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People with Down syndrome often present with balance deficits, which compromise safety during daily activity. While evidence shows that exercise can improve balance in the Down syndrome population, it is unclear if a telehealth method will elicit similar benefits. We aimed to examine the effects of a virtual exercise program on balance in adults with Down syndrome.Eighteen low-active participants with Down syndrome completed a 12-week telehealth exercise program based on the Mann Method. Balance testing took place before and after the intervention, which included: TUG, MCTSIB, FICSIT-4, and FRT. This study was registered as a clinical trial on ClinicalTrials.gov, identifier: NCT04647851.Significant improvement was seen in the TUG (p = .043), FICSIT-4 (p = .019) and FRT (p = .019). All participants achieved maximum scores on the MCTSIB in pre- and post-testing.Balance in low-active adults with Down syndrome significantly improved following the telehealth exercise program, which we attribute to the tailored exercises that address visual/vestibular deficits and hip muscle weakness.

Purpose of Review The goal of this review is to summarize the current knowledge of the epidemiology, clinical manifestations, diagnosis, and treatment of cutaneous, mucosal, and visceral leishmaniasis. We will describe the most recent findings and suggest areas of further research in the leishmaniasis field. Recent Findings This article reviews newer leishmaniasis tests (including rapid diagnostic tests using rK39 antibodies), vaccine candidates, and updated treatment recommendations. Summary While leishmaniasis is a complex disease, learning the prominent clinical manifestations and major parasite species can guide the recommendations for diagnosis and treatment.

OBJECTIVE People living with HIV (PLWH) are living longer and developing more non-AIDS comorbidities, which negatively impact antiretroviral therapy (ART) adherence. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a novel pharmacologic measure of cumulative ART adherence that is predictive of viral suppression and future viremia. However, the relationship between non-AIDS comorbidities and this adherence measure is unknown. We aimed to evaluate the association between 3 non-AIDS comorbidities (diabetes mellitus (DM), hypertension, and hyperlipidemia) and TFV-DP in DBS in PLWH. METHODS Blood for TFV-DP in DBS and HIV viral load was prospectively collected from PLWH on tenofovir disoproxil fumarate for up to 3 times over 48 weeks. Non-AIDS comorbidities were recorded. Mixed effect multivariable linear regression models were used to estimate the changes in TFV-DP concentrations in DBS according to the presence of comorbidities and to estimate the percent differences in TFV-DP concentrations between these groups. RESULTS A total of 1144 person-visits derived from 523 participants with available concentrations of TFV-DP in DBS were included in this analysis. In univariate analysis, no significant association between non-AIDS comorbidities (categorized as having 0, 1, 2, or 3 comorbidities) and the concentrations of TFV-DP in DBS was observed (P = 0.40). Participants who had DM had 25% lower (95% confidence interval: -36% to -12%; P < 0.001) TFV-DP in DBS than participants without DM after adjusting for age, gender, race, body mass index, estimated glomerular filtration rate, CD4 T-cell count, hematocrit, ART class, patient-level medication regimen complexity index, and 3-month self-reported adherence. CONCLUSIONS Diabetic PLWH have lower concentrations of TFV-DP in DBS compared with those without DM. Further research is required to identify the clinical implications and biological mechanisms underlying these findings.

We present two cases of Leishmania (V) panamensis in returning travelers from Central America successfully treated with miltefosine. The couple presented with ulcerative skin lesions nonresponsive to antibiotics. Skin biopsy with polymerase chain reaction (PCR) revealed L. (V) panamensis. To prevent the development of mucosal disease and avoid the inconvenience of parental therapy, we treated both patients with oral miltefosine. We suggest that miltefosine represents an important therapeutic alternative in the treatment of cutaneous lesions caused by L. panamensis and in preventing mucosal involvement.

