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Objective: To assess 5-year oncologic outcomes following primary partial gland cryo-ablation (PPGCA) in intermediate-risk prostate cancer., Methods: Of 476 men undergoing PPGCA enrolled in our prospective oncologic and functional outcomes study, 313 had magnetic resonance imaging (MRI) concordant intermediate-risk prostate cancer with no out-of-field Gleason grade group ≥2, gross extracapsular extension, or extreme apical disease on pre-treatment multi-parametric MRI. Prostatic-specific antigen was monitored every 6 months, and multi-parametric MRI at 6 to 12, 24, 42, and 60 months. Protocol biopsies at 6-12 months and 24 months were discontinued after interim analysis showing low rates of clinically significant prostate cancer (csPCa) defined as any Gleason grade group ≥2 disease. Freedom-from-failure was defined as no prostate cancer-specific mortality, metastatic disease, or whole-gland salvage treatment., Results: csPCa was detected in 33 (10.5%) subjects. Ninety-one had ≥4.5 years of follow-up data with a mean of 8.9, 3.4, and 2.0 surveillance prostatic-specific antigen tests, MRIs, and prostate biopsies; none were lost to follow-up. At 5 years, rates of freedom-from-recurrence of in-field, out-of-field, and overall csPCa were 86% (95% confidence interval [CI]: 78-96), 85% (95% CI: 63-94), and 70% (95% CI: 57-84). The proportion with freedom-from-failure at 5 years was 89% (95% CI: 83-95). None died from prostate cancer, 1 (1%) developed metastasis, 15 (16.5%) underwent whole-gland salvage treatment, and 15 (16.5%) underwent salvage focal therapy. Only 3 of 91 (3.3%) eligible men were non-compliant with 5-year surveillance protocol., Conclusion: Very encouraging intermediate-term oncological outcomes following PPGCA were observed with very high compliance to a rigorous prospective protocol for identifying recurrent csPCa., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Local disease recurrence following focal therapy (FT) for prostate cancer may be due to failure to eradicate focal disease or development of disease in the untreated prostate (in- and out-of-field recurrences). Several studies suggest in-field contrast enhancement (CE) on post-treatment multi-parametric (mp) MRI between 6-12 months following FT indicates residual disease. The present study assesses the incidence and oncologic implications of early CE observed following primary partial gland cryoablation (PPGCA)., Material and Methods: The surveillance protocol for men enrolled in our prospective outcomes study following PPGCA included mpMRI at 6-12 months, 2 years, 3.5 years, and 5 years. All cases of in-field early CE were re-reviewed retrospectively and graded using the previously described Prostate Imaging after Focal Ablation scoring system. All patients exhibiting early CE were re-evaluated by a single radiologist at 2-year mpMRI Results: A total of 320 men enrolled in our PPGCA outcomes study had at least 6 months of follow up. Three hundred fifteen (98%) of these men had undergone post-PPGCA mpMRI at 6-12 months. Of these men, 9 were found to have early in-field CE and 8 underwent repeat MRI at 2 years. In all 8 cases, the CE resolved on the 2-year mpMRI. Of these 8 patients, seven underwent repeat protocol biopsy at 2 years and in-field significant disease was detected in only 1 case., Conclusions: The most compelling evidence that early CE is not indicative of prostate cancer recurrence is that all lesions resolved within 24 months. While incidence of early CE is low, its consistent resolution calls into question the clinical significance of this finding after PPGCA.

Objectives: In 2018, approximately 2.3 million children in the United States had unmet healthcare needs (UHCN). To date, studies examining associations between UHCN and parent stress and support have had limited generalizability. This study aimed to investigate the relationship between children's UHCN and parenting stress and support using a nationally representative sample. Additionally, this study aimed to assess associations between unmet mental health needs and these parental well-being measures., Methods: Households with children ages 0-17 and complete data on UHCN in the combined 2016, 2017, 2018, and 2019 cohorts of the National Survey of Children's Health (NSCH) met inclusion criteria. Logistic regressions were used to evaluate associations between overall UHCN and outcome measures of parental coping, aggravation, emotional support, and neighborhood support. Associations between mental UHCN and these outcome measures were analyzed in a subset limited to children with mental health conditions. Regressions were adjusted for potential confounders, including demographics, household income, medical home status, and health insurance (adequacy/type)., Results: In our sample of 131,299 children, overall UHCN were associated with poorer parental coping (aOR = 5.35, 95% CI: [3.60, 7.95]), greater parental aggravation (aOR = 3.35, 95% CI: [2.73, 4.12]), and non-supportive neighborhood (aOR = 2.22, 95% CI: [1.86, 2.65]). Mental UHCN were similarly associated with parental coping and aggravation and neighborhood support in the mental health subset., Conclusions for Practice: Healthcare professionals must address the needs of children with UHCN and collaborate with community organizations and child advocates to promote coordinated and comprehensive care and adequately support caregivers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Post-vasectomy semen analysis (PVSA) completion rates after vasectomy are poor, and minimizing the need for an additional in-person visit may improve compliance. We hypothesized that providing PVSA specimen cup at time of vasectomy instead of at a postoperative appointment might be associated with higher PVSA completion rates., Methods: We performed a retrospective cohort study with historical control using medical records of all patients seen by a single provider for vasectomy consultation between October 2016 and June 2022. All patients who underwent vasectomy were included. Patients who underwent vasectomy prior to 05/01/2020 had PVSA specimen cup given at postoperative appointment two weeks following vasectomy, and those who underwent vasectomy after 05/01/2020 were given PVSA specimen cup at time of vasectomy. PVSA completion, demographic, and clinical outcomes data were collected. Logistic regressions were used to investigate associations between PVSA completion rates and timing of PVSA specimen cup provision., Results: There were no significant differences among study cohorts across all patient demographics analyzed, including age, body mass index (BMI), age of primary partner, presence of children, and history of prior genitourinary infection. A total of 491 patients were seen for vasectomy consultation between October 2016 and June 2022; among these patients, 370 underwent vasectomy. Of these, 173 (46.8%) patients underwent vasectomy prior to 05/01/2020 and were given PVSA specimen cup at postoperative visit; 197 (53.2%) patients underwent vasectomy after 05/01/2020 and were given PVSA specimen cup at vasectomy. Providing PVSA specimen cup at time of vasectomy was associated with higher odds of PVSA completion than providing PVSA specimen cup at postoperative visit [62.4% vs. 49.7%; odds ratio (OR) =1.68; 95% confidence interval (CI): 1.11, 2.55]. Adjusting for all identified confounders excludes 35 (9.5%) patients without a primary partner and shows no statistically significant association in cup timing [adjusted OR (aOR) =1.53; 95% CI: 0.98, 2.39]. Adjusting for all identified confounders except age of primary partner revealed timing of specimen cup provision at time of vasectomy was associated with higher odds of PVSA completion (aOR =1.64; 95% CI: 1.08, 2.52)., Conclusions: PVSA specimen cup provision at time of vasectomy versus at postoperative appointment is associated with higher rates of PVSA completion in this retrospective cohort study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-400/coif). The authors have no conflicts to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Background: Prostate cancer treatment-related regret (TRR) incorporates the myriad effects of diagnosis and treatment with associated behavioral, emotional, and interpersonal changes within the context of patient values and expectations. We aimed to investigate TRR following primary partial gland cryoablation (PPGCA)., Methods: Men with prostate cancer undergoing PPGCA since 3/2017 enrolled in a prospective outcome registry. Between June and August 2022, a validated prostate cancer related TRR decision scale was distributed. TRR score ≥40 was considered significant TRR. Men were considered potent if they reported ability to have penetration at least half the time sexual intercourse was initiated. Associations between significant TRR and baseline characteristics and longitudinal outcomes were assessed using logistic regressions., Results: Of 245 men who met inclusion criteria, 163 (67%) completed the survey with median time since cryoablation 2.3 years (IQR: 1.3, 3.6). Overall, the mean composite TRR score was 12.4/100. Significant TRR was expressed by 14% of men. Among those who were potent/had erectile function at baseline, loss of potency and erectile function were associated with higher probability of significant TRR, respectively. No associations were identified between TRR and recurrence of clinically significant prostate cancer or salvage treatment., Conclusions: The overwhelming majority of men do not express TRR following PPGCA. The loss of potency or development of erectile dysfunction predisposes to TRR. It is imperative to elucidate short-, intermediate- and long-term functional and oncological outcomes in order to define factors associated with TRR to improve counseling and reduce patient regret., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: ChatGPT is an artificial intelligence platform available to patients seeking medical advice. Traditionally, urology patients consulted official provider-created materials, particularly the Urology Care Foundation™ (UCF). Today, men increasingly go online due to the rising costs of health care and the stigma surrounding sexual health. Online health information is largely inaccessible to laypersons as it exceeds the recommended American sixth to eighth grade reading level. We conducted a comparative assessment of patient education materials generated by ChatGPT vs UCF regarding men's health conditions., Methods: All 6 UCF men's health resources were identified. ChatGPT responses were generated using patient questions obtained from UCF. Adjusted ChatGPT responses were generated by prompting, "Explain it to me like I am in sixth grade." Textual analysis was performed using sentence, word, syllable, and complex word count. Six validated formulae were used for readability analysis. Two physicians independently scored responses for accuracy, comprehensiveness, and understandability. Statistical analysis involved Wilcoxon matched-pairs test., Results: ChatGPT responses were longer and more complex. Both UCF and ChatGPT failed official readability standards, although ChatGPT performed significantly worse across all 6 topics (all P < .001). Conversely, adjusted ChatGPT readability typically surpassed UCF, even meeting the recommended level for 2 topics. Qualitatively, UCF and ChatGPT had comparable accuracy, although ChatGPT had better comprehensiveness and worse understandability., Conclusions: When comparing readability, ChatGPT-generated education is less accessible than provider-written content, although neither meets the recommended level. Our analysis indicates that specific artificial intelligence prompts can simplify educational materials to meet national standards and accommodate individual literacy.

