarding patients' perspectives on surgery is needed. The current study provides novel insights into patient experiences of surgical intervention and highlights the need for psychosocial support throughout the shared decision-making process. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Pathophysiologically, Guillain–Barré syndrome is divided into demyelinating and axonal subtypes. Recent studies have shown that serial nerve conduction studies (NCSs) are required to differentiate a demyelination–remyelination pathophysiology from one with axonal nodal reversible conduction failure. Cases with an overlap of pharyngeal–cervical–brachial weakness and Fisher syndrome (PCB/FS) are uncommon; the NCS findings of such cases have not been well described and the evolution of the NCS findings has not been previously studied. We describe the clinical features and serial NCS findings of a patient with PCB/FS. The evolution of abnormalities in NCS reflected a clinical pattern of weakness that progressed from the top of the body and descended toward the legs, and terminated before reaching the legs. The amplitudes of motor and sensory potentials were decreased, as is consistent with acute motor-sensory axonal neuropathy. However, the amplitudes recovered without the appearance of dispersed potentials seen in remyelination, implicating the pathophysiology of nodal reversible conduction failure. Together with the electrophysiological evidence of the pathophysiology of nodal reversible conduction failure in previously reported PCB patients and FS patients, our case suggests that PCB, FS and PCB/FS fall in a continuous spectrum with axonal GBS subtypes. [Copyright &y& Elsevier]

Abstract: GNRH1, the human gene that gives rise to GnRH, has long been an obvious candidate gene for idiopathic hypogonadotropic hypogonadism, particularly because the hpg mouse, a mouse model of isolated hypogonadotropic hypogonadism, carries a deletion that disrupts Gnrh1. In 2009, 25years after the sequence of human GNRH1 was initially determined, two groups independently reported homozygous frameshift mutations in GNRH1 in patients with idiopathic hypogonadotropic hypogonadism. In two additional families, heterozygous GNRH1 mutations segregated with reproductive disorders. In the first family, the mutation occurred alone in five female subjects with idiopathic hypogonadotropic hypogonadism, whereas in the second it co-existed with a mutation in NR0B1/DAX1 in two female subjects with delayed puberty. While hemizygous mutations the X-linked NR0B1 are a well-known cause of hypogonadotropic hypogonadism and adrenal hypoplasia in male patients, heterozygous female carriers are generally asymptomatic. Thus, mutations in GNRH1 have been associated with both mild and severe forms of GnRH deficiency, and may work in combination with other gene mutations to produce GnRH-deficient phenotypes. [Copyright &y& Elsevier]

Abstract: Previous studies have shown that the overexpression of tropomyosins leads to isoform-specific alterations in the morphology of subcellular compartments in neuronal cells. Here we have examined the role of the most abundant set of isoforms from the γ-Tm gene by knocking out the alternatively spliced C-terminal exon 9d. Despite the widespread location of exon 9d-containing isoforms, mice were healthy and viable. Compensation by products containing the C-terminal exon 9c was seen in the adult brain. While neurons from these mice show a mild phenotype at one day in culture, neurons revealed a significant morphological alteration with an increase in the branching of dendrites and axons after four days in culture. Our data suggest that this effect is mediated via altered stability of actin filaments in the growth cones. We conclude that exon 9d-containing isoforms are not essential for survival of neuronal cells and that isoform choice from the γ-Tm gene is flexible in the brain. Although functional redundancy does not exist between tropomyosin genes, these results suggest that significant redundancy exists between products from the same gene. [Copyright &y& Elsevier]

Abstract: The reproductive phenotypes of nearly two dozen patients with mutations in GPR54 have been reported, as have the phenotypes of four mouse lines mutant for Gpr54 and two lines mutant for Kiss1. These phenotypes demonstrate that kisspeptin/Gpr54 function is required at all phases of the life cycle when the secretion of gonadotropin-releasing hormone (GnRH) is robust. Furthermore, there is phenotypic variability ranging from severe hypogonadism to partial sexual development. Collectively, these findings suggest that kisspeptin and Gpr54 serve as an essential conduit for relaying developmental information to the GnRH neuron. [Copyright &y& Elsevier]

Abstract: The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent. [Copyright &y& Elsevier]

The complexity of biological membranes has motivated the development of a wide variety of simpler model systems whose size, geometry, and composition can be tailored with great precision. Approaches highlighted in this review are illustrated in Figure 1 including vesicles, supported bilayers, and hybrid membrane systems. These have been used to study problems ranging from phase behavior to membrane fusion. Experimental membrane models continue to advance in complexity with respect to architecture, size, and composition, as do computer simulations of their properties and dynamics. Analytical techniques such as imaging secondary ion mass spectrometry have also been developed and refined to give increasing spatial resolution and information content on membrane composition and dynamics. [Copyright &y& Elsevier]

