Seasonal climatic instability in the western Chinese Loess Plateau during Marine Isotope Stages 12-10.

Because of similar astronomical background, Marine Isotope Stage (MIS) 11 is viewed as an analogue of the Holocene, but the evolution of seasonal climatic instability during MIS 11 has not been well investigated. Here we present a time series of land-snail eggs-a recently-developed proxy of seasonal cooling events-from the Chinese Loess Plateau (CLP) to investigate seasonal climatic instability during MIS 11 and adjacent glacials. Due to the impact of low temperatures on egg hatching, egg-abundance peaks document seasonal cooling events. A total of five egg-abundance peaks were recorded in the CLP during MIS 12, MIS 11 and MIS 10. Three peaks are strong and occur close to glacial inception or interglacial-to-glacial transition; two weaker peaks occur during MIS11. These peaks imply seasonal climatic instability intensifies mainly during glacial initiation or transition. All these events correspond to ice-sheet growth and the loss of ice-rafted debris at high northern latitudes. Moreover, they occurred at the minima of local spring insolation during the MIS 12 and MIS 10 glacials, but at the maxima during the MIS 11 interglacial. This may contribute to the difference in the intensity of seasonal cooling events between low-eccentricity glacials and interglacials. Our results provide new evidence for understanding low-eccentricity interglacial-glacial evolution.

Retinal microvasculature is a potential biomarker for acute mountain sickness.

Increased cerebral blood flow resulting from altered capillary level autoregulation at high altitudes leads to capillary overperfusion and then vasogenic cerebral edema, which is the leading hypothesis of acute mountain sickness (AMS). However, studies on cerebral blood flow in AMS have been mostly restricted to gross cerebrovascular endpoints as opposed to the microvasculature. This study aimed to investigate ocular microcirculation alterations, the only visualized capillaries in the central neural system (CNS), during early-stage AMS using a hypobaric chamber. This study found that after high altitude simulation, the optic nerve showed retinal nerve fiber layer thickening (P=0.004-0.018) in some locations, and the area of the optic nerve subarachnoid space (P=0.004) enlarged. Optical coherence tomography angiography (OCTA) showed increased retinal radial peripapillary capillary (RPC) flow density (P=0.003-0.046), particularly on the nasal side of the nerve. The AMS-positive group had the largest increases in RPC flow density in the nasal sector (AMS-positive, Δ3.21±2.37; AMS-negative, Δ0.01±2.16, P=0.004). Among multiple ocular changes, OCTA increase in RPC flow density was associated with simulated early-stage AMS symptoms (beta=0.222, 95%CI, 0.009-0.435, P=0.042). The area under the receiver operating characteristics curve (AUC) for the changes in RPC flow density to predict early-stage AMS outcomes was 0.882 (95%CI, 0.746-0.998). The results further confirmed that overperfusion of microvascular beds is the key pathophysiologic change in early-stage AMS. RPC OCTA endpoints may serve as a rapid, noninvasive potential biomarker for CNS microvascular changes and AMS development during risk assessment of individuals at high altitudes.

The antidepressant potential of lactobacillus casei in the postpartum depression rat model mediated by the microbiota-gut-brain axis.

Lactobacillus casei, a kind of probiotic, was reported as antidepressant effects. However, little is known about the effect of Lactobacillus casei on postpartum depression (PPD). In this study, we investigated the effects of Lactobacillus casei in improving PPD and potential mechanisms. Four hours of daily maternal separation from postnatal day 2 to day 21 was performed to establish the PPD model in rats. From postnatal day 2 to day 28, rats were gavage-fed with an equal volume of normal saline, Lactobacillus casei (8 × 108 CFU/kg/day), or paroxetine (1.8 mg/kg/day), respectively. Rat behaviors were measured using the sucrose preference test, the elevated plus maze, the forced swim test, and the tail suspension test. Changes in gut microbiota were detected by real-time fluorescence quantitative PCR. Administration of Lactobacillus casei improved depressive-like behaviors, intestinal microflora, and oxidative stress in PPD model rats. Western Blot or HPLC assays showed that Lactobacillus casei intervention reversed the changes of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartic acid receptor 1 (NR1), ERK1/2, and monoamines in the brain of PPD rats. These results suggest that Lactobacillus casei could improve PPD through altering gut microbiota composition, brain monoamines and oxidative stress, which may be associated with the regulation of the BDNF-ERK1/2 pathway.

