Identification of the Vibrational Optical Coherence Tomography Corneal Cellular Peak

Purpose: Our team previously identified the presence of five corneal resonant frequency (RF) peaks in healthy volunteers using vibrational optical coherence tomography (VOCT). Prior studies have suggested that the ≤100 Hz RF peak represents the cellular element of tissue. The aim of this study was to confirm that this peak reflects the human corneal cellular component using VOCT and histological analysis. Methods: Two human research globes were obtained from the same donor, and VOCT measurements were collected from the full-thickness corneas. A microkeratome was then used to create serial-free corneal caps from each cornea, with VOCT performed on the residual stromal bed after each excision. All lamellar sections from both globes were sent for histological analysis to determine cellularity. Cell counts on the specimens were performed by two independent observers. Results: The average of the normalized ≤100 Hz peak values before lamellar sectioning was significantly higher than the average of this peak values after the first, second, and third cuts (P = 0.023), which was 33.9% less than before any cuts. The cell count values in the first slice were significantly higher than the average cell count values of the three deeper slices (P \u3c 0.001), and the cell count dropped 84.4% after the first slice was removed. Conclusions: The findings of this study suggest that the ≤100 Hz corneal peak identified by VOCT corresponds to the cellular component of the cornea. Translational relevance: This work furthers our understanding of the origin of the corneal ≤100 Hz peak identified using VOCT

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Overview of the instrumentation for the Dark Energy Spectroscopic Instrument

The Dark Energy Spectroscopic Instrument (DESI) embarked on an ambitious 5 yr survey in 2021 May to explore the nature of dark energy with spectroscopic measurements of 40 million galaxies and quasars. DESI will determine precise redshifts and employ the baryon acoustic oscillation method to measure distances from the nearby universe to beyond redshift z > 3.5, and employ redshift space distortions to measure the growth of structure and probe potential modifications to general relativity. We describe the significant instrumentation we developed to conduct the DESI survey. This includes: a wide-field, 3.°2 diameter prime-focus corrector; a focal plane system with 5020 fiber positioners on the 0.812 m diameter, aspheric focal surface; 10 continuous, high-efficiency fiber cable bundles that connect the focal plane to the spectrographs; and 10 identical spectrographs. Each spectrograph employs a pair of dichroics to split the light into three channels that together record the light from 360–980 nm with a spectral resolution that ranges from 2000–5000. We describe the science requirements, their connection to the technical requirements, the management of the project, and interfaces between subsystems. DESI was installed at the 4 m Mayall Telescope at Kitt Peak National Observatory and has achieved all of its performance goals. Some performance highlights include an rms positioner accuracy of better than 0.″1 and a median signal-to-noise ratio of 7 of the [O ii] doublet at 8 × 10−17 erg s−1 cm−2 in 1000 s for galaxies at z = 1.4–1.6. We conclude with additional highlights from the on-sky validation and commissioning, key successes, and lessons learned

In Vivo Determination of the Human Corneal Elastic Modulus Using Vibrational Optical Coherence Tomography

Purpose: To determine the in vivo elastic modulus of the human cornea using vibrational optical coherence tomography (VOCT). Methods: Vibrational analysis coupled with optical coherence tomography (OCT) was used to obtain the resonant frequency (RF) and elastic modulus of corneal structural components. VOCT corneal thickness values were measured using OCT images and correlated with corneal thickness determined with Pentacam (Oculus, Wetzlar, Germany). Moduli were obtained at two locations: central cornea (CC) and inferior cornea (IC). Measurements were obtained with and without anesthetic eye drops to assess their effect on the modulus measurements. Results: VOCT thickness values correlated positively (R2 = 0.97) and linearly (y = 1.039x-16.89) with those of Pentacam. Five RF peaks (1-5) were present, although their presence was variable across eyes. The RF for peaks 1 to 5 in the CC and IC ranged from 73.5 ± 4.9 to 239 ± 3 Hz and 72.1 ± 6.3 to 238 ± 4 Hz, respectively. CC and IC moduli for peaks 1 to 5 ranged from 1.023 ± 0.104 to 6.87 ± 0.33 MPa and 0.98 ± 0.15 to 6.52 ± 0.79 MPa, respectively. Topical anesthesia did not significantly alter the modulus (P \u3e 0.05 for all), except for peak 2 in the CC (P \u3c 0.05). Conclusions: This pilot study demonstrates the utility of VOCT as an in vivo, noninvasive technology to measure the elastic modulus in human corneas. The structural origin of these moduli is hypothesized based on previous reports, and further analyses are necessary for confirmation. Translational relevance: This work presents VOCT as a novel approach to assess the in vivo elastic modulus of the cornea, an indicator of corneal structural integrity and health

Signal Peptide Variants in Inherited Retinal Diseases: A Multi-Institutional Case Series

Signal peptide (SP) mutations are an infrequent cause of inherited retinal diseases (IRDs). We report the genes currently associated with an IRD that possess an SP sequence and assess the prevalence of these variants in a multi-institutional retrospective review of clinical genetic testing records. The online databases, RetNet and UniProt, were used to determine which IRD genes possess a SP. A multicenter retrospective review was performed to retrieve cases of patients with a confirmed diagnosis of an IRD and a concurrent SP variant. In silico evaluations were performed with MutPred, MutationTaster, and the signal peptide prediction tool, SignalP 6.0. SignalP 6.0 was further used to determine the locations of the three SP regions in each gene: the N-terminal region, hydrophobic core, and C-terminal region. Fifty-six (56) genes currently associated with an IRD possess a SP sequence. Based on the records review, a total of 505 variants were present in the 56 SP-possessing genes. Six (1.18%) of these variants were within the SP sequence and likely associated with the patients&rsquo; disease based on in silico predictions and clinical correlation. These six SP variants were in the CRB1 (early-onset retinal dystrophy), NDP (familial exudative vitreoretinopathy) (FEVR), FZD4 (FEVR), EYS (retinitis pigmentosa), and RS1 (X-linked juvenile retinoschisis) genes. It is important to be aware of SP mutations as an exceedingly rare cause of IRDs. Future studies will help refine our understanding of their role in each disease process and assess therapeutic approaches

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes

Links Between Socio-Economic Circumstances and Changes in Smoking Behavior in the Mexican Population: 2002–2010

While deleterious consequences of smoking on health have been widely publicized, in many developing countries, smoking prevalence is high and increasing. Little is known about the dynamics underlying changes in smoking behavior. This paper examines socio-economic and demographic characteristics associated with smoking initiation and quitting in Mexico between 2002 and 2010. In addition to the influences of age, gender, education, household economic resources and location of residence, changes in marital status, living arrangements and health status are examined. Drawing data from the Mexican Family Life Survey, a rich population-based longitudinal study of individuals, smoking behavior of individuals in 2002 is compared with their behavior in 2010. Logistic models are used to examine socio-demographic and health factors that are associated with initiating and quitting smoking. There are three main findings. First, part of the relationship between education and smoking reflects the role of economic resources. Second, associations of smoking with education and economic resources differ for females and males. Third, there is considerable heterogeneity in the factors linked to smoking behavior in Mexico indicating that the smoking epidemic may be at different stages in different population subgroups. Mexico has recently implemented fiscal policies and public health campaigns aimed at reducing smoking prevalence and discouraging smoking initiation. These programs are likely to be more effective if they target particular socio-economic and demographic sub-groups