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• Current American Urological Association guidelines do not recommend ultrasound for the evaluation of undescended testicles. • Children with an undescended testicle should be referred to a pediatric urologist at approximately 6 months of age. • Infants with bilateral nonpalpable testicles should be evaluated for possible congenital adrenal hyperplasia. • Infants with hypospadias and unilateral or bilateral undescended testicles should be evaluated for disorder of sexual development. • Repair of hypospadias is recommended at between 6 months and 1 year of age. • Bladder exstrophy repairs are currently delayed to 3 months of age. • A voiding cystourethrogram should be performed in infants with high-grade hydronephrosis and bilateral hydronephrosis. • Most hydroceles in infants are noncommunicating, and infants should be referred to a urologist if they fluctuate in size suggesting a communicating hydrocele. • Vesicoureteral reflux is more common in male infants and has a high rate of resolution.

The core features of borderline personality disorder (BPD) include problematic interpersonal relationships, behavioral and affective dysregulation, identity problems, and cognitive dysregulation. Cognitive dysregulation, such as catastrophizing, rumination, and thought suppression, contributes to emotion dysregulation in BPD. Previous research suggested that thought suppression fully mediated the relationship between negative affect intensity/reactivity and BPD symptoms. We predicted that catastrophizing similarly will serve as a mediator between negative affect intensity/reactivity and BPD symptoms. Two samples completed the study. First, students (N = 191) self-selected to participate in an online study through the university psychology research recruitment system. Additionally, a second sample using Amazon Mechanical Turk (MTurk; N = 172) was utilized. Catastrophizing partially mediated the relationship between negative affect intensity/reactivity and BPD symptoms. Across these samples, results suggest that catastrophizing may have a significant role in understanding BPD symptoms, which is similar with rumination. Limitations and future directions are also discussed.

Synapse or dendritic spine loss is the strongest correlate of cognitive decline in Alzheimer’s disease (AD), and neurofibrillary tangles (NFTs), but not amyloid-β plaques, associate more closely with transition to mild cognitive impairment. Yet, how dendritic spine architecture is affected by hyperphosphorylated tau is still an ongoing question. To address this, we combined cell and biochemical analyses of the Tau P301S mouse line (PS19). Individual pyramidal neurons in the hippocampus and medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D morphometry analysis. In the hippocampus, PS19 mice and non-transgenic (NTG) littermates displayed equivalent spine density at 6 and 9 months, but both genotypes exhibited age-related thin spine loss. PS19 mice exhibited significant increases in synaptic tau protein levels and mean dendritic spine head diameter with age. This suggests that CA1 pyramidal neurons in PS19 mice may undergo spine remodeling in response to tau accumulation and age. In the mPFC, spine density was similar among PS19 mice and NTG littermates at 6 and 9 months, but age-related reductions in synaptic tau levels were observed among PS19 mice. Collectively, these studies reveal brain region-specific changes in dendritic spine density and morphology in response to age and the presence of hyperphosphorylated tau in the PS19 mouse line.

Lefamulin is a novel oral and intravenous (IV) pleuromutilin developed as a twice-daily treatment for community-acquired bacterial pneumonia (CABP). It is a semi-synthetic pleuromutilin with a chemical structure that contains a tricyclic core of five-, six-, and eight-membered rings and a 2-(4-amino-2-hydroxycyclohexyl)sulfanylacetate side chain extending from C14 of the tricyclic core. Lefamulin inhibits bacterial protein synthesis by binding to the 50S bacterial ribosomal subunit in the peptidyl transferase center (PTC). The pleuromutilin tricyclic core binds to a pocket close to the A site, while the C14 side chain extends to the P site causing a tightening of the rotational movement in the binding pocket referred to as an induced-fit mechanism. Lefamulin displays broad-spectrum antibacterial activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria as well as against atypical bacteria that commonly cause CABP. Pleuromutilin antibiotics exhibit low rates of resistance development and lack cross-resistance to other antimicrobial classes due to their unique mechanism of action. However, pleuromutilin activity is affected by mutations in 23S rRNA, 50S ribosomal subunit proteins rplC and rplD, ATP-binding cassette (ABC)-F transporter proteins such as vga(A), and the methyltransferase cfr. The pharmacokinetic properties of lefamulin include: volume of distribution (Vd) ranging from 82.9 to 202.8 L, total clearance (CLT) of 19.5 to 21.4 L/h, and terminal elimination half-life (t1/2) of 6.9–13.2 h; protein binding of lefamulin is high and non-linear. The oral bioavailability of lefamulin has been estimated as 24% in fasted subjects and 19% in fed subjects. A single oral dose of lefamulin 600 mg administered in fasted patients achieved a maximum plasma concentration (Cmax) of 1.2–1.5 mg/L with a time of maximum concentration (Tmax) ranging from 0.8 to 1.8 h, and an area under the plasma concentration-time curve from 0 to infinity (AUC0−∞) of 8.5–8.8 mg h/L. The pharmacodynamic parameter predictive of lefamulin efficacy is the free plasma area under the concentration-time curve divided by the minimum inhibitory concentration (fAUC24h/MIC). Lefamulin efficacy has been demonstrated using various animal models including neutropenic murine thigh infection, pneumonia, lung infection, and bacteremia. Lefamulin clinical safety and efficacy was investigated through a Phase II clinical trial of acute bacterial skin and skin structure infection (ABSSSI), as well as two Phase III clinical trials of CABP. The Phase III trials, LEAP 1 and LEAP 2 established non-inferiority of lefamulin to moxifloxacin in both oral and IV formulations in the treatment of CABP. The United States Food and Drug Administration (FDA), European Medicines Agency (EMA), and Health Canada have each approved lefamulin for the treatment of CABP. A Phase II clinical trial has been completed for the treatment of ABSSSI, while the pediatric program is in Phase I. The most common adverse effects of lefamulin include mild-to-moderate gastrointestinal-related events such as nausea and diarrhea. Lefamulin represents a safe and effective option for treating CABP in cases of antimicrobial resistance to first-line therapies, clinical failure, or intolerance/adverse effects to currently used agents. Clinical experience and ongoing clinical investigation will allow clinicians and antimicrobial stewardship programs to optimally use lefamulin in the treatment of CABP.

Obesity rates are climbing, representing a confounding and contributing factor to many disease states, including cancer. With respect to breast cancer, obesity plays a prominent role in the etiology of this disease, with certain subtypes such as triple-negative breast cancer having a strong correlation between obesity and poor outcomes. Therefore, it is critical to examine the obesity-related alterations to the normal stroma and the tumor microenvironment (TME). Adipocytes and adipose stem cells (ASCs) are major components of breast tissue stroma that have essential functions in both physiological and pathological states, including energy storage and metabolic homeostasis, physical support of breast epithelial cells, and directing inflammatory and wound healing responses through secreted factors. However, these processes can become dysregulated in both metabolic disorders, such as obesity and also in the context of breast cancer. Given the well-established obesity-neoplasia axis, it is critical to understand how interactions between different cell types in the tumor microenvironment, including adipocytes and ASCs, govern carcinogenesis, tumorigenesis, and ultimately metastasis. ASCs and adipocytes have multifactorial roles in cancer progression; however, due to the plastic nature of these cells, they also have a role in regenerative medicine, making them promising tools for tissue engineering. At the physiological level, the interactions between obesity and breast cancer have been examined; here, we will delineate the mechanisms that regulate ASCs and adipocytes in these different contexts through interactions between cancer cells, immune cells, and other cell types present in the tumor microenvironment. We will define the current state of understanding of how adipocytes and ASCs contribute to tumor progression through their role in the tumor microenvironment and how this is altered in the context of obesity. We will also introduce recent developments in utilizing adipocytes and ASCs in novel approaches to breast reconstruction and regenerative medicine.

