Human long intrinsically disordered protein regions are frequent targets of positive selection

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher-order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here we address this question by investigating the evolutionary pattern of more than 6,600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a-priori knowledge of disordered protein regions and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs 4-fold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts

Comparative Analysis of LASIK Flap Diameter and its Centration Using Two Different Femtosecond Lasers

The aim of this study was to compare the diameter, accuracy, variability, and centration with respect to the limbus of corneal flaps created by two femtosecond lasers, the VisuMax, and Wavelight FS200, for laser in situ keratomileusis (LASIK) and how these flaps affect visual outcomes. This is a retrospective chart review of flap morphology created during LASIK Surgery. Overall, 168 eyes underwent flap creation using the WaveLight FS200 laser, and on 189 eyes, the VisuMax laser was used. Of these total number, flap morphology was analyzed in a random sample of 158 eyes; 80 with the Visumax laser and 78 with the WaveLight FS200 laser. Intraoperative photos of the flaps taken by the Wavelight Allegretto EX500 were analyzed. Flap diameters and centration were measured using Adobe Acrobat Pro. All patients had visual acuity measurements including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent refraction (SE) and refractive astigmatism recorded three months postoperatively. Greater than 90% of patients in both groups achieved a UDVA of 20/20 postoperatively. The mean difference between targeted and achieved flap diameter was 0.50 +/- 0.15 mm in the VisuMax group and 0.35 +/- 0.15 millimeters (mm) in the FS200 group (P<0.01). The flap diameters of the VisuMax group were more precise with a variance of 0.024 mm compared to a variance of 0.038 mm in the FS200 group (P<0.05). VisuMax flaps were more nasally displaced (log(NA/TA) = -0.21 +/- 0.10 mm) compared to the FS200 flaps (log(NA/TA) = 0.03 +/- 0.10 mm), (P< 0.01). We concluded that both the VisuMax and FS200 created flaps larger than the preoperative targeted diameter. VisuMax created corneal flaps that had a greater degree of deviation from the targeted diameter when compared to flaps from the FS200. However, there was less variance in the VisuMax flap diameter. In addition, VisuMax flaps were more nasally displaced. There were no statistically significant differences in visual outcomes when comparing the two femtosecond lasers

Special Care in Lichen Planus Patients Undergoing LASIK: A Review Article

Laser-Assisted in Situ Keratomileusis (LASIK) is a common surgery for the correction of refractive errors. The majority of patients who undergo this procedure often have excellent results. However, uncontrolled autoimmune disorders and dry eye have both been listed as contraindications to this surgery. Lichen planus (LP) is an autoimmune, inflammatory disorder that characteristically affects mucocutaneous membranes. The etiology is unknown, but it most commonly affects middle-aged adults and presents with bilateral, purple papules. Clinical presentation is used to diagnose the condition, and a punch biopsy is confirmatory. LP may present with multiple different symptoms depending on the type, with ocular manifestations being rare. Multiple viruses and autoimmune conditions have been associated with the disorder, and physicians should take care when gathering a full history of the patient. Exacerbation of symptoms may happen if mood disorders such as depression and anxiety are not well controlled. There are several additional factors physicians must carefully consider before recommending LASIK to patients with LP. These include lichenoid reactions, current medications, and past or present ocular lesions. LASIK may be carefully considered in patients with well-controlled LP in the absence of ocular manifestations. Patients with ocular LP are not candidates for LASIK

Comparative Analysis of LASIK Flap Diameter and its Centration Using Two Different Femtosecond Lasers

The aim of this study was to compare the diameter, accuracy, variability, and centration with respect to the limbus of corneal flaps created by two femtosecond lasers, the VisuMax, and Wavelight FS200, for laser in situ keratomileusis (LASIK) and how these flaps affect visual outcomes. This is a retrospective chart review of flap morphology created during LASIK Surgery. Overall, 168 eyes underwent flap creation using the WaveLight FS200 laser, and on 189 eyes, the VisuMax laser was used. Of these total number, flap morphology was analyzed in a random sample of 158 eyes; 80 with the Visumax laser and 78 with the WaveLight FS200 laser. Intraoperative photos of the flaps taken by the Wavelight Allegretto EX500 were analyzed. Flap diameters and centration were measured using Adobe Acrobat Pro. All patients had visual acuity measurements including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent refraction (SE) and refractive astigmatism recorded three months postoperatively. Greater than 90% of patients in both groups achieved a UDVA of 20/20 postoperatively. The mean difference between targeted and achieved flap diameter was 0.50 +/- 0.15 mm in the VisuMax group and 0.35 +/- 0.15 millimeters (mm) in the FS200 group (P<0.01). The flap diameters of the VisuMax group were more precise with a variance of 0.024 mm compared to a variance of 0.038 mm in the FS200 group (P<0.05). VisuMax flaps were more nasally displaced (log(NA/TA) = -0.21 +/- 0.10 mm) compared to the FS200 flaps (log(NA/TA) = 0.03 +/- 0.10 mm), (P< 0.01). We concluded that both the VisuMax and FS200 created flaps larger than the preoperative targeted diameter. VisuMax created corneal flaps that had a greater degree of deviation from the targeted diameter when compared to flaps from the FS200. However, there was less variance in the VisuMax flap diameter. In addition, VisuMax flaps were more nasally displaced. There were no statistically significant differences in visual outcomes when comparing the two femtosecond lasers

