The thinning of prelaminar tissue and prelamina cupping is known to occur by ischemia, as we see in anterior ischemic optic neuropathy. Since normal tension glaucoma (NTG) is thought to be more ...related to vascular factor than in primary open-angle glaucoma (POAG), we hypothesized that prelamina thinning may occur prominently in NTG patients. This study investigated the difference in prelaminar tissue thickness between patients with POAG and NTG and verified the factors related to prelaminar thinning.
Complete ophthalmic examination including standard automatic perimetry was performed in all patients. The prelaminar tissue thickness was measured in all patients by performing enhanced depth imaging with a Heidelberg Spectralis Optical Coherence Tomography. The retinal nerve fiber layer and optic nerve head parameters were obtained using the Heidelberg Retina Tomography II and Cirrus Optical Coherence Tomography. Various ocular factors and their relationships with prelaminar thickness were analyzed.
The mean prelaminar tissue thickness was significantly thinner in patients with POAG than in those with NTG. The difference in the prelaminar thickness between patients with POAG and those with NTG was greater in the early field defect group than in the moderate and severe field groups. In multivariate analysis, the mean prelaminar thickness was related to the intraocular pressure, mean deviation, cup-disc ratio, and cup volume.
The prelaminar tissue was thinner in patients with POAG than in patients with NTG, and intraocular pressure had a strong influence on the prelaminar thickness in both POAG and NTG. This may indicate that mechanical compression is the main pathogenic factor in both POAG and NTG.
Transgender health in medical education Hana, Tommy; Butler, Kat; Young, L Trevor ...
Bulletin of the World Health Organization,
04/2021, Letnik:
99, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Transforming our world the 2030 agenda for sustainable development is working towards a world that reflects equity, with universal respect for human dignity, pledging to leave no one behind. However, ...transgender and gender-diverse individuals experience significant health inequities, including negative health outcomes and multiple barriers to accessing care. In this article, we first highlight the health inequities that transgender and gender-diverse people face globally. We describe important aspects of transgender and gender-diverse health care, including the design and provision of health services, epidemiological considerations, transition-related care, changes in transition-related goals, cultural considerations, and political and legal issues. We then review the existing global literature on incorporating transgender health into medical curricula. We make a case for prioritizing improved education in medical schools on the specific health needs of transgender and gender-diverse people as part of addressing global health inequities in care. Our recommendations for comprehensive education on transgender health include cultural humility and anti-oppression training; involvement of transgender and gender-diverse community members; integration of transgender and gender-diverse health into curricula; practice-focused and in situ training; staff development in medical schools; and improving access to careers in medicine for transgender and gender-diverse people.
Abstract
Serotonin (5-hydroxytryptamine or 5-HT) is a multifunctional bioamine with important signaling roles in a range of physiological pathways. Almost all of the 5-HT in our bodies is synthesized ...in specialized enteroendocrine cells within the gastrointestinal (GI) mucosa called enterochromaffin (EC) cells. These cells provide all of our circulating 5-HT. We have long appreciated the important contributions of 5-HT within the gut, including its role in modulating GI motility. However, evidence of the physiological and clinical significance of gut-derived 5-HT outside of the gut has recently emerged, implicating 5-HT in regulation of glucose homeostasis, lipid metabolism, bone density, and diseases associated with metabolic syndrome, such as obesity and type 2 diabetes. Although a new picture has developed in the last decade regarding the various metabolic roles of peripheral serotonin, so too has our understanding of the physiology of EC cells. Given that they are scattered throughout the lining of the GI tract within the epithelial cell layer, these cells are typically difficult to study. Advances in isolation procedures now allow the study of pure EC-cell cultures and single cells, enabling studies of EC-cell physiology to occur. EC cells are sensory cells that are capable of integrating cues from ingested nutrients, the enteric nervous system, and the gut microbiome. Thus, levels of peripheral 5-HT can be modulated by a multitude of factors, resulting in both local and systemic effects for the regulation of a raft of physiological pathways related to metabolism and obesity.
Review of the emerging endocrine roles of peripheral serotonin.
