Germline Mutations in CIDEB and Protection against Liver Disease.

BACKGROUND: Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets. METHODS: We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations. RESULTS: The multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, -1.24 U per liter; 95% confidence interval [CI], -1.66 to -0.83; P = 4.8×10-9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P = 9.9×10-7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, -0.98; 95% CI, -1.54 to -0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets. CONCLUSIONS: Rare germline mutations in CIDEB conferred substantial protection from liver disease. (Funded by Regeneron Pharmaceuticals.).

Translational control of E2f1 regulates the Drosophila cell cycle.

E2F transcription factors are master regulators of the eukaryotic cell cycle. In Drosophila, the sole activating E2F, E2F1, is both required for and sufficient to promote G1→S progression. E2F1 activity is regulated both by binding to RB Family repressors and by posttranscriptional control of E2F1 protein levels by the EGFR and TOR signaling pathways. Here, we investigate cis-regulatory elements in the E2f1 messenger RNA (mRNA) that enable E2f1 translation to respond to these signals and promote mitotic proliferation of wing imaginal disc and intestinal stem cells. We show that small upstream open reading frames (uORFs) in the 5' untranslated region (UTR) of the E2f1 mRNA limit its translation, impacting rates of cell proliferation. E2f1 transgenes lacking these 5'UTR uORFs caused TOR-independent expression and excess cell proliferation, suggesting that TOR activity can bypass uORF-mediated translational repression. EGFR signaling also enhanced translation but through a mechanism less dependent on 5'UTR uORFs. Further, we mapped a region in the E2f1 mRNA that contains a translational enhancer, which may also be targeted by TOR signaling. This study reveals translational control mechanisms through which growth signaling regulates cell cycle progression.

Multi-Functional PEDOT:PSS as the Efficient Perovskite Solar Cells.

Poly(3,4-ethylenedioxythiophene) (PEDOT), particularly in its complex form with poly(styrene sulfonate) (PEDOT:PSS), stands out as a prominent example of an organic conductor. Renowned for its exceptional conductivity, substantial light transmissibility, water processability, and remarkable flexibility, PEDOT:PSS has earned its reputation as a leading conductive polymer. This study explores the unique effects of two additives, Bisphenol A diglycidyl ether (DGEBA) and Dimethyl sulfoxide (DMSO), on the PSS component of PEDOT:PSS films are shown. Both additives induce grain size growth, while DGEBA makes the PEDOT:PSS layer hydrophobic, which acts as a passivation to protect the perovskite layer, which is vulnerable to moisture. The other additive, DMSO, separates the PSS groups, resulting in increased conductivity through the free movement of holes. With these multi-modified p-type PEDOT:PSS, the ITO/M-PEDOT:PSS/Perovskite/PCBM/Ag structured reverse structure solar cell has improved the power conversion efficiency (PCE) from 15.28% to 17.80% compared to the control cell with conventional PEDOT:PSS. It also maintains 90% for 500 h at 60 °C and 300 h at 1 sun illuminating conditions.

Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.

BACKGROUND: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.

The effect of nondamaging subthreshold laser therapy in patients with chronic central serous chorioretinopathy.

PURPOSE: To evaluate the efficacy of nondamaging subthreshold laser therapy in Korean patients with chronic central serous chorioretinopathy (cCSC). METHODS: This retrospective interventional case series included 31 patients (31 eyes) with cCSC who underwent nondamaging laser therapy using Endpoint Management (EpM) software. Since a barely visible burn of the test spot was defined as 100% pulse energy, 30% pulse energy with a 200-µm spot was titrated to treat the macular area based on EpM settings. A 30% pulse laser with a spacing of 0.25-beam diameter was applied to cover the macular area where hyperfluorescent leaks were observed on fluorescein angiography. Changes in central macular thickness (CMT), subretinal fluid (SRF) height, subfoveal choroidal thickness (SCT), and logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) were measured at baseline and after 3 and 6 months. If the subretinal fluid persisted for 3 months, retreatment was performed. RESULTS: At 6 months post-treatment, the complete SRF resolution rate was 48.39% (15/31 eyes), and the partial SRF resolution rate was 12.90% (4/31 eyes). The change in mean BCVA (logMAR) was not significant (0.31 ± 0.29 at the baseline and 0.31 ± 0.40 at month 6) (p = 0.943). At the baseline, the mean CMT (µm) decreased from 350.74 ± 112.76 at baseline to 239.71 ± 130.25 at month 6 (p < 0.001), and the mean SRF height (µm) decreased from 193.16 ± 90.69 at baseline to 70.58 ± 100.00 at month 6 (p < 0.001). However, the change in SCT was not statistically significant (p = 0.516). In 15 patients who were retreated at month 3, the mean SRF height (µm) decreased significantly from 144.67 ± 74.01 at month 3 to 77.13 ± 63.77 at month 6 (p = 0.002). No side effects associated with laser therapy were observed during the 6-month follow-up. CONCLUSIONS: Nondamaging laser therapy with a modified macular treatment was effective in reducing CMT and SRF and showed favorable visual and anatomical outcomes in patients with cCSC.