Suicidal behavior and different mood states of bipolar I disorder (BD) have been shown to be associated with dysregulated proinflammatory cytokines. Only a few studies have examined the association between inflammation and SB in BD, and the association between proinflammatory cytokines, SB, and cognitive deficits in patients with BD remains unclear. 77 patients with BD and 61 age-/sex-matched healthy controls were recruited. Patients were divided into two groups: with suicidal ideation (SI; n = 21) and no SI (n = 56). SI was defined by a score of ≥1 in item 10 of Montgomery Åsberg Depression Rating Scale. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task. Patients with SI had higher levels of sTNF-αR1 than those without SI and the controls (p =.004). BD patients with or without a history of suicide attempt had higher levels of CRP than the controls. SI was associated with serum levels of sTNF-αR1 and IL-6sR, even after additionally controlling for working memory and inhibitory control (p <.05). This study indicates that serum levels of sTNF-αR1 have distinct differences between BD patients with or without SI, and our findings strengthen the hypothesis of a link between suicidal behavior and neuro-inflammation pathophysiology in BD. • BD patients with suicidal ideation (SI) had higher serum levels of sTNF-αR1 than controls and patients without SI. • BD patients with/without history of suicide attempt had higher serum levels of CRP. • Serum levels of sTNF-αR1 and sIL-6R were associated with SI in outpatients with BD. • Proinflammatory cytokines may play an important role in the identification of suicide risk among patients with BD. [ABSTRACT FROM AUTHOR]

Summary Introduction A central ethical dilemma in management of the patient with a disorder of sex development (DSD) is the potential conflict between respect for the fundamental right of the child for physical and emotional integrity and self-determination, and the right of parents to serve as surrogate decision-makers and act in their child's best interest. Methods Over the past 2 years we have encountered three complex DSD cases on the spectrum of mixed gonadal dysgenesis to ovotesticular DSD in which gender assignment and therefore optimal surgical management was uncertain. All patients had mosaic karyotypes with Y chromosome, dysgenetic ovary and dysgenetic testis, a urogenital sinus, and prominent phallus. In all three cases a team approach was taken to assess functional potential and risks along either gender pathway and to develop a spectrum of treatment options for parental consideration, including: 1. masculinization with removal of dysgenetic ovary; 2. initial vaginoplasty but with retention of the phallus (±bilateral gonadectomy); 3. initial vaginoplasty with "burial" of corporal bodies (Pippi Salle procedure) (±bilateral gonadectomy); 4. full feminization: vaginoplasty and clitoroplasty (with bilateral gonadectomy); 5. no surgical intervention. Results In all three cases, after consideration of risks and benefits of all options, parents selected option 2: gonadectomy to eliminate tumor risk and vaginoplasty, taking advantage of the child's young age to exteriorize urinary and reproductive tracts to avoid incontinence and infection and supporting parental bias toward female gender, but preservation of phallic structures to ensure a male option should the patient later declare a male gender identity. Parents of the three patients were contacted post-operatively (at 7, 17, and 22 months) for follow-up. All (3/3) regarded their child's development and wellbeing positively, and their own decisions regarding gender assignment and surgical plan favorably. All (3/3) regarded the team advisory process as balanced and supportive. Conclusion In the setting of exposure of the neonatal brain to testosterone, vaginoplasty and phallic preservation afforded a balance between parental preferences and preservation of anatomic options, allowing potential reconstruction of male or female phenotype as gender identity is ascertained thereby respecting both parent and patient rights. Parents valued a spectrum of options, transparency, and the team decision-making process. Table Patient characteristics. Table A B C Age at referral 14 months 23 months 6 weeks Karyotype 45,X/46,XY/47,XYY 45,X/46,XY 46XX/47XXY Gonads L Dysgenetic testis R Dysgenetic ovary L Dysgenetic testis R Dysgenetic ovary L Dysgenetic ovary R Dysgenetic testis Ductal structures Uterus R Fallopian tube Uterus L Fallopian tube Uterus UG sinus Mid confluence Low confluence Low confluence Phallus 4 × 1.5 cm 3 × 1 cm 2.7 × 1.3 cm Gender assignment Female Female Neutral [ABSTRACT FROM AUTHOR]

Abstract: trans-1,2-Diaryloxiranes were conveniently prepared in an one-pot reaction by the direct coupling of benzyl halides in the presence of silver oxide and DMSO under mild conditions. [Copyright &y& Elsevier]

Abstract: Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes. [Copyright &y& Elsevier]

Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1 , SLC4A2 and EHHADH. The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance. • Ductal adenocarcinoma of the prostate is more clinically aggressive than acinar adenocarcinoma. • Ductal adenocarcinoma has shorter time to metastasis. • This is the first large non-registry–based study to use metastasis-free survival as an end-point. • RB1 loss may be a key molecular driver in clinical difference. [ABSTRACT FROM AUTHOR]

Abstract Aβ 1-42 , which is highly toxic to neural cells, is commonly present in the brains of people with Alzheimer's disease. In this study, dynamic changes in cell mechanics were monitored under Aβ-induced toxicity. To investigate the changes in cellular mechanical properties, we used Aβ 1-42 oligomer at different concentrations to treat human neuroblastoma SH-SY5H cells. Results demonstrated a two-stage dynamic change in cell mechanics during neurodegeneration. Additionally, Young's modulus (YM) of the treated cells increased in a short period. The reasons include alteration in surface tension, osmotic pressure, and actin polymerization. Rough cellular membranes were observed from atomic force microscope (AFM) measurement. However, the cellular YM gradually decreased when the cells were continuously exposed to Aβ 1-42 or to a high concentration of Aβ 1-42. The major reason for the decreased YM was microtubule disassembly. Dynamic change in YM reflects different activities in cytoplasm in response to Aβ 1-42. The characteristic changes in cell mechanics provided insights into the dynamic neurodegeneration process of cells induced by Aβ 1-42 oligomer. [ABSTRACT FROM AUTHOR]