Background Vulvovaginal candidiasis is commonly diagnosed and has been associated in prospective studies with the acquisition of HIV. Little data is available on how the composition of the vaginal microbiota, and other risk factors, are associated with the molecular detection of Candida albicans-a common cause of vulvovaginal candidiasis. Methods In a cross-sectional study, self-collected vaginal swabs were obtained from 394 nonpregnant, reproductive-age women. C. albicans was detected using polymerase chain reaction targeting C. albicans ITS1/2 region. Vaginal microbiota was characterized by 16S rRNA gene amplicon sequencing of the V3 to V4 hypervariable regions and clustered into community state types (CSTs). Multiple logistic regression identified factors associated with C. albicans detection. Results Twenty-one percent had C. albicans detected and 46% reported vaginal symptoms in the prior 60 days. There was a 2-fold increase in the odds of C. albicans if a woman was in a L. crispatus-dominated CST compared to CSTs with low-Lactobacillus levels (adjusted odds ratio, 2.05; 95% confidence interval, 0.97-4.37). History of self-treatment with antifungals, L. crispatus relative abundance, and receptive oral sex were also significantly associated with C. albicans detection. Conclusions A L. crispatus-dominated vaginal microbiota is thought to protect women from both development of bacterial vaginosis and incidence of sexually transmitted infections; however, our data suggest that L. crispatus is associated with increased C. albicans detection. Receptive oral sex may also be a risk factor for vaginal C. albicans colonization.

Depression is a leading mental health concern across the U.S. and worldwide. There are myriad assessments to evaluate depressive symptoms, including the Edinburgh Postnatal Depression Scale (EPDS), which is widely used to evaluate women's pre- and postnatal depression but not as prevalent at other timepoints in adulthood, limiting its utility for longitudinal research. As part of the National Institutes of Health's (NIH) Environmental influences on Child Health Outcomes (ECHO) Research Program, the current study sought to develop a common metric so that scores on the EPDS can be converted to the standardized Patient-Reported Measurement Information System (PROMIS®) T-score metric. Drawing on data from the ECHO-Prenatal Alcohol in SIDS and Stillbirth cohort, this study used a single-group linking design, where 1,263 mothers completed the EPDS and PROMIS-Depression measures at the same time. Score linking was conducted using equipercentile and item response theory (IRT) methods. Results showed both linking methods provide robust, congruent results, and subgroup invariance held across age, race, ethnicity, education, and geographic location. The IRT-based unidimensional fixed-parameter calibration was selected due to its model simplicity, and a crosswalk table was established to convert scores from the EPDS to PROMIS T-scores. Overall, this study provides a way to aggregate data across various depression measures and timepoints, such that researchers and clinicians now have the ability to directly compare and combine EPDS data with PROMIS and other depression measures already score-linked to PROMIS. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The evaluation and diagnosis of shoulder pain is a common challenge encountered by primary care providers. The differential for shoulder pain is broad and the presentation may be varied. The patient’s history and physical examination alone are often enough to reach a diagnosis; however, plain films and advanced imaging studies are frequently helpful for further confirmation and to guide decision-making. In this section, we will review several common causes of shoulder pain related to soft tissue pathology: adhesive capsulitis, biceps tendinopathy, acromioclavicular joint pain, and rotator cuff pathology.

Objective This article describes the methodology used for the Pediatric Craniofacial Collaborative Group (PCCG) Consensus Conference. Design This is a novel Consensus Conference of national experts in Pediatric Craniofacial Surgery and Anesthesia, who will follow standards set by the Institute of Medicine and using the Research and Development/University of California, Los Angeles appropriateness method, modeled after the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Topics related to pediatric craniofacial anesthesia for open cranial vault surgery were divided into twelve subgroups with a systematic review of the literature. Setting A group of 20 content experts met virtually between 2019 and 2020 and will collaborate in their selected topics related to perioperative management for pediatric open cranial vault surgery for craniosynostosis. These groups will also identify where future research is needed. Conclusions Experts in pediatric craniofacial surgery and anesthesiology are developing recommendations on behalf of the Pediatric Craniofacial Collaborative Group for perioperative management of patients undergoing open cranial vault surgery for craniosynostosis and identifying future research priorities.

Cognitive resilience is often defined as the ability to remain cognitively normal in the face of insults to the brain. These insults can include disease pathology, such as plaques and tangles associated with Alzheimer’s disease, stroke, traumatic brain injury, or other lesions. Factors such as physical or mental activity and genetics may contribute to cognitive resilience, but the neurobiological underpinnings remain ill-defined. Emerging evidence suggests that dendritic spine structural plasticity is one plausible mechanism. In this review, we highlight the basic structure and function of dendritic spines and discuss how spine density and morphology change in aging and Alzheimer’s disease. We note evidence that spine plasticity mediates resilience to stress, and we tackle dendritic spines in the context of cognitive resilience to Alzheimer’s disease. Finally, we examine how lifestyle and genetic factors may influence dendritic spine plasticity to promote cognitive resilience before discussing evidence for actin regulatory kinases as therapeutic targets for Alzheimer’s disease.

INTRODUCTION AND OBJECTIVE:Retention of indwelling ureteral stents due to loss to follow-up can result in significant harm to patients, who often require multiple trips to the operating room for en...

Bacterial vaginosis-associated bacterium 1 (BVAB1) is an as-yet uncultured bacterial species found in the human vagina that belongs to the family Lachnospiraceae within the order Clostridiales. As its name suggests, this bacterium is often associated with bacterial vaginosis (BV), a common vaginal disorder that has been shown to increase a woman's risk for HIV, Chlamydia trachomatis, and Neisseria gonorrhoeae infections as well as preterm birth. BVAB1 has been further associated with the persistence of BV following metronidazole treatment, increased vaginal inflammation, and adverse obstetrics outcomes. There is no available complete genome sequence of BVAB1, which has made it difficult to mechanistically understand its role in disease. We present here a circularized metagenome-assembled genome (cMAG) of BVAB1 as well as a comparative analysis including an additional six metagenome-assembled genomes (MAGs) of this species. These sequences were derived from cervicovaginal samples of seven separate women. The cMAG was obtained from a metagenome sequenced with long-read technology on a PacBio Sequel II instrument while the others were derived from metagenomes sequenced on the Illumina HiSeq platform. The cMAG is 1.649 Mb in size and encodes 1,578 genes. We propose to rename BVAB1 to “Candidatus Lachnocurva vaginae” based on phylogenetic analyses, and provide genomic and metabolomic evidence that this candidate species may metabolize D-lactate, produce trimethylamine (one of the chemicals responsible for BV-associated odor), and be motile. The cMAG and the six MAGs are valuable resources that will further contribute to our understanding of the heterogeneous etiology of bacterial vaginosis.

Background Meniscal tears often accompany knee osteoarthritis, a disabling condition affecting 14 million individuals in the United States. While several randomized controlled trials have compared physical therapy to surgery for individuals with knee pain, meniscal tear, and osteoarthritic changes (determined via radiographs or magnetic resonance imaging), no trial has evaluated the efficacy of physical therapy alone in these subjects. Methods The Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial is a four-arm multi-center randomized controlled clinical trial designed to establish the comparative efficacy of two in-clinic physical therapy interventions (one focused on strengthening and one containing placebo) and two protocolized home exercise programs. Discussion The goal of this paper is to present the rationale behind TeMPO and describe the study design and implementation strategies, focusing on methodologic and clinical challenges. Trial registration The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004. on February 14, 2017. Electronic supplementary material The online version of this article (10.1186/s12891-018-2327-9) contains supplementary material, which is available to authorized users.