Comparison of intravitreal preservative-free triamcinolone versus posterior sub-tenon triamcinolone acetonide injection for bevacizumab-resistant diabetic macular edema.

BACKGROUND: Triamcinolone acetonide (TA) is administered as an intravitreal or posterior sub-Tenon's capsule injection, as treatment for diabetic macular edema (DME). The intravitreal use of TA is limited because commercially available triamcinolone acetonide contains benzyl alcohol, a neurotoxic preservative. Few studies have compared effects of preservative-free intravitreal TA (IVTA) and posterior sub-Tenon capsule TA (STTA) injections for DME. Thus, herein, we compared the effectiveness of preservative-free IVTA and STTA for treatment of bevacizumab-resistant DME. METHODS: In this retrospective cohort study, bevacizumab-resistant DME was defined as a lack of response to at least three consecutive intravitreal bevacizumab (IVB) injections. Changes in mean central macula thickness (CMT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) between IVTA and STTA groups were compared at baseline and at 1, 2, and 3 months after treatment. RESULTS: Forty eyes from 40 patients were included in this study. In the IVTA group, the mean CMT improved significantly from 400.2 ± 144.42 µm at baseline to 288.35 ± 151.74 µm at 3 months after treatment (p = 0.01). Similarly, in the STTA group, the mean CMT improved significantly from 446.65 ± 120.74 µm at baseline to 382.9 ± 113.58 µm at 3 months after treatment (p = 0.009). The mean BCVA of the IVTA group also showed improvement, decreasing from 0.75 ± 0.55 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.625 ± 0.50 logMAR at 3 months after treatment (p = 0.089). Similarly, the mean BCVA of the STTA group improved, from 0.6 ± 0.36 logMAR at baseline to 0.54 ± 0.35 logMAR at 3 months after treatment (p = 0.094). CONCLUSION: Given that IVTA and STTA demonstrated statistically equivalent anatomical and functional effects in patients with bevacizumab-resistant DME, the less invasive STTA may be considered the preferred treatment approach for the management of bevacizumab-resistant DME. TRIAL REGISTRATION: Retrospectively registered.

Drug Development from Natural Products Based on the Pathogenic Mechanism of Asthma.

Asthma is a chronic inflammatory disease of the pulmonary system associated with many wheeze-to-sleep apnea complications that may lead to death. In 2019, approximately 262 million patients suffered from asthma, and 455 thousand died from the disease worldwide. It is a more severe health problem in children and older adults, and as the aging of society intensifies, the problem will continue to worsen. Asthma inducers can be classified as indoor and outdoor allergens and can cause asthma due to their repeated invasion. There are several theories about asthma occurrence, such as the imbalance between Th1 and Th2, inflammation in the pulmonary system, and the abnormal apoptosis/cell proliferation of cells related to asthma. Although there are many medications for asthma, as it is an incurable disease, the purpose of the drugs is only to suppress the symptoms. The current drugs can be divided into relievers and controllers; however, as they have many adverse effects, such as immune suppression, growth retardation, promotion of cataracts, hyperactivity, and convulsions, developing new asthma drugs is necessary. Although natural products can have adverse effects, the development of asthma drugs from natural products may be beneficial, as some have anti-asthmatic effects such as immune modulation, anti-inflammation, and/or apoptosis modulation.

Tetraspanin 7 regulates osteoclast function through association with the RANK/αvß3 integrin complex.

