Immunosuppressive Medication Adherence in Kidney Transplant Recipients During the COVID-19 Pandemic: A Cross-Sectional Study in Hong Kong.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has put an enormous burden on health care systems worldwide. Limited access to medical care and fear of increased infective risks due to the use of immunosuppressive medication (IM) have increased concerns about IM adherence in kidney transplant recipients (KTRs). The aim of this study was to determine the various dimensions of IM nonadherence in KTRs during the COVID-19 pandemic. METHODS: This was a single-center, cross-sectional study using a convenient sampling approach. KTRs with follow-up in Queen Elizabeth Hospital, Hong Kong between May 1, 2020 and September 30, 2020, were invited to complete a self-reported questionnaire on IM adherence. The sociodemographic factors associated with IM adherence were extracted from medical records. RESULTS: Overall, 210 patients completed the questionnaires. The overall IM nonadherence rate was 35.2% in the 4 weeks before survey completion. None of the patients stopped taking IMs without instructions from their health care providers. The most common pattern of IM nonadherence was timing adherence (n = 63; 30.1%), followed by dose-skipping item. Among the different sociodemographic factors studied, only marital status was an independent risk factor of IM nonadherence (odds ratio, 1.97; 95% confidence interval, 1.04-3.72; P = .03). CONCLUSIONS: The impact of COVID-19 on IM adherence in KTRs was not significant. All the patients continued their IM despite of the pandemic. Good family support can have a positive influence on treatment adherence in KTRs during the COVID-19 pandemic.

Detyrosinated microtubule protrusions in suspended mammary epithelial cells promote reattachment.

Breast tumor cells enter the bloodstream long before the development of clinically evident metastasis. However, the early presence of such bloodborne cells predicts poor patient outcome. Nearly 90% of human breast tumors arise as carcinomas from mammary epithelial cells, so it is important to study how these cells respond to the detached conditions that they would experience in the bloodstream. We report here that mammary epithelial cell lines produce long and dynamic protrusions of the plasma membrane when detached. Although human and mouse mammary epithelial cell lines die by apoptosis within 16 h of detachment, this protrusive response persists for days in cells overexpressing either Bcl-2 or Bcl-xL. Unlike actin-dependent invadopodia and podosomes, these protrusions are actually enhanced by actin depolymerization with Cytochalasin-D or Latrunculin-A. Immunofluorescence and Western blotting demonstrate that the protrusions are enriched in detyrosinated Glu-tubulin, a post-translationally modified form of alpha-tubulin that is found in stabilized microtubules. Video microscopy indicates that these protrusions promote cell-cell attachment, and inhibiting microtubule-based protrusions correlates with reduced extracellular matrix attachment. Since bloodborne metastasis depends on both cell-cell and cell-matrix attachment, microtubule-based protrusions in detached mammary epithelial cells provide a novel mechanism that could influence the metastatic spread of breast tumors.

Validation of a questionnaire instrument for prediction of obstructive sleep apnea in Hong Kong Chinese children.

To develop and validate a questionnaire scale that can be used as a screening tool to investigate for the presence of childhood obstructive sleep apnea syndrome (OSAS) in Hong Kong Chinese children. Subjects suspected to have OSAS and controls were recruited. Parents completed a Hong Kong children sleep questionnaire (HK-CSQ) and all recruited subjects underwent at least one overnight polysomnographic study (PSG). An obstructive apnea index (OAI) >or= 1/h was diagnostic of OSAS. Receiver-operating characteristics (ROC) curve was constructed to determine optimal sensitivity and specificity. Reliability and validity of the questionnaire scale were also assessed. Two hundred twenty-nine children (149 boys and 80 girls) with a mean age of 10.0 years (SD = 2.1) were recruited. Their mean body mass index (BMI) and OAI were 19.8 (SD = 5.1) and 2.6 (SD = 7.6), respectively. Fifty-four boys and 12 girls were found to have OSAS. Three questions were found to be highly significant in predicting for the presence of OSAS-snoring, nocturnal mouth breathing, and sweating. A composite score of 7 from the three questions (range 0-12) was found to discriminate the OSAS cases best [ROC curve, AUC = 0.8 (95% CI = 0.8-0.9)]. The sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were 75.4, 80.5, 61.3, and 88.9%, respectively. Test-retest reliability was undertaken in 51 subjects and the measurement of agreement (Kappa value) was 0.6. This HK-CSQ is a useful, valid, and reliable screening instrument for the presence of OSAS in children.

Proteomic analysis of extracellular proteins from Escherichia coli W3110.