Purpose of review To highlight recent data on antiretroviral adherence in older people living with HIV (PLWH), describe the most relevant pharmacokinetic antiretroviral studies, and identify critical research gaps in this population. Recent findings Overall, studies have found that older PLWH are more likely to be adherent to antiretroviral therapy (ART). Although multiple methods to measure adherence are available (self-report, pharmacy refills, electronic device monitors, drug concentrations), there is currently no 'gold standard' adherence measure or sufficient evidence to suggest a preferred method in older patients. Recently, studies evaluating antiretroviral concentrations in hair and dried blood spots in older patients identified no major differences when compared with younger individuals. Similarly, although pharmacokinetic studies in older PLWH are scarce, most data reveal no significant pharmacokinetic differences in the aging population. Furthermore, no specific guidelines or treatment recommendations regarding ART dose modification or long-term toxicity in aging PLWH are available, mostly because of the exclusion of this population in clinical trials. Summary How aging influences adherence and pharmacokinetics remains poorly understood. As the population of older PLWH increases, research focusing on adherence, toxicity, drug--drug interactions, and the influence of comorbidities is needed.

In adults with Down syndrome, the combination of low physical activity and fitness levels and the high prevalence of musculoskeletal co-morbidities stresses the need for specialized exercise programs. The goal of this research study was to develop a specialized exercise program for individuals with Down syndrome using the physical therapy approach of a systems review as the foundation. We first conducted an overview of the literature on co-morbidities in adults with Down syndrome using the systems review method to categorize these findings. We extracted recommendations for content and delivery of an exercise program based on the literature review, and finally composed a specialized exercise program for individuals with Down syndrome adhering to these recommendations.

There is little research assessing the impact of providing men with information about prostate cancer (PCa) treatment options at the time of referral for a prostate biopsy. Study objectives were to determine whether receiving an information booklet about PCa treatment options prior to receiving biopsy results was acceptable to patients, and if receiving this information influenced levels of anxiety, depression, distress, and treatment decisional conflict. Between June 2016 and September 2017, a randomised block design was used to allocate patients from an Australian urology practice into the intervention or control group. Patients in the intervention group were provided with written information about treatment options for localised PCa prior to their biopsy. Outcome measures including the Distress Thermometer, Generalised Anxiety Disorder-7, Patient Health Questionnaire-9, and Decisional Conflict Scale were completed pre-biopsy and 2–3 weeks post-biopsy. Ninety-eight patients referred for an initial prostate biopsy for an elevated PSA test or suspicious digital rectal exam participated in the study (response rate = 78%). Multimodal repeated-measures analyses showed no significant differences between control and intervention groups in changes in distress, anxiety, or depression from pre- to post-biopsy, and in decisional conflict post-diagnosis (all p > .05). Thirty-five (87%) patients believed that the resource made it easier to understand subsequent explanation of treatment options, and 51 patients (98%) who received the intervention preferred to be given information at that time. Providing patients with information about treatment options prior to biopsy did not impact on changes in psychological distress and decisional conflict post-biopsy. However, the majority of patients preferred to be given such information at this time point.

Highlights • We describe communication campaigns in an intervention to reduce opioid deaths. • The community-engaged model includes three phases. • Five campaigns will focus on naloxone, MOUD, and stigma reduction. • Community surveys and fidelity measures gauge process and impact. • Our model could help communities address other public health issues., Background The HEALing Communities Study (HCS) is testing whether the Communities that Heal (CTH) intervention can decrease opioid overdose deaths through the implementation of evidence-based practices (EBPs) in highly impacted communities. One of the CTH intervention components is a series of communications campaigns to promote the implementation of EBPs, increase demand for naloxone and medications for opioid use disorder (MOUD), and decrease stigma toward people with opioid use disorder and the use of EBPs, especially MOUD. This paper describes the approach to developing and executing these campaigns. Methods The HCS communication campaigns are developed and implemented through a collaboration between communication experts, research site staff, and community coalitions using a three-stage process. The Prepare phase identifies priority groups to receive campaign messages, develops content for those messages, and identifies a “call to action” that asks people to engage in a specific behavior. In the Plan phase, campaign resources are produced, and community coalitions develop plans to distribute campaign materials. During the Implement stage, these distribution plans guide delivery of content to priority groups. Fidelity measures assess how community coalitions follow their distribution plan as well as barriers and facilitators to implementation. An evaluation of the communication campaigns is planned. Conclusions If successful, the Prepare-Plan-Implement process, and the campaign materials, could be adapted and used by other communities to address the opioid crisis. The campaign evaluation will extend the evidence base for how communication campaigns can be developed and implemented through a community-engaged process to effectively address public health crises.