Introduction: The COVID-19 pandemic has fueled widespread incorporation of telehealth into urology practices. Vasectomy consultation via telehealth is convenient and improves access to care for male contraception. However, it does not allow for physical examination, inherently leading to possible day-of-procedure cancellations due to unforeseen anatomic concerns. This study aimed to compare vasectomy completion rates between patients undergoing virtual vs in-person consultation., Methods: All patients seen by a single provider at NYU Langone Health for vasectomy consultation between October 2016 and June 2022 were included in the study. Most patients seen before March 2020 had in-person consultations, whereas the majority of patients seen afterwards had virtual consultations without option for in-person visit due to the emergence of COVID-19. All patients seen virtually were examined in a consult room prior to being prepped for the vasectomy in the procedure room. Visit type, demographic information, and clinical outcomes data were collected for all patients. A chi-square test was used to compare the rate of vasectomy completion between those with in-person and virtual consultation. Analysis was performed using R, version 4.0.5., Results: Four hundred ninety-one patients were seen by a single provider for vasectomy consultation between October 2016 and June 2022. One hundred ninety-seven (40.1%) consultations were performed virtually and 294 (59.9%) consultations were performed in person. Three hundred seventy (75.4%) of all patients seen for consultation (both virtual and in person) ultimately underwent vasectomy. There was no evidence of difference in rate of completing vasectomy after virtual (75.6%) and in-person (75.2%) consultation ( P = .91). Two of the 197 (1%) patients who consulted virtually had their vasectomy procedures cancelled on the day of the procedure based on their preoperative exam; one because of abnormal epididymal sensitivity after prior scrotal infection, the other because of a history of orchiopexy that the patient was not aware of until the surgeon started inquiring about scrotal scars present., Conclusions: Despite the lack of physical examination, virtual vasectomy consultation is both feasible and effective, with rates of vasectomy completion comparable to traditional in-person consultation.

Purpose: We evaluated 3-year oncologic outcomes following primary partial gland cryoablation., Materials and Methods: Men with unilateral intermediate-risk prostate cancer undergoing primary partial gland cryoablation since March 2017 enrolled in a prospective outcome registry. The postablation protocol for all men included surveillance prostate biopsy at 2 years postablation and reflex prostate biopsy for cases with high suspicion of recurrence (eg, progressive rise in PSA). Recurrence of clinically significant prostate cancer was defined as any Gleason grade group ≥2 disease on postablation biopsy. Freedom from failure represented no whole gland salvage treatment, metastatic prostate cancer, or prostate cancer mortality. Freedom from recurrence and freedom from failure were characterized using nonparametric maximum likelihood estimators., Results: A total of 132 men had at least 24 months of follow-up data. Biopsies identified clinically significant prostate cancer in 12 men. At 36 months, model-estimated rates of freedom from recurrence of in-field, out-of-field, and overall clinically significant cancer were 97% (95% CI: 92-100), 87% (95% CI: 80-94), and 86% (95% CI: 78-93), respectively. The model-estimated proportion with freedom from failure at 36 months was 97% (95% CI: 93-100)., Conclusions: The low in-field cancer detection rate at 3 years indicates successful ablation of localized cancers. Conversely, our observed out-of-field detection rate highlights the need for continued surveillance following partial gland cryoablation. Many of these recurrences exhibited very low volume of clinically significant disease below the detection threshold of multiparametric MRI, suggesting a limited role for multiparametric MRI in detecting clinically significant recurrences at 2 years. These findings emphasize the need for long-term surveillance and identification of predictors of clinically significant prostate cancer recurrences to guide biopsy timing.

Purpose: Children with chronic conditions are at increased risk of bullying involvement. In addition to examining associations between chronic health conditions and both victimization and perpetration, this study investigated whether condition severity is associated with bullying involvement., Methods: A secondary analysis of the 2018-2019 National Survey of Children's Health was performed. Children ages six-17 (n = 42,716) were classified as perpetrators (if bullied others ≥one-two times/month), victims-only (if victimized ≥one-two times/month and not a perpetrator) or uninvolved in bullying (neither perpetrator nor victim-only). Survey-weighted multinomial logistic regressions were used to investigate associations between bullying involvement and 13 chronic medical and developmental/mental health conditions. For children with conditions associated with being a victim and/or perpetrator, multinomial logistic regressions were used to further investigate associations between condition severity and victimization or perpetration., Results: All 13 conditions were associated with higher odds of victimization. Seven developmental/mental health conditions were associated with higher odds of perpetration. Condition severity was associated with at least one domain of bullying involvement for one chronic medical and six developmental/mental health conditions. Notably, among children with attention-deficit/hyperactivity disorder, learning disability, or anxiety, condition severity was associated with higher odds of being a victim or bully/bully-victim., Discussion: Condition severity may be a risk-factor for bullying involvement for many developmental/mental health conditions. Future condition-specific analyses are needed that directly examine bullying involvement among children with varying severity of individual conditions like attention-deficit/hyperactivity disorder, learning disability, and anxiety, using a clear operational definition for bullying, objective measures of condition severity, and multiple informants of bullying involvement., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), p < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), p < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.