Intereye Comparison of Focal Lamina Cribrosa Defect in Normal-Tension Glaucoma Patients with Asymmetric Visual Field Loss.

INTRODUCTION: To evaluate the association of focal lamina cribrosa (LC) defect with asymmetric visual field (VF) loss in normal-tension glaucoma (NTG) through intereye comparisons. METHODS: Paired eyes were divided into better and worse eyes according to the mean deviation (MD), and ocular parameters were compared between them. Furthermore, patients in the asymmetric group were classified as subgroup A (one eye with LC defect and the fellow one without), subgroup B (both eyes without LC defect), and subgroup C (both eyes with LC defect). Generalized estimation equation approach was used to evaluate the association between ocular parameters and asymmetric VF. RESULTS: A total of 140 eyes of 70 NTG patients were included in the asymmetric group. LC defects were more common in better eyes than that in worse eyes (27/70 [38.57%] vs. 10/70 [14.29%], p = 0.001), and all eyes with LC defect had myopia. Multivariate analysis revealed that the presence of LC defect was significantly associated with better eyes in the asymmetric group (odds ratio, 0.27; p = 0.001). For subgroup A, eyes with LC defects exhibited lower peak IOP (p = 0.011) and lower mean IOP (p = 0.018) than the fellow eyes without. In addition, longer AL (p = 0.025) and larger tilt ratio (p = 0.032) were found in eyes with LC defects. For subgroup B without LC defects, larger tilt ratio was shown to be a risk factor for VF loss (odds ratio, 6.13; p = 0.001). There was no significant difference of binocular parameters except for MD (p < 0.001) in subgroup C. CONCLUSIONS: LC defects in myopia were suggested to be associated with better eyes in NTG with asymmetric VF loss. However, in patients without LC defect, larger tilt ratio was a risk factor for VF defect. There might be different pathological mechanisms in asymmetric VF loss for different NTG subtypes.

The Relationship Between Nailfold Microcirculation and Retinal Microcirculation in Healthy Subjects.

OBJECTIVE: To evaluate whether the nailfold microcirculation is associated with retinal microcirculation in healthy subjects. METHODS: Fifty subjects without systematic and ocular diseases were enrolled. Thickness of peripapillary retinal nerve fiber layer (RNFL), vessel density (VD) of radial peripapillary capillaries (RPCs), and superficial capillary VD in macular zone were measured with optical coherence tomography angiography (OCTA) in left eyes. Nailfold microcirculation, including capillary density, avascular zones, dilated capillaries, and hemorrhages was examined on the fourth digit of each subject's non-dominant (left) hand with nailfold capillaroscopy (NFC). RESULTS: After adjustment for relatively systemic factors, multivariate regression analyses showed a significant direct relationship between RNFL thickness and nailfold capillary density (OR = 1.09; p = 0.046). RNFL thickness and RPCs VD were negatively correlated with nailfold avascular zones (OR = 0.855; p = 0.007; OR = 0.596; p = 0.010). Superficial VD of parafovea was negatively associated with dilated nailfold capillaries (OR = 0.794; p = 0.012). CONCLUSION: In healthy subjects, nailfold capillary lower density and abnormalities are associated with reduced RNFL thickness and retinal VD. The results provide a theoretical foundation for relevant studies on ocular diseases with microvascular abnormalities and could contribute to pathogenesis understanding in the future. NFC and OCTA have the potential to identify risk factors and improve accuracy of the early diagnosis and treatment of ocular diseases, even systemic diseases with any microvascular component in clinical practice. CLINICAL TRAIL REGISTRATION: http://www.chictr.org.cn/index.aspx, identifier ChiCTR 1800017875.

Finite element analysis of trans-lamina cribrosa pressure difference on optic nerve head biomechanics: the Beijing Intracranial and Intraocular Pressure Study.

