Posterior Segment Changes in Gaucher Disease.

This case report discusses posterior segment characteristics in a patient aged 24 years with low vision and a history of Gaucher disease.

Secondary glaucoma: Toward interventions based on molecular underpinnings.

Glaucoma is a heterogeneous group of progressive diseases that leads to irreversible blindness. Secondary glaucoma refers to glaucoma caused by a known underlying condition. Pseudoexfoliation and pigment dispersion syndromes are common causes of secondary glaucoma. Their respective deposits may obstruct the trabecular meshwork, leading to aqueous humor outflow resistance, ocular hypertension, and optic neuropathy. There are no disease-specific interventions available for either. Pseudoexfoliation syndrome is characterized by fibrillar deposits (pseudoexfoliative material) on anterior segment structures. Over a decade of multiomics analyses taken together with the current knowledge on pseudoexfoliative glaucoma warrant a re-think of mechanistic possibilities. We propose that the presence of nucleation centers (e.g., vitamin D binding protein), crosslinking enzymes (e.g., transglutaminase 2), aberrant extracellular matrix, flawed endocytosis, and abnormal aqueous-blood barrier contribute to the formation of proteolytically resistant pseudoexfoliative material. Pigment dispersion syndrome is characterized by abnormal iridolenticular contact that disrupts iris pigment epithelium and liberates melanin granules. Iris melanogenesis is aberrant in this condition. Cytotoxic melanogenesis intermediates leak out of melanosomes and cause iris melanocyte and pigment epithelium cell death. Targeting melanogenesis can likely decrease the risk of pigmentary glaucoma. Skin and melanoma research provides insights into potential therapeutics. We propose that specific prostanoid agonists and fenofibrates may reduce melanogenesis by inhibiting cholesterol internalization and de novo synthesis. Additionally, melatonin is a potent melanogenesis suppressor, antioxidant, and hypotensive agent, rendering it a valuable agent for pigmentary glaucoma. In pseudoexfoliative glaucoma, where environmental insults drive pseudoexfoliative material formation, melatonin's antioxidant and hypotensive properties may offer adjunct therapeutic benefits. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.

Serous Retinal Detachment in a Patient With a Port-Wine Birthmark Associated With Prostaglandin Analog Therapy.

An 11-year-old girl with a port-wine birthmark (PWB), diffuse choroid hemangioma (DCH), and glaucoma experienced decreased vision upon starting treatment with bimatoprost. The patient was switched to latanoprostene bunod. Her vision remained reduced. Shortly after, she was diagnosed with serous retinal detachment (SRD). Both SRD and vision improved following prostaglandin analog (PGA) cessation. Patients with PWB are likely to have DCH and glaucoma. DCH itself poses a risk factor for SRD. Certain glaucoma management modalities may further increase this risk. This report highlights the importance of regular surveillance for SRD in patients with DCH who are receiving PGA. [Ophthalmic Surg Lasers Imaging Retina 2023;54:723-729.].

Gender and Inconsistent Evaluations: A Mixed-methods Analysis of Feedback for Emergency Medicine Residents.

Objectives: Prior research has demonstrated that men and women emergency medicine (EM) residents receive similar numerical evaluations at the beginning of residency, but that women receive significantly lower scores than men in their final year. To better understand the emergence of this gender gap in evaluations we examined discrepancies between numerical scores and the sentiment of attached textual comments. Methods: This multicenter, longitudinal, retrospective cohort study took place at four geographically diverse academic EM training programs across the United States from July 1, 2013-July 1, 2015 using a real-time, mobile-based, direct-observation evaluation tool. We used complementary quantitative and qualitative methods to analyze 11,845 combined numerical and textual evaluations made by 151 attending physicians (94 men and 57 women) during real-time, direct observations of 202 residents (135 men and 67 women). Results: Numerical scores were more strongly positively correlated with positive sentiment of the textual comment for men (r = 0.38, P < 0.001) compared to women (r = -0.26, P < 0.04); more strongly negatively correlated with mixed (r = -0.39, P < 0.001) and negative (r = -0.46, P < 0.001) sentiment for men compared to women (r = -0.13, P < 0.28) for mixed sentiment (r = -0.22, P < 0.08) for negative; and women were around 11% more likely to receive positive comments alongside lower scores, and negative or mixed comments alongside higher scores. Additionally, on average, men received slightly more positive comments in postgraduate year (PGY)-3 than in PGY-1 and fewer mixed and negative comments, while women received fewer positive and negative comments in PGY-3 than PGY-1 and almost the same number of mixed comments. Conclusion: Women EM residents received more inconsistent evaluations than men EM residents at two levels: 1) inconsistency between numerical scores and sentiment of textual comments; and 2) inconsistency in the expected career trajectory of improvement over time. These findings reveal gender inequality in how attendings evaluate residents and suggest that attendings should be trained to provide all residents with feedback that is clear, consistent, and helpful, regardless of resident gender.