Background: To identify gaps in urologic oncology quality and evidence-based smoking cessation care by assessing how often smoking cessation pharmacotherapy (SCP) is given in the inpatient setting following cystectomy., Methods: The Premier Healthcare Database (PHD), a deidentified all-payer dataset, was used to generate nationally representative estimates of SCP receipt during hospitalization following cystectomy for patients with bladder cancer who smoke. Regressions were used to model associations between SCP receipt and patient- and hospital-level factors., Results: Of the 21,624 patients who underwent cystectomy for bladder cancer, 3,676 patients (17.0%) were identified as current smokers, representing a weighted estimate of 16,063 admissions. Among these admissions, 27.9% of patients received SCP, the vast majority of which (91.5%) received exclusively nicotine replacement therapy. Rates of SCP receipt varied substantially across hospitals (median: 25.0%, IQR: 20.0-33.3, range: 0.0-60.0). Older age and black race (aOR = 0.59, 95% CI: 0.42-0.82) were associated with lower odds of SCP receipt. Increased patient comorbidity score was associated with higher odds of SCP receipt (aOR = 1.02, 95% CI: 1.01-1.03); specifically, chronic pulmonary disease, alcohol abuse, and depression were independently associated with SCP receipt. Hospital teaching status, bed capacity, and mean annual cystectomy volume were not associated with SCP receipt. SCP receipt was not associated with hospital length of stay nor 90-day readmission or mortality following cystectomy., Conclusions: SCP is infrequently given to patients who smoke during their hospitalization following cystectomy for bladder cancer, representing a gap in quality urologic oncology care and a missed opportunity to effectively intervene with evidence-based treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The incidence of keratinocyte carcinomas (KCs), comprising basal and squamous cell carcinomas, is rising in the United States. Chemoprevention is one modality by which patients can reduce the incidence of KCs., Methods: We performed a retrospective review of 327 patients who employed a combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream in a field therapy regimen over the face/ears or scalp for chemoprevention., Results: Patients had dramatically lower odds of having KCs in the treatment location (face/ears or scalp) in the one-year period after field treatment than in the one-year period preceding field treatment (OR=0.06, 95% CI: [0.02, 0.15]). Patients were also at lower odds of having KCs in non-treated areas the year after field treatment than in the year preceding it (OR=0.25, 95% CI: [0.14, 0.42]). Additionally, fewer cryotherapy sessions were performed for actinic keratoses in the treatment areas in the year after treatment (mean=1.5, SD=1.21) than the year preceding treatment (mean=2.3, SD=0.99; t=11.68, P&lt;0.001)., Conclusions: A combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream were effective at reducing the incidence of new KCs for at least one year. Individualized treatment application frequency allowed for increased patient adherence. Prospective studies evaluating combination topical treatments for chemoprevention of KCs are needed to further assess the treatment effects found in this study. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7334.

Background and Objectives: Electronic vapor products (EVPs) have gained popularity among adolescents despite the health risks. This study aimed to evaluate whether sports team participation, a well-established protective factor against cigarette use, is similarly associated with decreased EVP use., Methods: This cross-sectional study analyzed the 2015-2019 Youth Risk Behavior Survey cohorts. Survey-weighted logistic regressions investigated associations between sports team participation and past 30-day exclusive cigarette use, exclusive EVP use, and dual cigarette/EVP use among US high school students, adjusting for sex, grade, and survey year., Results: The analytic cohort included 16 790 sports team participants (1.7% exclusive cigarette users, 18.3% exclusive EVP users, 5.5% dual users) and 13 972 nonparticipants (3.1% exclusive cigarette users, 13.4% exclusive EVP users, 7.6% dual users). Sports team participation was associated with lower odds of cigarette use (adjusted odds ratio [aOR], 0.58; 95% confidence interval [CI], 0.48-0.71) and dual use (aOR, 0.74; 95% CI, 0.63-0.88) and higher odds of EVP use (aOR, 1.39; 95% CI, 1.25-1.54). Among exclusive cigarette users and exclusive EVP users, sports team participation was associated with lower odds of frequent (≥20 days in the past month) than intermittent (1-19 days in the past month) cigarette use (aOR, 0.30; 95% CI, 0.19-0.49) and EVP use (aOR, 0.74; 95% CI, 0.61-0.91), respectively., Conclusions: Our findings suggest that risk profiles for cigarette and EVP use differ with respect to sports team participation. Given the health risks associated with EVP use, aggressive efforts must be taken to educate student athletes about the health risks of EVP use., (Copyright © 2023 by the American Academy of Pediatrics.)

Objective: To critically evaluate time dependent sexual function following primary partial gland cryo-ablation (PGCA) stratified according to baseline erectile function., Methods: Between March 2017 and March 2022, all men undergoing primary PGCA by 2 surgeons were enrolled in an IRB approved outcomes registry. All subjects with PIRADS 2-5 lesion concordant with unilateral GGG 1-3 disease, no gross extra-prostatic extension on mpMRI, GGG >1 contralateral to the ROI, or distal apical disease on mpMRI were enrolled. Patients completed the Sexual Health Inventory for Men (SHIM) scale at baseline, 6, and 24 months. Men were stratified by baseline erectile function. Men with SHIM Score < 8 were excluded. Ability to sustain erection (aka "potency") was defined as a score of 3 or greater on question 2 of the SHIM index. Median SHIM scores and the proportion of men reporting "potency" at baseline, 6, and 24 months was recorded with comparisons between each timepoint. A univariate analysis was used to determine if clinical factors were associated with loss of "potency" at 24 months., Results: 106 men met the inclusion criteria. There was a statistically significant decrease in the mean SHIM scores for the entire cohort between baseline to 6 months and baseline to 24 months. SHIM scores increased significantly for the total cohort between 6 and 24 months. "Potency" was preserved in 70% at 24 months., Conclusion: Those patients most likely to exhibit a decrease in sexual function have moderate ED at baseline. Only baseline ED was shown to predict preservation of "potency"., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lyme disease is the fastest growing vector-borne disease in the United States. However, current testing modalities are ill suited to detection of Lyme disease, leading to the diagnosis of many cases after treatment is effective. We present an improved, direct method Lyme disease diagnosis, where the Lyme specific biomarker Outer Surface Protein A (OspA) in clinical serum samples is identified using a diagnostic platform combining surface enhanced Raman scattering (SERS) and aptamers. Employing orthogonal projections to latent structures discriminant analysis, the system accurately identified 91% of serum samples from Lyme patients, and 96% of serum samples from symptomatic controls. In addition, the OspA limit-of-detection, determined to be 1 × 10 -4 ng/mL, is greater than four orders of magnitude lower than that found in serum samples from early Lyme disease patients. The application of this platform to detect this difficult-to-diagnose disease suggests its potential for detecting other diseases that present similar difficulties., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate associations between ADHD medication and household chore performance by children with ADHD., Methods: A parent questionnaire collected information about the adequacy and quality of their child's performance of two self-care and six family-care chores. Parent perceptions of ADHD medication effect duration were used to identify children with after-school medication benefits (ASMB). Mann-Whitney U tests compared children with and without ASMB across measures of chore performance., Results: A total of 565 parents of children with ADHD that regularly take medication completed the questionnaire. Children with ASMB were more likely to meet parental expectations for five of eight household chores and were more likely to be able to independently complete both self-care and family-care chores than those without ASMB. No differences were noted regarding their need for reminders or assistance with chores., Conclusion: Improvement in chore performance may be an additional consideration with respect to medication selection for children with ADHD.

