Bioaccumulation of therapeutic drugs by human gut bacteria.

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently1 and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth of the bacteria being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegans to duloxetine. Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner.

Failure to mate enhances investment in behaviors that may promote mating reward and impairs the ability to cope with stressors via a subpopulation of Neuropeptide F receptor neurons.

Living in dynamic environments such as the social domain, where interaction with others determines the reproductive success of individuals, requires the ability to recognize opportunities to obtain natural rewards and cope with challenges that are associated with achieving them. As such, actions that promote survival and reproduction are reinforced by the brain reward system, whereas coping with the challenges associated with obtaining these rewards is mediated by stress-response pathways, the activation of which can impair health and shorten lifespan. While much research has been devoted to understanding mechanisms underlying the way by which natural rewards are processed by the reward system, less attention has been given to the consequences of failure to obtain a desirable reward. As a model system to study the impact of failure to obtain a natural reward, we used the well-established courtship suppression paradigm in Drosophila melanogaster as means to induce repeated failures to obtain sexual reward in male flies. We discovered that beyond the known reduction in courtship actions caused by interaction with non-receptive females, repeated failures to mate induce a stress response characterized by persistent motivation to obtain the sexual reward, reduced male-male social interaction, and enhanced aggression. This frustrative-like state caused by the conflict between high motivation to obtain sexual reward and the inability to fulfill their mating drive impairs the capacity of rejected males to tolerate stressors such as starvation and oxidative stress. We further show that sensitivity to starvation and enhanced social arousal is mediated by the disinhibition of a small population of neurons that express receptors for the fly homologue of neuropeptide Y. Our findings demonstrate for the first time the existence of social stress in flies and offers a framework to study mechanisms underlying the crosstalk between reward, stress, and reproduction in a simple nervous system that is highly amenable to genetic manipulation.

Factors affecting optical coherence tomography angiography signal strength index in patients receiving intravitreal injection treatment.

PURPOSE: To investigate the clinical factors affecting optical coherence tomography angiography (OCTA) signal strength index (SSI) and its change after intravitreal injection treatment in patients with retinal disorders. METHODS: OCTA data from 186 eyes of 166 patients with various retinal disorders including age-related macular degeneration, diabetic macular edema (DME), and retinal vein occlusions who received intravitreal injections were analyzed. The associations between SSI and clinical factors, including age, best-corrected visual acuity (BCVA), media opacity severity, and central macular thickness (CMT), were evaluated both before and after injection. RESULTS: After injection, BCVA improved and CMT decreased significantly, and SSI increased significantly (p = 0.030). BCVA showed a significant positive correlation with media opacity severity before and after injection and with CMT only before injection. In the multivariate analysis, age, presence of DME, BCVA, and media opacity severity were negatively associated with SSI both before and after injection, while CMT was negatively associated with SSI only before injection. After injection, a negative correlation was found between SSI change and both BCVA and CMT change. CONCLUSION: Our findings suggest that OCTA SSI is influenced by various clinical factors, including age, visual acuity, media opacity severity, and macular thickening, especially in cases of DME. The results also indicate that SSI may decrease in patients with macular disorders due to the presence of macular edema and the associated decrease in visual acuity. Therefore, it is crucial to consider these factors when interpreting OCTA data and ensure an adequate level of SSI.

Adaptive laboratory evolution of microbial co-cultures for improved metabolite secretion.

Adaptive laboratory evolution has proven highly effective for obtaining microorganisms with enhanced capabilities. Yet, this method is inherently restricted to the traits that are positively linked to cell fitness, such as nutrient utilization. Here, we introduce coevolution of obligatory mutualistic communities for improving secretion of fitness-costly metabolites through natural selection. In this strategy, metabolic cross-feeding connects secretion of the target metabolite, despite its cost to the secretor, to the survival and proliferation of the entire community. We thus co-evolved wild-type lactic acid bacteria and engineered auxotrophic Saccharomyces cerevisiae in a synthetic growth medium leading to bacterial isolates with enhanced secretion of two B-group vitamins, viz., riboflavin and folate. The increased production was specific to the targeted vitamin, and evident also in milk, a more complex nutrient environment that naturally contains vitamins. Genomic, proteomic and metabolomic analyses of the evolved lactic acid bacteria, in combination with flux balance analysis, showed altered metabolic regulation towards increased supply of the vitamin precursors. Together, our findings demonstrate how microbial metabolism adapts to mutualistic lifestyle through enhanced metabolite exchange.

