Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials.

PURPOSE: Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials. DESIGN: YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials. PARTICIPANTS: Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes. METHODS: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse. MAIN OUTCOME MEASURES: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. RESULTS: In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (µm) at year 1 was greater with faricimab Q8W (-232.8; P < 0.0001) and faricimab T&E (-217.4; P = 0.0004) ) versus aflibercept Q8W (-190.4). In RHINE, this was faricimab Q8W (-214.2; P = 0.0006) and faricimab T&E (-206.6; P = 0.0116) versus aflibercept Q8W (-186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 µm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average. CONCLUSIONS: In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cross-Sectional Anatomy and Computed Tomography of the Coelomic Cavity in Juvenile Atlantic Puffins (Aves, Alcidae, Fratercula arctica).

In birds, unlike mammals, there is no complete separation between the thoracic and abdominal cavities. Instead, they have the coelomic cavity where most main organs are found. Therefore, an adequate knowledge of the anatomy of the coelomic cavity is of great importance for veterinarians, biologists and the scientific community. This study aimed to evaluate the coelomic cavity anatomy in the Atlantic puffin (Fratercula arctica) using anatomical sections and computed tomography images.

Reparación del músculo pronador cuadrado en fracturas de radio distal tratadas con fijación interna por abordaje palmar: una revisión sistemática y metaanálisis / Repair of the pronator quadratus muscle in distal radius fractures treated with internal fixation through a palmar approach: a systematic review and meta-analysis

Introducción: el músculo pronador cuadrado funciona como un estabilizador dinámico de la articulación radiocubital distal. Su reparación posterior a la fijación interna con placa de bloqueo volar en fracturas distales del radio es controvertida. Objetivo: determinar si la reparación del músculo pronador cuadrado influye en los resultados clínicos y funcionales de pacientes con fractura de radio distal que se sometieron a reducción abierta y fijación interna con placa de bloqueo volar. Materiales y métodos: se realizó una revisión sistemática y metanálisis. Las bases de datos analizadas fueron PubMed/Medline, Embase y Bireme/Lilacs (búsqueda realizada hasta el 20 de febrero del año 2023). Los términos de búsqueda fueron: distal radius fracture AND volar plate AND pronator quadratus. Se determinó la calidad metodológica según el manual de revisiones Cochrane. Resultados: en total se incluyeron 4 ensayos clínicos aleatorizados de adecuada calidad metodológica, lo cual corresponde al análisis de 213 participantes. Existen mejores resultados en la puntuación DASH a los 12 meses de seguimiento en el grupo de no reparación del músculo pronador cuadrado DM 2,8 [IC 95%: 0,51;5,10]. No hubo diferencias significativas al año de seguimiento en las puntuaciones de dolor, rangos de movilidad de la muñeca, fuerza de agarre e incidencia de complicaciones. Conclusión: no existe evidencia que sustente la reparación rutinaria del músculo pronador cuadrado posterior a la fijación interna con placa de bloqueo volar en las fracturas de radio distal. (AU)

Introduction: the pronator quadratus muscle functions as a dynamic stabilizer of the distal radioulnar joint, and its repair after internal fixation with volar locking plate in distal radius fractures is controversial. Objective: to determine whether the repair of the pronator quadratus muscle influences the clinical and functional outcomes of patients with distal radius fracture who underwent open reduction and internal fixation with volar locking plate. Materials and methods: a systematic review and meta-analysis were conducted. The analyzed databases were Pubmed/Medline, Embase, and Bireme/Lilacs (search performed until February 20th, 2023). The search terms were distal radius fracture AND volar plate AND pronator quadratus. Methodological quality was determined according to the Cochrane Reviewer's Handbook. Results: a total of 4 randomized clinical trials of adequate methodological quality, corresponding to the analysis of 213 participants, were included. Better DASH scores were observed at 12 months of follow-up in the non-repair group of the pronator quadratus muscle, with a mean difference of 2.8 [95% CI 0.51; 5.10]. There were no significant differences at one-year follow-up in pain scores, wrist mobility ranges, grip strength, and incidence of complications. Conclusion: there is no evidence to support routine repair of the pronator quadratus muscle after internal fixation with volar locking plate in distal radius fractures. (AU)

El Niño Southern Oscillation (ENSO) effects on local weather, arboviral diseases, and dynamics of managed and unmanaged populations of Aedes aegypti (Diptera: Culicidae) in Puerto Rico.

