Piezo1 (Piezo-Type Mechanosensitive Ion Channel Component 1)-Mediated Mechanosensation in Macrophages Impairs Perfusion Recovery After Hindlimb Ischemia in Mice.

BACKGROUND: Angiogenesis is a promising strategy for those with peripheral artery disease. Macrophage-centered inflammation is intended to govern the deficiency of the angiogenic response after hindlimb ischemia. However, little is known about the mechanism of macrophage activation beyond signals from cytokines and chemokines. We sought to identify a novel mechanical signal from the ischemic microenvironment that provokes macrophages and the subsequent inflammatory cascade and to investigate the potential role of Piezo-type mechanosensitive ion channels (Piezo) on macrophages during this process. METHODS: Myeloid cell-specific Piezo1 (Piezo-type mechanosensitive ion channel component 1) knockout (Piezo1ΔMΦ) mice were generated by crossing Piezo1fl/fl (LysM-Cre-/-; Piezo1 flox/flox) mice with LysM-Cre transgenic mice to assess the roles of Piezo1 in macrophages after hindlimb ischemia. Furthermore, in vitro studies were carried out in bone marrow-derived macrophages to decipher the underlying mechanism. RESULTS: We found that tissue stiffness gradually increased after hindlimb ischemia, as indicated by Young's modulus. Compared to Piezo2, Piezo1 expression and activation were markedly upregulated in macrophages from ischemic tissues in concurrence with increased tissue stiffness. Piezo1ΔMΦ mice exhibited improved perfusion recovery by enhancing angiogenesis. Matrigel tube formation assays revealed that Piezo1 deletion promoted angiogenesis by enhancing FGF2 (fibroblast growth factor-2) paracrine signaling in macrophages. Conversely, activation of Piezo1 by increased stiffness or the agonist Yoda1 led to reduced FGF2 production in bone marrow-derived macrophages, which could be blocked by Piezo1 silencing. Mechanistically, Piezo1 mediated extracellular Ca2+ influx and activated Ca2+-dependent CaMKII (calcium/calmodulin-dependent protein kinase II)/ETS1 (ETS proto-oncogene 1) signaling, leading to transcriptional inactivation of FGF2. CONCLUSIONS: This study uncovers a crucial role of microenvironmental stiffness in exacerbating the macrophage-dependent deficient angiogenic response. Deletion of macrophage Piezo1 promotes perfusion recovery after hindlimb ischemia through CaMKII/ETS1-mediated transcriptional activation of FGF2. This provides a promising therapeutic strategy to enhance angiogenesis in ischemic diseases.

The Co-Parenting Across Family Structures Scale: Replication for Mandarin parents.

Co-parenting, the undertaking of parents working together to raise their children, is well documented as an important consideration of children's adjustment in Western countries, but we know less about the role of co-parenting in other cultures. In China, for example, co-parenting has only recently emerged in the social science literature. This study aimed to examine the cultural sensitivity of the CoPAFS instrument among Chinese Mandarin-speaking parents. CoPAFS is a 27-item survey designed to assess co-parenting across married and unmarried family structures originally developed in English. Data were collected from 729 Chinese-speaking and 348 English-speaking respondents. Factor analyses and confirmatory factor analyses indicated that the overall model fit for the translated co-parenting measure was acceptable in Mandarin. However, the five CoPAFS subscales (trust, respect, communication, acrimony, and value) differed across comparison groups, with communication notable for its lack of endorsement among Chinese couples. Implications of measuring co-parenting within Chinese families are offered.

Augmented-Dose Unilateral Recession-Resection Procedure in Acute Acquired Comitant Esotropia.