AICAR upregulates ABCA1/ABCG1 expression in the retinal pigment epithelium and reduces Bruch's membrane lipid deposit in ApoE deficient mice.

The etiology of age-related macular degeneration (AMD) is diverse; however, recent evidence suggests that the lipid metabolism-cholesterol pathway might be associated with the pathophysiology of AMD. The ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1, are essential for the formation of high-density lipoprotein (HDL) and the regulation of macrophage cholesterol efflux. The failure of retinal or retinal pigment epithelium (RPE) cholesterol efflux to remove excess intracellular lipids causes morphological and functional damage to the retina. In this study, we investigated whether treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMP-activated protein kinase (AMPK) activator, improves RPE cholesterol efflux and Bruch's membrane (BM) lipid deposits. The protein and mRNA levels of ABCA1 and ABCG1 in ARPE-19 cells and retinal and RPE/choroid tissue from apolipoprotein E-deficient (ApoE-/-) mice were evaluated after 24 weeks of AICAR treatment. The cholesterol efflux capacity of ARPE-19 cells and the cholesterol-accepting capacity of apoB-depleted serum from mice were measured. The thickness of the BM and the degree of lipid deposition were evaluated using electron microscopy. AICAR treatment increased the phosphorylation of AMPK and the protein and mRNA expression of ABCA1 and ABCG1 in vitro. It promoted cholesterol efflux from ARPE-19 cells and upregulated the protein and mRNA levels of ABCA1 and ABCG1 in the retina and RPE in vivo. ApoB-depleted serum from the AICAR-treated group showed enhanced cholesterol-accepting capacity. Long-term treatment with AICAR reduced BM thickening and lipid deposition in ApoE-/- mice. In conclusion, AICAR treatment increased the expression of lipid transporters in the retina and RPE in vivo, facilitated intracellular cholesterol efflux from the RPE in vitro, and improved the functionality of HDL to accept cholesterol effluxed from the cell, possibly via AMPK activation. Collectively, these effects might contribute to the improvement of early age-related pathologic changes in the BM. Pharmacological improvement of RPE cholesterol efflux via AMPK activation may be a potential treatment strategy for AMD.

INTRAOCULAR AND INTEROCULAR DIFFERENCES IN PARAFOVEAL VASCULAR DENSITY IN DIABETIC PATIENTS WITHOUT DIABETIC RETINOPATHY.

PURPOSE: To evaluate the associations among optical coherence tomography angiography-measured vascular density (VD), intraocular and interocular VD differences, and clinical factors in diabetic patients without diabetic retinopathy. METHODS: We retrospectively reviewed 94 Type 2 diabetic patients without diabetic retinopathy who had undergone optical coherence tomography angiography. Vascular density and vessel skeleton density were measured in a 3-mm central zone in the total capillary plexus, superficial capillary plexus, deep capillary plexus (DCP), and choriocapillaris layers. Intraocular VD difference was determined between the superior and inferior zones, while interocular VD difference was determined between both eyes of the patient. Associations between optical coherence tomography angiography parameters and clinical factors were evaluated. RESULTS: Vascular density and intraocular and interocular VD differences were significantly associated with signal strength of the image, which was related with age and lens opacity. In multivariate analysis, diabetes duration was negatively associated with skeleton density in total capillary plexus and superficial capillary plexus layers, and positively associated with intraocular VD difference in superficial capillary plexus layer. Estimated glomerular filtration rate was negatively associated with intraocular skeleton density difference in total capillary plexus layer, interocular VD, and skeleton density differences in total capillary plexus layer. CONCLUSION: Intraocular and interocular VD difference may be an easy and sensitive way to detect subtle early microvascular changes in diabetic patients.

Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster males.

Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them. Olfactory conditioning experiments showed that winning is perceived as rewarding, while losing is perceived as aversive. Moreover, the effect of chronic fighting experience generalized to other behaviors, such as gap-crossing and courtship. We propose that in response to repeatedly winning or losing aggressive encounters, male flies form an internal state that displays persistence and generalization; fight outcomes can also have positive or negative valence. Furthermore, we show that the activities of the PPL1-γ1pedc dopaminergic neuron and the MBON-γ1pedc>α/ß mushroom body output neuron are required for aversion to an olfactory cue associated with losing fights.

Aqueous humor inflammatory cytokine levels and choroidal thickness in patients with macular edema associated with branch retinal vein occlusion.

