IQGAP3 promotes the progression of glioma as an immune and prognostic marker.

Background: IQGAP3 plays a crucial role in regulating cell proliferation, division, and cytoskeletal organization. Abnormal expression of IQGAP3 has been linked to various tumors, but its function in glioma is not well understood. Methods: Various methods, including genetic differential analysis, single-cell analysis, ROC curve analysis, Cox regression, Kaplan-Meier analysis, and enrichment analysis, were employed to analyze the expression patterns, diagnostic potential, prognostic implications, and biological processes involving IQGAP3 in normal and tumor tissues. The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence. Additionally, the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3. Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms. Results: High IQGAP3 expression in gliomas is associated with an unfavorable prognosis, particularly in wild-type IDH and 1p/19q non-codeleted gliomas. Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle, PI3K/AKT signaling, p53 signaling, and PLK1-related pathways. Furthermore, IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma. BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy. In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells, with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression. Conclusion: IQGAP3 shows promise as a valuable biomarker for diagnosis, prognosis, and immunotherapeutic strategies in gliomas.

Understanding the prevalence and distribution of fellowship trained female and male genitourinary reconstruction and men's health/andrology academic faculty in the United States.

Background: We evaluated the prevalence, distribution, and specialist to population ratio of male and female reconstruction and andrology/prosthetics faculty within United States urologic training programs. Our objective was to help determine the current need/demand for reconstructive fellowship trained faculty for necessary clinical exposure during residency in the midst of a nationwide residency expansion. Methods: All non-military urology residency programs were evaluated. Programs were sorted into their American Urologic Association Sections and websites were analyzed for evidence of fellowship training and/or clinical expertise/interest: (I) male genitourinary reconstruction (MGR); (II) female genitourinary reconstruction (FGR) and (III) infertility/andrology/men's health (AMH). The 2020 US Census data was used to determine specialist to population ratios by sections. Results: Of 137 evaluated programs, FGR had the highest percentage of fellowship-trained faculty (76%) followed by AMH (66%) and MGR (61%). Clinical/surgical interest was noted in pelvic organ prolapse (88%), inflatable penile prosthesis (79%) and urethral stricture disease (75%). Over 10% of training programs had two or more faculty with MGR, FGR and AMH fellowship training. Significant geographic variation amongst academic programs exists with the South and Southeastern parts of the US being relatively underserved, both in percentage of programs with fellowship-trained faculty, and by faculty per 1,000,000 inhabitants. Conclusions: The majority of US urology residencies have faculty with fellowship training and/or stated clinical interest in MGR, FGR and AMH. Still, many programs remain without these faculty while others have two or more in their respective fields. The geographic trends noted here have both educational and recruitment significance.

India Ink Tattooing of Ureteroenteric Anastomoses.

While upper tract access through the insensate conduit following urinary diversion takes less time and incurs fewer costs than percutaneous kidney access does for the treatment of ureter and kidney pathology, endoscopic ureteroenteric anastomoses (UEA) identification can be difficult. We injected India Ink into the bowel mucosa near the UEA during ileal conduit diversion (IC) to determine the safety and feasibility of ink tattooing. Patients undergoing IC were prospectively randomized to receive ink or normal saline (NS) injections. The injections were placed 1 cm from UEA in a triangular configuration, and loopogram exams and looposcopy were performed to identify reflux (UR), UEA, the tattooing site and strictures in 10 and 11 patients randomized with respect to ink and NS injections, respectively. Ink patients were older (72 vs. 61 years old, p = 0.04) and had a higher Charlson Comorbidity Index (5 vs. 2, p = 0.01). Looposcopy was performed in three ink and four NS patients. Visualization of UEA was achieved in 100% of the ink and 75% of the NS patients (p = 0.26). The ink ureteroenteric anastomotic stricture (UEAS) rate was higher (N = 3 vs. N = 1) and six patients vs. one patients underwent surgery, respectively, for UEAS (p = 0.31). The study was halted early due to safety concerns. Our pilot study demonstrates that ink can be well visualized following injection near UEA during IC. However, the ink cohort had more UEAS than previously cited in the literature and our prior institutional UEAS rate of 6%. While this study sample is small, the higher incidence of UEAS after ink injection led us to question the utility and safety of ink injection following IC.

