Observational cohort study of 100 patients presenting with functional visual loss: clinical characteristics and comparison with other functional neurologic disorders.

OBJECTIVE: Recent research has helped to develop a more detailed understanding of many functional neurologic disorders. The aim of this study was to increase our knowledge of functional visual loss and to compare the findings with those of other functional syndromes. DESIGN: Prospective and retrospective observational cohort study. METHODS: This study took place at neuro-ophthalmology clinics at 3 major hospitals in London, United Kingdom, over a 12-month period. The study population consisted of 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. All participants had their diagnosis confirmed with a full neuro-ophthalmic examination, neuroimaging, and visual electrophysiology. A full assessment of all participants' medical history was obtained from their general practitioner, and all participants completed a series of questionnaires assessing relevant associations. RESULTS: Data were obtained on 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. Participants with functional visual loss were typically female (74%) with a mean age at vision loss of 40.0 ± 16 years. Sixty-four percent of participants had bilateral vision loss; the remainder, unilateral loss. Twenty-six percent of the total cohort had organic visual loss with functional overlay. Fifty percent of participants with functional visual loss had a preexisting psychiatric diagnosis, the most common being a depressive disorder. Sixty-two percent of participants had an ocular history, and 87% had a previously diagnosed medical illness, most commonly neurologic (45%). Thirty-five percent of participants self-reported at least 1 additional functional symptom. CONCLUSIONS: Our population of functional visual loss subjects shares many similarities with the majority of patients with other functional neurologic disorders. They are generally young and female and have a greater than expected rate of psychiatric, medical, and coexisting ocular conditions. We found increased rates of precipitating stressors, clinical depression, and organic eye problems in subjects with functional visual loss.

Outcomes of iStent inject combined with cataract surgery in Asian eyes: Australian data from the Fight Glaucoma Blindness international registry.

PURPOSE: To analyse real-world outcomes in Asian eyes of iStent inject, a second-generation trabecular micro-bypass stent, combined with phacoemulsification. METHODS: This is a multi-centre, observational study of glaucomatous Asian eyes that have undergone iStent inject implantation combined with cataract surgery. Patient data were extracted from the Fight Glaucoma Blindness! Registry. Outcome measures included those of IOP reduction, glaucoma medication reduction, and adverse events including the need for secondary surgery. RESULTS: 123 eyes of 86 patients with a mean age of 68.4 ± 9.3 years underwent iStent inject implantation with phacoemulsification. At baseline, the mean ± SD preoperative intraocular pressure (IOP) was 16.0 ± 4.4 mmHg, and the mean preoperative number of topical glaucoma medications was 1.9 ± 1.4. At 12 months 30.8% of eyes demonstrated a reduction in IOP greater than 20%, the mean IOP reduction was 12.5% with an additional reduction of 0.7 glaucoma medications. 40% of eyes were using no medications at 12 months compared to 16.3% preoperatively. 8.2% of eyes required a subsequent procedure within the 12-month follow-up window. CONCLUSION: iStent inject implantation combined with phacoemulsification in Asian eyes showed a reduction of IOP and glaucoma medication use in a real-world clinical setting. The safety profile of the device is good with minimal adverse outcomes, however, a subset of patients required secondary procedures within the 12 month follow up.

Meaningful Engagement in Depression and Anxiety Collaborative Care: Associations With Systematic Case Review.

BACKGROUND: Collaborative care (CC) is an evidence-based model of care for treating behavioral health conditions in primary care settings. The CC team consists of a primary care provider, behavioral health care manager (CM), and a consultant psychiatrist who collaborate to create treatment plans. To date, there is limited data on factors associated with meaningful engagement in CC programs. OBJECTIVE: To identify the proportion of patients who were meaningfully engaged and to investigate the factors associated with meaningful engagement in a CC program. METHODS: Data was collected from a CC program implemented across 27 adult primary care clinics in a Midwestern, U.S. academic medical system. Logistic regression (n = 5218) was used to estimate the odds of receiving meaningful engagement. RESULTS: Data was collected from 6437 individuals with 68% being female and a mean age of 45 years old (standard deviation 17.6). Overall, 57% of patients were meaningfully engaged; however, this proportion differed based on demographic and clinical factors. Among modifiable clinical factors, systematic case reviews between the CM and psychiatrist (odds ratio: 10.2, 95% confidence interval: 8.6-12.1) and warm handoffs (odds ratio: 1.3, 95% confidence interval: 1.1-1.5) were associated with a higher likelihood of receiving meaningful engagement. CONCLUSIONS: The presence of systematic case reviews between the behavioral health CM and the consultant psychiatrist was highly associated with meaningful engagement. When implementing such programs, high fidelity to the core principles including regularly scheduled systematic case reviews should be pursued.

Novel Monoclonal Antibody Therapy in a Patient With Treatment-Refractory Warm Autoimmune Hemolytic Anemia.