PURPOSE: We aimed to investigate the association between subfoveal choroidal thickness (SCT) and the level of aqueous humor (AH) inflammatory cytokines in patients with macular edema (ME) associated with branch retinal vein occlusion (BRVO). METHODS: Twenty-eight eyes of 28 BRVO ME patients who underwent intravitreal injection treatment (ranibizumab, bevacizumab, or dexamethasone implant) were prospectively recruited. The concentrations of vascular endothelial growth factor (VEGF)-A and inflammatory cytokines were measured from AH samples. We analyzed clinical factors associated with visual gain or the degree of central macular thickness (CMT) decrease and the association between SCT and inflammatory cytokine levels. RESULTS: On multiple linear regression analysis, the AH interleukin (IL)-8 level was significantly associated with visual gain and CMT reduction at 6 months. Age, systemic hypertension, and AH monocyte chemo-attractant protein 1 level showed a significant association with baseline SCT, and VEGF-A showed a significant association with baseline SCT ratio (BRVO eye SCT/fellow eye SCT). Those with thick SCT showed a higher level of AH soluble VEGF receptors 2 and IL-8 and showed better visual gain and greater CMT reduction at 2 and 6 months compared to the thin SCT group. CONCLUSIONS: The level of AH inflammatory cytokines was significantly associated with the ischemic status of the retina, treatment outcomes, and SCT in BRVO ME patients. Thick baseline SCT might be a predictive sign for better treatment outcomes in BRVO ME patients which are thought to be related to a higher level of intraocular inflammatory cytokines in these patients.

Relationship between sleep and obesity among U.S. and South Korean college students.

BACKGROUND: Little is known about the relationship between sleep and obesity in young adults, particularly college students. This study examined the relationship between sleep (i.e., sleep duration and quality) and obesity in a large and diverse binational sample of college students. METHODS: Analyses were based on a 40-item paper survey from 2016/2017 to 2017/2018 academic years, with a 72% response rate. The samples were 1578 college students aged 18-25 years from five universities (two in the U.S. and three in South Korea). Weight and height were measured objectively; other measures (e.g., health behaviors) were self-reported. Multinomial logistic regression was used to assess the association between sleep duration and independent variables (race/nationality, gender, and BMI). Poisson regression was used to examine the relationship between sleep quality and independent variables. RESULTS: Overall, blacks had a higher adjusted odds ratio (AOR) of short sleep (< 7 h/night) than whites (AOR = 1.74, P < .01); overweight participants had a higher AOR of short sleep than normal weight participants (AOR = 1.52, P < .01); and obese participants had a higher AORs of both short and long sleep (> 9 h/night) (AOR = 1.67, P < .01; AOR = 1.79, P < .05, respectively). Among men, being black, overweight, and obesity were associated with short sleep (P < .05), whereas only obesity was related to short sleep among women (P < .05). In analyses stratified by race and nationality, overweight and obesity were related to short sleep among blacks only (P < .05). Overall, sleep quality (getting enough sleep to feel rested in the morning in the past 7 days) was worse in blacks and South Koreans than whites (P < .05), worse in women than men (P < .05), and worse in participants with obesity than normal weight participants (P < .05). CONCLUSIONS: Obesity was associated with both short (< 7 h/night) and long sleep duration (> 9 h/night) and poor sleep quality among all participants. In comparison with whites, blacks were more like to have short sleep, and blacks and South Koreans had worse sleep quality. Further investigations using a larger sample of college students in multiple countries may be helpful to identify target populations who are at a greater risk of obesity and sleep problems.

Serum and aqueous humor vitamin D levels in patients with diabetic macular edema.

PURPOSE: To compare serum and aqueous humor (AH) vitamin D levels between the patients with diabetic macular edema (DME) and controls. METHODS: A total of 65 subjects (30 DME, 35 control) were included. One-third of the control group had hypertension, dyslipidemia, or diabetes mellitus without diabetic retinopathy as underlying diseases. Serum and AH levels of 25-hydroxyvitamin D were measured in each subject. Multiple linear regression analysis was performed to investigate factors associated with serum and AH vitamin D levels. RESULTS: There were no significant differences in serum vitamin D levels between the DME (14.3 ± 9.1 ng/mL) and control (16.2 ± 8.0 ng/mL) groups (P = 0.374). However, eyes with DME (41.6 ± 8.0 ng/mL) had a higher AH level of vitamin D than control eyes (25.5 ± 4.1 ng/mL, P < 0.001). AH vitamin D level was significantly associated with the presence of DME (ß = 0.775, P < 0.001). Serum and AH levels of vitamin D were not significantly correlated (r = - 0.157, P = 0.211). CONCLUSION: Serum vitamin D levels did not significantly differ between the DME and control groups. Localized vitamin D level in the eye was independent from systemic vitamin D level and it might be another indicator of DME severity.