Background: The current study explored how to recruit patients soon after a traumatic event, to deliver a novel intervention in a new emergency department in Sweden. This brief behavioral intervention aims to prevent intrusive memories and is delivered soon after trauma in the emergency department. In the UK, it has shown promising results. Traumatic events resulting in admission to the emergency department (e.g., road traffic accidents) may result in subsequent mental health problems such as post-traumatic stress disorder, where intrusive memories of the trauma constitute a core clinical feature. Early interventions that prevent intrusive memories after psychological trauma are lacking. Specific aims were to explore identification of eligible patients (aim 1), fitting in with emergency department staff routines to deliver the study protocol (aim 2), and using the patients' own smartphones to deliver intervention/control task (aim 3). Two changes to the previous study were (i) extending the trauma types included (ii) a new control condition, also by smartphone., Methods: This is an explorative observational study. Data was both analyzed descriptively and using the Framework method., Results: We identified several possible ways to recruit patients, and establish a sense of embeddedness in the Swedish emergency department context and a positive appreciation from staff. The study protocol was tested with 8 participants. Tasks both in the intervention and control condition were readily delivered via patients' own smartphones., Conclusion: Recruitment of patients and smartphone delivery of the intervention indicates initial feasibility. Researcher presence and administration of study procedures was successfully fitted to emergency department routines and well received by staff. Further pilot work is warranted, underscoring the importance of our collaboration between nursing and psychology., (© 2021. The Author(s).)

Objective: As preschool enrollment increases, it is important to know whether children enrolled in preschool are more likely to be "healthy and ready to learn (HRTL)." Our objective was to assess whether there are detectable school readiness differences between children enrolled in preschool and those who are not in a large, cross-sectional, nationally representative US sample., Methods: Caregivers of 4931 3- to 4-year-old children in the 2016 National Survey of Children's Health indicated whether their child had started school and completed questions forming the "HRTL" School Readiness National Outcome Measure and its domains: early learning skills, self-regulation, social-emotional development, and physical health/motor development. Propensity score-matched logistic regression models estimated prevalence ratios (PRs) comparing children in versus not in preschool., Results: 49.1% of children had started preschool. After matching, children in preschool did not differ from children not in preschool on the composite (PR = 1.21; 95% confidence interval [CI]: 0.92-1.58) or any domains. Children in preschool were more likely to be "on track" with rhyming words (PR = 1.48; 95% CI: 1.11-1.96), writing their name (PR = 2.36; 95% CI: 1.82-3.08), and holding a pencil (PR = 1.55; 95% CI: 1.12-2.14) but less likely with explaining things they have seen/done (PR = 0.59; 95% CI: 0.44-0.79) and overall health (PR = 0.57; 95% CI: 0.33-0.97). Some associations were sex specific., Conclusion: The largely null findings of this study underscore the need for further research that incorporates information regarding the extent and quality of preschool exposure when evaluating the developmental benefits of preschool on a national level., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the relationship between ADHD and performance of household chores. Method: A 72-question online questionnaire was developed to collect demographic/clinical information as well as parents' assessment of their child's performance of self-care (SC) and family-care (FC) chores. Results: The sample consists of 797 primary caregivers of children with ADHD. The overwhelming majority of parents believed that ADHD to some extent affected their child's ability to independently and satisfactorily complete SC and FC chores. An inverse relationship was noted between parent ratings of a child's ability to do chores independently and satisfactorily and the likelihood they believed ADHD affected chore performance. There was no difference in chore performance between children with or without co-morbid oppositional defiant disorder. Conclusion: Given that household routines, including chores, play an important role in children's development and psychosocial adjustment, clinicians must be sensitive to the adverse impact that ADHD may have in this regard.

Background: School closures and other public health responses have decreased the extent that children interact with mandated reporters and other professionals trained to detect child maltreatment., Objective: To assess associations between the pandemic public health response and the number of allegations of child abuse or neglect., Methods: This study analyzed monthly data from New York City of the number of child maltreatment allegations, stratified by reporter type (e.g., mandated reporter, education personnel, healthcare personnel), as well as the number of Child Protective Services (CPS) investigations warranting child welfare preventative services. SARIMA models were trained using data from January 2015 to February 2020 to predict expected values for March, April, and May 2020. Observed values were compared against predicted values at an alpha of .05., Results: Substantially fewer allegations of child maltreatment were reported than expected in March (-28.8 %, deviation: 1848, 95 % CI: [1272, 2423]), April (-51.5 %, deviation: 2976, 95 % CI: [2382, 3570]), and May 2020 (-46.0 %, deviation: 2959, 95 % CI: [2347, 3571]). Significant decreases in child maltreatment reporting were also noted for all reporter subtypes examined for March, April, and May 2020. Fewer CPS investigations warranted preventative services than expected in March 2020 (-43.5 %, deviation: 303, 95 % CI: [132, 475])., Conclusions: Precipitous drops in child maltreatment reporting and child welfare interventions coincided with social distancing policies designed to mitigate COVID-19 transmission. In light of these findings, educators and healthcare providers must be especially vigilant when engaging online with children and their families for signs of child abuse and/or neglect., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Breastfeeding has been associated with a lower risk of attention-deficit/hyperactivity disorder (ADHD). However, most studies examining this association have focused on small samples outside the United States or were likely subject to substantial residual confounding. Our objectives were to investigate, in a nationally representative sample of preschool children in the United States, the associations between ADHD and both age of breastfeeding cessation and age of formula introduction, as well as associations between ADHD and exclusive breastfeeding duration., Methods: Analysis of data from children aged 3 to 5 years in the 2011/12 National Survey of Children's Health (n = 12,793). Logistic regressions were used to model current medical diagnosis of preschool ADHD as a function of breastfeeding duration, breastfeeding exclusivity, and the timing of formula introduction with adjustment for 12 potential confounders using propensity scores, including sex, age, race, household income, prematurity, insurance, and medical home., Results: After adjustment for potential confounders, exclusive breastfeeding for at least 6 months was associated with substantially reduced odds of ADHD (adjusted prevalence odds ratio [aPOR] = 0.38; 95% confidence interval [CI], 0.15-0.99). Breastfeeding duration was also associated with ADHD, with 8% reduced odds of ADHD for each additional month of breastfeeding (aPOR = 0.92; 95% CI, 0.86-0.99). The results for exclusive breastfeeding duration were similar, but the confidence interval included the null (aPOR = 0.92; 95% CI, 0.85-1.00). The age of formula introduction was not associated with ADHD (aPOR = 0.92; 95% CI, 0.81-1.05)., Conclusion: In a nationally representative sample of preschool children, breastfeeding was associated with a lower prevalence of ADHD. These findings provide evidence in support of the neurodevelopmental benefits of breastfeeding., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A growing body of evidence supports a potential link between autism spectrum disorder (ASD) and gender dysphoria, yet few studies have looked at sex differences in the co-occurrence of gender diversity and ASD. The aim of this study was to characterize sex differences in gender-diverse expressions and identities, as well as gender-related concerns, in youth with ASD. Parents of youth with ASD ages 6-21 (n = 163) completed an online questionnaire about their child's gender expression and identity. Sex-typed behaviors during childhood were measured using the Gender Identity Questionnaire (GIQ). Semi-partial Kendall correlations and chi-square tests were used to compare gender non-conformity, gender-diverse identities, and gender-related concerns between sexes. Sex-based differences in mean GIQ score and individual GIQ items were evaluated using a linear regression and semi-partial Kendall correlations, respectively. All regressions and correlations controlled for child age. Parents of girls were more likely to report child appearances and mannerisms that were less concordant with their child's birth sex. Based on parent-report, girls had lower mean GIQ scores, indicating greater cross-gendered/fewer same-gendered behaviors in childhood. Lastly, parents of girls with ASD were more likely to report that their daughters experienced anxiety due to gender-related concerns and discomfort during puberty than parents of boys. These findings suggest that girls with ASD seem more likely have gender-diverse preferences, mannerisms, and appearances that fall outside of traditional gender norms. Gender-related concerns appear to be a source of real distress in girls with ASD, highlighting the need for individualized support, especially during puberty. LAY SUMMARY: Despite evidence of a potential link between autism and gender diversity, few studies have explored differences in gender identity/expression between boys and girls with autism. Based on parent responses, we found that girls with autism are more likely than boys to have appearances and mannerisms, as well as behaviors during childhood, that fall outside of the traditional gender role. The unique profile of girls with autism and their elevated distress over gender-related concerns call for individualized support during adolescence., (© 2020 International Society for Autism Research, Wiley Periodicals, LLC.)