PURPOSE: To compare the surgical amount of unilateral medial rectus recession and lateral rectus resection (RR) in patients with acute acquired comitant esotropia (AACE) versus common forms of esotropia and to provide dose-response reference for surgical planning in AACE. DESIGN: Retrospective study. PARTICIPANTS: Consecutive patients who underwent unilateral RR for AACE or common forms of esotropia correction from January 2018 to January 2022. Only patients who achieved motor and sensory success with a minimum follow-up of 3 months were analyzed. METHODS: Group differences in the amount of medial rectus (MR) recession and lateral rectus (LR) resection were analyzed using multivariate regression models. Surgical dose responses in AACE were analyzed using multivariable regression models. Regression models were performed with and without adjustment for clinical confounders. Piecewise analysis was used to detect segmented results. MAIN OUTCOME MEASURES: Group difference in surgical amount and dose responses of unilateral RR in AACE. RESULTS: Fifty-four patients with AACE and 98 patients with common forms of esotropia were included. To correct comparable deviations, surgical amount performed was significant larger in AACE patients, with the adjusted group differences of 0.49 mm (95% confidence interval [CI], 0.34-0.65 mm; P < 0.001) in MR recession and 1.68 mm (95% CI, 1.25-2.11 mm; P < 0.001) in LR resection in patients with deviation < 40 prism diopters (Δ) and with a group difference of 1.22 mm (95% CI, 0.76-1.68 mm; P < 0.001) in LR resection in those with deviation ≥ 40 Δ. In AACE patients, in the adjusted model taking into account the intercept, dose responses of MR recession and LR resection in patients with deviation < 30 Δ were 5.11 Δ/mm (95% CI, 0.98-9.23 Δ/mm; P = 0.02) and 2.51 Δ/mm (95% CI, 0.57-4.45 Δ/mm; P = 0.02), respectively, and for those with deviation ≥ 30 Δ, the dose response of additional LR resection was 5.48 Δ/mm (95% CI, 4.56-6.40 Δ/mm; P < 0.001) to correct remaining deviation beyond 30 Δ. CONCLUSIONS: These findings provide quantitative evidence that augmented-dose unilateral RR should be performed in AACE for favorable surgical outcomes. The new surgical dose calculation proposed provides reference for surgical planning. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Knowledge Transmission and Skills Building Relating to Child Sexual Abuse in China.

Parents play a key role in child CSA prevention, but the mechanisms underlying the intergenerational knowledge transmission are not fully understood. This study explores the role of two parenting practices - parent-child communication and parent's protective behavior - as mediating factors in the relation between parents' knowledge and their children's knowledge and skills. Four hundred and ten dyads of early adolescents and their mother or father from rural China participated in the study. Parents were surveyed on their knowledge, protective behaviors, and parent-child communication regarding CSA, while children answered questions on relevant knowledge and skills. Results revealed that parental knowledge was positively and significantly related to communication and protective behavior, protective behavior was positively related to children's knowledge and skills, but the coefficient between communication and children's knowledge and skills was insignificant. The findings highlight direct parental protection as one of the most important mechanism for intergenerational knowledge transmission.

Cardiac-specific deletion of FDPS induces cardiac remodeling and dysfunction by enhancing the activity of small GTP-binding proteins.

The mevalonate pathway is essential for cholesterol biosynthesis. Previous studies have suggested that the key enzyme in this pathway, farnesyl diphosphate synthase (FDPS), regulates the cardiovascular system. We used human samples and mice that were deficient in cardiac FDPS (c-Fdps-/- mice) to investigate the role of FDPS in cardiac homeostasis. Cardiac function was assessed using echocardiography. Left ventricles were examined and tested for histological and molecular markers of cardiac remodeling. Our results showed that FDPS levels were downregulated in samples from patients with cardiomyopathy. Furthermore, c-Fdps-/- mice exhibited cardiac remodeling and dysfunction. This dysfunction was associated with abnormal activation of Ras and Rheb, which may be due to the accumulation of geranyl pyrophosphate. Activation of Ras and Rheb stimulated downstream mTOR and ERK pathways. Moreover, administration of farnesyltransferase inhibitors attenuated cardiac remodeling and dysfunction in c-Fdps-/- mice. These results indicate that FDPS plays an important role in cardiac homeostasis. Deletion of FDPS stimulates the downstream mTOR and ERK signaling pathways, resulting in cardiac remodeling and dysfunction. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Key Enzymes for the Mevalonate Pathway in the Cardiovascular System.