Highlights • HEALing Communities Study is a parallel-group cluster randomized controlled trial. • Communities That HEAL intervention’s goal is to reduce opioid overdose deaths. • Structured consensus decision-making strategy guided study measure development. • More than 80 study measure specifications and a common data model were developed. • The study will provide methodology and longitudinal community data for research., Background Opioid overdose deaths remain high in the U.S. Despite having effective interventions to prevent overdose deaths, there are numerous barriers that impede their adoption. The primary aim of the HEALing Communities Study (HCS) is to determine the impact of an intervention consisting of community-engaged, data-driven selection, and implementation of an integrated set of evidence-based practices (EBPs) on reducing opioid overdose deaths. Methods The HCS is a four year multi-site, parallel-group, cluster randomized wait-list controlled trial. Communities (n = 67) in Kentucky, Massachusetts, New York and Ohio are randomized to active intervention (Wave 1), which starts the intervention in Year 1 or the wait-list control (Wave 2), which starts the intervention in Year 3. The HCS will test a conceptually driven framework to assist communities in selecting and adopting EBPs with three components: 1) A community engagement strategy with local coalitions to guide and implement the intervention; 2) A compendium of EBPs coupled with technical assistance; and 3) A series of communication campaigns to increase awareness and demand for EBPs and reduce stigma. An implementation science framework guides the intervention and allows for examination of the multilevel contexts that promote or impede adoption and expansion of EBPs. The primary outcome, number of opioid overdose deaths, will be compared between Wave 1 and Wave 2 communities during Year 2 of the intervention for Wave 1. Numerous secondary outcomes will be examined. Discussion The HCS is the largest community-based implementation study in the field of addiction with an ambitious goal of significantly reducing fatal opioid overdoses.

Methylation of arginine residues occurs on a number of protein substrates, most notably the N-terminal tails of histones, and is catalyzed by a family of enzymes called the protein arginine methyltransferases (PRMTs). This modification can lead to transcriptional activation or repression of cancer-related genes. To date, a number of inhibitors, based on natural peptide substrates, have been developed for the PRMT family of enzymes. However, because peptides are easily degraded in vivo, the utility of these inhibitors as potential therapeutics is limited. The use of peptoids, which are peptide mimetics where the amino acid side chain is attached to the nitrogen in the amide backbone instead of the α-carbon, may circumvent the problems associated with peptide degradation. Given the structural similarities, peptoid scaffolds may provide enhanced stability, while preserving the mechanism of action. Herein, we have identified that peptoids based on natural peptide substrates are not catalyzed to the product by PRMT1, but instead are inhibitors of this enzyme. Reducing the length of the peptoid reduces inhibition and suggest the residues distal from the site of modification are important for binding. Furthermore, a positive charge on the N-terminus helps promote binding and improves inhibition. Selectivity among family members is likely possible based on inhibition being moderately selective for PRMT1 over PRMT5 and provides a scaffold that can be used to develop pharmaceuticals against this class of enzymes.

Cryptococcal meningitis (CM) is an opportunistic fungal infection associated with human immunodeficiency virus (HIV) and other forms of immunosuppression. We lack a clear understanding of CM associated mortality among HIV-negative, non-transplant patients in the United States (US). This article compares clinical features and outcomes across HIV status in patients with laboratory-confirmed CM. Methods: A retrospective cohort study was performed that included adult patients with laboratory-confirmed CM treated at an academic tertiary hospital between January 2000 and September 2018. Those with a history of organ transplant or non-meningeal infections were excluded. Data were gathered on demographics, HIV status, clinical presentation, cerebrospinal fluid (CSF) profiles, neurological outcomes, hospital course, and mortality. Results: A total of 70 patients with cryptococcal disease were identified. Our final sample included 36 CM patients, mean age was 48.8 ± 13.2 years; of this group, 66.7% ( n = 24) had HIV. Median [interquartile range (IQR)] absolute CD4 count for the HIV group was 35 cells/μl (10–80 cells/μl). Non-HIV/non-transplant patients were significantly older ( p Conclusion: Compared with HIV-infected individuals, non-HIV/non-transplant CM patients have a higher CSF WBC count at the time of diagnosis, higher rates of AMS on presentation, and higher rates of 90-day and 1-year all-cause mortality. Further prospective research is needed to identify the hallmarks of CM in non-HIV/non-transplant patients to facilitate early identification and intervention.