Researchers have long been interested in whether lateral preference is associated with giftedness, season of birth, and/or ADHD constructs (short attention span, high level of activity, and impulsivity). The objective of this study was to examine these associations in a large, longitudinal sample of U.S. children (National Collaborative Perinatal Project (CPP), 1959-1973). Children born to women in this pregnancy cohort underwent a neonatal exam and an exam at age 7 years to assess lateral preference of the hand and eye, IQ on the Wechsler Intelligence Scale for Children (WISC), and ADHD symptoms. Children with perinatal/neonatal risk factors for neurologic impairment or early signs of neurological abnormality were excluded from our analyses. The final sample included 25,385 children. Associations between laterality and IQ were examined using linear and logistic regression models adjusted for sex, race, and socioeconomic status. Associations between laterality and ADHD symptoms and between season of birth and laterality were estimated using multivariable logistic regression. In this large, longitudinal study of neurologically healthy children, modest associations were observed between hand/eye preference and IQ and hyperactivity only.

Objective: Half of US children with autism spectrum disorder (ASD) have attempted to elope from adult supervision at least once, elevating their risk for serious injury/death. This study aimed to assess, in a sample of children with ASD aged 4 to 18 years who had previously wandered, whether electronic tracking device (ETD) use is associated with changes in the elopement behavior and household quality of life (QOL)., Methods: An anonymous, online questionnaire assessing elopement interventions, elopement behavior, household QOL, attitudes toward ETDs, and sociodemographics was distributed via US autism-related organizations to caregivers of children with ASD. Differences in retrospective estimates of elopement behavior and household QOL before ETD use and during ETD use were evaluated using Wilcoxon signed-rank tests., Results: A total of 2563 participants completed the questionnaire; 1459 participants met the inclusion criteria. For the current (n = 361) and past (n = 96) ETD users, ETD use was associated with decreased frequency and duration of elopement and decreased risk for serious injury because of elopement (all p < 0.001). ETD use was similarly associated with improvements across all 5 measures of QOL. Among the past ETD users, reasons for discontinuation included device discomfort/fit (33.3%), burden of use (27.1%), and financial cost (14.6%). Among the non-ETD users (n = 1002), common barriers to ETD use were cost (47.5%) and lack of awareness of ETD technology (18.8%)., Conclusion: Electronic tracking devices represent a promising technology to help safeguard the well-being of children with ASD while reducing the emotional toll that elopement imposes on families. Cost concerns, burden of use, and lack of awareness seem to limit the widespread adoption of ETDs.

Background and Objectives: Little is known about the 2% of US children being raised by their grandparents. We sought to characterize and compare grandparent- and parent-headed households with respect to adverse childhood experiences (ACEs), child temperament, attention-deficit/hyperactivity disorder (ADHD), and caregiver aggravation and coping., Methods: Using a combined data set of children ages 3 to 17 from the 2016, 2017, and 2018 National Survey of Children's Health, we applied survey regression procedures, adjusted for sociodemographic confounders, to compare grandparent- and parent-headed households on composite and single-item outcome measures of ACEs; ADHD; preschool inattention and restlessness; child temperament; and caregiver aggravation, coping, support, and interactions with children., Results: Among 80 646 households (2407 grandparent-headed, 78 239 parent-headed), children in grandparent-headed households experienced more ACEs (β = 1.22, 95% confidence interval [CI]: 1.07 to 1.38). Preschool-aged and school-aged children in grandparent-headed households were more likely to have ADHD (adjusted odds ratio = 4.29, 95% CI: 2.22 to 8.28; adjusted odds ratio = 1.72, 95% CI: 1.34 to 2.20). School-aged children in these households had poorer temperament (β adj = .25, 95% CI: -0.63 to 1.14), and their caregivers experienced greater aggravation (β adj = .29, 95% CI: 0.08 to 0.49). However, these differences were not detected after excluding children with ADHD from the sample. No differences were noted between grandparent- and parent-headed households for caregiver coping, emotional support, or interactions with children., Conclusions: Despite caring for children with greater developmental problems and poorer temperaments, grandparent caregivers seem to cope with parenting about as well as parents., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objective: Although the benefits of diagnosis disclosure have been recognized for a number of pediatric medical conditions, there is a paucity of research about the process by which youth with autism spectrum disorder (ASD) are informed about their diagnosis. The aim of this study was to systematically characterize the antecedents, correlates, and outcomes of diagnosis disclosure to youth with ASD., Methods: In this cross-sectional study, parents and guardians of youth with ASD (ages 8-25) completed a detailed online questionnaire about their experiences with diagnosis disclosure. The perceived impact of disclosure on affected youth was also assessed., Results: Five hundred seventy-five parents of youth with ASD (mean age: 14 years) completed the questionnaire, of whom 81% reported their affected child had been told that he or she had ASD. Most youth who had been told about their diagnosis (86%) were currently aware that they had ASD, according to the parent report. Youth awareness of the diagnosis was reported to be associated with improved self-advocacy skills (60%), enhanced self-awareness of personal strengths (69%) and weaknesses (68%), and other benefits. Youth who had sought information about ASD from support groups and other individuals with ASD had better outcomes regarding self-esteem [adjusted odds ratio = 2.73, 95% confidence interval: (1.34, 3.98)] and acceptance of the diagnosis (p = 0.001) than those who exclusively learned about ASD from other sources., Conclusion: Given the numerous potential benefits of diagnosis disclosure, there is a need for physicians and other professionals to support parents in educating youth with ASD about their diagnosis.