ABSTRACT: Isoprenylation is an important post-transcriptional modification of small GTPases required for their activation and function. Isoprenoids, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate, are indispensable for isoprenylation by serving as donors of a prenyl moiety to small G proteins. In the human body, isoprenoids are mainly generated by the mevalonate pathway (also known as the cholesterol-synthesis pathway). The hydroxymethylglutaryl coenzyme A reductase catalyzes the first rate-limiting steps of the mevalonate pathway, and its inhibitor (statins) are widely used as lipid-lowering agents. In addition, the FPP synthase is also of critical importance for the regulation of the isoprenoids production, for which the inhibitor is mainly used in the treatment of osteoporosis. Synthetic FPP can be further used to generate geranylgeranyl pyrophosphate and cholesterol. Recent studies suggest a role for isoprenoids in the genesis and development of cardiovascular disorders, such as pathological cardiac hypertrophy, fibrosis, endothelial dysfunction, and fibrotic responses of smooth-muscle cells. Furthermore, statins and FPP synthase inhibitors have also been applied for the management of heart failure and other cardiovascular diseases rather than their clinical use for hyperlipidemia or bone diseases. In this review, we focus on the function of several critical enzymes, including hydroxymethylglutaryl coenzyme A reductase, FPP synthase, farnesyltransferase, and geranylgeranyltransferase in the mevalonate pathway which are involved in regulating the generation of isoprenoids and isoprenylation of small GTPases, and their pathophysiological role in the cardiovascular system. Moreover, we summarize recent research into applications of statins and the FPP synthase inhibitors to treat cardiovascular diseases, rather than for their traditional indications respectively.

Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1.

Schizophrenia is one of the foremost psychological illness around the world, and recent evidence shows that inflammation and oxidative stress may play a critical role in the etiology of schizophrenia. Andrographolide is a diterpenoid lactone from Andrographis paniculate, which has shown anti-inflammation and anti-oxidative effects. In this study, we explored whether andrographolide can improve schizophrenia-like behaviors through its inhibition of inflammation and oxidative stress in Phencyclidine (PCP)-induced mouse model of schizophrenia. We found that abnormal behavioral including locomotor activity, forced swimming and novel object recognition were ameliorated following andrographolide administration (5 mg/kg and 10 mg/kg). Andrographolide inhibited PCP-induced production of inflammatory cytokines, decreased p-p65, p-IκBα, p-p38 and p-ERK1/2 in the prefrontal cortex. Andrographolide significantly declined the level of MDA and GSH, as well as elevated the activity of SOD, CAT and GCH-px. In addition, andrographolide increased expression of NRF-2, HO-1 and NQO-1, promoted nuclear translocation of NRF-2 through blocking the interaction between NRF-2 and KEAP1, which may be associated with directly binding to NRF-2. Furthermore, antioxidative effects and anti-schizophrenia-like behaviors of andrographolide were compromised by the application of NRF-2 inhibitor ML385. In conclusion, these results suggested that andrographolide improved oxidative stress and schizophrenia-like behaviors induced by PCP through increasing NRF-2 pathway.

Effect of inferior oblique muscle belly transposition on versions and vertical alignment in primary position.