Actin rings are unique structures that facilitate the attachment of osteoclasts to the bone matrix during bone resorption. Previous studies have shown that tetraspanin7 (TSPAN7) plays an important role in the reorganization of the cytoskeleton necessary for the bone-resorbing activity of osteoclasts. However, questions remain as to the mechanisms by which TSPAN7 regulates this cytoskeletal rearrangement. In this study, we investigated the roles of TSPAN7 in osteoclasts by deleting the Tm4sf2 gene in mice, which encodes TSPAN7. The Tm4sf2 global knockout model showed protective effects on pathological bone loss, but no discernible changes in bone phenotypes under physiological conditions. In vitro study revealed that ablation of Tm4sf2 caused significant defects in integrin-mediated actin ring formation, thereby leading to significantly decreased bone resorption. Additionally, we demonstrated an association between TSPAN7 and the receptor activator of nuclear factor-кB/αvß3 integrin. Overall, our findings suggest that TSPAN7 acts as a novel modulator regulating the bone-resorbing function of osteoclasts.

Highly sensitive near-infrared SERS nanoprobes for in vivo imaging using gold-assembled silica nanoparticles with controllable nanogaps.

BACKGROUND: To take advantages, such as multiplex capacity, non-photobleaching property, and high sensitivity, of surface-enhanced Raman scattering (SERS)-based in vivo imaging, development of highly enhanced SERS nanoprobes in near-infrared (NIR) region is needed. A well-controlled morphology and biocompatibility are essential features of NIR SERS nanoprobes. Gold (Au)-assembled nanostructures with controllable nanogaps with highly enhanced SERS signals within multiple hotspots could be a breakthrough. RESULTS: Au-assembled silica (SiO2) nanoparticles (NPs) (SiO2@Au@Au NPs) as NIR SERS nanoprobes are synthesized using the seed-mediated growth method. SiO2@Au@Au NPs using six different sizes of Au NPs (SiO2@Au@Au50-SiO2@Au@Au500) were prepared by controlling the concentration of Au precursor in the growth step. The nanogaps between Au NPs on the SiO2 surface could be controlled from 4.16 to 0.98 nm by adjusting the concentration of Au precursor (hence increasing Au NP sizes), which resulted in the formation of effective SERS hotspots. SiO2@Au@Au500 NPs with a 0.98-nm gap showed a high SERS enhancement factor of approximately 3.8 × 106 under 785-nm photoexcitation. SiO2@Au@Au500 nanoprobes showed detectable in vivo SERS signals at a concentration of 16 µg/mL in animal tissue specimen at a depth of 7 mm. SiO2@Au@Au500 NPs with 14 different Raman label compounds exhibited distinct SERS signals upon subcutaneous injection into nude mice. CONCLUSIONS: SiO2@Au@Au NPs showed high potential for in vivo applications as multiplex nanoprobes with high SERS sensitivity in the NIR region.

Association between smokeless tobacco use and cigarette smoking amount by age.

BACKGROUND: The use of smokeless tobacco has increased worldwide among young people. This study aimed to investigate the association between smokeless tobacco use and cigarette smoking amount in adult smoker groups stratified by age. METHOD: 2013-2015 National Health Interview Survey was used. A total of 19,635 subjects were included in our analysis. Propensity score matching was used to adjust for selection and any other bias. Generalized estimating equation was used to analyze the association between smokeless tobacco use and cigarette smoking amount by age. RESULTS: All 580 smokeless tobacco users were matched to 2,900 non-smokeless tobacco users. Among those who were aged under 30, smokeless tobacco use was positively associated with the number of cigarettes used per day. Smokeless tobacco users who were aged under 30 and tried quitting smoking used more cigarettes than those who did non-smokeless tobacco users. CONCLUSIONS: The present study revealed that among those who were aged under 30, smokeless tobacco use was positively associated with the number of cigarettes used per day. This study could contribute to understand the behaviors and tendencies of smoking in young adulthood and to establish effective smoking cessation methods for their age.

The Effect of Selective Retina Therapy for Bevacizumab-Resistant Chronic Central Serous Chorioretinopathy.