Objective: This study investigates whether primary care pediatricians adhere to the American Academy of Pediatrics (AAP) recommendations by routinely evaluating patients' menstrual cycles and educating patients about menstruation and feminine products. Additionally, this study examines pediatricians' knowledge and attitudes surrounding menstrual health topics., Methods: A 53-item online questionnaire was developed to evaluate pediatricians' knowledge, attitudes and clinical practices regarding menstruation-related topics. The questionnaire was emailed to 2500 AAP members using a geographically-stratified sampling approach, with pediatricians in each state selected randomly. Mann-Whitney U tests, t-tests, and logistic regressions were used to assess associations between correlates and pediatricians' knowledge, attitudes and practices., Results: Five hundred and eighteen out of 2500 pediatricians participated (response rate = 20.7%), 462 met inclusion criteria; 78.8% were female, 79.2% were Caucasian. The majority of the pediatricians (58.2%) were "not at all" or only "slightly" familiar with the AAP guidelines on anticipatory guidance surrounding menarche. Many reported they do not routinely provide anticipatory guidance regarding menstruation to pre-menarchal patients (24.7%), discuss menstruation with post-menarchal patients (33.1%) or ask patients the date of their last period (28.4%). The majority were unlikely to discuss feminine products with patients. Gaps in menstruation-related knowledge were noted. Male pediatricians were significantly less likely to evaluate patients' menstrual cycles and provide patient-education regarding menstruation-related topics, and had significantly lower self-rated and measured knowledge of these topics., Conclusions: A concerning number of pediatricians in a national sample do not abide by AAP recommendations surrounding menstruation and exhibit knowledge gaps in this area. To effectively address the health needs of female patients, pediatricians should better incorporate menstrual health care into their clinical practice., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Galectins are involved in various biological processes, e.g. cell-cell and cell-matrix adhesion and the transmission of cellular signals. Despite the diversity of functions, little is known about the nature of their physiological cognate ligands on the cell surface and the localization of galectins in the glycocalyx, although this information is important for understanding the functional activity of galectins. In this work, localization of endogenous and exogenously loaded galectins in the glycocalyx was studied. The following main conclusions are drawn: 1) galectins are not evenly distributed within the glycocalyx, they are accumulated in patches. Patching is not the result of a cross-linking of cellular glycans by galectins. Instead, patch-wise localization is the consequence of irregular distribution of glycans forming the glycocalyx; 2) galectins are accumulated in the inner zone of the glycocalyx rather than at its outer face or directly in vicinity of the cell membrane; 3) patches are not associated with cell rafts.

Background: Human blood contains a big variety of natural antibodies, circulating throughout life at constant concentration. Previously, we have found natural antibodies capable of binding to trisaccharide Galα1-4Galβ1-4Glc (P k ) practically in all humans. Intriguingly, the same trisaccharide is a key fragment of glycosphingolipid globotriaosylceramide (Gb3Cer) - normal component of erythrocyte and endothelial cell membrane, i.e. the antibodies and their cognate antigen coexist without any immunological reaction., Aim: To explain the inertness of human anti-P k antibodies towards own cells., Materials and Methods: We used a combination of immunochemical and molecular dynamics (MD) experiments. Antibodies were isolated using affinity media with P k trisaccharide, their epitope specificity was characterized using ELISA (enzyme-linked immunosorbent assay) with a set of synthetic glycans related to P k synthetic glycans and FACS (Fluorescence-Activated Cell Sorting) analysis of cells with inserted natural Gb3Cer and its synthetic analogue. Conformations and clustering of glycolipids immersed into a lipid bilayer were studied using MD simulations., Results: Isolated specific antibodies were completely unable to bind natural Gb3Cer both inserted into cells and in artificial membrane, whereas strong interaction took place with synthetic analogue differing by the presence of a spacer between trisaccharide and lipid part. MD simulations revealed: i) although membrane-bound glycans do not form stable long-living aggregates, their transient packing is more compact in natural Gb3 as compared with the synthetic analog, ii) similar conformation of P k glycan in composition of the glycolipids, iii) no effect on the mentioned above results when cholesterol was inserted into membrane, and iv) better accessibility of the synthetic version for interaction with proteins., Conclusions: Both immunochemical and molecular dynamics data argue that the reason of the "tolerance" of natural anti-P k antibodies towards cell-bound Gb3Cer is the spatial inaccessibility of P k glycotope for interaction. We can conclude that the antibodies are not related to the blood group P system., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Directed transport of biological species across the surface of a substrate is essential for realizing lab-on-chip technologies. Approaches that utilize localized magnetic fields to manipulate magnetic particles carrying biological entities are attractive owing to their sensitivity, selectivity, and minimally disruptive impact on biomaterials. Magnetic domain walls in magnetic tracks produce strong localized fields and can be used to capture, transport, and detect individual superparamagnetic microbeads. The dynamics of magnetic microbead transport by domain walls has been well studied. However, demonstration of more complex functions such as selective motion and sorting using continuously driven domain walls in contiguous magnetic tracks is lacking. Here, a junction architecture is introduced that allows for branching networks in which superparamagnetic microbeads can be routed along dynamically-selected paths by a combination of rotating in-plane field for translation, and a pulsed out-of-plane field for path selection. Moreover, experiments and modeling show that the select-field amplitude is bead-size dependent, which allows for digital sorting of multiple bead populations using automated field sequences. This work provides a simple means to implement complex routing networks and selective transport functionalities in chip-based devices using magnetic domain wall conduits.

Galectins are β-galactoside-binding proteins sharing homology in amino acid sequence of their carbohydrate-recognition domain. Their carbohydrate specificity outside cells has been studied previously. The main conclusion of these studies was that several levels of glycan ligand recognition exist for galectins: (i) disaccharide Galβ1-4GlcNAc (LN, N-acetyllactosamine) binds stronger than β-galactopyranose; (ii) substitution at O-2 and O-3 of galactose residue as well as core fragments ("right" from GlcNAc) provides significant increase in affinity; (iii) similarly glycosylated proteins can differ significantly in affinity to galectins. Information about the natural cellular receptors of galectins is limited. Until recently, it was impossible to study specificity of cell-bound galectins. A model based on controlled incorporation of a single protein into glycocalyx of cells and subsequent interaction of loaded cells with synthetic glycoprobes measured by flow cytometry made this possible recently. In this review, data about glycan specificity of proto-, chimera-, and tandem-repeat type galectins on the cell surface are systematized, and comparative analysis of the results with data on specificity of galectins in artificial systems was performed. The following conclusions from these studies were made: (i) cellular galectins have practically no ability to bind disaccharide LNn, but display affinity to 3'-substituted oligolactosamines and oligomers LNn; (ii) tandem-repeat type galectins recognize another disaccharide, namely Galβ1-3GlcNAc (Le(c)); (iii) on the cell surface, tandem-repeat type galectins conserve the ability to display high affinity to blood group antigens of ABH system; (iv) in general, when galectins are immersed into glycocalyx, they are more selective regarding glycan interactions. Thus, we conclude that competitive interaction of galectins with cell microenvironment (endogenous cell glycans) is the main factor providing selectivity of galectins in vivo.

Background: Cannabis is the most frequently used illegal substance in the United States and Europe. There is a dramatic increase in the demand for treatment for cannabis dependence. Cannabis users frequently have co-morbid mood symptoms, especially depression and anxiety, and regular cannabis users may self-medicate for such symptoms., Objectives: We report a double-blind, placebo-controlled treatment study, for the prevention of cannabis use in cannabis-dependent individuals., Method: Regular cannabis-dependent users (n = 52) were treated for 9 weeks with weekly cognitive-behavior and motivation-enhancement therapy sessions together with escitalopram 10 mg/day. Urine samples were collected to monitor delta-9 tetrahydrocannabinol (THC) during treatment and questionnaires were administered to assess anxiety and depression., Results: We observed a high rate of dropout (50%) during the 9-week treatment program. Fifty-two patients were included in the intention-to-treat analysis. Of these, ten (19%) remained abstinent after 9 weeks of treatment as indicated by negative urine samples for THC. Escitalopram provided no advantage over placebo in either abstinence rates from cannabis or anxiety and depression scores during the withdrawal and abstinent periods., Conclusions: Escitalopram treatment does not provide an additional benefit either for achieving abstinence, or for the treatment of the cannabis withdrawal syndrome. Due to limitations of our study, namely, a high dropout rate and effects of low abstinence rates on measures of anxiety, depression and withdrawal, it is premature to conclude that selective serotonin reuptake inhibitors are not effective for treatment of the cannabis withdrawal syndrome.