PURPOSE: To evaluate the effect of inferior oblique muscle belly transposition (IOBT) on vertical deviation (VD) in primary position and inferior oblique overaction (IOOA). METHODS: Twenty-eight patients who underwent unilateral IOBT for mild hypertropia (≤ 10△) due to unilateral IOOA were included. Surgical results regarding the correction of hypertropia, IOOA, and fovea disc angle (FDA) were analyzed and compared between groups A (VD ≤ 5△) and B (5△ < VD ≤ 10△). RESULTS: IOBT showed an overall reduction of 5.86△ (± 2.24△) of primary position VD, a mean correction of 1.00 (± 0.27) of IOOA, and an average change of 1.83° (± 3.02°) of FDA. The surgical success rate of IOBT for VD correction and IOOA elimination in all patients was 68% and 71%, respectively. The correction of VD was correlated with preoperative VD significantly (r = 0.86, p < 0.001). Consistently, IOBT demonstrated comparable efficacy in reduction of VD between group A and group B (p = 0.507). Furthermore, the two groups were comparable in the success rates for correcting VD and IOOA (both p > 0.05). None of the patients developed consecutive hypotropia, postoperative contralateral IOOA, or anti-elevation syndrome postoperatively. CONCLUSIONS: IOBT achieved satisfactory outcomes in patients with mild primary position VD (≤ 10△) that is associated with unilateral IOOA, without any risk of overcorrection of VD and contralateral IOOA for a follow-up period of up to 12 months. This procedure is considered effective and safe alternative for weakening the IO in patients with appropriate surgical indications.

Lipopolysaccharide mediates time-dependent macrophage M1/M2 polarization through the Tim-3/Galectin-9 signalling pathway.

Macrophages are dynamic cells whose phenotypes and functions are regulated by surrounding inflammatory mediators after pathogenic infection. Imbalanced polarization of classically activated (M1) and alternatively activated (M2) macrophages is closely associated with infection-related complications and their severity. The pathway of T-cell immunoglobulin mucin 3 (Tim-3)/galectin-9 (Gal-9) plays an important role in infection by regulating macrophage function. However, the effects of Tim-3/Gal-9 signalling on M1/M2 macrophage polarization are unclear. Bone marrow-derived macrophages (BMDMs) were stimulated with 0.1 µg/mL lipopolysaccharide (LPS). M1/M2 phenotypic macrophage markers were measured 0, 1, 3, 6, 12, and 24 h after stimulation, α-lactose was used to inhibit Gal-9, anti-mouse Tim-3 antibody was used to block Tim-3, recombinant mouse-Gal-9 (rm-Gal-9) was used to activate Tim-3, which were aimed to verify the role of the Tim-3/Gal-9 pathway in the balance of M1/M2 macrophages when stimulated with LPS. Short-term LPS stimulation upregulated Gal-9 expression and secretion, enhanced the association between Gal-9 and Tim-3, and activated the Tim-3/Gal-9 signalling pathway, eventually inhibiting M1 polarization. Long-term stimulation downregulated Gal-9 expression and secretion, reduced the association between Gal-9 and Tim-3, and inhibited the Tim-3/Gal-9 signalling pathway, eventually promoting M1 polarization, however, decreased M2 polarization and Gal-9 autocrine functions. Overall, LPS had a biphasic effect on BMDMs polarization through the Tim-3/Gal-9 pathway, which was time-dependent.

The stability of horizontal ocular alignment of triad exotropia after one-step triple surgery.

PURPOSE: A-pattern exotropia, superior oblique muscle overaction, and dissociated vertical deviation may coexist and are referred to as triad exotropia. The present study evaluated the postoperative stability of horizontal ocular alignment of triad exotropia and possible prognostic factors. METHODS: Medical records of patients with triad exotropia who had one-step triple surgery of superior oblique muscle weakening, superior rectus muscle recession, and lateral rectus muscle recession were reviewed. The horizontal alignment and postoperative drift of triad exotropia were analyzed and compared with constant exotropia. RESULTS: The triad exotropia showed a mean of 7.7△ (± 8.5△) eso-drift, while the constant exotropia was (3.5△ ± 3.4△) exo-drift. Multiple linear regression analysis showed that the degree of superior oblique muscle overaction after surgery (P = 0.011) was the only factor associated with horizontal drift. Patients with superior oblique muscle underaction showed larger eso-drift when compared to patients without superior oblique muscle underaction (- 18.0△ ± 11.1△ vs. - 5.1△ ± 5.7△; P = 0.024). The final success rates of the triad exotropia and constant exotropia groups were 53.3% and 69.2%, respectively, and the overcorrection rates were 26.7% and 2.6% (P = 0.035). CONCLUSIONS: An overall trend of eso-drift in primary position occurred in triad exotropia after triple surgery up to a follow-up of 25 months. Patients presenting superior oblique muscle underaction after surgery seemed to have large angles of eso-drift, which might be taken into account in surgical planning and follow-up.