Choroidal volume changes following blow-out fracture repair.

PURPOSE: To investigate the serial choroidal volume change following orbital blow-out fracture (BOF) repair. METHODS: The choroidal volume was measured by optical coherence tomography in patients who underwent BOF repair, preoperatively and postoperatively at 1, 4, 12 and 24 weeks. The orbital volume ratio (OVR) was obtained by dividing the orbital volume of the traumatized orbit by that of the contralateral side using three-dimensional computed tomography imaging. The choroidal volume change was compared between both eyes using a linear mixed model. RESULTS: We analyzed the choroidal volume of 11 patients. Choroidal volume showed a trend of slight increase during the immediate postoperative period, and then, choroidal volume decreased abruptly between postoperative 1 to 4 weeks (ß-coefficient - 0.22, P < 0.001). Choroidal volume also showed gradual decrease between postoperative 4 to 24 weeks (ß-coefficient - 0.02, P < 0.001). During the study period, there were no significant differences in choroidal volume change between BOF and contralateral unaffected eyes (ß-coefficient - 0.20, P = 0.711). The hyperopic refractive errors (ß-coefficient 0.27, P = 0.028) and the larger preoperative OVR (ß-coefficient 10.37, P = 0.013) were associated with larger choroidal volume. CONCLUSIONS: Choroidal volume showed a similar decreasing change following BOF repair between the BOF and the contralateral unaffected eyes. Moreover, choroidal volume of both eyes was associated with the degree of orbital volume expansion due to BOF, suggesting that choroidal volume change after BOF repair was affected not only by trauma-associated local hemodynamic changes but also by systemic influences such as inflammatory response.

Metatranscriptomics reveals the hydrolytic potential of peat-inhabiting Planctomycetes.

Members of the phylum Planctomycetes are common inhabitants of northern Sphagnum-dominated wetlands. Evidence is accumulating that, in these environments, some planctomycetes may be involved in degrading polymeric organic matter. The experimental data, however, remain scarce due to the low number of characterized representatives of this phylum. In a previous study, we used metatranscriptomics to assess the activity response of peat-inhabiting microorganisms to biopolymers abundantly present in native peat. The community responses to cellulose, xylan, pectin, and chitin availability were analysed relative to unamended controls. Here, we re-analysed these metatranscriptomes and retrieved a total of 1,602,783 rRNA and 35,522 mRNA sequences affiliated with the Planctomycetes. Each of the four polymers induced specific planctomycete responses. These were most pronounced on chitin. The two groups with increased 16S rRNA transcript pools were Gemmata- and Phycisphaera-like planctomycetes. Among uncultivated members of the Planctomycetaceae, two increased transcript pools were detected in pectin-amended samples and belonged to Pirellula-like bacteria. The analysis of taxonomically assigned mRNA reads confirmed the specific response of Gemmata-related planctomycetes to chitin amendment suggesting the presence of chitinolytic capabilities in these bacteria.

Identification of microbial populations driving biopolymer degradation in acidic peatlands by metatranscriptomic analysis.

Northern peatlands play a crucial role in the global carbon balance, serving as a persistent sink for atmospheric CO2 and a global carbon store. Their most extensive type, Sphagnum-dominated acidic peatlands, is inhabited by microorganisms with poorly understood degradation capabilities. Here, we applied a combination of barcoded pyrosequencing of SSU rRNA genes and Illumina RNA-Seq of total RNA (metatranscriptomics) to identify microbial populations and enzymes involved in degrading the major components of Sphagnum-derived litter and exoskeletons of peat-inhabiting arthropods: cellulose, xylan, pectin and chitin. Biopolymer addition to peat induced a threefold to fivefold increase in bacterial cell numbers. Functional community profiles of assembled mRNA differed between experimental treatments. In particular, pectin and xylan triggered increased transcript abundance of genes involved in energy metabolism and central carbon metabolism, such as glycolysis and TCA cycle. Concurrently, the substrate-induced activity of bacteria on these two biopolymers stimulated grazing of peat-inhabiting protozoa. Alveolata (ciliates) was the most responsive protozoa group as confirmed by analysis of both SSU rRNA genes and SSU rRNA. A stimulation of alphaproteobacterial methanotrophs on pectin was consistently shown by rRNA and mRNA data. Most likely, their significant enrichment was due to the utilization of methanol released during the degradation of pectin. Analysis of SSU rRNA and total mRNA revealed a specific response of Acidobacteria and Actinobacteria to chitin and pectin, respectively. Relatives of Telmatobacter bradus were most responsive among the Acidobacteria, while the actinobacterial response was primarily affiliated with Frankiales and Propionibacteriales. The expression of a wide repertoire of carbohydrate-active enzymes (CAZymes) corresponded well to the detection of a highly diverse peat-inhabiting microbial community, which is dominated by yet uncultivated bacteria.