The present study aims to assess the potential difference of biomechanical response of the optic nerve head to the same level of trans-lamina cribrosa pressure difference (TLCPD) induced by a reduced cerebrospinal fluid pressure (CSFP) or an elevated intraocular pressure (IOP). A finite element model of optic nerve head tissue (pre- and post-laminar neural tissue, lamina cribrosa, sclera, and pia mater) was constructed. Computed stresses, deformations, and strains were compared at each TLCPD step caused by reduced CSFP or elevated IOP. The results showed that elevating TLCPD increased the strain in optic nerve head, with the largest strains occurring in the neural tissue around the sclera ring. Relative to a baseline TLCPD of 10 mmHg, at a same TLCPD of 18 mmHg, the pre-laminar neural tissue experienced 11.10% first principal strain by reduced CSFP and 13.66% by elevated IOP, respectively. The corresponding values for lamina cribrosa were 6.09% and 6.91%. In conclusion, TLCPD has a significant biomechanical impact on optic nerve head tissue and, more prominently, within the pre-laminar neural tissue and lamina cribrosa. Comparatively, reducing CSFP showed smaller strain than elevating IOP even at a same level of TLCPD on ONH tissue, indicating a different potential role of low CSFP in the pathogenesis of glaucoma.

Association Between Arterial Blood Gas Variation and Intraocular Pressure in Healthy Subjects Exposed to Acute Short-Term Hypobaric Hypoxia.

PURPOSE: To investigate the association between changes in arterial blood gases and intraocular pressure (IOP) after acute, short-term exposure to simulated elevation of 4000 m above sea level. METHODS: Twenty-five healthy young lowlanders participated in this prospective study. IOP was measured in both eyes with an Accupen tonometer. Arterial blood gas parameters (partial oxygen pressure [PaO2], partial carbon dioxide pressure [PaCO2], pH, and bicarbonate ion [HCO3 -]) were checked using a blood gas analyzer. Measurements were taken at sea level (T1), at 15-minute (T2) and at 2-hour (T3) exposure times to simulated 4000 m above sea level in a hypobaric chamber, and upon return to sea level (T4). Associations between arterial blood gas parameters and IOP were evaluated using multivariate linear regression. RESULTS: PaO2 significantly decreased at T2 and T3, resolving at T4 (P < 0.001). pH significantly increased at T2 and returned to baseline at T3 (P = 0.004). Actual and standard bicarbonate ion both dropped with IOP at T3 and T4. IOP significantly decreased from 16.4 ± 3.4 mm Hg at T1 to 15.1 ± 2.1 mm Hg (P = 0.041) at T3 and remained lower (14.9 ± 2.4 mm Hg; P = 0.029) at T4. IOP was not correlated with pH. Multivariate linear regression showed that lower IOP was associated with lower standard bicarbonate ion (beta = -1.061; 95% confidence interval, -0.049 to -2.074; P = 0.04) when adjusted for actual bicarbonate and diastolic blood pressure. CONCLUSIONS: Hypobaric hypoxia triggers plasma bicarbonate ion reduction which, rather than pH, may decrease aqueous humor formation and subsequently cause IOP reduction. These findings may shed light on the mechanism of IOP regulation at high altitude. TRANSLATIONAL RELEVANCE: Hypoxia-triggered reduction in plasma bicarbonate ion may decrease aqueous humor production, leading to IOP reduction at high altitude. These findings may provide new insight into a potential mechanism of IOP regulation. Hypobaric hypoxia at high altitude is an environmental factor that can reduce IOP and, therefore, deserves further study.

Longitudinal observation of intraocular pressure variations with acute altitude changes.