Comparison of transesophageal echocardiography findings after different anticoagulation strategies in patients with atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: High risk of embolic events exists in both patients with chronic atrial fibrillation (AF) and patients in the perioperative period of ablation (effective treatment for AF). Therefore, anticoagulant therapy is important. Oral anticoagulants can be divided into two major categories: vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs). VKAs, represented by warfarin, have been widely used as traditional anticoagulants, whereas NOACs have been used in clinical practice, but their anticoagulant effects and side effects are still the focus of research. We used a meta-analysis to compare the incidence of left atrial thrombi (LAT) between different anticoagulants. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library databases for observational studies that compared the transesophageal echocardiography (TEE) findings for patients treated with NOACs and VKAs. The incidence of LAT and dense spontaneous echocardiographic contrast (dense SEC) were extracted as the basis of the meta-analysis. RESULTS: Fifteen studies were included in the meta-analysis. We found that patients anticoagulated with NOACs and VKAs had similar incidence of LAT (OR = 0.74, 95%CI: 0.55-1.00). After excluding the heterogeneous article by sensitivity analysis, we found the incidence of LAT in patients anticoagulated with NOACs is lower than VKAs (OR = 0.59, 95%CI: 0.42-0.84). The results of subgroup analysis showed that the incidence of LAT among three types of NOACs have no significant difference (dabigatran vs. rivaroxaban, OR = 1.16 [0.75, 1.81]; rivaroxaban vs. apixaban, OR = 0.97 [0.54, 1.74]; dabigatran vs. apixaban, OR = 1.09 [0.55, 2.16]). CONCLUSION: Patients anticoagulated with NOACs may have lower incidence of LAT than VKAs. The incidence of LAT among different type of NOACs are similar.

Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration.

IMPORTANCE: Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration. BACKGROUND: The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration. DESIGN: This study is a prospective, interventional case series. PARTICIPANTS: Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients. METHODS: Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections. MAIN OUTCOME MEASURES: Aqueous vascular endothelial growth factor and aflibercept concentrations were measured. RESULTS: The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P < 0.001 [month 2] and P < 0.001 [month 4]). The mean aflibercept concentration was 20.3 ng/mL at month 2 and 28.0 ng/mL at month 4. The mean logarithm of the minimum angle of resolution visual acuity improved from 0.50 ± 0.36 at baseline to 0.36 ± 0.40 at month 6 (P < 0.001). The mean central retinal subfield thickness decreased from 353 ± 100 µm at baseline to 236 ± 45 µm at month 6 (P < 0.001). CONCLUSIONS AND RELEVANCE: Bimonthly aflibercept injections without loading doses may be considered a treatment option for age-related macular degeneration.

Response a chronic effects of PBDE-47: Up-regulations of HSP60 and HSP70 expression in freshwater bivalve Anodonta woodiana.