In autoimmune hemolytic anemia (AIHA), hemolysis is the hallmark symptom. Cold agglutinin disease (CAD) and warm autoimmune hemolytic anemia (wAIHA) are the two major forms of AIHA. Hemolysis is complement dependent in CAD, whereas wAIHA is a partially complement-mediated disorder. At the time of writing, sutimlimab-jome is the only FDA-approved monoclonal antibody in the treatment of CAD. In a case of severe treatment-refractory wAIHA, a two-week course with sutimlimab-jome resulted in a sustained decrease in total bilirubin level and a notable reduction in transfusion requirement, suggesting that it is also effective in the treatment of wAIHA.

Organotypic Rat Testicular Organoids for the Study of Testicular Maturation and Toxicology.

An in vitro system to study testicular maturation in rats, an important model organism for reproductive toxicity, could serve as a platform for high-throughput drug and toxicity screening in a tissue specific context. In vitro maturation of somatic cells and spermatogonia in organ culture systems has been reported. However, this has been a challenge for organoids derived from dissociated testicular cells. Here, we report generation and maintenance of rat testicular organoids in microwell culture for 28 days. We find that rat organoids can be maintained in vitro only at lower than ambient O2 tension of 15% and organoids cultured at 34°C have higher somatic cell maturation and spermatogonial differentiation potential compared to cultures in 37°C. Upon exposure to known toxicants, phthalic acid mono-2-ethylhexyl ester and cadmium chloride, the organoids displayed loss of tight-junction protein Claudin 11 and altered transcription levels of somatic cell markers that are consistent with previous reports in animal models. Therefore, the microwell-derived rat testicular organoids described here can serve as a novel platform for the study of testicular cell maturation and reproductive toxicity in vitro.

Patient preferences for GI cancer surveillance and telemedical follow-up.

INTRODUCTION: Surveillance care including routine physical exams and testing following gastrointestinal (GI) cancer treatment can be fiscally and emotionally burdensome for patients. Emerging technology platforms may provide a resource-wise surveillance strategy. However, effective implementation of GI cancer surveillance is limited by a lack of patient level perspective regarding surveillance. This study aimed to describe patient attitudes toward GI cancer surveillance and which care modalities such as telemedicine and care team composition best meet the patient's needs for follow-up care. METHODS: Focused interviews were conducted with 15 GI cancer patients undergoing surveillance following curative-intent surgery. All interviews were audio recorded, transcribed verbatim, and uploaded to NVivo. Study personnel trained in qualitative methods consensus coded 10% of data inductively and iteratively developed a codebook and code descriptions. Using all transcripts, data matrices were developed to identify themes inherent in the transcripts. RESULTS: Qualitative analysis revealed three overarching themes. First, increasing ease of access to surveillance care through telemedicine follow-up services may interfere with patients' preferred follow-up routine, which is an in-office visit. Second, specialist providers were trusted by patients to deliver surveillance care more than primary care providers (PCPs). Thirdly, patients desired improved psychosocial health support during the surveillance period. CONCLUSION: These novel patient-level qualitative data demonstrate that replacing conventional in-office GI cancer surveillance care with telemedicine is not what many patients desire. These data also demonstrate that his cohort of patients prefer to see specialists for GI cancer surveillance care rather than PCPs. Future efforts to enhance surveillance should include increased psychosocial support. Telemedicine implementation should be personalized toward specific populations who may be interested in fewer in-office surveillance visits.

A System-Wide Understanding of the Human Olfactory Percept Chemical Space.

The fundamental units of olfactory perception are discrete 3D structures of volatile chemicals that each interact with specific subsets of a very large family of hundreds of odorant receptor proteins, in turn activating complex neural circuitry and posing a challenge to understand. We have applied computational approaches to analyze olfactory perceptual space from the perspective of odorant chemical features. We identify physicochemical features associated with ~150 different perceptual descriptors and develop machine-learning models. Validation of predictions shows a high success rate for test set chemicals within a study, as well as across studies more than 30 years apart in time. Due to the high success rates, we are able to map ~150 percepts onto a chemical space of nearly 0.5 million compounds, predicting numerous percept-structure combinations. The chemical structure-to-percept prediction provides a system-level view of human olfaction and opens the door for comprehensive computational discovery of fragrances and flavors.

Patient and provider perceptions on utilizing a mobile technology platform to improve surgical outcomes in the perioperative setting.

BACKGROUND AND OBJECTIVES: Patient engagement software is a ubiquitous and expensive commercially available tool designed to improve transitions of care. There are currently no high-quality patient and provider-level data about the usability of these products for surgical oncology patients. This study aims to better understand patient and provider attitudes and perceptions about the implementation of such technology. METHODS: Focused interviews were conducted following the demonstration of a provider-built mobile technology platform. Interviews were audio-recorded, transcribed, and analyzed. Data were consensus coded inductively and categorized into themes regarding patient and provider perspectives on the usability and implementation of MobiMD. RESULTS: Our interviews revealed four consistent themes: (1) patients feel there is a lack of reliable resources for patient education; (2) both patients and providers are supportive of using a mobile application; (3) providers perceive patient onboarding as an added burden on current workflows; and (4) after onboarding, providers express that such an application would optimize current workflows. CONCLUSIONS: Patients perceive a need for improved perioperative education. Providers and patients agree that a mobile technology platform would be an effective solution in addressing this need. Effective implementation of such an intervention may improve patient education and engagement, leading to improved patient outcomes.