Pediatric urologists' confidence and accuracy in estimating penile curvature.

BACKGROUND: Assessment and management of congenital penile curvature (PC) can be variable. Methods for correction of PC usually are dependent on degree of PC which is reliant on how degree is assessed. We sought to assess the confidence and accuracy of measuring PC and hence management using case-based examples. METHODS: A survey was emailed to members of the Societies for Pediatric Urology. Demographic information, management strategies for PC, and self-reported confidence in measuring PC were assessed. A Likert scale measured self-confidence. Case scenarios were used to assess ability to measure PC and methods of correction. The cases consisted of three computer-generated penis model images with arc-type ventral curvature and one image of lateral curvature in an infant. RESULTS: The response rate was 30% (108/355). The mean confidence score was 3.6 ± 0.8 (3-fairly confident; 4-very confident). In clinic, 89% of urologists used eyeball estimates to assess PC; 5% used both eyeball and goniometer. In the operating room, 71% used eyeball estimates, 8% used goniometer, and 16% used both. If sole decision-maker, urologists recommend surgical correction of PC over observation at median 30° (IQR 21-30°). At a median of 45°, there was a shift in corrective surgical preference from dorsal plication (DP) (IQR 30-54°) to ventral lengthening (IQR 34-60°). Urologists underestimated PC degree for all cases (summary table). For all cases, there was no association between years in practice or confidence level on estimated PC degree. In case 1, only 24% of urologists would correct a mean estimate of 23° PC; those who would correct had a higher mean PC estimate vs those who would not (28° vs 21°, p < 0.001). Case 2 and 4 had similar estimations and correction methods. In case 2, those who chose VL had a higher mean PC estimate vs those who did not (43° vs 37°, p < 0.01), but no estimate difference was seen for DP (p = 0.52). In case 4 with lateral PC, those who chose DP had a higher mean PC estimate vs those who did not (41° vs 33°, p = 0.049). Yet in case 3, there was no difference in PC estimate in urologists who chose VL vs not (57° vs 53°, p = 0.16). CONCLUSIONS: A uniform underestimation of PC existed despite self-reported confidence in the ability to measure PC. An increasing willingness to perform surgical correction was demonstrated with a shift towards VL for ventral curvature and less so for lateral curvature as PC worsens.

Evaluation of the Educational Impact of the Urology Collaborative Online Video Didactics Lecture Series.

OBJECTIVE: To assess the impact of the Urology Collaborative Online Video Didactic (COViD) lecture series series on resident knowledge as a supplement to resident education during the coronavirus disease 2019 pandemic. METHODS: One hundred thirty-nine urology residents were voluntarily recruited from 8 institutions. A 20-question test, based on 5 COViD lectures, was administered before and after watching the lectures. Pre- and posttest scores (percent correct) and score changes (posttest minus pretest score) were assessed considering demographic data and number of lectures watched. Multiple linear regression determined predictors of improved scores. RESULTS: Of residents recruited, 95 and 71 took the pre- and posttests. Median number of lectures watched was 3. There was an overall increase in correct scores from pretest to posttest (45% vs 57%, P < .01). Watching any lectures vs none led to higher posttest scores (60% vs 44%, P < .01) and score changes (+16% vs +1%, P < .01). There was an increase in baseline pretest scores by post-graduate year (PGY) (P < .01); however there were no significant differences in posttest or score changes by PGY. When accounting for lectures watched, PGY, and time between lecture and posttest, being a PGY6 (P = .01) and watching 3-5 lectures (P < .01) had higher overall correct posttest scores. Watching 3-5 lectures led to greater score changes (P < .001-.04). Over 65% of residents stated the COViD lectures had a large or very large impact on their education. CONCLUSIONS: COViD lectures improved overall correct posttest scores and increased knowledge base for all resident levels. Furthermore, lectures largely impacted resident education during the coronavirus disease 2019 pandemic.

Differentiation of transverse sinus thrombosis from congenitally atretic transverse sinus with time-resolved contrast-enhanced magnetic resonance angiography.