We investigated the effects of interannual El Niño Southern Oscillation (ENSO) events on local weather, Aedes aegypti populations, and combined cases of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) viruses in 2 communities with mass mosquito trapping and 2 communities without mosquito control in southern Puerto Rico (2013-2019). Gravid adult Ae. aegypti populations were monitored weekly using Autocidal Gravid Ovitraps (AGO traps). Managing Ae. aegypti populations was done using 3 AGO traps per home in most homes. There were drought conditions in 2014-2015 concurrent with the emergence of a strong El Niño (2014-2016), wetter conditions during La Niña (2016-2018), a major hurricane (2017), and a weaker El Niño (2018-2019). The main factor explaining differences in Ae. aegypti abundance across sites was mass trapping. Populations of Ae. aegypti reached maximum seasonal values during the wetter and warmer months of the year when arbovirus epidemics occurred. El Niño was significantly associated with severe droughts that did not impact the populations of Ae. aegypti. Arbovirus cases at the municipality level were positively correlated with lagged values (5-12 mo.) of the Oceanic El Niño Index (ONI), droughts, and abundance of Ae. aegypti. The onset of strong El Niño conditions in Puerto Rico may be useful as an early warning signal for arboviral epidemics in areas where the abundance of Ae. aegypti exceeds the mosquito density threshold value.

Surveillance and Control of Culex quinquefasciatus Using Autocidal Gravid Ovitraps.

We monitored trap captures of Culex quinquefasciatus using an interrupted time-series study to determine if autocidal gravid ovitraps (AGO traps) were useful to control the population of this mosquito species in a community in southern Puerto Rico. Data for this report came from a previous study in which we used mass trapping to control Aedes aegypti, resulting in a significant 79% reduction in numbers of this species. The AGO traps used to monitor and control Ae. aegypti also captured numerous Cx. quinquefasciatus. Culex quinquefasciatus was monitored in surveillance AGO traps from October 2011 to February 2013, followed by a mosquito control intervention from February 2013 to June 2014. Optimal captures of this mosquito occurred on the 2nd wk after the traps were set or serviced, which happened every 8 wk. Changes in collection numbers of Cx. quinquefasciatus were positively correlated with rainfall and showed oscillations every 8 wk, as revealed by sample autocorrelation analyses. Culex quinquefasciatus was attracted to and captured by AGO traps, so mass trapping caused a significant but moderate reduction of the local population (31.2%) in comparison with previous results for Ae. aegypti, possibly resulting from female mosquitoes flying in from outside of the study area and decreased attraction to the traps past the 2nd wk of trap servicing. Because Ae. aegypti and Cx. quinquefasciatus are frequently established in urban areas, mass trapping to control the former has some impact on Cx. quinquefasciatus. Control of the latter could be improved by locating and treating its aquatic habitats within and around the community.

Eight weeks of combined exercise training do not alter circulating microRNAs-29a, -133a, -133b, and -155 in young, healthy men.

PURPOSE: Individuals with a family history of type 2 diabetes (FH +) have an increased risk of developing type 2 diabetes. Circulating microRNAs (miRNAs) have been implicated as biomarkers of type 2 diabetes risk. Here, we investigated if four circulating miRNAs related to glucose metabolism were altered in men with a FH + and we conducted a preliminary analysis to determine if miRNA expressions were responsive to 8 weeks of combined exercise training. METHODS: Sixteen young healthy men (mean ± SD; age 22.5 ± 2.5; BMI 26.4 ± 4.0) with FH + or without a family history of type 2 diabetes (FH -) underweight 8 weeks of combined endurance and resistance exercise training (n = 8 FH -; n = 8 FH +). The expression of miR-29a, miR-133a, miR-133b, and miR-155 were measured in serum before and after exercise training. QIAGEN's Ingenuity® Pathway Analysis was used to examine miRNA target genes and their involvement in glucose metabolism signaling pathways. RESULTS: There were no differences in miRNA expressions between FH - and FH + . Exercise training did not alter miRNA expressions in either FH - or FH + despite improvements in insulin sensitivity, aerobic capacity, and muscular strength. miR-29a and miR-155 were inversely related to fasting glucose, and miR-133a and miR-133b were negatively correlated with glucose tolerance; however, correlations were not observed with insulin sensitivity. CONCLUSIONS: The circulating miRNAs- miR-29a, miR-133a, miR-133b, and miR-155 are related to measures of glucose metabolism in healthy, normoglycemic men, but do not reflect peripheral insulin sensitivity or improvements in metabolic health following 8 weeks of combined exercise training.