Low systemic vitamin D as a potential risk factor in primary open-angle glaucoma: a review of current evidence.

Currently, intraocular pressure is the only modifiable risk factor for glaucoma; thus, identifying other modifiable determinants may have far-reaching outcomes. There has been increasing interest in vitamin D status and glaucoma pathogenesis as low vitamin D has been identified by some studies as an independent risk factor for glaucoma. Although the exact mechanism of vitamin D in glaucoma remains uncertain, there is sufficient evidence to continue research in this area. There is a potential physiological role for vitamin D as an anti-inflammatory agent in the oxidative stress-driven pathogenesis of primary open-angle glaucoma, and further studies are required to evaluate the temporal and causal relationship. Ocular vitamin D status in the tear, aqueous and vitreous fluid is a prospective gap in research.

Opposing functions of F-BAR proteins in neuronal membrane protrusion, tubule formation, and neurite outgrowth.

The F-BAR family of proteins play important roles in many cellular processes by regulating both membrane and actin dynamics. The CIP4 family of F-BAR proteins is widely recognized to function in endocytosis by elongating endocytosing vesicles. However, in primary cortical neurons, CIP4 concentrates at the tips of extending lamellipodia and filopodia and inhibits neurite outgrowth. Here, we report that the highly homologous CIP4 family member, FBP17, induces tubular structures in primary cortical neurons and results in precocious neurite formation. Through domain swapping and deletion experiments, we demonstrate that a novel polybasic region between the F-BAR and HR1 domains is required for membrane bending. Moreover, the presence of a poly-PxxP region in longer splice isoforms of CIP4 and FBP17 largely reverses the localization and function of these proteins. Thus, CIP4 and FBP17 function as an antagonistic pair to fine-tune membrane protrusion, endocytosis, and neurite formation during early neuronal development.

Association between periodontal pathogens and systemic disease.

A growing body of literature suggests that there is a link between periodontitis and systemic diseases. These diseases include cardiovascular disease, gastrointestinal and colorectal cancer, diabetes and insulin resistance, and Alzheimer's disease, as well as respiratory tract infection and adverse pregnancy outcomes. The presence of periodontal pathogens and their metabolic by-products in the mouth may in fact modulate the immune response beyond the oral cavity, thus promoting the development of systemic conditions. A cause-and-effect relationship has not been established yet for most of the diseases, and the mediators of the association are still being identified. A better understanding of the systemic effects of oral microorganisms will contribute to the goal of using the oral cavity to diagnose and possibly treat non-oral systemic disease.

ARbis Pictus: A Study of Vocabulary Learning with Augmented Reality.

We conducted a fundamental user study to assess potential benefits of AR technology for immersive vocabulary learning. With the idea that AR systems will soon be able to label real-world objects in any language in real time, our within-subjects lab-based study explores the effect of such an AR vocabulary prompter on participants learning nouns in an unfamiliar foreign language, compared to a traditional flashcard-based learning approach. Our results show that the immersive AR experience of learning with virtual labels on real-world objects is both more effective and more enjoyable for the majority of participants, compared to flashcards. Specifically, when participants learned through augmented reality, they scored significantly better on both same-day and 4-day delayed productive recall tests than when they learned using the flashcard method. We believe this result is an indication of the strong potential for language learning in augmented reality, particularly because of the improvement shown in sustained recall compared to the traditional approach.

Quantitative trait symmetry independent of Hsp90 buffering: distinct modes of genetic canalization and developmental stability.

The Hsp90 chaperone buffers development against a wide range of morphological changes in many organisms and in Drosophila masks the effects of hidden genetic variation. Theory predicts that genetic and nongenetic buffering will share common mechanisms. For example, it is argued that Hsp90 genetic buffering evolved solely as a by-product of environmental buffering, and that Hsp90 should mask morphological deviations from any source. To test this idea, we examined the effect of Hsp90 on purely nongenetic variation in phenotype, measured as differences between the left and right sides of several bilaterally symmetrical bristle and wing traits in individual flies. Consistent with previous reports, Hsp90 buffered the expression of rare morphogenic variants specific to particular genetic backgrounds. However, neither trait-by-trait nor global asymmetry was affected in outbred flies treated with an Hsp90 inhibitor or across a series of inbred genetic backgrounds from a wild population tested in isogenic F1 heterozygotes carrying either (i) a dominant negative Hsp90 allele on a mutant 3rd chromosome or (ii) a null P-insertion mutation, which was introgressed into the control genetic background on all chromosomes. By contrast, Hsp90-regulated trait means and significant effects of sex, temperature, and genetic background on trait symmetry were clearly detected. We conclude that, by maintaining the function of signaling proteins, Hsp90 masks variation affecting target pathways and traits in populations independent of purely nongenetic sources of variation, refuting the idea that a single Hsp90-dependent process generally controls genetic canalization and developmental stability.