AIM: To establish the value of time-resolved contrast-enhanced magnetic resonance angiography (TR-MRA) in identifying transverse sinus (TS) thrombosis in patients with a unilaterally absent TS signal on phase-contrast (PC) magnetic resonance venography (MRV). MATERIALS AND METHODS: Forty-five patients who were suspected of TS thrombosis clinically with a unilaterally absent TS signal on PC MRV were evaluated using TR-MRA. The image quality was compared between PC MRV and TR-MRA via calculating signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of the normal TS. Images obtained by PC MRV and TR-MRA were assessed independently by two neuroradiologists regarding whether the absent signal was thrombosis or hypoplastic TS. Then a consultant neurologist made the final diagnosis based on all available clinical, laboratory, and radiological results (delivered by a consultant neuroradiologist via computed tomography [CT]/CT venography, magnetic resonance imaging [MRI]/MRV or digital subtraction angiography [DSA]), which was set as the reference standard. The accuracy of the radiological diagnosis from both techniques was assessed. RESULTS: For image quality, the SNRs and CNRs of TR-MRA were 452.14 and 440.92, respectively, significantly higher than that of PC MRV (both p<0.001). The interobserver agreement of TR-MRA in identifying TS thrombosis from hypoplastic TS was excellent (κ = 0.951; 95% confidence interval [CI], 0.902-1), much higher than PC MRV (κ = 0.526; 95% CI, 0.389-0.663). Consensus of assessment based on TR-MRA was highly consistent with the reference standard (100% sensitivity, 96.67% specificity) and superior to PC MRV (60% sensitivity, 90% specificity). CONCLUSION: TR-MRA is better than PC MRV for visualising TS and distinguishing thrombosis from congenitally atretic TS.

Treatment Outcome of Children with Retinoblastoma in a Tertiary Care Referral Hospital in Indonesia.

Background: Although survival rates for retinoblastoma (RB) are over 95% in high-income countries, its high mortality rate in low and middle-income countries remains a great concern. Few studies investigated treatment outcome and factors contributing to RB survival in these latter settings. Aims of this study are to determine treatment outcome of Indonesian children diagnosed with RB and to explore factors predictive of treatment outcome. Methods: This study was a retrospective medical records review combined with an illustrative case report. Children newly diagnosed with RB between January 2011 and December 2016 at a tertiary care referral hospital in Indonesia were included. A home visit was conducted to perform an in-depth interview with a mother of two children affected by RB. Results: Of all 61 children with RB, 39% abandoned treatment, 21% died, 20% had progressive or relapsed disease and 20% event-free survival. Progressive or relapsed disease was more common in older (≥ 2 years at diagnosis, 29%) than young (<2 years at diagnosis, 0%) children (P=0.012). Event-free survival estimate at 5 years was higher in young (42%) than older (6%) children (P=0.045). Odds-ratio for event-free survival was 6.9 (95% CI: 1.747 ­ 27.328, P=0.006) for young versus older children. Other clinical and socio-demographic characteristics had no significant correlation with treatment outcome or event-free survival. The case report elucidated conditions and obstacles that Indonesian families face when their children are diagnosed with RB. Conclusion: Survival of children with RB in Indonesia is much lower compared to high-income and many other low and middle-income countries. Abandonment of treatment is the most common cause of treatment failure. Older age at diagnosis is associated with more progressive or relapsed disease and worse survival. Interventions to improve general public and health-care providers' awareness, early detection and treatment adherence are required.

Differentiating between micronucleus dose-responses induced by whole cigarette smoke solutions with Benchmark Dose potency ranking.

Dose-response modeling of in vitro micronucleus test (IVMNT) data was evaluated to determine if the approach has value in discriminating among different tobacco products. Micronucleus responses were generated in L5178Y/Tk+/- mouse lymphoma cells and TK6 human lymphoblastoid cells from a series of whole smoke solutions (WSSs) expected to have different levels of genotoxicity based on differences in their machine-generated smoke constituents. Eight WSSs were prepared by machine smoking different numbers (20 or 60) of two commercial cigarettes (Marlboro Silver or Red) under International Standardization Organization (ISO) or Health Canada Intense (HCI) smoking machine regimens and tested in the two cell lines with and without rat liver S9 activation. The S9-mediated IVMNT dose-response data from the WSSs were evaluated with PROAST software and Benchmark Doses (BMDs) and their upper and lower confidence intervals (CIs) were generated. IVMNT data differed based on the number and type of cigarettes smoked and smoking machine regimen. The IVMNT responses produced in mouse lymphoma cells generally were greater than in TK6 cells, but the ability of the two cell types to differentiate between WSSs was similar. The results indicate that BMD potency ranking was useful for differentiating between IVMNT responses.