Anti-VEGF PolysiRNA Polyplex for the Treatment of Choroidal Neovascularization.

Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present ocular siRNA delivery technology is limited due to poor delivery through the retina to the choroid, where CNV originates. Our goal was to develop an optimized nanosized polyRNAi-based therapeutic delivery system to the subretinal space. We developed it by siRNA multimerization (polysiRNA) followed by coating with branched polyethylenimine and hyaluronic acid, and then evaluated its efficacy in vitro and in vivo. The polysiRNA polyplex showed a narrow size distribution (260.7 ± 43.27 nm) and negative charge (-4.98 ± 0.47 mV) owing to the hyaluronic acid outer layer. In vitro uptake of the polysiRNA polyplex by human ARPE cells was discovered, and the direct inhibition of VEGF mRNA translation was confirmed in B16F10 cells. The intravitreally administered polysiRNA polyplex overcame both the vitreous and retina barriers in vivo and reached the subretinal space efficiently. Intravitreal injection of the polysiRNA polyplex was not toxic to the retina in histopathology. Furthermore, intravitreal injections of the polysiRNA polyplex at both 1 and 7 days after laser photocoagulation inhibited laser-induced choroidal neovascularization, compared to that of the control (p < 0.05). These results suggest that anti-VEGF polysiRNA polyplexes show great potential in delivering multimeric RNAi-based therapeutics to treat retinal or choroidal disorders.

CHOROIDAL THICKNESS CHANGE AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN RETINAL ANGIOMATOUS PROLIFERATION AND ITS RECURRENCE.

PURPOSE: To investigate choroidal thickness changes after anti-vascular endothelial growth factor (VEGF) treatment in retinal angiomatous proliferation (RAP) and correlate choroidal thickness with disease recurrence. METHODS: Twenty-six eyes from 21 patients with RAP were treated with 3 monthly intravitreal anti-VEGF injections and additional injections as needed. RAP was divided according to the component of pigment epithelial detachment. The subfoveal choroidal thickness and choroidal thickness under the RAP lesion were measured using spectral-domain optical coherence tomography and compared between recurrence and nonrecurrence groups during the first year. RESULTS: The subfoveal choroidal thickness and choroidal thickness under the RAP lesion showed a significant decrease during the first 3 months; however, this was not maintained for the first year. The recurrence group showed a significantly thicker subfoveal choroidal thickness (P = 0.021) and choroidal thickness under the RAP lesion (P = 0.020) during the first year in those with only drusen or drusenoid pigment epithelial detachment without serous component. A significant increase and decrease in choroidal thickness was observed during the recurrence and remission period. CONCLUSION: Increased choroidal thickness was associated with a higher rate of recurrence after anti-VEGF treatment in RAP with only drusen or drusenoid pigment epithelial detachment. Choroidal thickness could also reflect disease activity, even before manifestation of retinal disease activity.

DAFGA: diversity analysis of functional gene amplicons.

SUMMARY: Diversity analysis of functional marker genes provides physiological insights into microbial guilds that perform an ecologically relevant process. However, it is challenging to group functional gene sequences to valid taxonomic units, primarily because of differences in the evolutionary rates of individual genes and possible horizontal gene transfer events. We developed a python script package named DAFGA, which estimates the evolutionary rate of a particular functional gene in a standardized manner by relating its sequence divergence to that of the 16S rRNA gene. As a result, DAFGA provides gene-specific parameter sets for operational taxonomic unit clustering and taxonomic assignment at desired rank, and it can be implemented into the diversity measurements offered by QIIME. AVAILABILITY AND IMPLEMENTATION: DAFGA is freely available with a manual and test data from https://github.com/outbig/DAFGA.

Comparison of visual and anatomical outcomes of half-fluence and half-dose photodynamic therapy in eyes with chronic central serous chorioretinopathy.