We present a case of Cryptococcus neoformans pericarditis in a cardiac transplant recipient. This article reviews the diagnosis, treatment, and complications of cryptococcosis specifically in transplant patients. While pericarditis is a rare manifestation of Cryptococcus infection, this case highlights that cryptococcosis should be considered in the differential diagnosis for solid organ transplant and immunocompromised patients presenting with pericardial effusions.

Purpose To investigate the incidence and possible contributing factors of erectile dysfunction (ED) after transperineal template prostate biopsy (TTPB). Materials and methods Males undergoing TTPB were prospectively administered a Sexual Health Inventory for Men (SHIM) questionnaire before biopsy and one month after. SHIM questionnaires were repeated at 3- and 9-months for males not receiving interventional treatment. Sexually inactive males were excluded. Interval change in SHIM categories based upon baseline characteristics were evaluated. Multivariable logistic regression models were used to evaluate predictors of change in SHIM score category. Results A total of 576 males were included in our sample. Of these, 450 (78%) males underwent their first biopsy. A decline in SHIM category within the immediate 4-weeks post-biopsy was reported by 167 males (31% of total eligible sample). Age was the strongest predictor of decline in SHIM category, the predicted probability of a decline in SHIM at age 50 was 10% (95% confidence interval [CI], 1%-19%), 32% at age 60 (95% CI, 25%-40%) and 36% at age 70 (95% CI, 29%-44%). For new onset ED, the predicted probability of ED within 4-weeks post-TTPB were 6.7% at age 50 (95% CI, 0%-15%), 26% at age 60 (95% CI, 17%-34%) and 31% at age 70 (95% CI, 21%-40%). Conclusions Older age at biopsy is an independent predictor of immediate ED after TTPB in sexually active males. This association was observed in the subgroup with no pre-existing ED. These findings provide useful information when counselling males undergoing TTPB.

Background Penile prosthesis surgery is last-line treatment to regaining erectile function after radical prostatectomy (RP) for localized prostate cancer. Aims To assess quality of life, psychological functioning, and treatment satisfaction of men who underwent penile implantation after RP; the psychosocial correlates of treatment satisfaction and sexual function after surgery; and the relation between patients’ and partners’ ratings of treatment satisfaction. Methods 98 consecutive patients who underwent penile implantation after RP from 2010 and 2015 and their partners were invited to complete a series of measures at a single time point. Of these, 71 patients and 43 partners completed measures assessing sexual function, psychological functioning, and treatment satisfaction. Proportions of patients who demonstrated good sexual function and satisfaction with treatment and clinical levels of anxiety and depression were calculated. Hierarchical regression analyses were conducted to determine psychosocial factors associated with patient treatment satisfaction and sexual function and patient-partner differences in treatment satisfaction. Outcomes Patients completed the Expanded Prostate Cancer Index Composite Short Form (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Prostate Cancer-Related Quality of Life Scale, Self-Esteem and Relationship Questionnaire (SEAR), Generalized Anxiety Disorder–7 (GAD-7), and Patient Health Questionnaire–9 (PHQ-9). Partners completed the GAD-7, PHQ-9, EDITS (partner version), and SEAR. Results 94% of men reported satisfaction with treatment (EDITS score > 50). 77% of men reported good sexual function (EPIC-26 score > 60). Lower depression scores were associated with higher sexual confidence and sexual intimacy, and these were correlated with better treatment satisfaction and sexual function. Patients experienced higher sexual relationship satisfaction (median score = 90.6) than their partners (median score = 81.2), but there was no difference in treatment satisfaction between groups. Higher patient treatment satisfaction was more likely to be reported for couples whose depression scores were more similar. Clinical Implications It is important to provide preoperative penile implant counseling and encourage patients to seek postoperative counseling if needed. Strengths and Limitations This is one of the first Australian-based studies comprehensively assessing treatment satisfaction and psychosocial health of men after penile prosthesis surgery after RP. This was a retrospective cross-sectional study, so there is a possibility of recall bias, and causal associations could not be determined. Conclusion Men in this Australian series who underwent penile prosthesis surgery after RP generally reported good sexual function and treatment satisfaction. Nevertheless, patient and partner mental health influenced their reported experience of the treatment.