Heat shock proteins (HSPs) play an important role in adaption of environmental stress by protein folding, membrane translocation, degradation of misfolded proteins and other regulatory processes. Our previous study showed oxidative stress generated from polybrominated diphenyl ether-47 (PBDE-47) could cause an acute toxicity on freshwater bivalve Anodonta Woodiana, but the effect of chronic toxicity need to be elucidated. In order to further investigate the chronic effect of PBDE-47, clams A. Woodiana were randomly divided into the PBDE-47 treated group administrated with PBDE-47 at a concentration 3.36 µg/L and control group treated with a similar volume dimethyl sulfoxide. Two complete HSP sequences were isolated from A. Woodianaa and respectively named AwHSP60 and AwHSP70. They were widely distributed in foot, gill, hepatopancreas, adductor muscle, heart, hemocytes and mantle. Administration of PBDE-47 could result in a significant up-regulation of AwHSP60 and AwHSP70 expressions in the hepatopancreas, gill and hemocytes. In the hepatopancreas, compared with that of control group, mRNA level of AwHSP60 increased more than 89.9% (P < 0.05) from day 1-15, AwHSP70 increased more 2.79 times (P < 0.01). In the gill, during experiment observed, expression of AwHSP60 increased more 2.09 times (P < 0.01) in contrasted with that of control group. Significant up-regulation of AwHSP70 expression showed a reversed U shape. In the hemocytes, AwHSP60 and AwHSP70 expressions of PBDE-47 treated group respectively increased more 2.09 times (P < 0.05) and 1.81 times (P < 0.05) compared with that of control group. These results indicated that up-regulations of AwHSP60 and AwHSP70 expression are contribute to enhancing adaption of bivalve A. Woodiana exposed to PBDE-47 treatment.

Response of selenium-dependent glutathione peroxidase in the freshwater bivalve Anodonta woodiana exposed to 2,4-dichlorophenol,2,4,6-trichlorophenol and pentachlorophenol.

2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) pose a health risk to aquatic organism and humans, and are recognized as persistent priority pollutants. Selenium dependent glutathione peroxidase (Se-GPx) belongs to the family of selenoprotein, which acts mainly as an antioxidant role in the cellular defense system. In the current study, a Se-GPx full length cDNA was cloned from Anodonta woodiana and named as AwSeGPx. It had a characteristic codon at 165TGA167 that corresponds to selenocysteine(Sec) amino acid as U44. The full length cDNA consists of 870 bp, an open reading frame (ORF) of 585 bp encoded a polypeptide of 195 amino in which conserved domain (68LGFPCNQF75) and a glutathione peroxide-1 GPx active site (32GKVILVENVASLUGTT47) were observed. Additionally, the eukaryotic selenocysteine insertion sequence (SECIS) was conserved in the 3'UTR. The AwSeGPx amino acid sequence exhibited a high similarity with that of other Se-GPx. Real-time PCR analysis revealed that AwSeGPx mRNA had a widely distribution, but the highest level was observed in hepatopancreas. AwSeGPx mRNA expression was significantly up-regulated in hepatopancreas, gill and hemocytes after 2,4-DCP, 2,4,6-TCP and PCP exposure. Under similar environment, clams A. woodiana showed a more sensitive to PCP than that of 2,4-DCP and 2,4,6-TCP. These results indicate that AwSeGPx plays a protective role in eliminating oxidative stress derived from 2,4-DCP, 2,4,6-TCP and PCP treatment.

Molecular cloning, characterization, and the response of Cu/Zn superoxide dismutase and catalase to PBDE-47 and -209 from the freshwater bivalve Anodonta woodiana.

Polybrominated diphenyl ethers-47 (PBDE-47) and -209 are significant components of total PBDEs in water and can catalyze the production of reactive oxygen species (ROS) in the organisms. Anti-oxidant enzymes play an important role in scavenging the high level of ROS. In the current study, two full-length cDNAs of Cu/Zn superoxide dismutase (CuZnSODs) and catalase (CAT) were isolated from freshwater bivalve Anodonta woodiana by rapid amplification of cDNA ends approach and respectively named as AwSOD and AwCAT. The nucleotide sequence of AwSOD cDNA had an open reading frame (ORF) of 465 bp encoding a polypeptide of 155 amino acids in which signature 1 GKHGFHVHEFGDNT and signature 2 GNAGARSACGVI of SODs were observed. Deduced amino acid sequence of AwSOD showed a significant similarity with that of CuZnSODs. AwCAT had an ORF 1536 bp encoding a polypeptide of 512 amino acids which contains a conserved catalytic site motif, and a proximal heme-ligand signature motif of CATs. The time-course expressions of AwSOD and AwCAT in hepatopancreas were measured by quantitative real-time PCR. Expressions of AwSOD and AwCAT showed a significant up-regulation in groups at a low concentration treatment of PBDE-47, a biphasic pattern in groups with a high concentration treatment. Administration of PBDE-209 could result in an up-regulation of AwSOD and AwCAT expressions with time- and dose-dependent matter. These results indicate that up-regulations of AwSOD and AwCAT expression of hepatopancreas of freshwater bivalve A. woodiana contribute to eliminate oxidative stress derived from PBDE-47 and -209 treated.