Vaginolysin (VLY), a cytotoxic protein produced by Gardnerella vaginalis, may contribute to bacterial vaginosis. We observed that women with G. vaginalis, low levels of lactobacilli, history of vaginal douching, higher Nugent scores, and higher vaginal pH had increased VLY. Inflammatory markers were not highly expressed with increasing VLY. Vaginolysin's role in bacterial vaginosis warrants further evaluation.

In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery. We describe complex transcriptional responses in the injured spinal cord, and somewhat surprisingly, also in the brain. Transcriptional responses to SCI in lampreys included transcription factor networks that promote peripheral nerve regeneration in mammals such as Atf3 and Jun. Furthermore, a number of highly conserved axon guidance, extracellular matrix, and proliferation genes were also differentially expressed after SCI in lampreys. Strikingly, ~3% of differentially expressed transcripts belonged to the Wnt pathways. These included members of the Wnt and Frizzled gene families, and genes involved in downstream signaling. Pharmacological inhibition of Wnt signaling inhibited functional recovery, confirming a critical role for this pathway. These data indicate that molecular signals present in mammals are also involved in regeneration in lampreys, supporting translational relevance of the model.

Partial splenectomy has emerged as a surgical option for children with hereditary spherocytosis. The goal of reducing anemia and hypersplenism while preserving splenic immunologic function to avoid potential Overwhelming Post-Splenectomy Infection (OPSI) is logical.

Summary Background & aims Women with bacterial vaginosis (BV) have increased risk of sexually transmitted infections and other adverse health outcomes. Based on the composition of their vaginal microbiota, women can broadly be classified into low-Lactobacillus (termed molecular-BV) and Lactobacillus-dominated profiles. Our objective was to determine the association between dietary macronutrient intake and molecular-BV. Methods In a cross-sectional study of 104 reproductive-age women, dietary intake data were obtained using the Block Brief 2000 food frequency questionnaire. Vaginal microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3–V4 regions and clustering into community state types (CST). Logistic regression was used to determine the association of macronutrient intake with molecular-BV (low-Lactobacillus vs. Lactobacillus-dominated CSTs combined). Results Participants had a median age of 25.9 (interquartile range: 21.9–29.6), 58% were white (30% black), 51% overweight/obese and 52% on hormonal contraception. In multivariable models, diets richer in fiber were inversely associated with molecular-BV (adjusted odds ratio: 0.49 per standard deviation increase in energy-adjusted fiber intake, 95% confidence interval: 0.24–0.99; p = 0.049). Conclusions Our results indicate that diets richer in fiber were associated with lower odds of molecular-BV. Further studies are needed to confirm these findings and to test whether increasing fiber intake can modulate the microbiota towards a more optimal Lactobacillus-dominant profile.

Recent studies suggest that birth mode (Cesarean section [C-section] or vaginal delivery) is an important event in the initial colonization of the human microbiome and may be associated with long-term health outcomes. We sought to determine the association between a woman's birth mode and her vaginal microbiota in adulthood. We re-contacted 144 adult women from two U.S. studies and administered a brief survey. Vaginal microbiota was characterized on a single sample by amplicon sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene and clustered into community state types (CSTs). We evaluated the association between birth mode and a CST with low relative abundance of Lactobacillus spp. ("molecular bacterial vaginosis" [Molecular-BV]) compared to Lactobacillus-dominated CSTs in logistic regression modeling which adjusted for body mass index, a confounder in this analysis. Twenty-seven women (19%) reported C-section. Overall, C-section showed a non-significant trend towards increased odds of Molecular-BV (aOR = 1.22, 95% CI: 0.45, 3.32), and Prevotella bivia was the strongest single taxa associated with C-section. However, because the two archived studies had different inclusion criteria (interaction p = 0.048), we stratified the analysis by study site. In the study with a larger sample size (n = 88), women born by C-section had 3-fold higher odds of Molecular-BV compared to vaginally-delivered women (aOR = 3.55, p = 0.06, 95% CI: 0.97-13.02). No association was found in the smaller study (n = 56, aOR = 0.19, p = 0.14, 95% CI: 0.02-1.71). This pilot cross-sectional study suggests a possible association between C-section and Molecular-BV in adulthood. However, the analysis is limited by small sample size and lack of comparability in participant age and other characteristics between the study sites. Future longitudinal studies could recruit larger samples of women, address the temporal dynamics of vaginal microbiota, and explore other confounders, including maternal factors, breastfeeding history, and socioeconomic status, which may affect the relationship between birth mode and vaginal microbiota.

Background Observational studies have demonstrated a dose-dependent association between vaginal douching and bacterial vaginosis. We sought to estimate the effect of douching cessation on the vaginal microbiota in a pilot crossover study. Methods Thirty-two women self-collected vaginal swabs twice-weekly (n=950) during a douching observational phase (“D”, 4 weeks), followed by douching cessation (“DC”, 12 weeks). Vaginal microbiota were characterized by 16S rRNA gene sequencing (V3-V4) and clustered into community state types (CSTs). A conditional logistic regression model, adjusted for menstruation and sexual behaviors, allowed each woman to serve as her own control. Wilcoxon signed-rank tests were used to evaluate paired changes in microbiota between phases. Broad-range qPCR assays provided estimates of bacterial absolute abundance per swab. A piecewise linear mixed effects model was used to assess differences in rates of change in bacterial absolute abundance before and after douching. Results There was not a statistically significant change in the odds of Lactobacillus-dominated CSTs comparing DC to D (aOR 0.54, 95% CI: 0.27–1.11). There were no significant changes for four individual Lactobacillus spp. and no meaningful changes in other taxa investigated. The rates of change in bacterial absolute abundance was not significantly different in samples collected 3 days before and after douching (p=0.46). Women who had a Lactobacillus-dominated CST at baseline experienced shifts to low-Lactobacillus CST in DC, and vice versa for women who had a low-Lactobacillus CST at baseline (interaction on entry CST, p-value Conclusion In this pilot study, douching cessation was not associated with major changes in vaginal microbiota. Shifts in Lactobacillus-dominance may represent regression to the mean as the shifts occurred late in DC, giving ample time for fluctuations. Disparate findings between this study and prior analyses using Nugent score may be related to low-Lactobacillus CSTs receiving low/intermediate Nugent scores. Disclosure No significant relationships.

Bacterial Vaginosis Associated Bacteria 1 (BVAB1) is an uncultured bacterial species found in the human vagina that belongs to the familyLachnospiraceaewithin the orderClostridiales, and as its name suggests, is often associated with bacterial vaginosis (BV). In reproductive health, BV is of concern due to its associated risk for HIV,Chlamydia trachomatis, andNeisseria gonorrhoeaeacquisition as well as preterm birth. BVAB1 has been shown to be associated with BV persistence after metronidazole treatment and increased vaginal inflammation, and to confer a higher risk of puerperal infections. To date, no genome of BVAB1 is available, which has made it difficult to understand its disease-associated features. We present here a comparative analysis of seven metagenome-assembled genomes (MAGs) of BVAB1, derived from the cervicovaginal lavages of seven separate women. One metagenome was sequenced with long-read technology on a PacBio Sequel II instrument while the others were sequenced using the Illumina HiSeq platform. The MAGs were 1.5-1.7 Mb long, encoding an average of 1,499 genes and had >98% average nucleotide identity to each other. CheckM-estimated genome completion was 98.2%. We propose to rename BVAB1 toLachnovaginosumgenomospecies based on a phylogenetic analysis, and provide genomic evidence that this species may metabolize D-lactate, produce trimethylamine (the chemical responsible for BV-associated odor), and be motile. These MAGs will be a valuable resource and will contribute to our understanding of the heterogenous etiologies of bacterial vaginosis.