PURPOSE: The aim of this study was to evaluate the efficacy of selective retina therapy (SRT), used in conjunction with real-time feedback dosimetry (RFD), in the treatment of bevacizumab-resistant chronic central serous chorioretinopathy (CSC). PATIENTS AND METHODS: In this retrospective cohort study, 22 eyes of 22 patients with bevacizumab-resistant chronic CSC, showing focal or diffuse foveal leakages on fundus fluorescein angiography (FFA), were included. After evaluation of the test spots at temporal arcades, SRT (wavelength, 527 nm; pulse repetition rate, 100 Hz; ramping over maximal 15 micropulses; and spot diameter, 200 µm) using RFD was applied to the leakage sites observed on FFA. Changes in the mean best-corrected visual acuity (BCVA), central macular thickness (CMT), and subretinal fluid (SRF) height were evaluated at baseline and at 1, 3, 6, 9, and 12 months following treatment. RESULTS: SRF completely resolved in 81.8% (18/22 eyes) cases at 12 months post-treatment. The mean BCVA (logarithm of the minimum angle of resolution [logMAR]) improved from 0.49 ± 0.29 at baseline to 0.43 ± 0.36 at 12 months (p = 0.067). The mean BCVA gain was 0.06 logMAR, equivalent to 3 ETDRS letters. The CMT significantly decreased from 323 ± 85.6 µm at baseline to 221.5 ± 60.4 µm at 12 months (p < 0.001). The mean SRF height also significantly decreased from 174.6 ± 86.4 µm at baseline to 35.1 ± 75.4 µm at 12 months (p < 0.001). CONCLUSION: SRT showed favorable visual and anatomical outcomes in patients with bevacizumab-resistant chronic CSC.

Pleiotropic role of Drosophila phosphoribosyl pyrophosphate synthetase in autophagy and lysosome homeostasis.

Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme whose function is important for the biosynthesis of purines, pyrimidines, and pyridines. Importantly, while missense mutations of PRPS1 have been identified in neurological disorders such as Arts syndrome, how they contribute to neuropathogenesis is still unclear. We identified the Drosophila ortholog of PRPS (dPRPS) as a direct target of RB/E2F in Drosophila, a vital cell cycle regulator, and engineered dPRPS alleles carrying patient-derived mutations. Interestingly, while they are able to develop normally, dPRPS mutant flies have a shortened lifespan and locomotive defects, common phenotypes associated with neurodegeneration. Careful analysis of the fat body revealed that patient-derived PRPS mutations result in profound defects in lipolysis, macroautophagy, and lysosome function. Significantly, we show evidence that the nervous system of dPRPS mutant flies is affected by these defects. Overall, we uncovered an unexpected link between nucleotide metabolism and autophagy/lysosome function, providing a possible mechanism by which PRPS-dysfunction contributes to neurological disorders.

Highly Bright Silica-Coated InP/ZnS Quantum Dot-Embedded Silica Nanoparticles as Biocompatible Nanoprobes.

Quantum dots (QDs) have outstanding optical properties such as strong fluorescence, excellent photostability, broad absorption spectra, and narrow emission bands, which make them useful for bioimaging. However, cadmium (Cd)-based QDs, which have been widely studied, have potential toxicity problems. Cd-free QDs have also been studied, but their weak photoluminescence (PL) intensity makes their practical use in bioimaging challenging. In this study, Cd-free QD nanoprobes for bioimaging were fabricated by densely embedding multiple indium phosphide/zinc sulfide (InP/ZnS) QDs onto silica templates and coating them with a silica shell. The fabricated silica-coated InP/ZnS QD-embedded silica nanoparticles (SiO2@InP QDs@SiO2 NPs) exhibited hydrophilic properties because of the surface silica shell. The quantum yield (QY), maximum emission peak wavelength, and full-width half-maximum (FWHM) of the final fabricated SiO2@InP QDs@SiO2 NPs were 6.61%, 527.01 nm, and 44.62 nm, respectively. Moreover, the brightness of the particles could be easily controlled by adjusting the amount of InP/ZnS QDs in the SiO2@InP QDs@SiO2 NPs. When SiO2@InP QDs@SiO2 NPs were administered to tumor syngeneic mice, the fluorescence signal was prominently detected in the tumor because of the preferential distribution of the SiO2@InP QDs@SiO2 NPs, demonstrating their applicability in bioimaging with NPs. Thus, SiO2@InP QDs@SiO2 NPs have the potential to successfully replace Cd-based QDs as highly bright and biocompatible fluorescent nanoprobes.

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease.

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.

Association between hyperuricemia and metabolic risk components in Korean women.

The researchers evaluated the association between hyperuricemia and metabolic risk components in Korean women of reproductive and postmenopausal ages. The study data were collected from the Korea National Health and Nutrition Examination Survey 2016. Among a total of 4305 female participants, the data of 2958 women were analyzed. Of the 2958 participants, 57.6% (n = 1508) were of reproductive age. After adjusting for factors, hyperuricemia was significantly associated with abdominal obesity (OR 4.30, p = .046), high blood pressure (OR 3.23, p = .002), and hypertriglyceridemia (OR 3.08, p = .005) in reproductive women. In contrast, no metabolic risk was significantly associated with hyperuricemia in postmenopausal women.