BACKGROUND: Higher intraocular pressure (IOP) is a major risk factor for developing glaucoma, and the leading cause of irreversible blindness worldwide. High altitude (HA) may be involved in IOP, but the reported results were conflicting. Ascent to HA directly by plane from low altitude regions is an acute, effortless exposure. However, the effects of such exposure to different altitudes on IOP have rarely been reported. AIM: To investigate changes in IOP after rapid effortless exposure to HA in stages and compare it with systemic parameters. METHODS: Fifty-eight healthy subjects (116 eyes) were divided into three groups: 17 low-altitude (LA) residents [44 m above sea level (ASL)], 22 HA residents (2261 m ASL) and 19 very HA (VHA) residents (3750 m ASL). The LA group flew to HA first. Three days later, they flew with the HA group to VHA where both groups stayed for 2 d. Then, the LA group flew back to HA and stayed for 1 d before flying back to 44 m. IOP, oxygen saturation (SpO2) and pulse rate were measured. The linear mixed model was used to compare repeated measurements. RESULTS: IOP in the LA group significantly decreased from 18.41 ± 2.40 mmHg at 44 m to 13.60 ± 3.68 mmHg at 2261 m ASL (P < 0.001), and then to 11.85 ± 2.48 mmHg at 3750 m ASL (P = 0.036 compared to IOP at 2261 m ASL) and partially recovered to 13.47 ± 2.57 mmHg upon return to 44 m. IOP in the LA group at HA and VHA was comparable to that in the local residents (12.2 ± 2.4 mmHg for HA,11.5 ± 1.8 mmHg for VHA). IOP was positively associated with SpO2. CONCLUSION: IOP in the LA group gradually reduced as altitude elevated in stages and became comparable to IOP in local residents. Hypoxia may be associated with IOP, which deserves further study.

Intraocular Pressure Changes of Healthy Lowlanders at Different Altitude Levels: A Systematic Review and Meta-Analysis.

Background: High altitude, characterized by hypobaric hypoxia, low temperature, and intensive ultraviolet radiation, is identifiably one of the examples of scientific enquiry into aviation and space analogs. However, little is known about the ocular physiological response, especially intraocular pressure (IOP) changes at high altitude. Objectives: This study aimed to systematically review of high altitude exposure on IOP for healthy lowlanders with unoperated eyes. Methods: A comprehensive systematic literature search was conducted in the electronic databases until September 1st, 2019. A meta-analysis was performed following the preferred reporting items for systematic review and meta-analysis statement (PRISMA). We systematically searched the studies conducted over 2,000 m above sea level (a.s.l) in healthy lowlanders with measurements of IOP. Meta-analyses (random effect model and heterogeneity tests), subgroup analyses (altitude, duration, type, and pattern of exposure), sensitivity analysis, funnel plot, Begger's and Egger's test for publication bias were performed. Quality assessment was conducted using the Newcastle-Ottawa scale. The meta-analysis was registered in the PROSPERO database (CRD42019136865). Results: Of 9595 publications searched, 20 publications (n = 745) qualified for inclusion, with non-significant decrease in overall IOP [standardized mean difference (SMD): 0.14, 95% CI: -0.12-0.40; p = 0.30] with high heterogeneity (p < 0.001, I 2 = 82%). However, subgroup analyses revealed significant decrease of IOP at high altitude of 3,000-5,500 m a.s.l (SMD: 0.57, 95% CI: 0.07-1.06; p = 0.03) whereas increase of IOP at extreme altitude of over 5,500 m a.s.l (SMD: -0.34, 95% CI: -0.61-0.06; p = 0.02). And the duration of exposure more than 72 hours (h) was likely to induce a decrease of IOP bordering on statistical significance at the 5% level (SMD: 1.29, 95% CI: 0.02-2.56; p = 0.05). Simultaneously, we also observed significant decrease of IOP for active exposure (e.g., physical activity and hiking, SMD: 0.81, 95% CI: 0.05-1.57; p = 0.04). Conclusion: Our analysis shows exposure to the altitude over 3,500 m a.s.l, duration of exposure more than 72 h and active exposure pattern may have modest, but significant effects on IOP. The higher altitude, the duration of exposure as well as physical activity seem to play crucial roles in the effects of high-altitude exposure on IOP.

Retinal vessel oxygen saturation and vessel diameter in healthy individuals during high-altitude exposure.

