A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila

In Drosophila, enhancer trap strategies allow rapid access to expression patterns, molecular data, and mutations in trapped genes. However, they do not give any information at the protein level, e.g., about the protein subcellular localization. Using the green fluorescent protein (GFP) as a mobile artificial exon carried by a transposable P-element, we have developed a protein trap system. We screened for individual flies, in which GFP tags full-length endogenous proteins expressed from their endogenous locus, allowing us to observe their cellular and subcellular distribution. GFP fusions are targeted to virtually any compartment of the cell. In the case of insertions in previously known genes, we observe that the subcellular localization of the fusion protein corresponds to the described distribution of the endogenous protein. The artificial GFP exon does not disturb upstream and downstream splicing events. Many insertions correspond to genes not predicted by the Drosophila Genome Project. Our results show the feasibility of a protein trap in Drosophila. GFP reveals in real time the dynamics of protein's distribution in the whole, live organism and provides useful markers for a number of cellular structures and compartments.     

Hearing impairment and health-related quality of life: the Blue Mountains Hearing Study

OBJECTIVES: To assess the association between hearing impairment and health-related quality of life (HRQOL) in an older population, using the self-administered 36-item Short-Form Health Survey (SF-36). DESIGN: Participants of the Blue Mountains Hearing Study (BMHS, N = 2956) attended a comprehensive interview and hearing examination in which both self-reported and measured hearing impairments were assessed. Hearing impairment was defined as the pure-tone average of air-conduction hearing thresholds >25 decibels hearing level (dB HL) for the four frequencies (0.5 to 4.0 kHz) in the better ear. RESULTS: Of the 2431 participants with complete data (mean age, 67.0 yr), 1347 (55.4%) did not have measured hearing loss, whereas 324 (13.3%) had unilateral (285 mild, 22 moderate, 17 severe) and 760 (31.3%) had bilateral hearing impairment (478 mild, 207 moderate, 75 severe). After adjusting for demographic and medical confounders, bilateral hearing impairment was associated with poorer SF-36 scores in both physical and mental domains (fall in physical component score, PCS of 1.4 points, p = 0.025; fall in mental component score, MCS of 1.0 point, p = 0.13), with poorer scores associated with more severe levels of impairment (PCS p(trend) = 0.04, MCS p(trend) = 0.003). Participants with bilateral hearing impairment who habitually used hearing aids had a slightly better PCS (mean, 43.1; standard error [SE], 0.9) than those with the same impairment who did not have hearing aids or who only used them occasionally (mean, 41.2; SE 0.5), although this finding was not statistically significant (p = 0.055). Persons with self-reported hearing loss had significantly poorer HRQOL than corresponding persons without, but persons with unilateral or high-frequency hearing loss did not have significantly different HRQOL scores than their corresponding counterparts. CONCLUSIONS: This study quantifies the associated disease burden of age-related hearing impairment on health-related quality of life in a population-based cohort of older persons.     

Risk of second malignant neoplasms after childhood central nervous system malignant tumours: an international study

PurposeThe aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study.MethodsIndividual data on cases of CNS cancer in children (0–14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943–2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed.ResultsWe observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85–20.1) for thyroid cancer (nine cases), 2.75 (1.01–5.99) for leukaemia (six cases) and 2.47 (0.90–5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95–5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29–0.82%).ConclusionThis population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour.     

Use of an arterialized venous flap for resurfacing a circumferential soft tissue defect of a digit.

Circumferential defects of digit are uncommon but present a challenging problem to the clinician. The use of simple skin grafts tends to cause tendon adhesions and can limit digital range of motion. The use of local skin flaps, such as a cross-finger flap, is limited by the considerable skin loss in a defect that is circumferential in nature. Other options have included the use of reversed forearm flap or some free tissue transfer. We report a case in which the circumferential defect of an index finger, measuring 6 cm around the digit and 3 cm long, is resurfaced by the use of a free arterialized venous flap raised from the volar forearm skin.     

Office blood pressure measurement: A comprehensive review

The conventional auscultatory methods for measuring blood pressure have been used to screen, diagnose, and manage hypertension since long. However, these have been found to be prone to errors especially the white coat phenomena which cause falsely high blood pressure readings. The Mercury sphygmomanometer and the Aneroid variety are no longer recommended by WHO for varying reasons. The Oscillometric devices are now recommended with preference for the Automated Office Blood Pressure measurement device which was found to have readings nearest to the Awake Ambulatory Blood Pressure readings. The downside for this device is the cost barrier. The alternative is to use the simple oscillometric device, which is much cheaper, with the rest and isolation criteria of the SPRINT study. This too may be difficult due to space constraints and the post‐clinic blood measurement is a new concept worth further exploration.     

Cardiovascular Disease and Use of Renin-Angiotensin System Inhibitors in COVID-19

There is ongoing debate on the safety of renin-angiotensin system (RAS) inhibitors in COVID-19. Recently published studies highlight a potential relationship between cardiovascular disease (CVD) and COVID-19. This article aims to summarize the evidence on the use of RAS inhibitors in CVD patients with COVID-19, focusing on safety issues of the RAS inhibitors and their relationship with COVID-19.