BACKGROUND To compare perioperative, renal and oncological outcomes after robotic-assisted partial nephrectomy (RAPN) versus open partial nephrectomy (OPN) for the treatment of renal tumours. METHODS All partial nephrectomies performed at a Metropolitan Urology Centre between 2010 and 2016 were analysed. Baseline data was collected for patient demographics, tumour characteristics (tumour size, laterality and polarity, RENAL scores), and perioperative variables (e.g. warm ischaemic time, operation time, estimated blood loss (EBL), length of stay). Tumour characteristics included malignancy, clinical stage, Fuhrman nuclear grade and surgical margin status. Day-1 post-operative serum creatinine, estimated glomerular filtration rate (eGFR) and 6-month eGFR stage were used for assessing renal function. RESULTS Two hundred patients underwent partial nephrectomy between 2010 and 2016 (n = 200; 55 OPN versus 145 RAPN). Baseline data was similar between groups, except for lower age (P = 0.0001) and higher RENAL scores (P = 0.001) in the RAPN group. RAPN demonstrated significantly lower complication rates (P = 0.015), lesser EBL (P =

Background: Late-onset sepsis (LOS) in preterm infants is a leading cause of mortality and morbidity. Timely recognition and initiation of antibiotics are important factors for improved outcomes. Identification of risk factors could allow selection of infants at an increased risk for LOS. Objectives: The aim was to identify risk factors for LOS. Methods: In this multicenter case-control study, preterm infants born at ≤30 weeks of gestation were included at 9 neonatal intensive care units. Detailed demographical and clinical data were collected daily up to day 28 postnatally. Clinical and demographic risk factors were identified using univariate and multivariate regression analyses in a 1: 1 matched case-control cohort. Results: In total, 755 infants were included, including 194 LOS cases (41 gram-negative cases, 152 gram-positive cases, and 1 fungus). In the case-control cohort, every additional day of parenteral feeding increased the risk for LOS (adjusted OR = 1.29; 95% CI 1.07–1.55; p = 0.006), whereas antibiotics administration decreased this risk (OR = 0.08; 95% CI 0.01–0.88; p = 0.039). These findings could largely be attributed to specific LOS-causative pathogens, since these predictive factors could be identified for gram-positive, but not for gram-negative, LOS cases. Specifically cephalosporins administration prior to clinical onset was inversely related to coagulase-negative staphylococcus LOS (CoNS-LOS) development. Formula feeding was an independent risk factor for development of CoNS-LOS (OR = 3.779; 95% CI 1.257–11.363; p = 0.018). Conclusion: The length of parenteral feeding was associated with LOS, whereas breastmilk administration was protective against CoNS-LOS. A rapid advancement of enteral feeding, preferably with breastmilk, may proportionally reduce the number of parenteral feeding days and consequently the risk for LOS.