PURPOSE: To assess changes of retinal vessel oxygen saturation and vessel diameter in healthy individuals during high-altitude exposure. METHODS: Retinal oxygen saturation and vessel diameter were obtained at sea level (SL, 40 m) and high altitude (HA, 3681 m) on 17 healthy individuals from Beijing (six males, 28.06 ± 8.06 years) using Oxymap T1 and then compared with 21 residents from Yushu (10 males, 28.63 ± 6.00 years). Systemic and ocular parameters were also measured before and after high-altitude exposure. Data were presented as mean ± SD and analysed using paired and independent Student t-test with significance accepted at p < 0.05. RESULTS: Short-term high-altitude exposure of Beijing Group significantly affected all the systemic and ocular parameters, as well as retinal oxygen saturation and vessel diameter ranging from overall quadrant to different quadrants, other than retinal venous oxygen saturation and retinal arterial diameter. However, these changes were not evident in those permanently living at HA. Pearson's correlation analysis revealed correlations between retinal oxygen saturation and systemic and ocular parameters (all p < 0.05). The multivariate linear regression analysis indicated that retinal arterial oxygen saturation was significantly associated with arterial peripheral arterial oxygen saturation (SpO2 ) and subfoveal choroidal thickness. CONCLUSION: Short-term exposure to HA induces retinal microcirculation disturbance and auto-regulatory response in healthy individuals, which is probably attributed to arterial SpO2 and endothelial dysfunction under hypoxic conditions.

Pupil Size Associated with the Largest Iris Volume in Normal Chinese Eyes.

BACKGROUND: To determine the range of pupil size that has the largest iris volume in normal eyes. METHODS: 31 healthy adult Chinese volunteers underwent swept-source anterior segment OCT examination in both eyes. Pilocarpine 1% was instilled in a randomly selected eye (eye with induced miosis (ME)) of each participant to obtain iris volume (IV) measurements over a range of pupil sizes. OCT was performed prior to and one hour after pilocarpine in both ME and fellow eye (FE). Iris volume (IV), anterior chamber volume (ACV), anterior chamber depth (ACD), and pupil size (PS) were recorded. A scatter plot was used to depict the association between each pupil size and IV. RESULTS: The pupillary sizes for which IV was recorded in ME and FE ranged from 1.161 mm to 6.665 mm. The mean IV increased with miosis in both ME and FE; in 13 eyes, IV decreased with a decrease in pupillary size. PS between 3.812 and 6.665 mm was associated with an increase in IV, while PS between 3.159 and 5.54 mm was associated with a decrease. The relationship between PS and IV was in the shape of a downward parabola and was modeled using a quadratic equation (y = -1.3121x 2 + 8.8429x + 16.423, R 2 = 0.26886). The largest IV occurred at PS between 3 and 4 mm. CONCLUSIONS: The relationship between PS and IV in this study was in the shape of a downward parabola. The largest IV was recorded at a pupillary size between 3 and 4 mm. This trial is registered with ChiCTR-ROC-17013572.

Reproducibility of Perfusion Parameters of Optic Disc and Macula in Rhesus Monkeys by Optical Coherence Tomography Angiography.

BACKGROUND: Optical coherence tomography (OCT) angiography is a novel technique by which we can detect the local perfusion of fundus directly. The aim of this study was to evaluate the reproducibility of optic disc and macular flow perfusion parameters in rhesus monkeys using OCT angiography. METHODS: Eighteen healthy monkeys (18 eyes) were subjected to optic disc and macula flow index measurements via a high-speed and high-resolution spectral-domain OCT XR Avanti with a split-spectrum amplitude de-correlation angiography algorithm. Right eye was imaged 3 times during the first examination and once during each of the two following examinations. The intra-visit and inter-visit intraclass correlation coefficients (ICCs) were both determined. RESULTS: The average flow indices of the four optic disc area layers were 0.171 ± 0.009 (optic nerve head), 0.015 ± 0.004 (vitreous), 0.052 ± 0.009 (radial peripapillary capillary), and 0.167 ± 0.011 (choroid). Average flow indices of the four macula area layers were 0.044 ± 0.011 (superficial retina), 0.036 ± 0.011 (deep retina), 0.016 ± 0.009 (outer retina), and 0.155 ± 0.013 (choroid). Intra-visit (ICC value: 0.821-0.954) and inter-visit (ICC value: 0.844-0.899) repeatability were both high. CONCLUSIONS: The study is about the reproducibility of optic disc and macular perfusion parameters as measured by OCT angiography in healthy rhesus monkeys. Flow index measurement reproducibility is high for both the optic disc and macula of normal monkey eyes. OCT angiography might be a useful technique to assess changes when examining monkeys with experimental ocular diseases.