While GM1 may interact with α-synuclein in vitro to inhibit aggregation, the ability of GM1 to protect against α-synuclein toxicity in vivo has not been investigated. We used targeted adeno-associated viral vector (AAV) overexpression of human mutant α-synuclein (A53T) in the rat substantia nigra (SN) to produce degeneration of SN dopamine neurons, loss of striatal dopamine levels, and behavioral impairment. Some animals received daily GM1 ganglioside administration for 6 weeks, beginning 24 hours after AAV-A53T administration or delayed start GM1 administration for 5 weeks beginning 3 weeks after AAV-A53T administration. Both types of GM1 administration protected against loss of SN dopamine neurons and striatal dopamine levels, reduced α-synuclein aggregation, and delayed start administration of GM1 reversed early appearing behavioral deficits. These results extend prior positive results in MPTP models, are consistent with the results of a small clinical study of GM1 in PD patients that showed slowing of symptom progression with chronic use, and argue for the continued refinement and development of GM1 as a potential disease modifying therapy for PD.

Objectives Bacterial vaginosis (BV), a clinical condition characterized by decreased vaginal Lactobacillus spp., is difficult to treat. We examined associations between micronutrient intake and a low-Lactobacillus vaginal microbiota as assessed by molecular methods (termed “molecular-BV”). Methods This cross-sectional analysis utilized data collected at the baseline visit of the Hormonal Contraception Longitudinal Study, a cohort of reproductive-aged women followed over 2 years while initiating or ceasing hormonal contraception (HC). The Block Brief 2000 Food Frequency Questionnaire was administered and micronutrient intakes were ranked. Vaginal microbiota composition was assessed using 16S rRNA gene amplicon sequencing and clustered into community state types (CSTs) based on the types and relative abundance of bacteria detected. Associations between the lowest estimated quartile intake of nutrients and having a low-Lactobacillus CST (molecular-BV) were evaluated by logistic regression. Separate models were built for each nutrient controlling for age, body mass index, behavioral factors, HC use and total energy intake. We also conducted a literature review of existing data on associations between micronutrient intakes and BV. Results Samples from 104 women were included in this analysis. Their mean age was 25.8 years (SD 4.3), 29.8% were African American, 48.1% were using HC, and 25% had molecular-BV. In adjusted multivariable analyses, the lowest quartile of betaine intake was associated with an increased odds of molecular-BV (aOR 9.2, p value Conclusions This is the first study to assess the association between estimated micronutrient intake and molecular-BV. Lower energy-adjusted intake of betaine was associated with an increased risk of molecular-BV. Betaine might have direct effects on the vaginal microenvironment or may be mediated through the gut microbiota. Additional research is needed to determine reproducibility of this finding and whether improved intake of select micronutrients such as betaine decreases the risk of BV and its sequelae.

Background/Aims: Animal studies suggest that leptin may adversely affect bone mineral density (BMD). Clinical studies have yielded conflicting results. We therefore investigated associations between leptin and bone parameters in children. Methods: 830 healthy children (age = 11.4 ± 3.1 years; 75% female; BMI standard deviation score [BMIz] = 1.5 ± 1.1) had fasting serum leptin measured with ELISA and body composition by dual-energy X-ray absorptiometry. The main effects for leptin and BMIz plus leptin’s interactions with sex and BMIz were examined using hierarchical linear regressions for appendicular, pelvis, and lumbar spine BMD as well as bone mineral content (BMC), and bone area (BA). Results: Accounting for demographic, pubertal development, and anthropometric variables, leptin was negatively and independently associated with lumbar spine BMC and BA, pelvis BA, and leg BA (p < 0.05 for all). Sex, but not BMIz, moderated the associations of leptin with bone parameters. In boys, leptin was negatively correlated with leg and arm BMD, BMC at all bone sites, and BA at the subtotal and lumbar spine (p < 0.01 for all). In girls, leptin was positively correlated with leg and arm BMD (p < 0.05 for both). Conclusion: Independent of body size, leptin is negatively associated with bone measures; however, these associations are moderated by sex: boys, but not girls, have a negative independent association between leptin and BMD.

Prospective data suggest depressive symptoms worsen insulin resistance and accelerate type 2 diabetes (T2D) onset.We sought to determine whether reducing depressive symptoms in overweight/obese adolescents at risk for T2D would increase insulin sensitivity and mitigate T2D risk.We conducted a parallel-group, randomized controlled trial comparing a 6-week cognitive-behavioral (CB) depression prevention group with a 6-week health education (HE) control group in 119 overweight/obese adolescent girls with mild-to-moderate depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D] ≥16) and T2D family history. Primary outcomes were baseline to post-intervention changes in CES-D and whole body insulin sensitivity index (WBISI), derived from 2-h oral glucose tolerance tests. Outcome changes were compared between groups using ANCOVA, adjusting for respective baseline outcome, puberty, race, facilitator, T2D family history degree, baseline age, adiposity, and adiposity change. Multiple imputation was used for missing data.Depressive symptoms decreased (p 0.001) in CB and HE from baseline to posttreatment, but did not differ between groups (ΔCESD = -12 vs. -11, 95 % CI difference = -4 to +1, p = 0.31). Insulin sensitivity was stable (p 0.29) in CB and HE (ΔWBISI = 0.1 vs. 0.2, 95 % CI difference = -0.6 to +0.4, p = 0.63). Among all participants, reductions in depressive symptoms were associated with improvements in insulin sensitivity (p = 0.02).Girls at risk for T2D displayed reduced depressive symptoms following 6 weeks of CB or HE. Decreases in depressive symptoms related to improvements in insulin sensitivity. Longer-term follow-up is needed to determine whether either program causes sustained decreases in depressive symptoms and improvements in insulin sensitivity.The trial was registered with clinicaltrials.gov (NCT01425905).

Summary Introduction Limited data exist on patient-reported outcomes in adults with bladder exstrophy (BE). We partnered with the Association for the Bladder Exstrophy Community (A-BE-C) using social media to survey adult females with BE. The aim of the study was to assess long-term patient-reported sexual, reproductive and continence outcomes. Materials and methods Between December 3, 2018 and January 18, 2019, A-BE-C promoted an anonymous survey of adult females with BE on social media. The survey included the Female Sexual Function Index (FSFI) and International Consultation on Incontinence Questionnaire – Short Form (ICIQ-SF) in addition to questions on demographics, reproductive and gynecological outcomes. Results A total of 130 women with a median age of 30 years (IQR 26, 41) completed the survey. The majority of women were born in the United States (N = 86, 66.2%). Women reported a median of 10 (IQR 5, 17) surgeries performed for their condition. The mean ICIQ-SF score was 6.2 ± 6.2 (moderate). Only 19.2% (N = 25) reported volitionally voiding and the majority reported intermittent catheterization through a catheterizeable channel or the urethra (Summary Table). The mean FSFI score was (20.1 ± 9.0), indicating risk for sexual dysfunction (FSFI Conclusion This is the largest study of patient-reported outcomes in females with BE achieved through partnership with an advocacy group and social media. We found that continence and sexual function were both impaired in adult women with BE. Respondents reported poor obstetric and gynecological outcomes including infertility, uterine prolapse, vaginal stenosis, and need for multiple surgeries. BE surgeons, through multi-institutional collaboration, should continue to reassess surgical techniques at initial repair to better address these functional issues. These results should be a part of counseling parents of newborns with BE. Summary Table . Patient Characteristics, Urinary and Sexual Outcomes. Number of women 130 Median age, years (Interquartile Range, IQR) 30 (26, 41) Country of birth United States 86/130, 66.2% Canada 9/130, 7.0% United Kingdom 6/130, 4.6% Australia 8/130, 6.2% Others (Algeria, Croatia, Germany, Italy, Finland, South American countries, Spain, Switzerland, Sweden, Turkey) 21/130, 16.2% Median number of surgeries (IQR) 10∗ (5, 17) Bladder Management Voids per urethra 25/130, 19.2% Catheterization per urethra 20/130, 15.4% Catheterizable channel 57/130, 43.8% Suprapubic tube 4/130, 3.1% Urostomy 11/130, 8.5% Other 13/130, 10.0% Mean ICIQ-SF ± SD (N=127) 6.2 ± 6.2 Mean FSFI ± SD (N=125) 20.1 ± 9.0 ∗n = 126 respondents for this question.