Intraepithelial lymphocytes (IELs) are T cells defined by direct contact with epithelial surfaces. While important for barrier integrity, the mechanisms of recruitment and functional maturation remain unknown. We identified sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) as highly enriched in the IEL population compared to lamina propria T cells by microarray, suggesting importance in IEL recruitment. Blockade of S1P signaling using FTY720 significantly reduced recruitment of TCRab+ IELs, but not TCRgd+ IELs, following bacterial recolonization of antibiotic-treated mice, which is known to recruit IELs. Since mice lacking either Myd88 or an intact microbiome lack IELs, we hypothesized that either the epithelium or mononuclear phagocytes responded to microbial TLR ligands and produced S1P. Myeloid lineage cells were deemed the cells responsible for Myd88/microbe dependent IEL recruitment. In vitro, cecal contents stimulated LysM-Cre+ Myd88fl/fl bone-marrow derived macrophages do not upregulate sphk1, the enzyme responsible for most S1P production, and fail to induce S1P dependent T cell migration in a transwell assay. To understand how the IEL-IEC synapse affects IEL function, we utilized Villin-Cre+ MHCIIfl/fl mice. We observed altered maturation in both CD4+ and CD4− CD8− IEL compartments, associated with increased CD44− CD62L+ naive and CD44+ CD62L+ central memory IELs, and decreased CD44+ CD62L− effector, and CD44− CD62L− “revertant” IELs, suggesting a block in T cell maturation. Together these data show a coordinated, multi-system process by which IELs are first recruited to, and then functionally matured by the IECs. Further work will investigate how inflammation of the mucosal barrier alters these processes.

Background Since 2008, the AdVance male urethral sling has emerged as a minimally invasive option for stress urinary incontinence. We aimed to evaluate the success of the AdVance sling using validated continence outcome measures. Methods A total of 72 patients treated with the AdVance sling completed validated questionnaires reporting on quality of life and functional outcomes. Incontinence was assessed according to pad weight, pad usage per day (PPD), International Consultation on Incontinence Questionnaire scores and Patient Global Impression of Improvement scores. Results At a median 52-month follow-up, 37 (51%) patients were pad free or used a security pad; 18 (25%) used ≥50% fewer PPDs; and the remaining 17 (24%) patients were classified as 'failed'. According to pad weights, 27 (38%) patients were dry; 32 (44%) had mild incontinence ( 400 mL/day) incontinence. Patient satisfaction was high, with 57 (79%) very much or much better, six (8%) somewhat better and only nine (13%) unchanged or worse. There was a trend of declining continence over time, although the majority remained improved. Patients with severe preoperative incontinence performed significantly worse postoperatively (P = 0.02), as did those who had had prior pelvic radiotherapy (P = 0.02). Conclusions The AdVance sling offers a high rate of success for the treatment of mild to moderate post-prostatectomy incontinence according to PPD; however, when using objective measures of continence, the success rates are lower. The improvement in urinary control is largely durable over the medium term; however, they may decline beyond 4 years. Reduced efficacy is seen in those with a history of radiotherapy and severe incontinence, although the majority of these men are still improved with surgery.

Ewing sarcoma family of tumors predominantly affect the pediatric population in the long bones of the extremities or the pelvis, and only 8% of cases arise within the spine. Primary Ewing’s sarcoma of the cervical spine is extremely rare and less than 30 cases have been reported in the literature thus far. Here we present a case of primary Ewing’s sarcoma of the cervical spine in a 28-year-old female who presented with a three-month history of neck pain and right arm radiculopathy. MRI revealed a homogeneously contrast enhancing, eccentric mass with dural tail at C2-C7. After undergoing a hemilaminectomy, histopathology confirmed extraosseous Ewing’s sarcoma with CD99 positivity. A comprehensive systemic and neuraxis work-up ruled out overt metastasis. We extrapolated data from children’s cooperative group studies and IESS-II clinical trial to formulate a three phase treatment protocol as described below. To date, patient is in remission with no evidence of any residual disease in the cervical spine. In conclusion, although Primary Ewing’s sarcoma of the cervical spine is extremely rare it should be considered a differential diagnosis in patients with neck pain and a spinal mass under the age of thirty. Less than 25% of EFT’s present with overt metastasis and almost all have subclinical metastatic disease at the time of diagnosis, therefore, a comprehensive evaluation and systemic chemotherapy is recommended. We recommend a multidisciplinary approach of surgical decompression to preserve neurological functions, followed by compressed chemotherapy regimens, reevaluation for local treatment, and adjuvant chemotherapy.

