White matter plasticity following cataract surgery in congenitally blind patients.

The visual system develops abnormally when visual input is absent or degraded during a critical period early in life. Restoration of the visual input later in life is generally thought to have limited benefit because the visual system will lack sufficient plasticity to adapt to and utilize the information from the eyes. Recent evidence, however, shows that congenitally blind adolescents can recover both low-level and higher-level visual function following surgery. In this study, we assessed behavioral performance in both a visual acuity and a face perception task alongside longitudinal structural white matter changes in terms of fractional anisotropy (FA) and mean diffusivity (MD). We studied congenitally blind patients with dense bilateral cataracts, who received cataract surgery at different stages of adolescence. Our goal was to differentiate between age- and surgery-related changes in both behavioral performance and structural measures to identify neural correlates which might contribute to recovery of visual function. We observed surgery-related long-term increases of structural integrity of late-visual pathways connecting the occipital regions with ipsilateral fronto-parieto-temporal regions or homotopic contralateral areas. Comparison to a group of age-matched healthy participants indicated that these improvements went beyond the expected changes in FA and MD based on maturation alone. Finally, we found that the extent of behavioral improvement in face perception was mediated by changes in structural integrity in late visual pathways. Our results suggest that sufficient plasticity remains in adolescence to partially overcome abnormal visual development and help localize the sites of neural change underlying sight recovery.

Metal content and kinetic properties of yeast RNA lariat debranching enzyme Dbr1.

In eukaryotic cells, intron lariats produced by the spliceosome contain a 2'5' phosphodiester linkage. The RNA lariat debranching enzyme, Dbr1, is the only enzyme known to hydrolyze this bond. Dbr1 is a member of the metallophosphoesterase (MPE) family of enzymes, and recent X-ray crystal structures and biochemistry data demonstrate that Dbr1 from Entamoeba histolytica uses combinations of Mn2+, Zn2+, and Fe2+ as enzymatic cofactors. Here, we examine the kinetic properties and metal dependence of the Dbr1 homolog from Saccharomyces cerevisiae (yDbr1). Elemental analysis measured stoichiometric quantities of Fe and Zn in yDbr1 purified following heterologous expression E. coli We analyzed the ability of Fe2+, Zn2+, and Mn2+ to reconstitute activity in metal-free apoenzyme. Purified yDbr1 was highly active, turning over substrate at 5.6 sec-1, and apo-yDbr1 reconstituted with Fe2+ was the most active species, turning over at 9.2 sec-1 We treated human lymphoblastoid cells with the iron-chelator deferoxamine and measured a twofold increase in cellular lariats. These data suggest that Fe is an important biological cofactor for Dbr1 enzymes.

Patient and Health Care Professional Perspectives on Stigma in Integrated Behavioral Health: Barriers and Recommendations.

PURPOSE: Stigma related to mental health is well documented and a major barrier to using mental and physical health care. Integrated behavioral health (IBH) in primary care, in which behavioral/mental health care services are located within a primary care setting, may reduce the experience of stigma. The purpose of this study was to assess the opinions of patients and health care professionals about mental illness stigma as a barrier to engagement with IBH and to gain insight into strategies to reduce stigma, encourage discussion of mental health, and increase uptake of IBH care. METHODS: We conducted semistructured interviews with 16 patients referred to IBH in a prior year and 15 health care professionals (12 primary care physicians and 3 psychologists). Interviews were transcribed and inductively coded separately by 2 coders for common themes and subthemes under the topic headings of barriers, facilitators, and recommendations. RESULTS: We identified 10 converging themes from interviews with patients and the health care professionals, representing important complementary perspectives, with respect to barriers, facilitators, and recommendations. Barriers included professionals, families, and the public as sources of stigma, as well as self-stigma or avoidance, or internalizing negative stereotypes. Facilitators and recommendations included normalizing discussion of mental health and mental health care-seeking action, using patient-centered and empathetic communication strategies, sharing by health care professionals of their own experiences, and tailoring the discussion of mental health to patients' preferred understanding. CONCLUSIONS: Health care professionals can help reduce perceptions of stigma by having conversations with patients that normalize mental health discussion, use patient-centered communication, promote professional self-disclosure, and are tailored to patients' preferred understanding.

Prehospital Fluid Administration for Suspected Sepsis in a Large EMS System: Opportunities to Improve Goal Fluid Delivery.