Over-expression of stromal periostin correlates with poor prognosis of cutaneous squamous cell carcinomas.

Periostin, an extracellular matrix macromolecule implicated in tumorigenesis, serves as a prognostic marker for many cancer types. However, there are no data on periostin expression in cutaneous squamous cell carcinoma (cSCC). This study examined periostin expression in patients with cSCC and explored its clincopathological relationship and prognosis. Using immunohistochemistry and ImageJ analysis, we compared periostin expression in 95 cSCCs across a spectrum of cSCC aggressiveness: cSCC in situ (SCCIS) (n = 25), low-risk cSCC (LR-cSCC) (n = 26), high-risk cSCC (HR-cSCC) (n = 38), and cSCC in recessive dystrophic epidermolysis bullosa patients (RDEB cSCC) (n = 6). Immunohistochemistry demonstrated periostin expression within the intra-tumoral stroma but not within tumor cells. Periostin levels significantly (P < 0.001) increased from SCCIS, LR-cSCC, HR-cSCC to RDEB SCC. The stroma of most of the cSCCs we evaluated contained cancer-associated fibroblasts with a myofibroblastic (α -SMA-positive) phenotype. Co-localization of periostin with α-SMA, evidence of fibroblast periostin expression, and absence of keratinocyte or tumor cell periostin expression suggest that, in cSCC, periostin is a product of the peritumoral microenvironment and not the tumor cells themselves. Our data indicate that fibroblast periostin expression is highly correlated with the aggressiveness of cSCC, and may thereby provide a molecular marker that will be useful for subtyping and diagnosing cSCCs according to their biological nature.

Transfer learning of memory kernels for transferable coarse-graining of polymer dynamics.

The present work concerns the transferability of coarse-grained (CG) modeling in reproducing the dynamic properties of the reference atomistic systems across a range of parameters. In particular, we focus on implicit-solvent CG modeling of polymer solutions. The CG model is based on the generalized Langevin equation, where the memory kernel plays the critical role in determining the dynamics in all time scales. Thus, we propose methods for transfer learning of memory kernels. The key ingredient of our methods is Gaussian process regression. By integration with the model order reduction via proper orthogonal decomposition and the active learning technique, the transfer learning can be practically efficient and requires minimum training data. Through two example polymer solution systems, we demonstrate the accuracy and efficiency of the proposed transfer learning methods in the construction of transferable memory kernels. The transferability allows for out-of-sample predictions, even in the extrapolated domain of parameters. Built on the transferable memory kernels, the CG models can reproduce the dynamic properties of polymers in all time scales at different thermodynamic conditions (such as temperature and solvent viscosity) and for different systems with varying concentrations and lengths of polymers.

Retinal pigment epithelial responses based on the irradiation density of selective retina therapy.

PURPOSE: We evaluated the response of the retinal pigment epithelium (RPE) to high-density (HD) or low-density (LD)-selective retina therapy (SRT) with real-time feedback-controlled dosimetry (RFD) in rabbits. METHODS: Sixteen eyes of 8 Chinchilla Bastard rabbits underwent SRT with RFD (527-nm wavelength, 1.7-µs pulse duration), using automatically titrated pulse energy, by using optoacoustic dosimetry or real-time reflectometry. Fifty-six 25-µJ SRT, including LD-SRT (1-spot or 2-spot-spacing) and HD-SRT (4-spot, 7-spot, or 9-spot-no-spacing), were applied per eye. Color fundus photography and fundus fluorescein angiography (FFA) were used to confirm SRT spots 1-h post-SRT. Light microscopy and scanning electron microscopy (SEM) were performed at 2-h, 3-day, 7-day, and 1-month post-treatment. RESULTS: We tested 896 spots irradiated by SRT with RFD and confirmed that SRT lesions were adequate, based on invisibility on fundoscopy and visibility on FFA. On SEM, at 2-h post-SRT, flattened RPE cells were observed in the center of the SRT lesion. While normal RPE cells were clearly observed between LD-SRT lesions, healthy RPE cells were rare in HD-SRT lesions at 2-h post-treatment. At 7-day post-SRT, SEM revealed completely restored LD-SRT lesions with small or large RPE cells with microvilli, whereas HD-SRT lesions were covered with RPE cells without microvilli. At 1-month post-SRT, SEM revealed restored RPE cells with microvilli in HD-SRT lesions. On light microscopy, both HD- and LD-SRT lesions were completely restored with adjacent RPE cells and spared photoreceptors at 1-month post-treatment. CONCLUSIONS: Although both HD- and LD-SRT lesions had recovered at 1-month post-SRT, LD-SRT lesions healed faster than HD-SRT lesions.