As an environmental pollutant, cadmium (Cd) has been widely reported to induce male infertility due to its gonadotoxicity. However, the specific mechanism of Cd-induced testicular damage remains ...unclear. We investigated whether Cd causes testicular injury through ferroptosis. Male C57BL/6 J mice were exposed to 0, 0.5, or 5 ppm Cd via drinking water, starting in utero, and continuing through 24 weeks post-weaning. The results showed that Cd accumulated in the testes in a dose-dependent manner. Cd exposure at a concentration of 5 ppm, but not 0.5 ppm, caused a mass loss and detachment of germ cells, as well as a decreased meiotic index and testis weight. Exposure to 5 ppm Cd caused iron accumulation, increased levels of malondialdehyde (MDA) and nitro tyrosine (3-NT), and decreased expression of Nrf2, HO-1 and SOD2. We also found that exposure to 5 ppm Cd significantly decreased the expression of SLC7A11, a marker of ferroptosis in mice, along with the expression of SLC40A1 mRNA and ferritin heavy chain (FTH) protein, whereas there was no obvious change in the mRNA expression of Tfrc, ZIP8, ZIP14, and NCOA4. These findings indicate that 5 ppm Cd exposure increased testicular ferroptosis, which may be attributed to the reduction of stored iron export.
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•C57/6J mice suffered from whole-life exposure to low-dose Cd (cadmium).•Cd exposure triggered testicular cells ferroptosis in a dose-dependent manner.•5 ppm Cd exposure caused iron accumulation by inhibiting iron storage and export.•5 ppm Cd exposure triggered ferroptosis partially by suppressing SLC7A11 activity.
Protein fusion tags are indispensible tools used to improve recombinant protein expression yields, enable protein purification, and accelerate the characterization of protein structure and function. ...Solubility‐enhancing tags, genetically engineered epitopes, and recombinant endoproteases have resulted in a versatile array of combinatorial elements that facilitate protein detection and purification in microbial hosts. In this comprehensive review, we evaluate the most frequently used solubility‐enhancing and affinity tags. Furthermore, we provide summaries of well‐characterized purification strategies that have been used to increase product yields and have widespread application in many areas of biotechnology including drug discovery, therapeutics, and pharmacology. This review serves as an excellent literature reference for those working on protein fusion tags.
Protein fusion tags are indispensible tools in protein expression and purification studies: This review highlights various protein fusion tags, including the calmodulin‐binding peptide, and their use for protein isolation and purification, including best practices for fusion constructs. This information should be a useful reference to a broad audience, from experts to those new to the protein expression field.
For the smallest nanostructures (<5 nm), small changes in structure can lead to significant changes in properties and reactivity. In the case of nanoparticle (NP)-functionalized electrodes, NP ...structure and composition, and the nature of the NP-electrode interface have a strong influence upon electrochemical properties that are critical in applications such as amperometric sensing, photocatalysis and electrocatalysis. Existing methods to fabricate NP-functionalized electrodes do not allow for precise control over all these variables, especially the NP-electrode interface, making it difficult to understand and predict how structural changes influence NP activity. We investigated the electrochemical properties of small (d core < 2.5 nm) gold nanoparticles (AuNPs) on boron doped diamond electrodes using three different electrode fabrication techniques with varying degrees of nanoparticle-electrode interface definition. Two methods to attach AuNPs to the electrode through a covalently bound molecular linker were developed and compared to NP-functionalized electrodes fabricated using solution deposition methods (drop-casting and physiadsorption of a monolayer). In each case, a ferrocene redox probe was tethered to the AuNP surface to evaluate electron transfer through the AuNPs. The AuNPs that were molecularly interfaced with the electrode exhibited nearly ideal, reproducible electrochemical behavior with narrow redox peaks and small peak separations, whereas the solution deposited NPs had broader redox peaks with large peak separations. These data suggest that the molecular tether facilitates AuNP-mediated electron transfer. Interestingly, the molecularly tethered NPs also had significantly more electrochemically active surface area than the solution deposited NPs. The enhanced electrochemical behavior of the molecularly interfaced NPs demonstrates the significant influence of the interface on NP-mediated electron transfer and suggests that similar modified electrodes can serve as versatile platforms for studies and applications of nanoparticles.