Galectins are multifunctional effectors, for example acting as regulators of cell growth via protein-glycan interactions. The observation of capacity to kill bacteria for two tandem-repeat-type galectins, which target histo-blood epitopes toward this end (Stowell et al. Nat. Med. 16:295-301, 2010), prompted us to establish an array with bacterial polysaccharides. We addressed the question whether sugar determinants other than β-galactosides may be docking sites, using human galectins-4, -8, and -9. Positive controls with histo-blood group ABH-epitopes and the E. coli 086 polysaccharide ascertained the suitability of the set-up. Significant signal generation, depending on type of galectin and polysacchride, was obtained. Presence of cognate β-galactoside-related epitopes within a polysaccharide chain or its branch will not automatically establish binding properties, and structural constellations lacking galactosides, like rhamnan, were found to be active. These data establish the array as valuable screening tool, giving direction to further functional and structural studies.

An integrated platform for the capture, transport, and detection of individual superparamagnetic microbeads is described for lab-on-a-chip biomedical applications. Magnetic domain walls in magnetic tracks have previously been shown to be capable of capturing and transporting individual beads through a fluid at high speeds. Here it is shown that the strong magnetostatic interaction between a bead and a domain wall leads to a distinct magneto-mechanical resonance that reflects the susceptibility and hydrodynamic size of the trapped bead. Numerical and analytical modeling is used to quantitatively explain this resonance, and the magneto-mechanical resonant response under sinusoidal drive is experimentally characterized both optically and electrically. The observed bead resonance presents a new mechanism for microbead sensing and metrology. The dual functionality of domain walls as both bead carriers and sensors is a promising platform for the development of lab-on-a-bead technologies.

Background: Profiling of donor's antibodies using glycan arrays demonstrated presence of antibodies capable of binding to >100 mammalian glycans or their fragments. For example, relatively high binding to Galα1-4Galβ1-4GlcNAc (P(1)), Galα1-4Galβ1-4Glc (P(k)), Galβ1-3GlcNAc (Le(c)), 4-O-SuGalβ1-4GlcNAc, and GalNAcα1-3GalNAc (Fs) was found in all tested individuals. Affinity isolation using hapten-specific chromatography in combination with epitope mapping revealed their glycotopes. Notably, a significant part of the antibodies was capable of recognizing a fragment of larger glycans, for example, -Galβ1-4Glc of glycolipids, or Fucα1-3GlcNAc motif of Le(X)/Le(Y) antigens. Their epitope specificity did not vary between different healthy individuals. Nominally, all the mentioned immunoglobulins could be classified as auto-antibodies., Methods: In this work we re-evaluated results published earlier and analyzed new data to address the question why autologous antibodies found in healthy individuals do not cause severe auto-immune reactions., Results: In all cases the presumably "auto" antibodies were found to bind short fragments "subtracted" from larger glycans whereas recognition of the same fragment in the context of the whole natural chain was completely abolished. Thus, in spite of numerous formally positive signals observed on the printed glycan array, we are yet unable to identify in blood serum of healthy individuals true auto-antibodies capable of binding carbohydrate chains in their naturally occurring form., General Significance: The identified natural anti-glycan antibodies were found to be specific, high-titer and population conservative immunoglobulins - all of this suggesting as yet unknown biological role(s) of the studied proteins. This article is part of a Special Issue entitled Glycoproteomics., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The network of adhesion/growth-regulatory galectins in chicken (chicken galectin, CG) has only one tandem-repeat-type protein, CG8. Using a cell-based assay and probing galectin reactivity with a panel of fluorescent neoglycoconjugates (glycoprobes), its glycan-binding profile was determined. For internal validation, human galectin-8 (HG8) was tested. In comparison to HG8, CG8 showed a rather similar specificity: both galectins displayed high affinity to blood group ABH antigens as well as to 3'-sialylated and 3'-sulfated lactosamine chains. The most remarkable difference was found to be an ability of HG8 (but not CG8) to bind the disaccharide Galβ1-3GlcNAc (Le(c)) as well as branched and linear oligolactosamines. The glycan-binding profile was shown to be influenced by glycocalix of the cell, where the galectin is anchored. Particularly, glycosidase treatment of galectin-loaded cells led to the change of the profile. Thus, we suppose the involvement of cis-glycans in the interaction of cell-anchored galectins with external glycoconjugates.

Influenza virus is known to bind sialoglycans located on the surface of the host cell. In addition, recent data suggest the involvement of other molecular targets in viral reception. Of note, a high density of terminal galactose residues is created on the surface of virions because of the influenza virus' own neuraminidase activity. Thus, we suggested the possibility for an interaction of the influenza virus with galactose-binding proteins--galectins. In the present work we studied the influence of several galectins on the adhesion and further internalization of virus into the cell; six virus strains and three cell lines were studied. Chicken galectins CG-1A and -2 as well as human galectins HGal-1 and -8 promote virus binding in dose dependent manner, but they do not influence the internalization stage. Also, galectins are able to restore the ability of influenza virus to infect desialylated cells up to the level of native cells. When CG-1A in physiological concentrations was loaded onto viruses, the adhesion level was higher than in the case of on-cell loading. The effect of adhesion increase depends on the glycan structure of target-cell as well as of virus. The aggregated data suggest a promotional effect of galectins during the stage of influenza virus binding with the surface of target-cell.

We have recently shown that the carbohydrate-binding pattern of galectins in cells differs from that determined in artificial (non-cellular) test-systems. To understand the observed discrepancy, we compared several test-systems differing in the mode of galectin presentation on solid phase. The most representative system was an assay where the binding of galectin (human galectins-1 and -3 were studied) to asialofetuin immobilized on solid phase was inhibited by polyacrylamide glycoconjugates, Glyc-PAA. This approach permits us to range quantitatively glycans (Glyc) by their affinity to galectin, i.e. to study both high and low affinity ligands. Our attempts to imitate the cell system by solid-phase assay were not successful. In the cell system galectin binds glycoconjugates by one carbohydrate-recognizing domain (CRD), and after that the binding to the remaining non-bound CRD is studied by means of fluorescein-labeled Glyc-PAA. In an "imitation" variant when galectins are loaded on adsorbed asialofetuin or Glyc-PAA followed by revealing of binding by the second Glyc-PAA, the interaction was not observed or glycans were ordered poorly, unlike in the inhibitory assay. When galectins were adsorbed on corresponding antibodies (when all CRDs were free for recognition by carbohydrate), a good concentration dependence was observed and patterns of specificities were similar (though not identical) for the two methods; notably, this system does not reflect the situation in the cell. Besides the above-mentioned, other variants of solid-phase analysis of galectin specificity were tested. The results elucidate the mechanism and consequence of galectin CRD cis-masking on cell surface.