Normative Values of Retinal Oxygen Saturation in Rhesus Monkeys: The Beijing Intracranial and Intraocular Pressure (iCOP) Study.

OBJECTIVE: To study the normal values of the retinal oxygen saturation in Rhesus monkeys and to evaluated repeatability and reproducibility of retinal oxygen saturation measurements. METHODS: Eighteen adult Rhesus macaque monkeys were included in this experimental study. An Oxymap T1 retinal oximeter (Oxymap, Reykjavik, Iceland) was used to perform oximetry on all subjects. Global arterial (SaO2) and venous oxygen saturation (SvO2), arteriovenous difference in SO2 were measured. In the first examination, each eye was imaged three times. At the following two examinations, each eye was imaged once. All examinations were finished in one month. P values were calculated to evaluate the difference between the measurements during three visits by performing an ANOVA. Intra-visit and inter-visit intraclass correlation coefficient (ICC) was determined. RESULTS: At baseline, the average SaO2 and SvO2 were 89.48 ± 2.64% and 54.85 ± 2.18%, respectively. The global A-V difference was 34.63 ± 1.91%. The difference between the three visits was not significant (p>0.05). The highest A-V difference in SO2 and lowest saturations were found in the inferotemporal quadrant. Intra-session and inter-visit repeatability were both high. For all oxygen saturation parameters, the ICC values of the intra-session repeatability ranged between 0.92 and 0.96. As found previously, a relatively high ICC value for inter-visit repeatability also was found for all oxygen saturation measurements, ranging between 0.86 and 0.94, with the lowest values in the infero-nasal quadrant. CONCLUSIONS: Our study is the first to describe retinal SO2 in healthy Rhesus monkeys. In normal monkey eyes, the reproducibility and repeatability of retinal oximetry oxygen saturation measurements were high in the retinal arterioles and venules. Our results support that Oxymap T1 retinal oximetry is a suitable and reliable technique in monkey studies.

[Preliminary investigation on the safety and efficacy of Trabectome].

OBJECTIVE: To evaluate the safety and efficacy of ab interno trabeculectomy (Trabectome) surgery in Chinese open angle glaucoma patients. METHODS: Prospective non-comparative case series study. A total of 41 cases (34 primary open angle glaucoma patients, 3 developmental glaucoma patients and 4 pigmentary glaucoma patients) were included in the study. All the cases underwent Trabectome, including 9 cases combined with phacoemulsification cataract extraction. Major outcomes include intraocular pressure (IOP), number of glaucoma medications, secondary glaucoma surgery and postoperative complications. Criteria for successful operation were defined as IOP ≤ 21 mmHg (1 mmHg = 0.133 kPa), at least 20% IOP reduction in any two consecutive visits after 3 months with or without IOP-lowering drugs and no additional glaucoma surgery. IOP and number of glaucoma medications were compared to baseline using Wilcoxon signed-rank test with Bonferroni correction. Kaplan-Meier analysis was performed to analyze the success rate of surgery. RESULTS: In the all 41 patients, 21 cases (51.2%) were followed up for up to 12 months. IOP was reduced from (22.5 ± 8.1) mmHg to (17.6 ± 6.4) mmHg (P = 0.02), meanwhile number of glaucoma medications was reduced from 2.0 ± 0.9 to 1.2 ± 0.9 (P = 0.02) at 12 months. The success rate at one year was 85% and 4 cases required additional glaucoma surgery. CONCLUSIONS: Trabectome has many advantages, such as shorter surgery time, simple post-operative care, less intraoperative and postoperative complications and clear IOP-lowering effect. But it slong-term efficacy is still need a large sample, long-term follow-up to verify.