The RNA recognition motif (RRM) is the most common RNA-binding domain in eukaryotes. Differences in RRM sequences dictate, in part, both RNA and protein-binding specificities and affinities. We used ...a deep mutational scanning approach to study the sequence-function relationship of the RRM2 domain of the Saccharomyces cerevisiae poly(A)-binding protein (Pab1). By scoring the activity of more than 100,000 unique Pab1 variants, including 1246 with single amino acid substitutions, we delineated the mutational constraints on each residue. Clustering of residues with similar mutational patterns reveals three major classes, composed principally of RNA-binding residues, of hydrophobic core residues, and of the remaining residues. The first class also includes a highly conserved residue not involved in RNA binding, G150, which can be mutated to destabilize Pab1. A comparison of the mutational sensitivity of yeast Pab1 residues to their evolutionary conservation reveals that most residues tolerate more substitutions than are present in the natural sequences, although other residues that tolerate fewer substitutions may point to specialized functions in yeast. An analysis of ∼40,000 double mutants indicates a preference for a short distance between two mutations that display an epistatic interaction. As examples of interactions, the mutations N139T, N139S, and I157L suppress other mutations that interfere with RNA binding and protein stability. Overall, this study demonstrates that living cells can be subjected to a single assay to analyze hundreds of thousands of protein variants in parallel.
This study sought to investigate the associations between metabolic health status, obesity, and incidence of primary open-angle glaucoma (POAG).
In this nationwide, population-based, longitudinal ...prospective cohort study conducted using the Korean National Health Insurance System, we categorized all subjects based on presence and severity of metabolic syndrome and obesity. Insurance claims data were used to identify POAG development. Then, Cox regression was applied to calculate the hazard of developing POAG in people with various components of metabolic syndrome, obesity, or their combination.
Of the total 287,553 subjects, 4,970 (1.3%) developed POAG. High fasting glucose, blood pressure, and total cholesterol levels were all associated with increased risk of developing POAG. Regarding obesity level, people with body mass index (BMI) greater than 30 kg/m2 were more likely to develop POAG than those with normal BMI. Also, people with greater number of metabolic syndrome components showed a greater POAG incidence. People who are metabolically unhealthy and obese (adjusted hazard ratio HR, 1.574; 95% confidence interval CI, 1.449 to 1.711) and those who are metabolically unhealthy nonobese (MUNO: adjusted HR, 1.521; 95% CI, 1.405 to 1.645) but not those who are metabolically healthy obese (MHO: adjusted HR, 1.019; 95% CI, 0.907 to 1.144) had an increased hazard of developing POAG compared with metabolically healthy nonobese (MHNO) subjects.
Metabolic health status and obesity were significantly associated with increased risk of POAG incidence. MUNO subjects but not MHO subjects showed a higher risk of POAG development than did MHNO subjects, suggesting that metabolic status is more important than obesity in POAG.
Five studies across cultures involving 661 American Democrats and Republicans, 995 Israelis, and 1,266 Palestinians provide previously unidentified evidence of a fundamental bias, what we term the ..."motive attribution asymmetry," driving seemingly intractable human conflict. These studies show that in political and ethnoreligious intergroup conflict, adversaries tend to attribute their own group's aggression to ingroup love more than outgroup hate and to attribute their outgroup's aggression to outgroup hate more than ingroup love. Study 1 demonstrates that American Democrats and Republicans attribute their own party's involvement in conflict to ingroup love more than outgroup hate but attribute the opposing party's involvement to outgroup hate more than ingroup love. Studies 2 and 3 demonstrate this biased attributional pattern for Israelis and Palestinians evaluating their own group and the opposing group's involvement in the current regional conflict. Study 4 demonstrates in an Israeli population that this bias increases beliefs and intentions associated with conflict intractability toward Palestinians. Finally, study 5 demonstrates, in the context of American political conflict, that offering Democrats and Republicans financial incentives for accuracy in evaluating the opposing party can mitigate this bias and its consequences. Although people find it difficult to explain their adversaries' actions in terms of love and affiliation, we suggest that recognizing this attributional bias and how to reduce it can contribute to reducing human conflict on a global scale.
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