Polyacrylamide glycoconjugates, Glyc-PAA, having various tags or labels are convenient tools for analysis of cellular lectins. Adaptation of such glycoprobes for flow cytometry allows us to reveal lectins expressed on cell surface and analyze their carbohydrate specificity as well as functionality. Localization of lectins is visualized by labeling of cells with fluorescein-tagged glycoprobes, Glyc-PAA-fluo, in combination with fluorescent microscopy techniques. Additionally, biotinylated glycoprobes can be immobilized on magnetic particles making it possible to separate a cell population according to its carbohydrate-binding profile. Here, we exemplify application of glycoprobes in the study of cellular siglecs and galectins, as well as lectin patterning of tumor cells. The specificity of sialic acid binding membrane-anchored lectins, siglecs-1, -5, -7, -8 and -9 was determined using this methodology. To study the carbohydrate-binding profile of soluble galactoside-binding lectins, galectins-1 or -3, these were loaded on (initially galectin free) Raji cells and probed using Glyc-PAA-fluo. Lessons learned from this model system allowed us to study the galectin distribution pattern of tumors: cells obtained from mice carrying mammary adenocarcinoma or lymphoma were probed with Glyc-PAA-fluo using flow cytometry. Disaccharide 6OSuLacdiNAc was shown to be the most potent probe for adenocarcinoma cells, demonstrating that 6OSuLacdiNAc-binding molecules accumulate on cell surface in a patch-wise distribution., (Copyright 2009 Elsevier GmbH. All rights reserved.)

Galectins are a family of beta-galactoside binding lectins, homological by a sequence of the carbohydrate-binding site. In this review literature data about structure and carbohydrate specificity of galectins are discussed. The role of galectins in the regulation of cell adhesion in immune response, inflammation, and cancer progression is considered.

Objective: To assess the impact of a structured intervention, the "primary intervention for memory structuring and meaning acquisition" (PIMSMA) performed randomly in the emergency department with survivors of suicide bombing attacks, on their medium-term mental health outcome., Design: Follow up and assessment 3-9 months postinjury, and 24 months thereafter., Setting: A tertiary referral general hospital in Tel Aviv, Israel., Participants: Injured survivors of 9 suicide bombing and suicide shooting, men and women aged 16-72 at the time of the incident., Main Outcome Measures: Diagnosis of posttraumatic stress disorder (PTSD) was made using the Hebrew validated version of the DSM-IV SCID-PTSD rating scale. Other psychiatric symptoms were assessed using the following rating scales: impact of event scale (IES), Hamilton rating scale for depression (HAM-D) and for anxiety (HAM-A), and the Pittsburgh sleep quality index (PSQI). Effects of PIMSMA and PTSD level of psychological distress were analyzed using ANOVA and for change over time for continuous variables repeated measured multivariate analyses was performed, and for categorical variables nonparametric-related sample McNemar. Logistic regression for variable associated with PTSD was performed., Results: Out of 213 eligible injured survivors evacuated to our ER, 129 were retrieved 3-9 months after the incident, and 53 were available for assessment 2 years later. Multivariate analyses for being PTSD vs non-PTSD at the first evaluation, being hospitalized OR = 5.6 (95 percent CI 1.1-27.6) and treated OR = 24.5 (95 percent CI 2.8-200) were the only predictors, with no effect (p = 0.9) for PIMSMA vs other supportive intervention. Predictor for PTSD at the second evaluation were IES severity score at first evaluation OR = 1.1 (95 percent CI 1.04-1.2)., Conclusion: The PIMSMA approach is as good as the nonspecific supportive treatment performed routinely in the ED with all survivors of traumatic events of any origin. Further studies are needed to establish valid, evidence-based treatment approaches for the acute aftermath of exposure to severe potentially traumatic events.

Soluble siglecs-1, -4, -5, -6, -7, -8, -9, and -10 were probed with polyacrylamide glycoconjugates in which: 1) the Neu5Ac residue was substituted by a sulfate group (Su); 2) glycoconjugates contained both Su and Neu5Ac; 3) sialoglycoconjugates contained a tyrosine-O-sulfate residue. It was shown that sulfate derivatives of LacNAc did not bind siglecs-1, -4, -5, -6, -7, -8, -9, and -10; binding of 6'-O-Su-LacNAc to siglec-8 was stronger than binding of 3'SiaLacNAc. The relative affinity of 3'-O-Su-TF binding to siglecs-1, -4, and -8 was similar to that of 3'SiaTF. 3'-O-Su-Le(c) displayed two-fold weaker binding to siglec-1 and siglec-4 than 3'SiaLe(c). The interaction of soluble siglecs with sulfated oligosaccharides containing sialic acid was also studied. It was shown that siglecs-1, -4, -5, -6, -7, -9, and -10 did not interact with these compounds; binding of 6-O-Su-3'SiaLacNAc and 6-O-Su-3'SiaTF to siglec-8 was weaker than that of the corresponding sulfate-free sialoside probes. Siglec-8 displayed affinity to 6'-O-Su-LacNAc and 6'-O-Su-SiaLe(x), and defucosylation of the latter compound led to an increase in the binding. Sialoside probes containing tyrosine-O-sulfate residue did not display increased affinity to siglecs-1 and -5 compared with glycoconjugates containing only sialoside. Cell-bound siglecs-1, -5, -7, and -9 did not interact with 6-O-Su-3'SiaLacNAc, whereas the sulfate-free probe 3'SiaLacNAc demonstrated binding. In contrast, the presence of sulfate in 6-O-Su-6'SiaLacNAc did not affect binding of the sialoside probe to siglecs. 6'-O-Su-SiaLe(x) displayed affinity to cell-bound siglecs-1 and -5; its isomer 6-O-Su-SiaLe(x) bound more strongly to siglecs-1, -5, and -9 than SiaLe(x).

Sialyl oligosaccharides have long been considered to be the sole receptors for influenza virus. However, according to [1] some viruses are able to grow in sialic-free MDCK cells. Here we attempted to reveal a possible second, non-sialic receptor, hypothesizing the involvement of additional carbohydrate lectin recognition in influenza virus reception process, first of all in situations when a lectin of the host cell could recognize the viral carbohydrate ligand. We tested the presence of galactose- and sialic acid-binding lectins, as well as mannoside- and sulfo-N-acetyllactosamine-recognizing properties of MDCK and Vero cells using polyacrylamide neoglycoconjugates and antibodies. MDCK cells bind galactoside probes stronger than Vero cells, whereas Vero cells bind preferentially sialoside, mannoside and various sulfo-oligosaccharide probes. The probing of viruses with the neoglycoconjugates revealed specific 6'-HSO (3) LacNAc (but not other sulfated oligosaccharides) binding property of A and B human strains. Affinity of 6'-HSO (3) LacNAc probe was comparable with affinity of 6'-SiaLac probe but the binding was not inhibited by the sialooligosaccharide.

We studied the capacity of myelopeptide-4 (regulatory peptide of the bone marrow origin) to induce terminal differentiation of HL-60 and K-562 leukemic cells. Myelopeptide-4 increased the expression of CD14 and CD38 differentiation antigens on the surface of HL-60 cells and of CD44 antigen on K-562 cells, induced the appearance of mature monocyte/macrophages in HL-60 culture and hemoglobin-producing cells in K-562 cell culture, and stimulated phagocytic activity of THP-1 leukemic cells. Myelopeptide-4 is an endogenous factor of cell differentiation, a prospective agent for antileukemic therapy.