Multi-Year Mass-Trapping With Autocidal Gravid Ovitraps has Limited Influence on Insecticide Susceptibility in Aedes aegypti (Diptera: Culicidae) From Puerto Rico.

Mass-trapping has been used to control outbreaks of Aedes aegypti (Linnaeus) (Diptera: Culicidae) in Puerto Rico since 2011. We investigated the effect of multi-year, insecticide-free mass trapping had on the insecticide susceptibility profile of Ae. aegypti. Eggs collected in southern Puerto Rico were used to generate F1 populations that were tested for susceptibility to permethrin, sumethrin, bifenthrin, deltamethrin, and malathion according to CDC bottle bioassays protocols. All populations of Ae. aegypti were resistant to the synthetic pyrethroids and mosquitoes from two locations were partially resistant to malathion. Population genetic analysis, using a double digest restriction sites associated DNA sequencing (ddRADseq) approach, indicated a large amount of migration between study sites effectively homogenizing the mosquito populations. Mass-trapping using noninsecticidal autocidal gravid ovitraps did not restore susceptibility to five active ingredients that are found in commercial insecticides. Migration between communities was high and would have brought outside alleles, including resistant alleles to the treatment communities. Further investigation suggests that household use of commercially available insecticide products may continue to select for resistance in absence of public health space spraying of insecticides.

CHOROIDAL IMAGING BIOMARKERS TO PREDICT HIGHLY RESPONSIVE AND RESISTANT CASES TREATED WITH STANDARDIZED ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR REGIMEN IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine structural predictors of treatment response in neovascular age-related macular degeneration analyzing optical coherence tomography (OCT)-related biomarkers. METHODS: A retrospective review of patients undergoing treatment for neovascular age-related macular degeneration at a tertiary institute was performed at presentation. High-intensity regimen included eyes on long-term anti-vascular endothelial growth factor treatment with the inability to extend beyond a month without a relapse and needed double the dose of medication (n = 25). Low-intensity regimen had eyes that went into long-term remission after at least three injections and remained dry for more than a year until the last visit (n = 20). Multimodal imaging including fluorescein angiogram, OCT, and comprehensive ocular evaluation were done. Choroidal vascularity index, total choroidal area, luminal area, subfoveal choroidal thickness, choriocapillaris thickness and Haller and Sattler layer thickness were analyzed for statistical significance. RESULTS: The groups had no significant difference at baseline in age, gender, incidence of reticular pseudodrusen, polypoidal choroidal vasculopathy feature on OCT, type of choroidal neovascular membrane, and geographic atrophy. Multinomial logistic regression revealed that thicker subfoveal choroidal thickness and larger total choroidal area were the significant predictors of poor response to anti-vascular endothelial growth factor treatment (E = 0.02; P = 0.02; E = 1.82; P = 0.0075). CONCLUSION: Thicker subfoveal choroidal thickness and higher total choroidal area are useful variables to predict a poor treatment response.

Improving the Safety and Acceptability of Autocidal Gravid Ovitraps (AGO Traps).

Gravid traps that collect eggs or adult mosquitoes use color, size, or volume as well as water or plant infusions as attractants. Biorational larvicides have been used to prevent these devices from producing adult mosquitoes within the traps. Results from field assays on the use of several biorational larvicides for various mosquito species have provided mixed results in terms of increased, neutral, or reduced attraction. We investigated the use of Bacillus thuringiensis var. israelensis, spinosad, and novaluron in field assays in Puerto Rico to evaluate the behavioral response of Aedes aegypti and Culex spp. to autocidal gravid ovitraps (AGO traps). The purpose of the study was to increase the safety of these traps by preventing accidental release of adult mosquitoes when traps are opened or damaged. We also investigated whether trap color (blue, green, terracotta) that may be more amenable for use by residents in their properties induced a similar attraction response to the original black trap color. We found that the use of biorational larvicides did not significantly change the behavioral attraction of these mosquito species to AGO traps. For Ae. aegypti, green traps yielded the lowest captures while black, terracotta, and blue produced similar higher yields. Culex spp. in black traps showed significantly higher captures compared with other colors. These results suggest that black, terracotta, or blue AGO traps can be used for the surveillance and control of Ae. aegypti.