Inhibition of p53/p21 by TWIST alleviates TNF-α induced nucleus pulposus cell senescence in vitro.

OBJECTIVE: This study aims to reveal the TWIST protein expression in the degenerated nucleus pulposus (NP), its effect on the TNF-α treated NP cells, and to explore its specific mechanism of anti-senescence. PATIENTS AND METHODS: NP tissues from spine fracture patients without intervertebral disc degeneration (IDD) and the IDD patients were collected to detect the TWIST1/2 protein expression by Western blot (WB). NP cells isolated from the healthy tissue was treated with TNF-α to induce senescence, and the TWIST1/2 protein expression was also analyzed. We transfected NP cells with the plasmid coding TWIST to upregulate its expression, which was also cultured in the TNF-α condition. Besides, the TNF-α pretreated NP cells were further stimulated with the recombinant human TWIST1/2 protein. The collagen II and senescent marker ß-galactosidase (ß-gal) were determined by immunofluorescence (IF); the MMP-13, TIMP-3, IL-10, IL-1ß mRNA expression level was detected by quantitative Real Time PCR; the cell proliferation was analyzed by CCK8 assay; the cell cycle was measured by flow cytometry. RESULTS: TWIST1/2 protein was decreased both in the degenerated NP tissue, and TNF-α treated NP cells. The overexpression of TWIST1/2 could prevent the p53, p21, ß-gal, MMP-13, and IL-1ß expression, moreover, it protected the collagen II, TIMP-3, and IL-10 expression in the TNF-α treated NP cells. Additionally, TWIST overexpression also promoted cell proliferation by ensuring the process of the cell cycle. Furthermore, the supplement of TWIST protein was functional to reverse these senescent phenotypes caused by TNF-α partly. CONCLUSIONS: TWIST alleviates the TNF-αinduced NP cells senescence via the inhibition of the p53/p21 pathway.

Global Problem of Hospital Detention Practices.

Although an official definition by the World Health Organization (WHO) or any other authority is currently lacking, hospital detention practices (HDP) can be described as: "refusing release of either living patients after medical discharge is clinically indicated or refusing release of bodies of deceased patients if families are unable to pay their hospital bills." Reports of HDP are very scarce and lack consistent terminology. Consequently, the problem's scale is unknown. This study aimed to find evidence of HDP worldwide, explore characteristics of HDP reports, and compare countries with or without reports. PubMed and Google were examined for relevant English, Spanish, and French publications up to January 2019. Of 195 countries, HDP reports were found in 46 countries (24%) in Africa, Asia, South-America, Europe, and North-America. Most reports were published by journalists in newspapers. In most countries reports concern living adults and children who are imprisoned in public hospitals. A majority (52%) of reports were of individuals detained for at least a month. Almost all countries, with or without HDP reports, have signed the Universal Declaration of Human Rights. Countries with reported HDP have larger population size (P<.001), worse Corruption Perception Index score (P=.025), higher out-of-pocket expenditure (P=.024), lower Universal Health Coverage Index score (P=.015), and worse Press Freedom Index score (P=.012). We conclude that HDP are more widespread than currently acknowledged. Urgent intervention by stakeholders is required to stop HDP.

Urinary Incontinence Research: Compliance With Research Standards for Clinical Studies.

