Outcomes of Descemet's membrane endothelial keratoplasty performed in combination with, before, or after cataract surgery in Fuchs' endothelial dystrophy: A review of the literature and meta-analysis

This review aimed to compare the outcomes of Descemet's membrane endothelial keratoplasty (DMEK) in combination with (category 1), before (category 2), or after cataract surgery (category 3) in patients with Fuchs' endothelial dystrophy (FED). Primary outcome was gain in best-corrected log of minimum angle of resolution (logMAR) visual acuity (BCVA). Secondary outcomes were graft detachment, rebubbling rates, rejection, failure, and endothelial cell loss (ECL). In category 1, 2, and 3, 12 studies (N = 1932) were included (five in category 1 [n = 696], one in category 2 [n = 286], and two in category 3 [n = 950], and the remaining four compared between two of the three categories). At 6 months, the gain in BCVA was 0.34 ± 0.04, 0.25 ± 0.03, and 0.38 ± 0.03 logMAR in category 1, 2, and 3, respectively. The difference was significant between categories 1 and 2 (Chi2 = 11.47, P < 0.01) and categories 2 and 3 (Chi2 = 35.53, P < 0.01). At 12 months, the gain in BCVA was 0.52 ± 0.05 and 0.38 ± 0.06 logMAR in categories 1 & 3 (Chi2 = 14.04, P < 0.01). The rebubbling rates were 15%, 4%, and 10% (P < 0.01) and the graft detachment rates were 31%, 8%, and 13% (P < 0.01) in categories 1, 2, and 3, respectively. However, graft rejection, survival rates, and ECL at 12 months were not different between categories 1 and 3. There is low certainty evidence that gain in BCVA in category 1 was comparable to category 3 at 6 months; however, it was significantly better with category 3 at 12 months. Although rebubbling and graft detachment rates were highest in category 1, there was no significant difference in graft rejection, survival rates, and ECL. Further high-quality studies are likely to change the effect estimate and have an impact on the confidence of the estimate

Swallowing the bait: Is recreational fishing in Australia ecologically sustainable?

Recreational fishing is a growing component of the total fishery harvest in many countries, but the impacts of this sector on aquatic resources are often ignored in the management of aquatic systems. Recreational fishing is open-access, and in many inshore regions, the recreational harvest exceeds the commercial harvest. The environmental impacts from recreational angling can be both ecologically significant and broad in scope and include: the removal of a considerable biomass of a wide variety of species; discarded by-catch; possible trophic cascades through the removal of higher order carnivores; impacts on habitat through bait harvesting; impacts of introduced and translocated species to support angling fisheries; direct impacts on sea-birds, marine mammals and reptiles; and angler generated pollution. Management, for several reasons, has largely ignored these environmental impacts from recreational fishing. Recreational fishing impacts are cumulative, whereas there is a tendency for consideration of impacts in isolation. Recreational fishing lobbyists have generally been successful in focusing public and political attention on other impacts such as commercial fishing, and recreational fishing has tended not to come under close scrutiny from conservation and environmental groups. Without changes to the monitoring and management of recreational fisheries that incorporate the broad ecological impacts from the activity, it may not be ecologically sustainable in the long term and Australia will not meet its international obligations of protecting aquatic biodiversity. The definition of property rights and appropriate measures to prevent or manage large scale marine restocking are two emerging issues that also need to be addressed

Biochemical characterization of New Delhi metallo-beta-lactamase variants reveals differences in protein stability

Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Rhodes Trust (UK); a Clarendon Scholarship; a St Hugh's College W. Louey Scholarship; the Biotechnology & Biological Sciences Research Council (BBSRC); a Royal Society Dorothy Hodgkin Research Fellowship; and the Medical Research Council (MRC)/Canadian Grant G1100135