Role of Abandoned and Vacant Houses on Aedes aegypti Productivity.

The control of container Aedes species by house inspections usually achieves insufficient coverage and impact because a percentage of residents are absent and some residents refuse inspections and treatments. In addition, another fraction of the buildings may be uninhabited, such as those for rent or sale, or abandoned. Although the productivity of Aedes aegypti has been investigated in abandoned lots, less is known about the importance of uninhabited buildings. We investigated Ae. aegypti pupal productivity in inhabited, vacant, and abandoned houses and its interaction with socioeconomic levels (SELs). We found pupae in containers of 386 houses (66 abandoned, 62 vacant, and 258 inhabited) in 19 neighborhoods in southern Puerto Rico from May to August 2017. Using a generalized linear model, we found a significant interaction between the status of the house (abandoned, vacant, and inhabited) and SELs (low, medium) on Ae. aegypti pupal abundance. More pupae were found in abandoned and inhabited houses of low SELs. The lowest productivity was found in vacant houses, regardless of the SEL. Most containers producing Ae. aegypti in low-SEL houses were discarded on backyards, whereas in medium SELs, most productivity came from containers in use. Septic tanks producing Ae. aegypti were found only in houses of low SELs, where most emerging mosquitoes came from inhabited houses. We did not find any pupae of Ae. aegypti on roofs. These results indicate that proper yard management could significantly reduce the production of Ae. aegypti and the risk of dengue infections in low-SEL neighborhoods.

Design of a AFLP-PCR and PCR-RFLP test that identify the majority of discrete typing units of Trypanosoma cruzi.

BACKGROUND: Chagas disease, caused by the intracellular parasite Trypanosoma cruzi, is one of the most important parasitological infections in the Americas. It is estimated to infect approximately 6 million people from mostly low income countries in Latin America, although recent infections have been reported in southern US states. Several studies have described an extensive genetic diversity among T. cruzi isolates throughout its geographic distribution in the American continent. This diversity has been correlated with the pathology developed during an infection. However, due to a lack of a single reliable test, current diagnosis practices of the disease are not straightforward since several different tests are applied. The use of current genomic sequence data allows for the selection of molecular markers (MM) that have the ability to identify the Discrete Typing Unit (DTU) of T. cruzi in a given infection, without the need of any sequencing reaction. METHODOLOGY/PRINCIPAL FINDINGS: Applying three criteria on the genomic sequencing data of four different phylogenetic lineages of T. cruzi, we designed several molecular tests that can be used for the molecular typing of the parasite. The criteria used were: (1) single-copy orthologs of T. cruzi, (2) T. cruzi unique loci, and (3) T. cruzi polymorphic loci. All criteria combined allowed for the selection of 15 MM, 12 of which were confirmed to be functional and replicable in the laboratory with sylvatic samples. Furthermore, one MM produced distinct polymerase chain reaction (PCR) amplicon sizes among distinct T. cruzi DTUs, allowing the use of a AFLP-PCR test to distinguish DTUs I, II/IV, V and VI. Whereas two MM can differentiate DTUs I, II, IV and V/VI out of the six current DTUs with a PCR-RFLP test. CONCLUSIONS/SIGNIFICANCE: The designed molecular tests provide a practical and inexpensive molecular typing test for the majority of DTUs of T. cruzi, excluding the need to perform any sequencing reaction. This provides the scientific community with an additional specific, quick and inexpensive test that can enhance the understanding of the correlation between the DTU of T. cruzi and the pathology developed during the infection.

Exercise-Induced Improvements in Insulin Sensitivity Are Not Attenuated by a Family History of Type 2 Diabetes.