OBJECTIVE: To perform an updated literature review to assess compliance with outcomes use and reporting guidelines. In 1997, the Urodynamics Society recommended standards of efficacy to be used for evaluation of treatment outcomes in urinary incontinence (UI). Studies published shortly after the release of these standards reported generally low rates of adherence. METHODS: We reviewed all 2017 articles related to UI in 3 urologic journals (Journal of Urology [JU], Neurourology and Urodynamics [NU], and Urology [UR]). Articles were assessed for compliance with 19 standards across 3 categories (methodology, pretreatment, and post-treatment). Analysis focused on overall and category specific compliance, as well as comparison of compliance between journals. RESULTS: A total of 78 articles met inclusion criteria for analysis. The mean overall compliance was 52% for all standards. JU demonstrated a higher compliance (63%) as compared to NU (50%) and UR (46%) (P <.01). No articles reviewed demonstrated 100% compliance with all standards. Only 23%, 6%, and 12% of JU, NU, and UR articles, respectively, demonstrated at least 75% compliance with all standards. In comparison of subcategory compliance, JU demonstrated a statistically higher methodology compliance (P <.01). In contrast, compliance with both pre- and post-treatment standards across all 3 journals demonstrated no statistically significant differences. CONCLUSION: Overall, we found that a significant percentage of recent study on UI fails to meet suggested standards for use and reporting of outcomes. These data suggest that continued efforts are needed to improve the quality and reporting of UI research.

Thermal ablation of the small renal mass: a critical analysis of current literature.

INTRODUCTION: Thermal ablation is increasingly utilized as a management strategy for small renal masses (<4 cm). Partial nephrectomy is recognized as the gold standard; thermal ablation has been reserved for older patients with comorbidities due to concern for local tumor recurrence. As long-term data regarding the safety and efficacy of ablative techniques accumulate with encouraging results, clinicians are widening the utility in select patient populations. This review summarizes the currently available technologies in terms of procedural differences, oncologic outcomes, renal function, and complication rates. EVIDENCE ACQUISITION: A structured literature review was conducted using PubMed and Web of Science, using the keywords: "renal cell carcinoma," "ablation techniques," "cryosurgery," "radiofrequency ablation," "microwave ablation," "outcomes assessment," "post-operative complication," and "hospital costs." Articles were reviewed to summarize oncologic outcomes, complications, and impact on renal function of cryoablation, radiofrequency ablation, and microwave ablation. EVIDENCE SYNTHESIS: Thermal ablation is a safe and effective management option for small renal masses in select patients, particularly in those with multiple tumors and/or those unable or unwilling to undergo more invasive surgery. Slightly higher rates of local recurrence rates (~1-10%) with thermal ablation are offset by lower complication rates and reduced morbidity, and equivalent or better renal function outcomes compared to surgery. CONCLUSIONS: The established modalities of cryo-, radiofrequency, and microwave ablation offer equivalent outcomes with similar complication rates; technique choice is primarily based on tumor characteristics and operator preference. Better quality evidence comparing thermal ablation with surgical nephron-sparing intervention is needed to make informed conclusions on efficacy.

Health-care providers' perspectives on health-insurance access, waiving procedures, and hospital detention practices in Kenya.

BACKGROUND: Patients at Kenyan public hospitals are detained if their families cannot pay their medical bills. Access to health insurance and waiving procedures to prevent detention may be limited. This study explores the perspectives of health-care providers (HCP) on health-insurance access, waiving procedures, and hospital detention practices. PROCEDURE: A self-administered structured questionnaire was completed by 104 HCP (response rate 78%) involved in childhood cancer care. RESULTS: The perspectives of respondents were as follows: all children with cancer should have health insurance according to 96% of HCP. After parents apply for health insurance, it takes too long before treatment costs are covered (67% agree). Patients with childhood cancer without health insurance have a higher chance of abandoning treatment (82% agree). Hospitals should waive bills of all children with cancer when parents have payment difficulties (69% agree). Waiving procedures take too long (75%). Parents are scared by waiving procedures and may decide never to return to the hospital again (68%). Poor families delay visiting the hospital because they fear hospital detention and first seek alternative treatment (92%). When poor families finally come to the hospital, the disease is in advanced stage already (94%). Parents sometimes have to abandon their detained child at the hospital if they cannot pay hospital bills (68%). Detention of children at the hospital if parents cannot pay their medical bills is not approved by 84% of HCP. CONCLUSIONS: HCP acknowledge that access to health insurance needs improvement and that waiving procedures contribute to treatment abandonment. By far, most HCP disapprove of hospital detention practices. These factors warrant urgent attention and adjustment.

Size-separated particle fractions of stainless steel welding fume particles - A multi-analytical characterization focusing on surface oxide speciation and release of hexavalent chromium.