Cultivation and genomic characterization of novel and ubiquitous marine nitrite-oxidizing bacteria from the Nitrospirales.

Nitrospirales, including the genus Nitrospira, are environmentally widespread chemolithoautotrophic nitrite-oxidizing bacteria. These mostly uncultured microorganisms gain energy through nitrite oxidation, fix CO2, and thus play vital roles in nitrogen and carbon cycling. Over the last decade, our understanding of their physiology has advanced through several new discoveries, such as alternative energy metabolisms and complete ammonia oxidizers (comammox Nitrospira). These findings mainly resulted from studies of terrestrial species, whereas less attention has been given to marine Nitrospirales. In this study, we cultured three new marine Nitrospirales enrichments and one isolate. Three of these four NOB represent new Nitrospira species while the fourth represents a novel genus. This fourth organism, tentatively named "Ca. Nitronereus thalassa", represents the first cultured member of a Nitrospirales lineage that encompasses both free-living and sponge-associated nitrite oxidizers, is highly abundant in the environment, and shows distinct habitat distribution patterns compared to the marine Nitrospira species. Partially explaining this, "Ca. Nitronereus thalassa" harbors a unique combination of genes involved in carbon fixation and respiration, suggesting differential adaptations to fluctuating oxygen concentrations. Furthermore, "Ca. Nitronereus thalassa" appears to have a more narrow substrate range compared to many other marine nitrite oxidizers, as it lacks the genomic potential to utilize formate, cyanate, and urea. Lastly, we show that the presumed marine Nitrospirales lineages are not restricted to oceanic and saline environments, as previously assumed.

Glaucomatous aqueous humor vesicles are smaller and differ in composition compared to controls.

Cells communicate with each other using vesicles of varying sizes, including a specific repertoire known as exosomes. We isolated aqueous humor (AH)-derived vesicles using two different methods: ultracentrifugation and an exosome isolation kit. We confirmed a unique vesicle size distribution in the AH derived from control and primary open-angle glaucoma (POAG) patients using various techniques, including Nanotracker, dynamic light scattering, atomic force imaging, and electron microscopy. Bonafide vesicle and/or exosome markers were present by dot blot in both control and POAG AH-derived vesicles. Marker levels differed between POAG and control samples, while non-vesicle negative markers were absent in both. Quantitative labeled (iTRAQ) proteomics showed a reduced presence of a specific protein, STT3B, in POAG compared to controls, which was further confirmed using dot blot, Western blot, and ELISA assays. Along the lines of previous findings with AH profiles, we found vast differences in the total phospholipid composition of AH vesicles in POAG compared to controls. Electron microscopy further showed that the addition of mixed phospholipids alters the average size of vesicles in POAG. We found that the cumulative particle size of type I collagen decreased in the presence of Cathepsin D, which normal AH vesicles were able to protect against, but POAG AH vesicles did not. AH alone had no effect on collagen particles. We observed a protective effect on collagen particles with an increase in artificial vesicle sizes, consistent with the protective effects observed with larger control AH vesicles but not with the smaller-sized POAG AH vesicles. Our experiments suggest that AH vesicles in the control group provide greater protection for collagen beams compared to POAG, and their increased vesicle sizes are likely contributing factors to this protection.

Cable bacteria with electric connection to oxygen attract flocks of diverse bacteria.

Cable bacteria are centimeter-long filamentous bacteria that conduct electrons via internal wires, thus coupling sulfide oxidation in deeper, anoxic sediment with oxygen reduction in surface sediment. This activity induces geochemical changes in the sediment, and other bacterial groups appear to benefit from the electrical connection to oxygen. Here, we report that diverse bacteria swim in a tight flock around the anoxic part of oxygen-respiring cable bacteria and disperse immediately when the connection to oxygen is disrupted (by cutting the cable bacteria with a laser). Raman microscopy shows that flocking bacteria are more oxidized when closer to the cable bacteria, but physical contact seems to be rare and brief, which suggests potential transfer of electrons via unidentified soluble intermediates. Metagenomic analysis indicates that most of the flocking bacteria appear to be aerobes, including organotrophs, sulfide oxidizers, and possibly iron oxidizers, which might transfer electrons to cable bacteria for respiration. The association and close interaction with such diverse partners might explain how oxygen via cable bacteria can affect microbial communities and processes far into anoxic environments.