Mixed lineage leukemia results from chromosomal rearrangements of the gene mixed lineage leukemia (MLL). MLL-AF9 is one such rearrangement that recruits the lysine methyltransferase, human disruptor of telomere silencing 1-like (DOT1L) and lysine specific demethylase 1 (LSD1), resulting in elevated expression of the Homeobox protein A9 (HOXA9), and leukemia. Inhibitors of LSD1 or DOT1L reduce HOXA9 expression, kill MLL-rearranged cells, and may treat leukemia. To quantify their effects on histone modifying enzyme activity and expression in MLL-rearranged leukemia, we tested inhibitors of DOT1L (EPZ-5676), LSD1 (GSK2879552), and HDAC (mocetinostat), in the MLL-AF9 cell line MOLM-13. All inhibitors reduced MOLM-13 viability but only mocetinostat induced apoptosis. EPZ-5676 increased total histone lysine dimethylation, which was attributed to a reduction in LSD1 expression, and was indistinguishable from direct LSD1 inhibition by GSK2879552. All compounds directly inhibit, or reduce the expression of, HOXA9, DOT1L and LSD1 by qPCR, increase total histone lysine methylation and acetylation by LC-MS/MS, and specifically reduce H3K79Me2 and increase H3K14Ac. Each inhibitor altered the expression of many histone modifying enzymes which may precipitate additional changes in expression. To the extent that this decreases HOXA9 expression it benefits mixed lineage leukemia treatment, all other expression changes are off-target effects.

Lipodystrophy (LD) is an ultra-rare disease associated with significant morbidity and mortality. Effects of LRT on metabolic disease in GL and PL have been studied; but effects on mortality are unknown. We investigated these effects using data from GL and PL patients treated with LRT at NIH (N=114) and cared for but not treated with LRT at 3 centers in the U.S. and Turkey (N=178). Four abnormalities (liver, kidney, heart, and HbA1c ≥6.5%) were considered. LRT patients had a mean of 2.8 abnormalities prior to treatment, while the mean for untreated patients was 0.7 at a similar age. We used a matching approach to create comparable samples of treated and untreated patients. Each treated patient was matched (using Mahalanobis distance) to an untreated patient to balance across age, gender, type of LD, and number of abnormalities. LRT treatment effect was examined via Cox proportional hazards models of 1) mortality and 2) development of subsequent abnormalities. Additionally, the relationship between abnormalities and mortality was studied in the sample of untreated patients. Results: A Cox proportional hazards model relating treatment to mortality yielded a hazard ratio (HR) for LRT of 0.34 (p=0.047), meaning that LRT was associated with a 66% decrease in mortality risk. Adjusting for covariates including gender, type of LD, and type of abnormality resulted in a larger decrease in mortality risk (HR 0.21, p One possible mechanism for the effect of LRT on mortality is its role in mitigating or resolving abnormalities. A time-varying Cox proportional hazards model relating number of abnormalities present (0 to 4) to mortality among untreated patients found a positive relationship between additional abnormalities and mortality (HR 3.2, p In conclusion, these are the first data suggesting that LRT reduces mortality in LD. Disclosure O.A. Ali: Consultant; Self; Aegerion Pharmaceuticals. K. Cook: Consultant; Self; Aegerion Pharmaceuticals. D. Gupta: Consultant; Self; Aegerion Pharmaceuticals. D. Holmqvist: Consultant; Self; Aegerion Pharmaceuticals. D. Lee: Consultant; Self; Aegerion Pharmaceuticals. C.K. Ng: Consultant; Self; Aegerion Pharmaceuticals. P. Bradt: Employee; Self; Aegerion Pharmaceuticals. R. Brown: None.

Purpose Extant research indicates that some of the comorbidities associated with adult obesity may be adversely affected by the stress resulting from negative body image and weight-related stigma. This study examined the association between weight-related pressure and insulin sensitivity in adolescents, who are vulnerable to both weight-based teasing and the onset of metabolic dysregulation. Methods Participants were 215 adolescent healthy volunteers (55% female; 59% white; 35% overweight/obese; mean ± standard deviation age = 15.4 ± 1.4 year), who completed a self-report measure of pressure to be thin from parents, friends, and romantic partners. Fasting blood samples were obtained to assess serum insulin and glucose, which were used to calculate insulin sensitivity; fat mass (kg) and fat-free mass (%) were measured with air-displacement plethysmography. Pubertal stage was determined by physical examination. Results Pressure to be thin was positively associated with fasting insulin ( p = .01) and negatively associated with insulin sensitivity ( p = .02), after controlling for pubertal stage, sex, race, height, fat-free mass, and adiposity. Pressure to be thin was associated with a greater odds of having hyperinsulinemia (fasting insulin ≥ 15 μIU/mL; odds ratio (95% confidence interval): 1.65 [1.08–2.50], p = .02), adjusting for the same covariates. Conclusions Results indicate that adolescents perceiving more pressure to be thin have greater elevations of fasting insulin and poorer insulin sensitivity above and beyond the effect of fat mass. Future research is warranted to elucidate the mechanisms responsible for this relationship.

Summary Background Adults with binge eating disorder may have an exaggerated or blunted cortisol response to stress. Yet, limited data exist among youth who report loss of control (LOC) eating, a developmental precursor to binge eating disorder. Methods We studied cortisol reactivity among 178 healthy adolescents with and without LOC eating. Following a buffet lunch meal adolescents were randomly assigned to watch a neutral or sad film clip. After, they were offered snacks from a multi-item array to assess eating in the absence of hunger. Salivary cortisol was collected at −80, 0, 30 and 50 min relative to film administration, and state mood ratings were reported before and after the film. Results Adolescents with LOC had greater increases in negative affect during the experimental paradigm in both conditions (ps > 0.05). Depressive symptoms, but not LOC, related to a greater cortisol response in the sad film condition (ps > 0.05). Depressive symptoms and state LOC were related to different aspects of eating behaviour, independent of film condition or cortisol response (ps > 0.05). Conclusions A film clip that induced depressed state affect increased salivary cortisol only in adolescents with more elevated depressive symptoms. Adolescents with and without LOC were differentiated by greater increases in state depressed affect during laboratory test meals but had no difference in cortisol reactivity. Future studies are required to determine if adolescents with LOC manifest alterations in stress reactivity to alternative stress-inducing situations.

Data suggest that depressed affect and dietary restraint are related to disinhibited eating patterns in children and adults. Yet, experimental research has not determined to what extent depressed affect acutely affects eating in the absence of physiological hunger (EAH) in adolescents. In the current between-subjects experimental study, we measured EAH in 182 adolescent (13-17y) girls (65%) and boys as ad libitum palatable snack food intake after youth ate to satiety from a buffet meal. Just prior to EAH, participants were randomly assigned to view either a sad or neutral film clip. Dietary restraint was measured with the Eating Disorder Examination. Adolescents who viewed the sad film clip reported small but significant increases in state depressed affect relative to adolescents who viewed the neutral film clip (p < .001). Yet, there was no main effect of film condition on EAH (p = .26). Instead, dietary restraint predicted greater EAH among girls, but not boys (p < .001). These findings provide evidence that adolescent girls’ propensity to report restrained eating is associated with their greater disinhibited eating in the laboratory. Additional experimental research, perhaps utilizing a more potent laboratory stressor and manipulating both affective state and dietary restraint, is required to elucidate how state affect may interact with dietary restraint to influence EAH during adolescence.