OBJECTIVES: Despite EMS-implemented screening and treatment protocols for suspected sepsis patients, prehospital fluid therapy is variable. We sought to describe prehospital fluid administration in suspected sepsis patients, including demographic and clinical factors associated with fluid outcomes. METHODS: A retrospective cohort of adult patients from a large, county-wide EMS system from January 2018-February 2020 was identified. Patient care reports for suspected sepsis were included, as identified by EMS clinician impression of sepsis, or keywords "sepsis" or "septic" in the narrative. Outcomes were the proportions of suspected sepsis patients for whom intravenous (IV) therapy was attempted and those who received ≥500 mL IV fluid if IV access was successful. Associations between patient demographics and clinical factors with fluid outcomes were estimated with multivariable logistic regression adjusting for transport interval. RESULTS: Of 4,082 suspected sepsis patients identified, the mean patient age was 72.5 (SD 16.2) years, 50.6% were female, and 23.8% were Black. Median (interquartile range [IQR]) transport interval was 16.5 (10.9-23.2) minutes. Of identified patients, 1,920 (47.0%) had IV fluid therapy attempted, and IV access was successful in 1,872 (45.9%). Of those with IV access, 1,061 (56.7%) received ≥500mL of fluid from EMS. In adjusted analyses, female (versus male) sex (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.69-0.90), Black (versus White) race (OR 0.57, 95% CI 0.49-0.68), and end stage renal disease (OR 0.51, 95% CI 0.32-0.82) were negatively associated with attempted IV therapy. Systolic blood pressure (SBP) <90 mmHg (OR 3.89, 95% CI 3.25-4.65) and respiratory rate >20 (OR 1.90, 95% CI 1.61-2.23) were positively associated with attempted IV therapy. Female sex (OR 0.72, 95% CI 0.59-0.88) and congestive heart failure (CHF) (OR 0.55, 95% CI 0.40-0.75) were negatively associated with receiving goal fluid volume while SBP <90 mmHg (OR 2.30, 95% CI 1.83-2.88) and abnormal temperature (>100.4 F or <96 F) (OR 1.41, 95% CI 1.16-1.73) were positively associated. CONCLUSIONS: Fewer than half of EMS sepsis patients had IV therapy attempted, and of those, approximately half met fluid volume goal, especially when hypotensive and no CHF. Further studies are needed on improving EMS sepsis training and prehospital fluid delivery.

Effectiveness of a Novel Rapid Infusion Device and Clinician Education for Early Fluid Therapy by Emergency Medical Services in Sepsis Patients: A Pre-Post Observational Study.

OBJECTIVE: Emergency medical services (EMS) clinicians are tasked with early fluid resuscitation for patients with sepsis. Traditional methods for prehospital fluid delivery are limited in speed and ease-of-use. We conducted a comparative effectiveness study of a novel rapid infusion device for prehospital fluid delivery in suspected sepsis patients. METHODS: This pre-post observational study evaluated a hand-operated, rapid infusion device in a single large EMS system from July 2021-July 2022. Prior to device deployment, EMS clinicians completed didactic and simulation-based device training. Data were extracted from the EMS electronic health record. Eligible patients included adults with suspected sepsis treated by EMS with intravenous fluids. The primary outcome was the proportion of patients receiving goal fluid volume (at least 500 mL) prior to hospital arrival. Secondary outcomes included in-hospital mortality, disposition, and length of stay. Multivariable logistic regression was used to compare outcomes between 6-month pre- and post-implementation periods (July-December 2021 and February-July 2022, respectively), adjusting for patient demographics, abnormal prehospital vital signs, and EMS transport interval. RESULTS: Of 1,180 eligible patients (552 in the pre-implementation period; 628 in the post-implementation period), the mean age was 72 years old, 45% were female, and 25% were minority race-ethnicity. Median (interquartile range) fluid volume (in mL) increased between the pre- and post-implementation periods (600 [400,1,000] and 850 [500-1,000], respectively). Goal fluid volume was achieved in 70% of pre-implementation patients and 82% of post-implementation patients. In adjusted analysis, post-implementation patients were significantly more likely to receive goal fluid volume than pre-implementation patients (adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.51-2.66). Pre-post in-hospital mortality was not significantly different (aOR 0.91, 95% CI 0.59-1.39). CONCLUSION: In a single EMS system, sepsis education and introduction of a rapid infusion device was associated with achieving goal fluid volume for suspected sepsis. Further research is needed to assess the clinical effectiveness of infusion device implementation to improve sepsis patient outcomes.

Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia.