Welding fume of stainless steels is potentially health hazardous. The aim of this study was to investigate the manganese (Mn) and chromium (Cr) speciation of welding fume particles and their extent of metal release relevant for an inhalation scenario, as a function of particle size, welding method (manual metal arc welding, metal arc welding using an active shielding gas), different electrodes (solid wires and flux-cored wires) and shielding gases, and base alloy (austenitic AISI 304L and duplex stainless steel LDX2101). Metal release investigations were performed in phosphate buffered saline (PBS), pH 7.3, 37°, 24h. The particles were characterized by means of microscopic, spectroscopic, and electroanalytical methods. Cr was predominantly released from particles of the welding fume when exposed in PBS [3-96% of the total amount of Cr, of which up to 70% as Cr(VI)], followed by Mn, nickel, and iron. Duplex stainless steel welded with a flux-cored wire generated a welding fume that released most Cr(VI). Nano-sized particles released a significantly higher amount of nickel compared with micron-sized particle fractions. The welding fume did not contain any solitary known chromate compounds, but multi-elemental highly oxidized oxide(s) (iron, Cr, and Mn, possibly bismuth and silicon).

Comparing Health-Care Providers' Perspectives on Complementary and Alternative Medicine in Childhood Cancer Between Netherlands and Indonesia.

BACKGROUND: Use of complementary and alternative medicine (CAM) is common among patients with childhood cancer. Health-care providers (HCP) should address this need properly. Geographical and cultural differences seem likely. This study explores perspectives on CAM of HCP involved in the care of children with cancer in Netherlands and Indonesia. Health beliefs, components of CAM, encouraging or discouraging CAM, and knowledge about CAM were assessed. PROCEDURE: We conducted a cross-sectional study using semi-structured questionnaires at a Dutch and Indonesian academic hospital. RESULTS: A total of 342 HCP participated: 119 Dutch (response rate 80%) and 223 Indonesian (response rate 87%). Chemotherapy can cure cancer according to more Dutch than Indonesian HCP (87% vs. 53% respectively, P < 0.001). Combination of chemotherapy and CAM is the best way to cure cancer according to more Indonesian than Dutch HCP (45% vs. 25%, P < 0.001). Dutch and Indonesian HCP recommend and discourage CAM use differently. Most Dutch (77%) and Indonesian HCP (84%) consider their knowledge about CAM to be inadequate (P = ns). Fewer Dutch doctors than other HCP want to learn more about CAM (51% vs. 76%, P = 0.007), whereas there is no significant difference in eagerness to learn about CAM between Indonesian doctors (64%) and other HCP (72%). CONCLUSIONS: Indonesian HCP have more positive views about CAM than their Dutch colleagues. Both Dutch and Indonesian HCP consider their knowledge about CAM to be inadequate. Therefore, education programs about CAM tailored to the needs of HCP are recommended, knowing that CAM is used frequently.

The bifunctional liposomes constructed by poly(2-ethyl-oxazoline)-cholesteryl methyl carbonate: an effectual approach to enhance liposomal circulation time, pH-sensitivity and endosomal escape.

PURPOSE: A novel bifunctional liposome with long-circulating and pH-sensitive properties was constructed using poly(2-ethyl-oxazoline)-cholesteryl methyl carbonate (PEtOz-CHMC) in this study. METHODS: PEtOz-CHMC was synthesized and characterized by TLC, IR and (1)H-NMR. The obtained PEtOz lipid was inserted into liposomes by the post-insertion method. Through a series of experiments, such as drug release, tumor cell uptake, cytotoxicity, calcium-induced aggregation, pharmacokinetic experiments, etc., the pH-sensitive and long-circulating properties of PEtOzylated liposomes was identified. RESULTS: PEtOz-CHMC modified liposomes (PEtOz-L) showed increased calcein release at low pH. Flow cytometric analysis results showed that the fusion and cellular uptake of PEtOz-L could be promoted significantly at pH 6.4 compared with those at pH 7.4. Confocal laser scanning microscope observations revealed that PEtOz-L could respond to low endosomal pH and directly released the fluorescent tracer into the cytoplasm. MTT assays in HeLa cells demonstrated that doxorubicin hydrochloride (DOX) loaded PEtOz-L exhibited stronger anti-tumor activity in a medium at pH 6.4 than in a medium pH 7.4. PEtOz-L remained stable when these liposomes were incubated in calcium chloride solution. The cumulative calcein release rate of PEtOz-L was significantly lower than that of CL when the liposomes were dialysed in PBS. The pharmacokinetic experiments of liposomes in rats showed that t 1/2 and AUC of PEtOz-L were 4.13 times and 4.71 times higher than those of CL. CONCLUSIONS: PEtOzylated liposomes exhibits excellent long-circulating and pH-sensitive properties. Our results suggest that PEtOz is a promising biomaterial for the modification of liposome in drug delivery.