Culturally responsive assessment of suicidal thoughts and behaviors in youth of color.

The significance of youth suicide as a public health concern is underscored by the fact that it is the second-leading cause of death for youth globally. While suicide rates for White groups have declined, there has been a precipitous rise in suicide deaths and suicide-related phenomena in Black youth; rates remain high among Native American/Indigenous youth. Despite these alarming trends, there are very few culturally tailored suicide risk assessment measures or procedures for youth from communities of color. This article attempts to address this gap in the literature by examining the cultural relevancy of currently widely used suicide risk assessment instruments, research on suicide risk factors, and approaches to risk assessment for youth from communities of color. It also notes that researchers and clinicians should consider other, nontraditional but important factors in suicide risk assessment, including stigma, acculturation, and racial socialization, as well as environmental factors like health care infrastructure and exposure to racism and community violence. The article concludes with recommendations for factors that should be considered in suicide risk assessment for youth from communities of color. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pharmacological and metabolic effects of drospirenone as a progestin-only pill compared to combined formulations with estrogen.

The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-ß-estradiol are used to treat climacteric symptoms. A drospirenone-only formulation has been introduced for contraception. Here, the pharmacological properties of drospirenone, the impact of the different formulations on metabolic and laboratory parameters, and the resulting clinical implications are reviewed. Ethinylestradiol, an inhibitor of CYP metabolic enzymes, changes the pharmacokinetics of drospirenone, leading to a higher drospirenone exposure with ethinylestradiol/drospirenone compared to the drospirenone-only preparation. In addition, several metabolic alterations have been described. The impact of estetrol is less pronounced, and for 17-ß-estradiol/drospirenone and drospirenone-only, decreased triglyceride and cholesterol levels were observed. Ethinylestradiol induces various pro-coagulatory factors, leading to hypercoagulability. The effect is significantly reduced with estetrol, and no influence was observed with the drospirenone-only preparation. The anti-mineralocorticoid activity of drospirenone seems to positively counteract the renin-angiotensin-aldosterone-system-activating action of ethinylestradiol. There is no influence on blood pressure with ethinylestradiol/drospirenone and estetrol/drospirenone formulations, while in clinical trials, a reduction has been observed with 17-ß-estradiol/drospirenone and drospirenone-only. Anti-aldosterone activity via non-renal mineralocorticoid receptors is associated with cardiovascular health, while interactions with parathyroid hormone signaling impact bone structure and vascular calcification. Though the clinical relevance is unclear for drospirenone, data in this context are reviewed. To sum up, the advantages of drospirenone in hormonal contraception and treatment of menopausal symptoms have been demonstrated for all the formulations described here. Combination with estrogen confers benefits and risks, which must be considered.

Quantifying the robustness of causal inferences: Sensitivity analysis for pragmatic social science.

Social scientists seeking to inform policy or public action must carefully consider how to identify effects and express inferences because actions based on invalid inferences may not yield the intended results. Recognizing the complexities and uncertainties of social science, we seek to inform inevitable debates about causal inferences by quantifying the conditions necessary to change an inference. Specifically, we review existing sensitivity analyses within the omitted variables and potential outcomes frameworks. We then present the Impact Threshold for a Confounding Variable (ITCV) based on omitted variables in the linear model and the Robustness of Inference to Replacement (RIR) based on the potential outcomes framework. We extend each approach to include benchmarks and to fully account for sampling variability represented by standard errors as well as bias. We exhort social scientists wishing to inform policy and practice to quantify the robustness of their inferences after utilizing the best available data and methods to draw an initial causal inference.

Differential carbon utilization enables co-existence of recently speciated Campylobacteraceae in the cow rumen epithelial microbiome.

The activities of different microbes in the cow rumen have been shown to modulate the host's ability to utilize plant biomass, while the host-rumen interface has received little attention. As datasets collected worldwide have pointed to Campylobacteraceae as particularly abundant members of the rumen epithelial microbiome, we targeted this group in a subset of seven cows with meta- and isolate genome analysis. We show that the dominant Campylobacteraceae lineage has recently speciated into two populations that were structured by genome-wide selective sweeps followed by population-specific gene import and recombination. These processes led to differences in gene expression and enzyme domain composition that correspond to the ability to utilize acetate, the main carbon source for the host, at the cost of inhibition by propionate. This trade-off in competitive ability further manifests itself in differential dynamics of the two populations in vivo. By exploring population-level adaptations that otherwise remain cryptic in culture-independent analyses, our results highlight how recent evolutionary dynamics can shape key functional roles in the rumen microbiome.