Hyponatremia and hypernatremia are electrolyte disorders that can be associated with poor outcomes. Hyponatremia is considered mild when the sodium concentration is 130 to 134 mEq per L, moderate when 125 to 129 mEq per L, and severe when less than 125 mEq per L. Mild symptoms include nausea, vomiting, weakness, headache, and mild neurocognitive deficits. Severe symptoms of hyponatremia include delirium, confusion, impaired consciousness, ataxia, seizures, and, rarely, brain herniation and death. Patients with a sodium concentration of less than 125 mEq per L and severe symptoms require emergency infusions with 3% hypertonic saline. Using calculators to guide fluid replacement helps avoid overly rapid correction of sodium concentration, which can cause osmotic demyelination syndrome. Physicians should identify the cause of a patient's hyponatremia, if possible; however, treatment should not be delayed while a diagnosis is pursued. Common causes include certain medications, excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise. Management to correct sodium concentration is based on whether the patient is hypovolemic, euvolemic, or hypervolemic. Hypovolemic hyponatremia is treated with normal saline infusions. Treating euvolemic hyponatremia includes restricting free water consumption or using salt tablets or intravenous vaptans. Hypervolemic hyponatremia is treated primarily by managing the underlying cause (e.g., heart failure, cirrhosis) and free water restriction. Hypernatremia is less common than hyponatremia. Mild hypernatremia is often caused by dehydration resulting from an impaired thirst mechanism or lack of access to water; however, other causes, such as diabetes insipidus, are possible. Treatment starts with addressing the underlying etiology and correcting the fluid deficit. When sodium is severely elevated, patients are symptomatic, or intravenous fluids are required, hypotonic fluid replacement is necessary.

Surface Area and Local Curvature: Why Roughness Improves the Bioactivity of Neural Implants.

While roughening the surface of neural implants has been shown to significantly improve their performance, the mechanism for this improvement is not understood, preventing systematic optimization of surfaces. Specifically, prior work has shown that the cellular response to a surface can be significantly enhanced by coating the implant surface with inorganic nanoparticles and neuroadhesion protein L1, and this improvement occurs even when the surface chemistry is identical between the nanoparticle-coated and uncoated electrodes, suggesting the critical importance of surface topography. Here, we use transmission electron microscopy to characterize the topography of bare and nanoparticle-coated implants across 7 orders of magnitude in size, from the device scale to the atomic scale. The results reveal multiscale roughness, which cannot be adequately described using conventional roughness parameters. Indeed, the topography is nearly identical between the two samples at the smallest scales and also at the largest scales but vastly different in the intermediate scales, especially in the range of 5-100 nm. Using a multiscale topography analysis, we show that the coating causes a 76% increase in the available surface area for contact and an order-of-magnitude increase in local surface curvature at characteristic sizes corresponding to specific biological structures. These are correlated with a 75% increase in bound proteins on the surface and a 134% increase in neurite outgrowth. The present investigation presents a framework for analyzing the scale-dependent topography of medical device-relevant surfaces, and suggests the most critical size scales that determine the biological response to implanted materials.

Portal Message Language Use Prior to Suicide, Suicide Attempts, and Hospitalization for Depression.

Introduction: Previous research suggests patients may be willing to communicate serious psychiatric concerns through patient portals. Methods: Retrospective chart review of portal messages sent by patients who had an emergency department (ED) visit or hospitalization for depression, self-harm, or suicidality or had a completed suicide (cases) was reviewed for content that was suggestive of depression or self-harm and language indicating emotional distress. Comparison with a randomly selected group (controls) was performed. Results: During the study period 420 messages were sent by 149 patients within 30 days of death by suicide, ED visit, and/or hospitalization related to depression, suicidality, or suicide attempt. Thirteen patients died by suicide but only 23% (3 of 13) sent one or more portal messages within 30 days before their death. None mentioned thoughts of self-harm. There were 271 messages sent by patients who were hospitalized, 142 messages by those who presented to the ED, and 56 messages patients who attempted suicide. Patient messages from cases were more likely than messages from controls to convey a depressed mood (17.1% vs. 3.1%, odds ratio 6.5; 95% confidence interval 3.6-11.9, p < 0.0001), thoughts of suicide or self-harm (4.8% vs. 0% p < 0.0001), or have a distressed tone (24.0% vs. 1.7%, odds ratio 18.7; 95% confidence interval 8.6-41, p < 0.0001). Conclusions: Patient portal messages from patients with subsequent hospitalizations for depression and suicidality do report thoughts of depression, distress, and thoughts of self-harm. However, portal use before completed suicide was not helpful at identifying at-risk patients although total numbers were small.