Protein arginine methyltransferases (PRMTs) are a family of mammalian enzymes catalyzing the symmetric dimethylation (Type I), asymmetric dimethylation (Type II), or monomethylation (Type III) of arginine residues within proteins. This family is composed of 11 isozymes, however the vast majority of asymmetric and symmetric dimethylation in mammals is completed by either PRMT1 or PRMT5, respectively. In recent years, a number of chemical probes targeting this family of enzymes have been developed, but the majority of these probes lack isozyme specificity. Herein, we report the development of a chemical probe, based on a non-natural peptide sequence, which specifically labels PRMT1 over PRMT5 with high selectivity and sensitivity.

Engineering the properties of nanoparticles (NPs) to limit non-specific cellular interactions is critical for developing effective drug delivery systems. In this study we investigate the differences in non-specific cell association between polymer NPs prepared with linear polyethylene glycol (PEG) and brush PEG both in vitro and ex vivo. Most studies to investigate the non-fouling properties of NPs have been performed using cell-line based assays. However, in this study we demonstrate a whole blood assay using fresh human blood. It is likely this assay reflects more accurately the fate of NPs when injected into human blood in vivo. Non-linear PEG analogues such as poly(poly(ethylene glycol)methacrylate) (PEGMA) are attractive alternatives to linear PEG as hydrophilic coatings for NP drug delivery systems due to their simple and versatile synthesis. We prepared NPs composed of a poly(2-diethylamino)ethyl methacrylate (PDEAEMA) core and a diblock copolymer of PDEAEMA and either linear PEG or brush PEGMA. These NPs depend on low-fouling properties of the hydrophillic PEG coating to avoid uptake by the mononuclear phagocyte system (MPS). In vitro cell association assays showed brush PEGMA NPs exhibited lower association with 3T3 fibroblast and C1R lymphoblast cells compared to linear PEG NPs. In an ex vivo whole blood assay, brush PEGMA nanoparticles showed similar low association with monocytes and granulocytes as linear PEG NPs with a similar length PEG component. Higher association with blood cells was observed for NPs containing a lower molecular weight PEGMA component, despite having the same molecular weight as the linear PEG NPs (2 kDa). The results demonstrate that trends observed in cell-lines are not always consistent with assays in more complex systems such as blood. Based on these results the reported PEGMA NPs are attractive alternatives to our previously reported linear PEG NPs.

The entropy-driven affinity of trivalent (in)organic arsenicals for closely spaced dithiols has been exploited to develop a novel route to peptide/protein-polymer conjugation. A trivalent arsenous acid (As(III)) derivative (1) obtained from p-arsanilic acid (As(V)) was shown to readily undergo conjugation to the therapeutic peptide salmon calcitonin (sCT) via bridging of the Cys(1)-Cys(7) disulfide, which was verified by RP-HPLC and MALDI-ToF-MS. Conjugation was shown to proceed rapidly (t < 2 min) in situ and stoichiometrically through sequential reduction-conjugation protocols, therefore exhibiting conjugation efficiencies equivalent to those reported for the current leading disulfide-bond targeting strategies. Furthermore, using bovine serum albumin as a model protein, the trivalent organic arsenical 1 was found to demonstrate enhanced specificity for disulfide-bond bridging in the presence of free cysteine residues relative to established maleimide functional reagents. This specificity represents a shift toward potential orthogonality, by clearly distinguishing between the reactivity of mono- and disulfide-derived (vicinal or neighbors-through-space) dithiols. Finally, p-arsanilic acid was transformed into an initiator for aqueous single electron-transfer living radical polymerization, allowing the synthesis of hydrophilic arsenic-functional polymers which were shown to exhibit negligible cytotoxicity relative to a small molecule organic arsenical, and an unfunctionalized polymer control. Poly(poly[ethylene glycol] methyl ether acrylate) (PPEGA480, DPn = 10, Mn,NMR = 4900 g·mol(-1), Đ = 1.07) possessing a pentavalent arsenic acid (As(V)) α-chain end was transformed into trivalent As(III) post-polymerization via initial reduction by biological reducing agent glutathione (GSH), followed by binding of GSH. Conjugation of the resulting As(III)-functional polymer to sCT was realized within 35 min as indicated by RP-HPLC and verified later by thermodynamically driven release of sCT, from the conjugate, in the presence of strong chelating reagent ethanedithiol.