PURPOSE: To compare visual and anatomical outcomes of half-fluence (HF) and half-dose (HD) photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSC). Particular focus was given to photoreceptor recovery rate following treatment. METHODS: Retrospective review of 52 chronic CSC patients who underwent HF- or HD-PDT (26 patients per group). Best-corrected visual acuity and spectral-domain optical coherence tomography findings were compared between groups. RESULTS: Average follow-up for HF- and HD-PDT was 20.7 ± 7.2 and 22.3 ± 6.1 months respectively. Both groups had significant visual acuity improvements, as well as central foveal and subfoveal choroidal thickness reductions. Measured parameters were not significantly different between groups at any time point examined. Complete photoreceptor recovery, defined as a continuous ellipsoid zone with a discernible interdigitation zone, was observed at 12 months in 19 (73 %) and 14 patients (54 %) in the HF- and HD-PDT groups respectively (p = 0.150). Overall photoreceptor recovery rate was not different between groups (p = 0.301, log-rank test). Delayed (>12 months) photoreceptor recovery was significantly associated with baseline external limiting membrane disruption (OR: 21.7, 95 % CI: 1.7-285.4, p = 0.019), disease duration (years, OR: 1.9, 95 % CI: 1.2-3.0, p = 0.005), and fovea-to-PDT spot center distance (100 µm unit, OR: 0.74, 95 % CI 0.56-0.97, p = 0.027). However, delayed photoreceptor recovery was not significantly associated with PDT modality. CONCLUSION: Both HF- and HD-PDT are effective in treating chronic CSC. No significant differences in visual or anatomical outcomes were observed.

No evidence of sexual selection in a repetition of Bateman's classic study of Drosophila melanogaster.

We are unique in reporting a repetition of Bateman [Bateman AJ (1948) Heredity (Edinb) 2:349-368] using his methods of parentage assignment, which linked sex differences in variance of reproductive success and variance in number of mates in small populations of Drosophila melanogaster. Using offspring phenotypes, we inferred who mated with whom and assigned offspring to parents. Like Bateman, we cultured adults expressing dramatic phenotypes, so that each adult was heterozygous-dominant at its unique marker locus but had only wild-type alleles at all other subjects' marker loci. Assuming no viability effects of parental markers on offspring, the frequencies of parental phenotypes in offspring follow mendelian expectations: one-quarter will be double-mutants who inherit the dominant gene from each parent, the offspring from which Bateman counted the number of mates per breeder; half of the offspring must be single mutants inheriting the dominant gene of one parent and the wild-type allele of the other parent; and one-quarter would inherit neither of their parent's marker mutations. Here we show that inviability of double-mutant offspring biased inferences of mate number and number of offspring on which rest inferences of sex differences in fitness variances. Bateman's method overestimated subjects with zero mates, underestimated subjects with one or more mates, and produced systematically biased estimates of offspring number by sex. Bateman's methodology mismeasured fitness variances that are the key variables of sexual selection.

Cerebral Angiographic Findings of Cosmetic Facial Filler-related Ophthalmic and Retinal Artery Occlusion.

Cosmetic facial filler-related ophthalmic artery occlusion is rare but is a devastating complication, while the exact pathophysiology is still elusive. Cerebral angiography provides more detailed information on blood flow of ophthalmic artery as well as surrounding orbital area which cannot be covered by fundus fluorescein angiography. This study aimed to evaluate cerebral angiographic features of cosmetic facial filler-related ophthalmic artery occlusion patients. We retrospectively reviewed cerebral angiography of 7 patients (4 hyaluronic acid [HA] and 3 autologous fat-injected cases) showing ophthalmic artery and its branches occlusion after cosmetic facial filler injections, and underwent intra-arterial thrombolysis. On selective ophthalmic artery angiograms, all fat-injected patients showed a large filling defect on the proximal ophthalmic artery, whereas the HA-injected patients showed occlusion of the distal branches of the ophthalmic artery. Three HA-injected patients revealed diminished distal runoff of the internal maxillary and facial arteries, which clinically corresponded with skin necrosis. However, all fat-injected patients and one HA-injected patient who were immediately treated with subcutaneous hyaluronidase injection showed preserved distal runoff of the internal maxillary and facial arteries and mild skin problems. The size difference between injected materials seems to be associated with different angiographic findings. Autologous fat is more prone to obstruct proximal part of ophthalmic artery, whereas HA obstructs distal branches. In addition, hydrophilic and volume-expansion property of HA might exacerbate blood flow on injected area, which is also related to skin necrosis. Intra-arterial thrombolysis has a limited role in reconstituting blood flow or regaining vision in cosmetic facial filler-associated ophthalmic artery occlusions.