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.

Use of the McIsaac Score to Predict Group A Streptococcal Pharyngitis in Outpatient Nurse Phone Triage and Electronic Visits Compared With In-Person Visits: Retrospective Observational Study.

BACKGROUND: The McIsaac criteria are a validated scoring system used to determine the likelihood of an acute sore throat being caused by group A streptococcus (GAS) to stratify patients who need strep testing. OBJECTIVE: We aim to compare McIsaac criteria obtained during face-to-face (f2f) and non-f2f encounters. METHODS: This retrospective study compared the percentage of positive GAS tests by McIsaac score for scores calculated during nurse protocol phone encounters, e-visits (electronic visits), and in person f2f clinic visits. RESULTS: There was no difference in percentages of positive strep tests between encounter types for any of the McIsaac scores. There were significantly more phone and e-visit encounters with any missing score components compared with f2f visits. For individual score components, there were significantly fewer e-visits missing fever and cough information compared with phone encounters and f2f encounters. F2f encounters were significantly less likely to be missing descriptions of tonsils and lymphadenopathy compared with phone and e-visit encounters. McIsaac scores of 4 had positive GAS rates of 55% to 68% across encounter types. There were 4 encounters not missing any score components with a McIsaac score of 0. None of these 4 encounters had a positive GAS test. CONCLUSIONS: McIsaac scores of 4 collected during non-f2f care could be used to consider empiric treatment for GAS without testing if significant barriers to testing exist such as the COVID-19 pandemic or geographic barriers. Future studies should evaluate further whether non-f2f encounters with McIsaac scores of 0 can be safely excluded from GAS testing.

The impact of obesity on outcomes in patients receiving extracorporeal life support.

Extracorporeal life support (ECLS) has been increasingly utilized to manage cardiac and pulmonary dysfunction. The impact of obesity on outcomes of ECLS is poorly defined. The purpose of the study was to compare in-hospital mortality, resource use, complications, and readmissions in obese versus non-obese patients receiving ECLS. We performed a retrospective cohort study of all adult ECLS patients with and without an obesity diagnosis using the 2010-2016 Nationwide Readmissions Database (NRD). Mortality, length of stay (LOS), hospital charges, complications, and readmissions were evaluated using multivariable logistic and linear regression. Of 23 876, patients who received ECLS, 1924 (8.1%) were obese. Obese patients received ECLS more frequently for respiratory failure (29.5% vs. 23.7%, P = .001). After adjustment for patient and hospital factors, obesity was not associated with increased odds of mortality (AOR = 1.06, P = .44) and was associated with decreased LOS (13.7 vs. 21.2 days, P < .001), hospital charges ($171 866 vs. $211 445, P < .001), and 30-day readmission (AOR = 0.71, P = .03). Obesity was also associated with reduced odds of hemorrhage (AOR = 0.43, P < .001), neurologic complications (AOR = 0.55, P = .004), and acute kidney injury (AOR=0.83, P = .04). After stratification by ECLS indication, obesity remained predictive of shorter LOS (AOR range: 0.53-0.78, all P < .05 ) and did not impact mortality (all P > .05). Respiratory support remains the most common indication for ECLS among obese patients. Among all patients, as well as by individual ECLS indication, obesity was not associated with increased odds of mortality. These findings suggest that obesity should not be considered a high-risk contraindication to ECLS.

A model for rapid emergency department expansion for the COVID-19 pandemic.

COVID-19 has caused global dramatic change in medical practices including the introduction of temporary screening and assessment areas outside the footprint of the main hospital structures. Following the initial surge of patients with novel coronavirus (2019-nCoV) in the United States, our medical center rapidly designed and constructed an alternative assessment and treatment site in a converted parking garage deck for emergency department patients with suspected or confirmed 2019-nCoV. During the first month after opening, 651 patients were treated in this alternative assessment area including 54 patients who tested positive for 2019-nCoV. This accounted for 55% of the 98 patients with confirmed novel coronavirus (2019-nCoV) who were treated in our ED. This report provides a blueprint for the necessary steps, materials, labor needs and barriers, both anticipated and unanticipated, to rapidly construct an alternative ED treatment site during a pandemic.

Individual differences in apology acceptance and forgiveness: the influence of handedness.