To compare perioperative, renal and oncological outcomes after robotic-assisted partial nephrectomy (RAPN) versus open partial nephrectomy (OPN) for the treatment of renal tumours.All partial nephrectomies performed at a Metropolitan Urology Centre between 2010 and 2016 were analysed. Baseline data was collected for patient demographics, tumour characteristics (tumour size, laterality and polarity, RENAL scores), and perioperative variables (e.g. warm ischaemic time, operation time, estimated blood loss (EBL), length of stay). Tumour characteristics included malignancy, clinical stage, Fuhrman nuclear grade and surgical margin status. Day-1 post-operative serum creatinine, estimated glomerular filtration rate (eGFR) and 6-month eGFR stage were used for assessing renal function.Two hundred patients underwent partial nephrectomy between 2010 and 2016 (n = 200; 55 OPN versus 145 RAPN). Baseline data was similar between groups, except for lower age (P = 0.0001) and higher RENAL scores (P = 0.001) in the RAPN group. RAPN demonstrated significantly lower complication rates (P = 0.015), lesser EBL (P =0.0001), shorter hospital stays (P =0.001) and reduced positive tumour resection margins (P = 0.039). There was no significant difference in mean operation time between RAPN and OPN (137.2 (±48.0) OPN versus 146.07 (±35.91) RAPN; P = 0.16). No statistical difference was shown for post-operative eGFR stage between groups at Day-1 and 6-month post-surgery (P = 0.15 and P = 0.861, respectively).We present the largest reported Australian series on partial nephrectomy, confirming that a robotic-assisted approach is equivalent to OPN, with reduced complications, EBL, length of hospital stays and fewer positive margins, even when resecting more complex tumours.

Abstract: This essay explores the queer world of Toronto’s Operation Snatch (formerly known as The Scandelles), focusing in particular on two of their productions related to sex work, Les Demimondes and Neon Nightz. The essay details the performances, which focus on prostitution and exotic dance, respectively, and discusses whether performances about sex work ought to be considered queer performance art. Arguing that Operation Snatch’s performances constitute “queer world-making,” this essay considers how Operation Snatch leverages affect to engage their audiences in the composition of a queer “world” that critiques popular and burlesque images of sex workers, in which their critical self-representations as sex workers can come to life. By adapting burlesque’s ironic “gaze back” to the “world-making” capacities of cabaret, Operation Snatch produces sex work-related performances that can critique sex workers’ marginalization in both popular and burlesque culture.

Since 2008, the AdVance male urethral sling has emerged as a minimally invasive option for stress urinary incontinence. We aimed to evaluate the success of the AdVance sling using validated continence outcome measures.A total of 72 patients treated with the AdVance sling completed validated questionnaires reporting on quality of life and functional outcomes. Incontinence was assessed according to pad weight, pad usage per day (PPD), International Consultation on Incontinence Questionnaire scores and Patient Global Impression of Improvement scores.At a median 52-month follow-up, 37 (51%) patients were pad free or used a security pad; 18 (25%) used ≥50% fewer PPDs; and the remaining 17 (24%) patients were classified as 'failed'. According to pad weights, 27 (38%) patients were dry; 32 (44%) had mild incontinence (100 mL/day); and 13 (18%) had moderate (100-400 mL/day) or severe (400 mL/day) incontinence. Patient satisfaction was high, with 57 (79%) very much or much better, six (8%) somewhat better and only nine (13%) unchanged or worse. There was a trend of declining continence over time, although the majority remained improved. Patients with severe preoperative incontinence performed significantly worse postoperatively (P = 0.02), as did those who had had prior pelvic radiotherapy (P = 0.02).The AdVance sling offers a high rate of success for the treatment of mild to moderate post-prostatectomy incontinence according to PPD; however, when using objective measures of continence, the success rates are lower. The improvement in urinary control is largely durable over the medium term; however, they may decline beyond 4 years. Reduced efficacy is seen in those with a history of radiotherapy and severe incontinence, although the majority of these men are still improved with surgery.