Objective The purpose of this investigation was to examine the relationship of dispositional mindfulness to binge eating and associated eating attitudes and behaviors among adolescent girls at risk for type 2 diabetes (T2D). Methods Participants were 114 overweight or obese adolescents enrolled in a study of girls with a family history of T2D and mild depressive symptoms. Adolescent self-reports of mindfulness, eating in the absence of hunger, and depressive symptoms were collected. An interview was administered to determine presence of binge eating episodes and a behavioral task was used to assess the reinforcing value of food relative to other nonsnack food rewards. Body composition was assessed using dual-energy X-ray absorptiometry. Results In analyses accounting for race, percent body fat, lean mass, height, age, and depressive symptoms, dispositional mindfulness was associated with a lower odds of binge eating (p = .002). Controlling for the same potential confounds, mindfulness was also inversely associated with eating concern, eating in the absence of hunger in response to fatigue/boredom, and higher food reinforcement relative to physical activity (all p

Objective Limited data suggest that the children of U.S. service members may be at increased risk for disordered-eating. To date, no study has directly compared adolescent military-dependents to their civilian peers along measures of eating pathology and associated correlates. We, therefore, compared overweight and obese adolescent female military-dependents to their civilian counterparts along measures of eating-related pathology and psychosocial functioning. Method Adolescent females with a BMI between the 85th and 97th percentiles and who reported loss-of-control eating completed interview and questionnaire assessments of eating-related and general psychopathology. Results Twenty-three military-dependents and 105 civilians participated. Controlling for age, race, and BMI-z, military-dependents reported significantly more binge episodes per month (p

Introduction Laryngomalacia can have a significant impact on swallowing function. Most of the studies in literature have focused on evaluating swallowing dysfunction in children with Laryngomalacia using clinical assessment and swallowing studies i.e. functional endoscopic evaluation of swallowing or videofluroscopic evaluation of swallowing. Objective The objective of the current study was to evaluate the parental perception of swallowing using a newly devised 10-point swallowing index before and after supraglottoplasty. Material and methods This was a prospective study performed at a tertiary care Aerodigestive center over a period of 18 months. A total of 51 supraglottoplasties were performed by a single surgeon over an 18-month period. Parents were asked to fill a non validated 10-point questionnaire before and after supraglottoplasty. Of the 51 surgeries, 34 surveys were completed, and 28 surveys were included in the study. All the patients were classified in to mild, moderate and severe laryngomalacia based on the established criterion. Each point in the index was graded on the Likert scale. Results A total of 28 patients who underwent supraglottoplasty were included in the study. There was a significant improvement in the overall parental perception in the swallowing of children with laryngomalacia following supraglottoplasty. There was statistically significant improvement in 9 out of 10 indices on the questionnaire. Conclusion Supraglottoplasty has an overall positive impact on parental perception of swallowing in children with Laryngomalacia. Caregivers had fewer concerns postoperatively, with fewer choking spells and breathing issues during feeds, and a greater satisfaction with the amount consumed at each feed. This Index adds a valuable subjective component to pediatric swallowing assessments pre and post supraglottoplasty. This tool could be used in conjunction with MBSS and FEES measures to provide a more comprehensive assessment.

Background: Chorioamnionitis (CHORIO) is a major risk factor for neonatal sepsis. In 2013, the Committee on the Fetus and Newborn (COFN) issued CHORIO guidelines, which specified extending the duration of antibiotics in asymptomatic, CHORIO-exposed neonates with abnormal screening laboratory. Our publication in 2014 (Kiser C, Pediatrics) showed a large number of asymptomatic …

There have been few prior studies on patient-centered outcomes of adults with bladder exstrophy; those performed have been single institution reviews. In collaboration with the Association for the Bladder Exstrophy Communities (ABeC) - an international support network for patients and families living with bladder exstrophy - an anonymous social media survey was performed of patient-reported genital appearance and erectile function.The study evaluated the Penile Perception Score (PPS) and the International Index of Erectile Function (IIEF-15) in adult men with bladder exstrophy. It was hypothesized that scores would be significantly lower than prior reported scores for men without the condition.After review by an anonymous patient advocate volunteer, the ABeC performed an anonymous online survey using social media.Adult men with bladder exstrophy reported PPS, and satisfaction with penile length and axis that were lower than prior published controls (n = 54, P 0.05). Orgasmic function, sexual desire, and overall satisfaction were also lower (n = 46, P 0.05). There was no difference in erectile function or intercourse satisfaction compared to controls. There was an association between PPS and erectile function, intercourse satisfaction, and overall satisfaction (P 0.05) (Summary Fig.). Respondents identified urinary issues, genital appearance, and sexual function as the three main domains that warranted further research.This study found that PPS and IIEF-15 were low in adult men with bladder exstrophy, and worse perception of genital appearance was associated with worse sexual satisfaction. Social media is a novel tool for patient-centered outcomes research, and continued collaboration with patients and patient advocate groups is vital.

Patient adherence to treatment recommendations is an important issue for healthcare providers, in a multitude of specialties, and is critical when assessing the efficacy and effectiveness of a particular treatment approach. Patients who have swallowing impairment often require complex and specific interventions requiring altered daily patterns of behavior. Patients with dysphagia who do not follow recommendations or prescribed exercises may not receive maximum benefit of an intervention. Poor adherence also makes it more difficult to evaluate efficacy of a treatment both clinically and in experimental settings. Further, swallow safety can be compromised if certain recommendations are not followed. Our purpose was to systematically review the literature to understand what is known about adherence within the field of dysphagia treatment. We systematically identified 12 studies that tracked and reported patient-specific adherence. In this review, we found that the average adherence rate from these studies ranges between 21.9 and 51.9%. Adherence to prophylactic treatment recommendations for patients with head and neck cancer was the focus in 9/12 studies. The findings of this review identify a large gap in knowledge regarding adherence to dysphagia treatment. Few studies account for adherence within their study designs. When planning dysphagia treatment studies, it is imperative that investigators include information regarding patient adherence to accurately interpret findings. Given the variable adherence rates found in this review, factors influencing patient adherence with dysphagia treatments should be identified to increase adherence in future trials.

Schizophrenia is a severe mental illness affecting approximately 1% of the population worldwide. Despite its prevalence, the cause remains unknown, and treatment is not effective in all patients. Dopamine is thought to play a role in schizophrenia pathology, yet the substantia nigra (SN), the origin of dopaminergic pathways, has not been studied extensively in schizophrenia. In this study, electron microscopy was used to examine neurons, oligodendrocytes, and myelinated axons in the SN of normal controls (NCs, n=9) and schizophrenia subjects with varying response to antipsychotic drugs [SZ, n=14; treatment resistant (TR)=6, treatment responsive (RESP)=6, unknown=2]. Postmortem tissue was analyzed for qualitative and quantitative markers of ultrastuctural integrity. A significantly higher percentage of axons in the schizophrenia group had inclusions in the myelin sheath compared to NCs (SZ: 3.9±1.7, NC: 2.6±2.0). When considering treatment response, a significantly higher percentage of axons lacked cytoplasm (TR: 9.7±5.5, NC: 3.5±2.3), contained cellular debris (TR: 7.5±3.2, NC: 2.3±1.3) or had protrusions in the myelin sheath (TR: 0.4±0.5, NC: 0.2±0.3). The G-ratio, a measure of myelin thickness, was significantly different between treatment response groups and was greater in TR (0.72±0.02) as compared to NCs (0.68±0.03), indicating decreased myelination in TR. These findings, which suggest myelin pathology in the SN in schizophrenia, are consistent with findings elsewhere in the brain. In addition, our results suggest cytoskeletal abnormalities, which may or may not be associated with myelin pathology.