Implementation of Ambulance Hotspot Strategy in Reducing Ambulance Response Time

Introduction:Ambulance response time (ART) has an inseparable relationship with mortality rates and therefore is important to be reduced. However, an unprecedented increase in road traffic congestion has led to longer ART, especially during peak hours. To reduce ART despite congested traffic, a pre-dispatched ambulance is deployed at hotspot locations during peak hours. This study aims to determine if the hotspot strategy is able to reduce ART in an Urban Emergency Medical Services system.Methods: This is an intervention study at the Emergency and Trauma Department, Sabah Women and Children Hospital (SWACH). Since January 2017, ambulance temporally stations were set up at two hotspot locations. The pre-dispatched ambulance is deployed at hotspots during peak hours (8 – 10 a.m., 4 – 6 p.m.). Information on ambulance runs departed from mobile locations was collected from January to December 2017. Ambulance runs which departed from the hospital in the year 2016 were taken as the control group. A total of 312 runs were enrolled, only runs during peak hours on weekdays were included. The main outcome measure is ART. Mann-Whitney test was used to compare the response time of ambulance runs before and after the establishment of the hotspot strategy. Results:Results show a significant decrease in average ART from 17.31 minutes to 12.23 minutes with the hotspot strategy. When separated, both pre-travel delay times and travel times experienced significant reduction of 2.35 minutes and 2.75 minutes respectively. Meanwhile, travel distances show no significant difference between pre- and post-strategy periods (p = 0.196). Conclusion:The present study shows that the hotspots strategy has successfully reduced ART at SWACH. However, the “ping” time problem from the GPS detection could affect the accuracy in calculating the travel distances. Further studies are suggested to overcome the “ping” time to increase the accuracy level. Overall, this study ascertains the potential benefits of ambulance hotspot strateg

Regulation of thymocyte positive selection and motility by GIT2

Thymocytes are highly motile cells that migrate under the influence of chemokines in distinct thymic compartments as they mature. The motility of thymocytes is tightly regulated; however, the molecular mechanisms that control thymocyte motility are not well understood. Here we report that G protein–coupled receptor kinase-interactor 2 (GIT2) was required for efficient positive selection. Notably, Git2−/− double-positive thymocytes showed greater activation of the small GTPase Rac, actin polymerization and migration toward the chemokines CXCL12 (SDF-1) and CCL25 in vitro. By two-photon laser-scanning microscopy, we found that the scanning activity of Git2−/− thymocytes was compromised in the thymic cortex, which suggests GIT2 has a key role in regulating the chemokine-mediated motility of double-positive thymocytes.National Institutes of Health (U.S.) (R01AI064227)Leukemia & Lymphoma Society of Americ

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

A RAC/CDC-42–Independent GIT/PIX/PAK Signaling Pathway Mediates Cell Migration in C. elegans

P21 activated kinase (PAK), PAK interacting exchange factor (PIX), and G protein coupled receptor kinase interactor (GIT) compose a highly conserved signaling module controlling cell migrations, immune system signaling, and the formation of the mammalian nervous system. Traditionally, this signaling module is thought to facilitate the function of RAC and CDC-42 GTPases by allowing for the recruitment of a GTPase effector (PAK), a GTPase activator (PIX), and a scaffolding protein (GIT) as a regulated signaling unit to specific subcellular locations. Instead, we report here that this signaling module functions independently of RAC/CDC-42 GTPases in vivo to control the cell shape and migration of the distal tip cells (DTCs) during morphogenesis of the Caenorhabditis elegans gonad. In addition, this RAC/CDC-42–independent PAK pathway functions in parallel to a classical GTPase/PAK pathway to control the guidance aspect of DTC migration. Among the C. elegans PAKs, only PAK-1 functions in the GIT/PIX/PAK pathway independently of RAC/CDC42 GTPases, while both PAK-1 and MAX-2 are redundantly utilized in the GTPase/PAK pathway. Both RAC/CDC42–dependent and –independent PAK pathways function with the integrin receptors, suggesting that signaling through integrins can control the morphology, movement, and guidance of DTC through discrete pathways. Collectively, our results define a new signaling capacity for the GIT/PIX/PAK module that is likely to be conserved in vertebrates and demonstrate that PAK family members, which are redundantly utilized as GTPase effectors, can act non-redundantly in pathways independent of these GTPases

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age