Lipidomics Analysis with Triple Quadrupole Mass Spectrometry.

Lipids serve an essential role in multiple cellular functions including signaling, metabolism, energy storage, and membrane constitution. Lipidomics, the study of lipids using analytical chemistry, allows for the study of disease states and cellular metabolism. Shotgun lipidomics is a technique that involves direct-infusion electrospray ionization (ESI) and analysis with a triple quadrupole mass spectrometer. Triple quadrupole mass spectrometry is ideally suited for lipidomics analysis because it allows for class-specific identification of lipids. Individual lipid class can be identified by the adjustment of three parameters-collision energy, ion mode, and scan type. This chapter describes the use of a triple quadrupole mass spectrometer, the TSQ Quantum Access MAX, to perform lipidomics analysis with high sensitivity, accuracy, and precision.

The Roles of Adolescent Occupational Expectations and Preparation in Adult Suicide and Drug Poisoning Deaths within a Shifting Labor Market.

Research suggests that economic declines contribute to mortality risks from suicide and drug poisoning, but how the economy impacts individuals' risks of these deaths has been challenging to specify. Building on recent theoretical advances, we investigate how adolescent occupational expectations and preparation contribute to suicide and drug poisoning deaths in a shifting economy. We use High School and Beyond data linked to adult mortality records for men that were exposed to a decline in labor market share and wages in predominantly blue-collar occupations during early adulthood. We find that adolescent men who expected these occupations had increased risks of suicide and drug poisoning death as adults net of educational and occupational attainment in early adulthood. Family background and occupational preparation are risk factors for death by drug poisoning but not suicide. Our findings improve our understanding of how labor market uncertainty shapes individuals' vulnerability to suicide and drug poisoning death.

Stem Cells and Natural Agents in the Management of Neurodegenerative Diseases: A New Approach.

Neurodegenerative diseases refer to a group of neurological disorders as a consequence of various destructive illnesses, that predominantly impact neurons in the central nervous system, resulting in impairments in certain brain functions. Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and other neurodegenerative disorders represent a major risk to human health. In order to optimize structural and functional recovery, reconstructive methods integrate many approaches now, to address the complex and multivariate pathophysiology of neurodegenerative disorders. Stem cells, with their unique property of regeneration, offer new possibilities in regenerative and reconstructive medicine. Concurrently, there is an important role for natural products in controlling many health sufferings and they can delay or even prevent the onset of various diseases. In addition, due to their therapeutic properties, they have been used as neuroprotective agents to treat neurodegenerative disorders. After decades of intensive research, scientists made advances in treating these disorders so far, but current therapies are still not capable of preventing the illnesses from progressing. Therefore, in this review, we focused on a new perspective combining stem cells and natural products as an innovative therapy option in the management of neurodegenerative diseases.

Multifunctionality of Calebin A in inflammation, chronic diseases and cancer.

Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of classical anti-inflammatory drugs, chemotherapeutic agents or to overcome drug resistance of cancer cells. Currently, research on Calebin A, a polyphenolic component of turmeric (Curcuma longa), is becoming of growing interest with regard to novel treatment strategies and has already been shown health-promoting as well as anti-tumor properties, including anti-oxidative and anti-inflammatory effects, in diverse cancer cells. Within this review, we describe already known anti-inflammatory activities of Calebin A via modulation of NF-κB and its associated signaling pathways, linked with TNF-α, TNF-ß and COX-2 and further summarize Calebin A's tumor-inhibiting properties that are known up to date such as reduction of cancer cell viability, proliferation as well as metastasis. We also shed light on possible future prospects of Calebin A as an anti-cancer agent.

ß1-Integrin plays a major role in resveratrol-mediated anti-invasion effects in the CRC microenvironment.

Background: Tumor microenvironment (TME) is one of the most important factors in tumor aggressiveness, with an active exchange between tumor and other TME-associated cells that promotes metastasis. The tumor-inhibitory effect of resveratrol on colorectal cancer (CRC) cells has been frequently reported. However, whether resveratrol can specifically suppress TME-induced CRC invasion via ß1-integrin receptors has not been fully elucidated yet. Methods: Two CRC cell lines (HCT116, RKO) were cultured in multicellular, pro-inflammatory 3D-alginate TME cultures (containing fibroblasts, T-lymphocytes) to investigate the role of ß1-integrin receptors in the anti-invasive and anti-metastatic effect of resveratrol by antisense oligonucleotides (ASO). Results: Our results show that resveratrol dose-dependently suppressed the migration-promoting adhesion adapter protein paxillin and simultaneously enhanced the expression of E-cadherin associated with the phenotype change of CRC cells, and their invasion. Moreover, resveratrol blocked TME-induced phosphorylation and nuclear translocation of p65-NF-κB, which was associated with changes in the expression pattern of epithelial-mesenchymal-transition-related biomarkers (slug, vimentin, E-cadherin), metastasis-related factors (CXCR4, MMP-9, FAK), and apoptosis (caspase-3). Finally, transient transfection of ß1-integrin, in contrast to knockdown of NF-κB, abrogated most anti-invasive, anti-metastatic effects as well as downstream signaling of resveratrol, resulting in a concomitant increase in CRC cell invasion, indicating a central role of ß1-integrin receptors in the anti-invasive function of resveratrol. Conclusion: These results demonstrate for the first time that silencing ß1-integrins may suppress, at least in part the inhibitory effects of resveratrol on invasion and migration of CRC cells, underscoring the crucial homeostatic role of ß1-integrin receptors.