Summary Introduction and background Although the pediatric urologic community has embraced a multidisciplinary genetic and endocrine evaluation for newborns with ambiguous genitalia, this approach has been reserved for the most severe cases of undervirilized 46,XY individuals despite growing evidence that genetic differences are found even in patients whose only genitourinary anomaly appears to be proximal hypospadias. Identifying these genetic differences is vital for counseling patients as they move through puberty to parenthood as well as parents on future pregnancies. Objective The primary objective was to evaluate genetic diagnosis in patients with proximal hypospadias. The authors hypothesized the more sensitive genetic evaluation available in the modern era will reveal a high rate of patients with proximal hypospadias and descended testicles who are found to have a genetic difference, supporting a thorough genetic evaluation in these patients. Study design A retrospective review was performed of all patients who underwent surgical correction for proximal hypospadias at a single institution from January 1, 2010, to December 31, 2016. Those with midshaft hypospadias were excluded as were patients whose primary surgery was performed at an outside institution. Patient characteristics, including demographics, clinical presentation, genetic evaluation, and referral to a multidisciplinary difference of sex development (DSD) clinic, were collected. The chi-squared test and t-test were used for analysis. Results There were 112 patients with proximal hypospadias who met the inclusion criteria. Of these, 91 had bilaterally descended testicles, whereas 21 had one or more undescended testicles. Thirty-three percent of patients with isolated proximal hypospadias received genetic testing of some kind, with 24% seen in the multidisciplinary DSD clinic. Four patients had an associated genetic syndrome identified, and 5 had a genetic difference of unknown clinical significance. Overall, 10% of patients with proximal hypospadias and descended testicles had an identifiable genetic difference vs 33% with associated cryptorchidism. Of these, one patient with proximal hypospadias and descended testicles had a genetic difference of known clinical significance that was likely to have been missed in the absence of an evaluation by a geneticist. Discussion and conclusion There was a high rate of identifiable genetic differences in patients whose only genitourinary abnormality was proximal hypospadias, especially with the 1% risk of a likely missed diagnosis. These findings support the discussion of a genetic evaluation for all patients with proximal hypospadias, regardless of the testicular location. Download : Download high-res image (73KB) Download : Download full-size image Fig. A1 . Proximal hypospadias with bilateral descended testicles.

That diet can influence eye health has been recognized for centuries, but the role of specific nutrients has only recently begun to be understood. Vitamin A, the first essential dietary component identified in the early 20th century, was isolated and proven to be the critical lipid factor in liver and dairy products that prevented night blindness and keratomalacia, two eye conditions that often accompany more generalized malnutrition. Since the 1980s, results from epidemiological studies and clinical trials have suggested nutrients and non-nutritive diet components that slow the development of human age-related eye diseases—cataract, macular degeneration, and diabetic retinopathy—and animal and cell culture studies have elucidated the mechanisms for many of these effects. Unique to the eye is the concentrated exposure to sunlight that can cause direct photochemical damage and exacerbate oxidative stress and inflammation, which also promote chronic eye disease. Evidence indicates that a variety of dietary substances may protect against cataract, age-related macular degeneration, and diabetic retinopathy through the lowering of oxidative stress, inflammation, hyperglycemia, hypertension, and inappropriate angiogenesis. Nutrients thought to protect against chronic eye disease are discussed and include carotenoids lutein and zeaxanthin, zinc, vitamin C, vitamin E, omega-3 fatty acids, and vitamin D. A variety of non-nutritive food substances may influence eye health but are less well understood. However, single nutrient strategies for lowering the onset and progression of eye diseases are not likely to be as effective as strategies that involve nutrient-rich diet patterns as part of a healthy lifestyle. Evidence from clinical trials and observational studies suggests that introducing nutrient-rich dietary patterns and physical activity slow the destructive physiological processes that contribute to aging of the eye and are more likely than single nutrients to improve eye health as people age. Research is also emerging about the potential importance of obtaining lutein and zeaxanthin early in life. Specific levels of nutrients or types of nutrient-rich dietary patterns needed for optimal eye health and vision throughout life are largely unknown and likely depend on other aspects of lifestyle and genetic makeup.

Persons with disabilities have been underrepresented in the science, technology, engineering, and mathematics (STEM) fields for many years. Reasons for this include low expectations for students with disabilities, limited exposure to prerequisite courses, lack of role models, and lack of access to individualized supports. This article identifies the issues related to the participation of students with learning disabilities and emotional and behavioral disorders in STEM college programs and provides transition planning strategies for assisting and encouraging students as they prepare for and succeed in STEM programs. A case study of a student with a disability who had a goal of pursuing a STEM career illustrates the issues commonly faced by students with disabilities. Research-based planning strategies addressing these issues that help ensure student success are provided.

Objective To identify factors predictive of negative ureteroscopy (URS). Although computed tomography (CT) scans are sensitive in assessing upper tract calculi, there is increased effort to limit CT radiation exposure. On occasion, patients undergo URS and it is discovered that the stone has already passed. Methods Retrospective chart review was conducted on all URS cases for renal and ureteral stones performed by a single surgeon from August 2003 to May 2008. Renal units were examined separately and excluded for stone size >10 mm, staged procedures, and previously placed ureteral stents. Negative URS cases were compared with those where stones were identified for differences in stone size, location, presence of preoperative pain, time interval since CT, presence of hydronephrosis, and use of medical expulsive therapy (MET). Results Two-hundred fifty-six cases were identified. Twenty-five of 256 renal units (9.8%) did not have stones upon direct visualization. Stone size ( P P = .043) were significantly associated with outcome on univariate analysis. On multivariate analysis, only stone size was significant ( P Conclusion Negative URS occurred in almost 10% of cases, with reasonable chance of spontaneous stone passage. Our data support smaller stone size and distal location as predictive of negative URS as opposed to preoperative pain, presence of hydronephrosis, and use of MET. Time interval since CT was not predictive. Rate of negative ureteroscopy is not insignificant, thus patients with small, distal stones who elect to undergo URS should be counseled regarding negative URS with an alternative being repeat imaging.