Bimonthly injections of ranibizumab for age-related macular degeneration.

PURPOSE: To evaluate the efficacy of bimonthly intravitreal injections of ranibizumab for age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in a pilot study. METHODS: This study was a prospective, interventional case series. Thirty eyes of 30 patients received prospectively at least three bimonthly intravitreal injections of ranibizumab (0.5 mg/0.05 ml) without loading doses. The best-corrected visual acuity (BCVA) and the central retinal subfield thickness (CRST) were measured before and monthly after the injections. RESULTS: Twenty-eight patients received the three planned injections; one patient refused the third injection, one patient did not receive the third injection because blood pressure was raised, and one patient received a rescue injection at month 5 because of increased retinal thickness. The mean logarithm of the minimum angle of resolution (logMAR) BCVA was 0.44 ± 0.37 before treatment and significantly improved to 0.25 ± 0.34 at month 6 (p < 0.001). The mean CRST was 335 ± 85.9 µm before treatment and decreased significantly to 261 ± 78.1 µm at month 6 (p < 0.001). Nine of 30 patients received six planned injections for 12 months. The mean logMAR BCVA was 0.38 ± 0.39 before treatment and significantly improved to 0.18 ± 0.33 at month 12 (p = 0.005). The mean CRST was 360 ± 110.8 µm before treatment and decreased significantly to 249 ± 57.0 µm at month 12 (p = 0.025). CONCLUSIONS: Bimonthly injections of ranibizumab may be effective for treating AMD and PCV.

Aqueous vascular endothelial growth factor and ranibizumab concentrations after monthly and bimonthly intravitreal injections of ranibizumab for age-related macular degeneration.

PURPOSE: To evaluate vascular endothelial growth factor (VEGF) and ranibizumab concentrations in eyes with age-related macular degeneration (AMD) after monthly and bimonthly intravitreal ranibizumab (IVR) injections. METHODS: Aqueous humor samples were obtained from 26 eyes with AMD before and after IVR injections. Nine eyes received three monthly injections and 17 eyes received two bimonthly injections. The VEGF and ranibizumab concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: The aqueous VEGF concentrations in the monthly injection group decreased below the lowest detectable limit in eight of nine eyes 1 month after the first injection and seven of nine eyes 1 month after the second injection (P < 0.001, mean baseline value, 94.7 pg/ml); the aqueous VEGF concentrations in the bimonthly injection group decreased below the lowest detectable limit in two of 17 eyes 2 months after the first injection (P < 0.001, mean baseline value, 152.4 pg/ml). The mean aqueous ranibizumab concentrations with monthly injections were 71.2 ng/ml 1 month after the first injection, and 96.3 ng/ml 1 month after the second injection. The mean aqueous ranibizumab concentrations in the bimonthly injection group were 2.5 ng/ml in 15 of 17 eyes, and below the lowest detectable limit in two of 17 eyes 2 months after the first injection. CONCLUSIONS: In this pilot study with limited follow-up, intravitreal injection of ranibizumab can suppress aqueous VEGF completely for 1 month in most cases. Its effect does not last for 2 months enough to suppress VEGF completely in most cases, although aqueous VEGF at 2 months after intravitreal injection of ranibizumab is less than that before injection in most cases.