Introduction: A family history of type 2 diabetes (FH+) is a major risk factor for the development of insulin resistance and type 2 diabetes. However, it remains unknown whether exercise-induced improvements in insulin sensitivity and metabolic flexibility are impacted by a FH+. Therefore, we investigated whether improvements in insulin sensitivity, metabolic flexibility, body composition, aerobic fitness and muscle strength are limited by a FH+ following eight weeks of combined exercise training compared to individuals without a family history of type 2 diabetes (FH-). Methods: Twenty (n = 10 FH-, n = 10 FH+) young, healthy, sedentary, normoglycemic, Mexican-American males (age: FH- 22.50 ± 0.81, FH+ 23.41 ± 0.86 years; BMI: FH- 27.91 ± 1.55, FH+ 26.64 ± 1.02 kg/m2) underwent eight weeks of combined aerobic and resistance exercise training three times/week (35 min aerobic followed by six full-body resistance exercises). Insulin sensitivity was assessed via hyperinsulinemic euglycemic clamps. Metabolic flexibility was assessed by the change in respiratory quotient from fasted to insulin-stimulated states. Body composition was determined using dual-energy x-ray absorptiometry. Aerobic fitness was determined by a graded exercise test, and upper- and lower-body strength were assessed via one-repetition maximum bench press and leg strength dynamometer, respectively. Results: Insulin sensitivity, metabolic flexibility, aerobic fitness and strength were not different between groups (p > 0.05). Eight weeks of combined aerobic and resistance exercise training improved insulin sensitivity (FH- p = 0.02, FH+ p = 0.002), increased fat free mass (FH- p = 0.006, FH+ p = 0.001), aerobic fitness (FH- p = 0.03, FH+ p = 0.002), and upper- (FH- p = 0.0001, FH+ p = 0.0001) and lower-body strength (FH- p = 0.0009, FH+ p = 0.0003), but did not change metabolic flexibility (p > 0.05) in both groups. Exercise-induced improvements in metabolic outcomes were similar between groups. Conclusions: Insulin sensitivity, metabolic flexibility, aerobic fitness and strength were not compromised by a FH+. Additionally, a FH+ is not a limiting factor for exercise-induced improvements in insulin sensitivity, aerobic fitness, body composition, and strength in normoglycemic young Mexican-American men.

Entomological Investigation Detects Dengue Virus Type 1 in Aedes (Stegomyia) albopictus (Skuse) during the 2015-16 Outbreak in Hawaii.

A dengue outbreak occurred on Hawaii Island between September 2015 and March 2016. Entomological investigations were undertaken between December 2015 and February 2016 to determine which Aedes mosquito species were responsible for the outbreak. A total of 3,259 mosquitoes were collected using a combination of CDC autocidal gravid ovitraps, Biogents BG-Sentinel traps, and hand-nets; immature mosquitoes were collected during environmental surveys. The composition of species was Aedes albopictus (58%), Aedes aegypti (25%), Wyeomyia mitchelli (7%), Aedes vexans (5%), Culex quinquefasciatus (4%), and Aedes japonicus (1%). Adult mosquitoes were analyzed by real-time reverse transcription polymerase chain reaction (PCR) for the presence of dengue virus (DENV) RNA. Of the 185 pools of female mosquitoes tested, 15 containing Ae. albopictus were positive for the presence of DENV type 1 RNA. No virus was detected in pools of the remaining species. Phylogenetic analysis showed the virus strain belonged to genotype I and was closely related to strains that were circulating in the Pacific between 2008 and 2014. This is the first report of detection of DENV in Ae. albopictus from Hawaii.

Factors Modulating Captures of Gravid Aedes aegypti Females.

To improve detection and assessment of Aedes aegypti abundance, we investigated whether microhabitat factors of the location of autocidal gravid ovitraps (AGO traps) influenced captures of gravid females in 2 locations in southern Puerto Rico. One location had been under vector control for several years using mass AGO trapping (intervention site), where Ae. aegypti abundance was several times lower than in the other study site without mosquito control (nonintervention site). We observed 10 environmental factors describing trap microhabitat location, and monitored water volume and minimum, maximum, and average temperature in AGO traps. Air temperature, relative humidity, and rainfall were recorded at each site. We conducted a hot-spot analysis of AGO traps to understand whether trap captures were influenced by the local abundance of mosquitoes rather than or in addition to trap microhabitat factors. AGO traps were classified using a 2-step cluster analysis based on attributes of trap microhabitats, water temperature, and water volume. Captures of female Ae. aegypti in each cluster per site were compared between resulting clusters to determine whether trap microhabitat factors defining the clusters were associated with trap captures. Trap captures in both study sites were mostly correlated with captures in nearby traps regardless of trap microhabitat factors, possibly reflecting the influence of the spatial aggregation of mosquitoes coming from nearby aquatic habitats or the concentration of dispersing adults. These results indicated that AGO traps can be located at places that can be easily reached during periodic inspections, such as in front of houses, without much regard to local microhabitat conditions.