Influence of Anterior-Posterior External Surface Perturbation on Trunk Stability During Abdominal Stabilization Strategies While Sitting.

BACKGROUND Spinal and pelvic injuries during an unexpected perturbation are closely related to spinal stability, which is known to be controlled by abdominal stabilization maneuvers. This study aimed to evaluate the effects of unexpected perturbations on trunk stability and abdominal stabilization strategies in 42 sedentary adults while sitting. MATERIAL AND METHODS Abdominal stabilization strategies consisted of bracing and hollowing maneuvers. Abdominal bracing maneuvers (ABM) were focused on the abdominal wall muscles [inferior oblique (IO), exterior oblique (EO)], and abdominal hollowing maneuvers (AHM) were focused on deep muscle (TrA) activation. The subjects were instructed in abdominal stabilization maneuvers. Afterward, subjects were seated in a chair that could be moved forward or backward suddenly with the support surface. RESULTS Angular displacements of the upper thorax, lower thorax, and lumbopelvic during unexpected perturbation, with different abdominal stabilization maneuvers, were measured. During forward perturbation (d=0.71, F=10.324, P=0.001) and backward perturbation in high speed (d=0.62, F=9.265, P=0.011), there were significant differences in angular displacements of the upper thorax between hollowing and bracing maneuvers. Additionally, significant differences were found in the lumbopelvic angular displacement between the hollowing and bracing maneuvers (d=0.62, F=4.071, P=0.044). CONCLUSIONS Our findings indicate that the ABM is a better stabilizing technique for the upper thorax, and the AHM is a better stabilizing technique for the lumbopelvic region during unexpected perturbations at high speed in the seated position.

One-Year Functional and Anatomical Outcomes After Selective Retina Therapy With Real-Time Feedback-Controlled Dosimetry in Patients With Intermediate Age-Related Macular Degeneration: A Pilot Study.

BACKGROUND AND OBJECTIVES: This pilot study sought to evaluate changes in macular function and drusen volume (DV) after selective retina therapy (SRT) in patients with intermediate age-related macular degeneration (iAMD). STUDY DESIGN/MATERIALS AND METHODS: Twenty participants with bilateral iAMD were included in this prospective interventional case series study. After titrating pulse energy by real-time feedback-controlled dosimetry, SRT with a wavelength of 527 nm was applied around the macula of one eye of each patient. Changes in best-corrected visual acuity (BCVA), DV within the central 5-mm ring (C5), and retinal sensitivity (RS) of the SRT-treated eyes (treated eyes) and untreated fellow eyes (untreated eyes) were evaluated at baseline and then at 3, 6, 9, and 12 months after treatment using linear mixed models. RESULTS: The mean BCVA did not change significantly between baseline and 12 months in both treated and untreated eyes (P = 0.06, P = 0.24, respectively), whereas the BCVA increase rate was faster for treated than for untreated eyes at the 12-month visit (-0.072 logMAR; 95% confidence interval [CI], -0.085 to -0.059 logMAR; P = 0.006). The mean cube root transformation of DV (cube root DV) within C5 in the untreated eyes increased significantly from 0.278 ± 0.115 at baseline to 0.295 ± 0.132 mm (P = 0.027) at 12 months, whereas the cube root DV change in treated eyes was not significant (P = 0.553). The rate of increase in the cube root DV was lower in treated than in untreated eyes at the 12-month visit (-0.016 mm; 95% CI, -0.018 to -0.011 mm; P = 0.015). The mean RS was increased from 22.49 ± 2.40 dB to 24.09 ± 2.19 dB (P < 0.001) in the treated eyes, whereas the change of mean RS in the untreated eyes was not significant at the 12-month visit (P = 0.18). The treated eyes had a higher rate of increase in RS than untreated eyes at the 12-month visit (1.012 dB; 95% CI, 0.776-1.251 dB; P = 0.037). The RS change was significantly associated with the interaction between SRT treatment and time (P = 0.028), whereas it was not associated with cube root DV change (P = 0.106). No SRT-related adverse effects were observed in all participants during the 1-year follow-up. CONCLUSION: Since SRT improved the mean RS and reduced the rate of change in drusen load in the treated eyes, as compared to the untreated eyes, SRT might slow the progression of iAMD. However, further large randomized clinical trials are necessary to confirm the efficacy of SRT for iAMD. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.