Prevalence and determinants of depression among survivors 8 months after the Wenchuan earthquake.

The current study assessed the estimated rate of depression and associated risk factors among survivors 8 months after the 2008 Wenchuan earthquake in China. A stratified random sample of 1514 participants was recruited from all temporary camp communities in a county town 45 km away from the epicenter. The estimated rate of depression was 35.7%. The severity of depressive symptoms was significantly associated with female sex, perceived livelihood security, loss of a family member, residential house damage or collapse, and not living in an urban area, whereas married status is a protector against depressive symptoms. The results suggest that community-based effective, sustainable, and culturally sensitive interventions and services are warranted and should be directed to the groups at high risk for mental health problems.

Performance enhancement for a GPS vector-tracking loop utilizing an adaptive iterated extended Kalman filter.

This paper deals with the problem of state estimation for the vector-tracking loop of a software-defined Global Positioning System (GPS) receiver. For a nonlinear system that has the model error and white Gaussian noise, a noise statistics estimator is used to estimate the model error, and based on this, a modified iterated extended Kalman filter (IEKF) named adaptive iterated Kalman filter (AIEKF) is proposed. A vector-tracking GPS receiver utilizing AIEKF is implemented to evaluate the performance of the proposed method. Through road tests, it is shown that the proposed method has an obvious accuracy advantage over the IEKF and Adaptive Extended Kalman filter (AEKF) in position determination. The results show that the proposed method is effective to reduce the root-mean-square error (RMSE) of position (including longitude, latitude and altitude). Comparing with EKF, the position RMSE values of AIEKF are reduced by about 45.1%, 40.9% and 54.6% in the east, north and up directions, respectively. Comparing with IEKF, the position RMSE values of AIEKF are reduced by about 25.7%, 19.3% and 35.7% in the east, north and up directions, respectively. Compared with AEKF, the position RMSE values of AIEKF are reduced by about 21.6%, 15.5% and 30.7% in the east, north and up directions, respectively.

[Predictive value of placenta-derived RASSF1A sequence expression in maternal plasma for pre-eclampsia].

OBJECTIVE: To investigate the expression of placenta-derived RASSF1A gene in maternal plasma during first and second trimesters, and to explore its value for the prediction of pre-eclampsia. METHODS: For 325 pregnant women of the first trimester, free DNA of plasma samples was extracted at 7-12, 13-18, and 19-24 gestational weeks, respectively. Methylation-sensitive restriction enzyme digestion followed by fluorescence quantitative PCR (MSRE+ PCR) was employed for analyzing the concentrations of hypermethylated RASSF1A gene. Blood pressure, proteinuria and clinical feature were monitored at the same time. Those who had subsequently developed pre-eclampsia were selected as the pre-eclamptic group, 30 normal pregnant women were selected as the control group. Hypermethylated RASSF1A gene in maternal plasma was retrospectively analyzed. The relationship between clinical classification, type of pre-eclampsia and concentrations of the gene were further analyzed. RESULTS: Twenty-six out of the 325 pregnant women developed pre-eclampsia as their only complication. At 13-18 gestational weeks, the mean concentrations of fetus-specific RASSF1A sequences were 141.62 copies/mL in maternal plasma of pre-eclamptic pregnancies, which was significantly greater than that of the controls (98.90 copies/mL). Fetus-derived RASSF1A levels were 2.03 fold higher in pre-eclamptic subjects than controls at 19-24 gestational weeks. There was a significant difference in the level of hypermethylated RASSF1A gene between the mild and severe pre-clamptic subjects at 13-24 gestational weeks (P< 0.05). The concentrations of the sequences were significantly higher in early-onset severe pre-eclampsia than late-onset severe pre-eclampsia at 19-24 gestational weeks (P< 0.05). CONCLUSION: Altered expression of hypermethylated RASSF1A gene may be detected in maternal plasma during second trimester, which has important significance for early prediction of pre-eclampsia.