Objectives: Fruit and vegetable consumption may impact development of diabetes, but limited research has addressed whether daily consumption of fruits and vegetables differs by those with and without diabetes, especially within high-risk groups. Thus, the purpose of this study was to determine whether daily fruit and vegetable consumption differs by diabetes status in middle-aged females in the general US population. Methods: This cross-sectional analysis used 2017 Behavioral Risk Factor Surveillance System data for females ages 45–64 years old in Arizona (n = 2609), Florida (n = 3768), Georgia (n = 1018), and Texas (n = 2092). Multiple logistic regression analysis by state assessed the relationship between the daily consumption of fruit (fruit, 100% fruit juice) and vegetables (green leafy or lettuce salad, potatoes, other vegetables) and diabetes status, while controlling for health status, health behaviors, demographic factors, and socioeconomic status. Results: Across states, relatively similar proportions of participants with and without diabetes reported daily fruit consumption (with: 58%–63%; without: 61%–68%) and daily vegetable consumption (with: 58%–63%; without: 61%–68%). The results of adjusted analyses indicated that daily fruit and vegetable consumption did not differ by diabetes status across states. Conclusion: Across states, daily fruit and vegetable consumption did not differ by diabetes status in middle-aged females. In the primary care setting, providers should educate all females ages 45–64 on the importance of eating fresh fruits and vegetables and may consider sharing information about flavonoid-rich fruit and vegetable consumption for diabetes.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To determine if preoperative variables, including gender, age and tumour size, influence the decision for active surveillance of renal masses, as due to the increasing detection of incidental renal masses within the ageing population there is a need to identify reliable means of selecting patients who require therapy. PATIENTS AND METHODS We retrospectively identified all renal masses resected at our institution between 1 December 1999, and 1 October 2005. The size of tumour, patient age and gender were compared between those with and without malignancy on final pathology. The influence of these variables in predicting malignancy, high grade, and high stage were assessed by univariate and multivariate analysis using logistic regression models, with a significance level of P 3 cm and those aged ≤75 or >75 years. RESULTS Among 466 of 501 patients with evaluable data, univariate analysis showed that both male gender and increasing size positively predicted malignancy (odds ratio 1.13 and 1.40, respectively), but age, treated as a continuous variable, did not. On multivariate analysis both remained independent predictors of malignancy (odds ratio 1.13 and 1.40, respectively). Size was the only independent predictor of high-stage and high-grade disease on both univariate and multivariate analysis. Among 156 patients with tumours of ≤3 cm, on multivariate analysis, male gender was only weakly associated with the risk of malignancy, whereas size remained strongly predictive (odds ratio 1.98, P = 0.076; and 2.16, P = 0.015, respectively). Neither male gender, size nor age increased the risk of high-stage or high-grade disease in this cohort. Patients who were aged >75 years had a greater risk of high-stage disease than those aged 75 years remained an independent predictor of malignancy and high-stage, along with size (odds ratio 2.75, P = 0.014; and 1.35, P 75 years there was a higher risk of malignancy and high-stage disease than in those aged ≤75 years. As such, the decision for observation should not be based upon age alone, and should be approached with caution in patients aged >75 years, particularly for larger lesions.

Recent preclinical data have indicated that erythropoietin (Epo) can protect organs from ischemic damage. We evaluated the ability of Epo to protect the kidney from the effects of ischemia.Thirty dogs underwent a laparoscopic nephrectomy and were allowed to recover for 2 weeks. The dogs were then divided into five groups. Animals in groups 1 and 2 underwent 1.5 hours of abdominal insufflation with placebo (saline) injection (group 1) or Epo injection (group 2) before; groups 3 to 5 underwent 1 hour of laparoscopic renal artery clamping after placebo injection (group 3), Epo injection (group 4), or mannitol injection (group 5). Serum evaluations and 24-hour urine collections were performed weekly. After 28 days, the animals were sacrificed. Statistical analysis was performed with the Kruskal-Wallis test.After recovery from the initial nephrectomy, all dogs had similar serum hematocrit and creatinine levels. Hematocrit was not significantly affected by Epo administration at any time point. Immediately after the second surgery, dogs that underwent renal artery clamping (groups 3-5) had significantly lower 24-hour urine creatinine levels than those that were not clamped (groups 1-2). After 4 weeks of recovery, the dogs that had received Epo before ischemia (group 4) had recovered significantly more renal function than the dogs that received placebo or mannitol before ischemia (urine creatinine level = Epo 149.1 mg/dL v placebo 70.7 mg/dL v mannitol 80.7 mg/dL). At sacrifice, microalbuminuria was also significantly less in dogs receiving Epo before ischemia than their mannitol or placebo counterparts.The current study demonstrates that administering Epo before warm ischemia can improve the recovery of renal function after ischemia better than placebo or mannitol.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy associated with thrombocytopenia and thrombosis. The diagnosis of HIT is based on clinical criteria and laboratory tests, including the serotonin release assay (SRA). Because HIT patients are thrombocytopenic, platelet (PLT) transfusions may be contemplated; however, many published reviews have concluded that PLT transfusions are contraindicated in HIT because they may precipitate thrombotic events. This study reports four patients with clinically suspected HIT who received PLT transfusions without complications, and the literature regarding this subject has been reviewed. STUDY DESIGN AND METHODS: Patients with a SRA ordered for suspected HIT were retrospectively identified. Charts of patients with positive SRAs who received a PLT transfusion when HIT was clinically suspected were reviewed for evidence of PLT transfusion safety and efficacy. A comprehensive search of the published literature regarding PLT transfusions in patients with HIT was conducted. RESULTS: A SRA was performed on 189 patients with suspected HIT. Thirteen patients tested positive and 4 of these received a PLT transfusion. No patient developed a thrombotic complication. All 4 patients had adequate posttransfusion PLT increments. Two of the 3 patients with active bleeding had cessation of bleeding after transfusion. Review of the literature revealed no case of a complication clearly attributable to PLT transfusion. CONCLUSION: Four patients with clinically suspected HIT and a positive SRA were transfused PLTs both efficaciously and safely. These outcomes, combined with the results of the literature review, suggest that PLT transfusions should not be withheld when clinically indicated in patients with HIT.

Localized articular cartilage lesions of the humeral head can be a source of persistent pain and functional decline in patients who have failed conservative treatment measures. Many are younger, active patients who pose a challenging management decision for surgeons. The goals of treatment should focus on maintaining humeral bone stock, restoring the contour of the articular surface, minimizing soft-tissue disruption, and relieving symptoms. There has been a trend toward humeral resurfacing arthroplasty and away from stemmed components over the past few decades for younger patients potentially requiring future revision surgery. More recently, the HemiCAP resurfacing system (Arthrosurface, Franklin, MA) has been used for localized defects in patients with Hill-Sachs and reverse Hill-Sachs lesions, avascular necrosis, focal chondral defects, and humeral head osteoarthritis. Early, short-term outcome results of the HemiCAP system are encouraging. In this article, we describe our technique for management of localized articular cartilage defects of the humeral head using the HemiCAP resurfacing system.

In the past decade, remarkable relationships have been documented between dysbiosis of the human microbiota and adverse health outcomes. This review seeks to highlight some of the challenges and pitfalls that may be encountered during all stages of microbiota research, from study design and sample collection, to nucleic acid extraction and sequencing, and bioinformatic and statistical analysis.Literature focused on human microbiota research was reviewed and summarized.Although most studies have focused on surveying the composition of the microbiota, fewer have explored the causal roles of these bacteria, archaea, viruses, and fungi in affecting disease states. Microbiome research is in its relatively early years and many aspects remain challenging, including the complexity and personalized aspects of microbial communities, the influence of exogenous and often confounding factors, the need to apply fundamental principles of ecology and epidemiology, the necessity for new software tools, and the rapidly evolving genomic, technological, and analytical landscapes.Incorporating human microbiome research in large epidemiologic studies will soon help us unravel the intricate relationships that we have with our microbial partners and provide interventional opportunities to improve human health.

Normal hip range of motion (ROM) is essential in running and transfer of energy from lower to upper extremities during overhead throwing. Dysfunctional hip ROM may alter lower extremity kinematics and predispose athletes to hip and groin injuries. The purpose of this study is characterize hip internal/external ROM (Arc) and its effect on the risk of hip, hamstring, and groin injuries in professional baseball players. Bilateral hip internal and external ROM was measured on all baseball players (N=201) in one professional organization (major and minor league) during spring training. Players were organized according to their respective positions. All injuries were documented prospectively for an entire MLB season (2010 to 2011). Data was analyzed according to position and injuries during the season. Total number of players (N=201) with an average age of 24±3.6 (range=17-37). Both pitchers (N=93) and catchers (N=22) had significantly decreased mean hip internal rotation and overall hip arc of motion compared to the positional players (N=86). Players with hip, groin, and hamstring injury also had decreased hip rotation arc when compared to the normal group. Overall, there is a correlation between decreased hip internal rotation and total arc of motion with hip, hamstring, and groin injuries.