Foveal Avascular Zone Distortion in Epiretinal Membrane by Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To show the morphologic changes on the foveal avascular zone (FAZ) in patients with epiretinal membrane (ERM) using optical coherence tomography angiography (OCTA) and to demonstrate the correlation between distortion of FAZ and features of the ERM. PATIENTS AND METHODS: FAZ eccentricity index (longest diameter of FAZ/shortest diameter of FAZ) was measured in 52 patients with ERM and compared with 27 healthy subjects' values. The density of the ERM was quantified using a grading scale (0-3) on multicolor scanning laser images, and spectral-domain OCT characteristics of the eyes were assessed. RESULTS: Of the 52 eyes with ERM, 31 eyes (59.61%) showed some foveal remodeling, including full (13.46%) or partial (30.76%) apparent vascularization of FAZ, presence of a vessel crossing the fovea (9.61%), and horizontal or vertical elongation of FAZ (5.76%). The mean FAZ eccentricity index was 0.84 ± 0.46 (range: 0.0-1.86) in eyes with ERM and 0.98 ± 0.07 (range: 0.96-1.02) in the control subjects, respectively (P = .02). There was a negative significant correlation between FAZ eccentricity index and central macular thickness (P = .04). CONCLUSIONS: Thickening of the central fovea leads to foveal remodeling in ERM eyes, and OCTA enables the visualization of architectural FAZ changes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:295-301.].

Impacts of Hurricanes Irma and Maria on Aedes aegypti Populations, Aquatic Habitats, and Mosquito Infections with Dengue, Chikungunya, and Zika Viruses in Puerto Rico.

Puerto Rico was severely impacted by Hurricanes Irma and Maria in September 2017. The island has been endemic for dengue viruses (DENV) and recently suffered epidemics of chikungunya (CHIKV 2014) and Zika (ZIKV 2016) viruses. Although severe storms tend to increase the number of vector and nuisance mosquitoes, we do not know how they influence Aedes aegypti populations and arboviral transmission. We compared the abundance of female Ae. aegypti in autocidal gravid ovitraps (AGO traps), container habitats, and presence of RNA of DENV, CHIKV, and ZIKV in this vector before and after the hurricanes in Caguas city and in four communities in southern Puerto Rico. Two of these communities were under vector control using mass AGO trapping and the other two nearby communities were not. We also investigated mosquito species composition and relative abundance (females/trap) using Biogents traps (BG-2 traps) in 59 sites in metropolitan San Juan city after the hurricanes. Mosquitoes sharply increased 5 weeks after Hurricane Maria. Ensuing abundance of Ae. aegypti was higher in Caguas and in one of the southern communities without vector control. Aedes aegypti did not significantly change in the two areas with vector control. The most abundant mosquitoes among the 26 species identified in San Juan were Culex (Melanoconion) spp., Culex quinquefasciatus, Culex nigripalpus, and Ae. aegypti. No arboviruses were detected in Ae. aegypti following the hurricanes, in contrast with observations from the previous year, so that the potential for Aedes-borne arboviral outbreaks following the storms in 2017 was low.

Citywide Control of Aedes aegypti (Diptera: Culicidae) during the 2016 Zika Epidemic by Integrating Community Awareness, Education, Source Reduction, Larvicides, and Mass Mosquito Trapping.