While numerous proteomic analyses have been carried out on Escherichia coli, the vast majority have focused on expression of intracellular proteins. Yet, recent literature reports imply that even in laboratory strains, significant proteins may be found outside the cell. Here, we identify extracellular proteins associated with nonpathogenic E. coli strain W3110. Two-dimensional gel electrophoresis (2DE) revealed approximately 66 prominent protein spots during exponential growth (4 and 8 h shake flask culture) in minimal medium. The absence of detectable nucleic acids in the culture supernatant implies these proteins did not result from cell lysis. MALDI-TOF MS was used to identify 44 proteins, most of which have been previously identified as either outer membrane or extracellular proteins. In addition, 2DE protease zymogram analysis was carried out which facilitated identification of three extracellular proteases, one of which was not observed during standard 2DE. Our results are consistent with previous findings which imply outer membrane proteins are shed during growth.

Is a 2-night polysomnographic study necessary in childhood sleep-related disordered breathing?

BACKGROUND AND OBJECTIVES: There are limited data on the night-to-night variability of childhood sleep-related disordered breathing (SDB). We aim to assess for the presence of first-night effect (FNE) and to examine whether a single-night sleep study is adequate in the assessment of childhood SDB. DESIGN: In a case-control study investigating whether obesity is a risk factor for childhood SDB, the night-to-night variability of sleep and respiratory variables were studied. PARTICIPANTS AND SETTING: Forty-six obese children from a pediatric obesity clinic and 44 age- and sex-matched normal weight control subjects from local schools. INTERVENTIONS: All subjects underwent two consecutive overnight polysomnographic studies. An obstructive apnea index (OAI) >/= 1/h was considered diagnostic of SDB. RESULTS: The mean age of the children was 11.21 years (SD 2.21). Forty-four obese children and 43 control subjects completed the 2-night study. Based on the criterion of the worst OAI over the 2 nights, 13 subjects were found to have SDB, 12 subjects were primary snorers, and 62 were normal subjects. In all subjects, the sleep efficiency improved and sleep-onset latency was reduced on the second night. While there was a rebound of rapid eye movement sleep with the associated worsening of respiratory indexes (mainly accounted for by an increase in central apneas and hypopneas) evident in normal subjects, there was a significant improvement of respiratory disturbances in the SDB group on the second night. The first-night polysomnography would have correctly identified 84.6% of cases as defined by the criteria of the worst OAI over the 2 nights. All cases missed by the first-night study had only borderline OAI. CONCLUSIONS: The phenomenon of FNE in children was well demonstrated in our study. We proposed that a single-night sleep study is adequate and more cost-effective in assessing for childhood SDB.

Quantitative comparison and evaluation of two commercially available, two-dimensional electrophoresis image analysis software packages, Z3 and Melanie.

While a variety of software packages are available for analyzing two-dimensional electrophoresis (2-DE) gel images, no comparisons between these packages have been published, making it difficult for end users to determine which package would best meet their needs. The goal here was to develop a set of tests to quantitatively evaluate and then compare two software packages, Melanie 3.0 and Z3, in three of the fundamental steps involved in 2-DE image analysis: (i) spot detection, (ii) gel matching, and (iii) spot quantitation. To test spot detection capability, automatically detected protein spots were compared to manually counted, "real" protein spots. Spot matching efficiency was determined by comparing distorted (both geometrically and nongeometrically) gel images with undistorted original images, and quantitation tests were performed on artificial gels with spots of varying Gaussian volumes. In spot detection tests, Z3 performed better than Melanie 3.0 and required minimal user intervention to detect approximately 89% of the actual protein spots and relatively few extraneous spots. Results from gel matching tests depended on the type of image distortion used. For geometric distortions, Z3 performed better than Melanie 3.0, matching 99% of the spots, even for extreme distortions. For nongeometrical distortions, both Z3 and Melanie 3.0 required user intervention and performed comparably, matching 95% of the spots. In spot quantitation tests, both Z3 and Melanie 3.0 predicted spot volumes relatively well for spot ratios less than 1:6. For higher ratios, Melanie 3.0 did much better. In summary, results suggest Z3 requires less user intervention than Melanie 3.0, thus simplifying differential comparison of 2-DE gel images. Melanie 3.0, however, offers many more optional tools for image editing, spot detection, data reporting and statistical analysis than Z3. All image files used for these tests and updated information on the software are available on the internet (http://www.umbc.edu/proteome), allowing similar testing of other 2-DE image analysis software packages.