Naringenin: A potential flavonoid phytochemical for cancer therapy.

Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies show the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anti-cancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/ß-catenin, PI3K/Akt, NF-ĸB, and TGF-ß pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.

Herpes Zoster Ophthalmicus Complicated by Unilateral Ptosis and Abducens Nerve Palsy: A Case Report.

Herpes zoster ophthalmicus (HZO) is a viral condition that presents as a painful vesicular rash in the trigeminal nerve dermatome. In some cases, self-limiting extraocular muscle palsies may occur several weeks after the onset of HZO and last for weeks to months. A 71-year-old man developed a debilitating binocular horizontal diplopia and ptosis about four weeks after the onset of HZO symptoms. He had no uveitis, keratitis, or changes in visual acuity. Examination revealed left abducens palsy and ptosis. Symptoms resolved within eight weeks without any intervention.

Fertility preservation: improved neovascularization and follicle viability in cryopreserved bovine ovarian cortex transplants by remaining medulla tissue.

OBJECTIVE: To investigate the advantages of cryopreserved medulla-containing ovarian cortex grafts with those of commonly used sole cortex grafts for fertility preservation by analyzing tissue quality, neovascularization processes, and the number of vital follicles. DESIGN: Experimental setting of cryopreserved bovine ovarian cortex tissue grafts with or without medulla tissue. SETTING: Laboratory animal research at Ulm University, Ulm, Germany. ANIMALS: Bovine ovaries and fertilized chicken eggs. INTERVENTION(S): Experimental setting of bovine ovarian tissue samples grafted on the chicken chorioallantoic membrane (CAM) after cryopreservation and thawing to examine histologic tissue integrity, apoptosis and proliferation immunohistochemically, blood vessel counts and determine the presence of neutral red-stained vital follicles. MAIN OUTCOME MEASURE(S): We used hematoxylin and eosin staining to visualize tissue structures, immunohistochemistry with anti-caspase 3 to detect apoptosis, anti-Ki67 to examine proliferation, blood vessel count on the chicken CAM to investigate neovascularization processes, and neutral red staining to evaluate vital follicles. RESULT(S): We demonstrated that in all analyzed tissue samples, after cryopreservation, thawing, and grafting on the chicken CAM, there was excellent tissue integrity and quality, as shown by extremely rare apoptosis processes analyzed using immunohistochemical caspase 3 staining (sole cortex, 0.54%; thin medulla-containing cortex, 0.43%; thick medulla-containing cortex, 0.13%; and sole medulla, 2.82%). Moreover, we detected increased neovascularization in the vicinity of medulla and medulla-containing grafts (small blood vessels: cortex 8.7, thin medulla-containing cortex 9.9, thick medulla-containing cortex 9.7, and medulla 9.8; very small blood vessels: cortex 7.0, thin medulla-containing cortex 13.0, thick medulla-containing cortex 12.0, and medulla 15.0), with higher Ki67-detected proliferation (cortex, 17.58%; thin medulla-containing cortex, 20.28%; thick medulla-containing cortex, 20.56%; and medulla, 29.9%). Additionally, we identified an increased number of vital follicles in medulla-containing cortex grafts compared with the number of vital follicles in sole cortex tissue (cortex, 256.1; thin medulla-containing cortex, 338.2; thick medulla-containing cortex, 346.6; and medulla, 8.1). CONCLUSION(S): In this experimental setting, bovine medulla-containing cortex tissue had excellent tissue structure and quality after cryopreservation and thawing and increased neovascularization and an augmented vital follicle count after grafting than the commonly used sole cortex tissue. Therefore, we suggest reconsidering the current cryopreservation and grafting processes in humans for fertility preservation by favoring retain medulla tissue at the ovarian cortex.