This investigation was initiated to control Aedes aegypti and Zika virus transmission in Caguas City, Puerto Rico, during the 2016 epidemic using Integrated Vector Management (IVM), which included community awareness and education, source reduction, larviciding, and mass-trapping with autocidal gravid ovitraps (AGO). The epidemic peaked in August to October 2016 and waned after April 2017. There was a preintervention period in October/November 2016 and IVM lasted until August 2017. The area under treatment (23.1 km2) had 61,511 inhabitants and 25,363 buildings. The city was divided into eight even clusters and treated following a cluster randomized stepped-wedge design. We analyzed pools of female Ae. aegypti adults for RNA detection of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) viruses using 360 surveillance AGO traps every week. Rainfall, temperature, and relative humidity were monitored in each cluster. Mosquito density significantly changed (generalized linear mixed model; F8, 14,588 = 296; P < 0.001) from 8.0 ± 0.1 females per trap per week before the intervention to 2.1 ± 0.04 after the percentage of buildings treated with traps was 60% and to 1.4 ± 0.04 when coverage was above 80%. Out of a total 12,081 mosquito pools, there were 1 DENV-, 7 CHIKV-, and 49 ZIKV-positive pools from October 2016 to March 2017. Afterward, we found only one positive pool of DENV in July 2017. This investigation demonstrated that it was possible to scale up effective Ae. aegypti control to a medium-size city through IVM that included mass trapping of gravid Ae. aegypti females.

COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.

PURPOSE: To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. METHODS: This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. RESULTS: The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. CONCLUSION: Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

A protein chimera strategy supports production of a model "difficult-to-express" recombinant target.

Due in part to the needs of the biopharmaceutical industry, there has been an increased drive to generate high quality recombinant proteins in large amounts. However, achieving high yields can be a challenge as the novelty and increased complexity of new targets often makes them 'difficult-to-express'. This study aimed to define the molecular features that restrict the production of a model 'difficult-to-express' recombinant protein, Tissue Inhibitor Metalloproteinase-3 (TIMP-3). Building from experimental data, computational approaches were used to rationalize the redesign of this recombinant target to generate a chimera with enhanced secretion. The results highlight the importance of early identification of unfavourable sequence attributes, enabling the generation of engineered protein forms that bypass 'secretory' bottlenecks and result in efficient recombinant protein production.

Integrated vector control of Aedes aegypti mosquitoes around target houses.

BACKGROUND: The developing fetuses of pregnant women are at high risk of developing serious birth defects following Zika virus infections. We applied an Integrated Vector Control (IVC) approach using source reduction, larviciding, and mass trapping with non-insecticidal sticky traps to protect targeted houses by reducing the density of female Aedes aegypti mosquitoes. METHODS: We tested the hypothesis that Ae. aegypti density could be reduced to below three female mosquitoes/trap/week around a target house in the center of a circular area with a 150 m radius using IVC. Two non-adjacent areas within the same neighbourhood were selected and randomly designated as the treatment or control areas. Sentinel Autocidal Gravid Ovitraps (SAGO traps) were placed in each study area and were sampled weekly from May to November, during the 2016 Zika epidemic in Puerto Rico. The experimental design was longitudinal with pre-and post-IVC treatment observations between treatment and control areas, and a partial cross-over design, where IVC was applied to the original control area after 2 months to determine if Ae. aegypti density converged to levels observed in the treatment area. Pools of female Ae. aegypti mosquitoes were analyzed by RT-PCR to detect Zika, dengue and chikungunya virus RNA. RESULTS: Overall, pre-treatment mosquito densities in the inner (0-50 m; 15.6 mosquitoes/trap/week), intermediate (50-100 m; 18.1) and outer rings (100-150 m; 15.6) were reduced after treatment to 2.8, 4.1, and 4.3 in the inner, middle, and outer rings, respectively. Density at the target house in the treatment area changed from 27.7 mosquitoes/trap/week before IVC to 2.1 after IVC (92.4% reduction), whereas after treating the original control area (cross-over) density changed from 22.4 to 3.5 (84.3% reduction). Vector reductions were sustained in both areas after IVC. Zika virus was detected in Ae. aegypti, but the low incidence of the virus precluded assessing the impact of IVC on Zika transmission during the study. CONCLUSIONS: Applying IVC to circular areas that were surrounded by untreated areas significantly decreased the number of mosquitoes around target houses located in the center. Gravid Ae. aegypti females in the center of the 150 m areas fell below threshold levels that possibly protect against novel invading arboviruses, such as chikungunya and Zika.