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Background: Given that an individual’s age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options? Methods: An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15–49 years) and peri-/post-menopausal (> 50 years). Results: The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is higher in women than men (by about + 15%) and, in contrast, the fatality rate is higher in men (about + 50%). Interestingly, the relationships between these quantities are linked to age: pre-adolescent girls and boys had the same risk of infection and fatality rate, while adult premenopausal women had a significantly higher risk of infection than men in the same 5-year age stratum (about 16,000 vs. 12,000 cases). This ratio changed again in peri- and postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years, there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17ß-estradiol influences expression of the human angiotensin-converting enzyme 2 (ACE2) protein, which plays a role in SARS-CoV-2 cellular entry, propensity score matching was performed for the women’s sub-cohort, comparing users vs. non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women > 50 years receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95% CI [0.18, 0.62] and the hazard ratio (HR) was 0.29, 95% CI [0.11,0.76]. For younger, pre-menopausal women (15–49 years), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels. Conclusions: As of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone

A Century of Change towards Prevention and Minimal Intervention in Cariology

Publisher Copyright: © International & American Associations for Dental Research 2019. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Better understanding of dental caries and other oral conditions has guided new strategies to prevent disease and manage its consequences at individual and public health levels. This article discusses advances in prevention and minimal intervention dentistry over the last century by focusing on some milestones within scientific, clinical, and public health arenas, mainly in cariology but also beyond, highlighting current understanding and evidence with future prospects. Dentistry was initially established as a surgical specialty. Dental caries (similar to periodontitis) was considered to be an infectious disease 100 years ago. Its ubiquitous presence and rampant nature—coupled with limited diagnostic tools and therapeutic treatment options—meant that these dental diseases were managed mainly by excising affected tissue. The understanding of the diseases and a change in their prevalence, extent, and severity, with evolutions in operative techniques, technologies, and materials, have enabled a shift from surgical to preventive and minimal intervention dentistry approaches. Future challenges to embrace include continuing the dental profession’s move toward a more patient-centered, evidence-based, less invasive management of these diseases, focused on promoting and maintaining oral health in partnership with patients. In parallel, public health needs to continue to, for example, tackle social inequalities in dental health, develop better preventive and management options for existing disease risk groups (e.g., the growing aging population), and the development of reimbursement and health outcome models that facilitate implementation of these evolving strategies. A century ago, almost every treatment involved injections, a drill or scalpel, or a pair of forceps. Today, dentists have more options than ever before available to them. These are supported by evidence, have a minimal intervention focus, and result in better outcomes for patients. The profession’s greatest challenge is moving this evidence into practice.preprintPeer reviewe

Effect of polycrystallinity on the optical properties of highly oriented ZnO grown by pulsed laser deposition

We report the results of photoluminescence and reflectance measurements on highly c-axis oriented polycrystalline ZnO grown by pulsed laser deposition. The samples measured were grown under identical conditions and were annealed in-situ at various temperatures for 10-15 min. The band-edge photoluminescence spectra of the material altered considerably with an increase in grain size, with increased free exciton emission and observable excitonic structure in the reflectance spectra. The green band emission also increased with increasing grain size. A deformation potential analysis of the effect of strain on the exciton energy positions of the A- and B-excitons demonstrated that the experimental exciton energies could not be explained solely in terms of sample strain. We propose that electric fields in the samples due to charge trapping at grain boundaries are responsible for the additional perturbation of the excitons. This interpretation is supported by theoretical estimates of the exciton energy perturbation due to electric fields. The behaviour of the green band in the samples provides additional evidence in favour of our model