A medication diary-book for pediatric patients with acute lymphoblastic leukemia in Indonesia.

BACKGROUND: Event-free survival of pediatric patients with acute lymphoblastic leukemia (ALL) in Yogyakarta, Indonesia was low (20%). The aim of the study was to evaluate the effectiveness of using a medication diary-book on the treatment outcome of childhood ALL. PROCEDURE: A randomized study was conducted with 109 pediatric patients with ALL in a pediatric oncology center in Yogyakarta, Indonesia. Both intervention and control groups received a structured parental education program and donated chemotherapy. The intervention group received a medication diary-book to remind parents and families to take oral chemotherapy and present for scheduled appointments or admissions. Event-free survival estimate (EFS) at 3 years was assessed. RESULTS: Among pediatric patients with ALL with highly educated mothers (senior high school or higher), the EFS-estimate at 3 years of the intervention group was significantly higher than the EFS-estimate at 3 years of the control group (62% vs. 29%, P = 0.04). Among pediatric patients with ALL with low-educated mothers, no significant difference was found in the EFS-estimates at 3 years between the intervention and control group (26% vs. 18%, P = 0.86). CONCLUSIONS: We conclude that a medication diary-book might be useful to improve the survival of pediatric patients with ALL in resource-limited settings, particularly in patients with highly educated mothers.

Textures in polygonal arrangements of square nanoparticles in nematic liquid crystal matrices.

A systematic analysis of defect textures in faceted nanoparticles with polygonal configurations embedded in a nematic matrix is performed using the Landau-de Gennes model, homeotropic strong anchoring in a square domain with uniform alignment in the outer boundaries. Defect and textures are analyzed as functions of temperature T, polygon size R, and polygon number N. For nematic nanocomposites, the texture satisfies a defect charge balance equation between bulk and surface (particle corner) charges. Upon decreasing the temperature, the central bulk defects split and together with other -1/2 bulk defects are absorbed by the nanoparticle's corners. Increasing the lattice size decreases confinement and eliminates bulk defects. Increasing the polygon number increases the central defect charge at high temperature and the number of surface defects at lower temperatures. The excess energy per particle is lower in even than in odd polygons, and it is minimized for a square particle arrangement. These discrete modeling results show for first time that, even under strong anchoring, defects are attached to particles as corner defects, leaving behind a low energy homogeneous orientation field that favors nanoparticle ordering in nematic matrices. These new insights are consistent with recent thermodynamic approaches to nematic nanocomposites that predict the existence of novel nematic/crystal phases and can be used to design nanocomposites with orientational and positional order.

Does aid reach the poor? Experiences of a childhood leukaemia outreach-programme.

Previously, we found that the access to donated chemotherapy for childhood leukaemia patients in Indonesia was limited: only 16% of eligible families received donations. After the introduction of a structured parental education programme, we examined the access of parents of children with leukaemia to donated chemotherapy in an Indonesian academic hospital. The programme consisted of a video-presentation in hospital, information-booklet, audiocassette, DVD, procedures for informed-consent, statement of understanding for donated chemotherapy and a complaints-mechanism. Of 72 new patients, 51 parents (71%) were interviewed by independent psychologists using questionnaires. Parents of 21 patients (29%) did not participate because their children dropped-out (n=10) or died (n=11) before an interview took place. Four patients had health insurance and did not need donated chemotherapy. Access to donated chemotherapy was improved: 46/47 patients (98%) received donations. Structured parental education improved the access to donated chemotherapy. Outreach-programmes may benefit from this approach. This may enable more patients from poor socio-economic backgrounds in the developing countries to receive aid and achieve cure.