The purpose of the current study was to determine if the relationship between interhemispheric interaction and cognitive flexibility extends to explanations of forgiveness and apology acceptance. A growing body of research indicates that consistency of handedness may be reflective of an individual's degree of interhemispheric interaction and access to processes of the right hemisphere. As such, individual differences in processing that require interhemispheric interaction, such as belief updating, are associated with consistency of handedness. Participants completed the Edinburgh Handedness Inventory (EHI) and read descriptions of interpersonal transgressions, then rated their willingness to forgive before and after an apology was offered. There was a main effect such that the presence of apology increased forgiveness. However, inconsistent handedness was associated with greater forgiveness prior to apology compared to consistent handedness. A second study was conducted to determine if the individual differences in forgiveness were mediated by different dimensions of empathy (personal distress, perspective taking, empathic concern and fantasy). Participants completed the Interpersonal Reactivity Index, the Forgiveness Scale and the EHI. Results revealed those with inconsistent handedness who scored lower on personal distress reported decreased negative thoughts about transgressors compared to those with consistent handedness.

Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons.

OBJECTIVES: Bipolar disorder has been studied from numerous angles, from pathological studies to large-scale genomic studies, overall making moderate gains toward an understanding of the disorder. With the advancement of induced pluripotent stem (iPS) cell technology, in vitro models based on patient samples are now available that inherently incorporate the complex genetic variants that largely are the basis for this disorder. A number of groups are starting to apply iPS technology to the study of bipolar disorder. METHODS: We selectively reviewed the literature related to understanding bipolar disorder based on using neurons derived from iPS cells. RESULTS: So far, most work has used the prototypical iPS cells. However, others have been able to transdifferentiate fibroblasts directly to neurons. Others still have utilized olfactory epithelium tissue as a source of neural-like cells that do not need reprogramming. In general, iPS and related cells can be used for studies of disease pathology, drug discovery, or stem cell therapy. CONCLUSIONS: Published studies have primarily focused on understanding bipolar disorder pathology, but initial work is also being done to use iPS technology for drug discovery. In terms of disease pathology, some evidence is pointing toward a differentiation defect with more ventral cell types being prominent. Additionally, there is evidence for a calcium signaling defect, a finding that builds on the genome-wide association study results. Continued work with iPS cells will certainly help us understand bipolar disorder and provide a way forward for improved treatments.

Phacoemulsification with Either Endocyclophotocoagulation or Ab-Interno Canaloplasty with or without Trabeculotomy in Uveitic Glaucoma.

PURPOSE: Understanding the current role and efficacy of endocyclophotocoagulation (ECP) compared to ab-interno canaloplasty with or without trabeculotomy (OMNI), combined with cataract extraction and lens implantation (CEIOL), for the management of uveitic glaucoma (UG) is limited. METHODS: All UG patients ≥18 years old with ≥6 months of follow-up data (15.2 ± 5.9 months) after CEIOL combined with either ECP or OMNI from August 2019 to May 2022 at a single academic center were retrospectively reviewed [22 eyes of 15 patients (8 ECP, 14 OMNI)]. Surgical success was considered intraocular pressure (IOP) ≤21 mmHg and a reduction of baseline by ≥20% for two consecutive final visits without hypotony, additional surgery, or loss of light perception. Uveitic control was considered a <2-step increase in anterior chamber (AC) cell grade, <3+ AC cell grade, and no increase in steroid drop use at 3 months postoperatively. Secondary outcome measurements included postoperative change in IOP, glaucoma medications, best corrected visual acuity (VA), AC cell grade, and steroid drop frequency. RESULTS: Baseline ocular and preoperative characteristics of eyes (age, sex, laterality, uveitic location, systemic immunomodulating therapy, visual acuity, IOP, number of glaucoma medications, AC cell grade, and steroid drop frequency) did not significantly differ except for greater racial diversity in the ECP group. 62.5% eyes were surgically successful in the ECP group and 85.71% in the OMNI. Between-group analysis showed greater IOP reduction in the OMNI group (p < .05), but no difference in reduction of glaucoma medications (p = .33). No eyes displayed a two-step increase in or >3+ AC cell grade, however, 50% and 64.29%, respectively, increased steroid drop use. Between groups, no difference in the change of AC cell grade (p = .98) or steroid drop use (p = .84) was seen. CONCLUSIONS: Both interventions improved visual acuity, IOP, and glaucoma medication use, however, OMNI was more successful at reducing IOP long term. An increase in steroid drop frequency may be the cost of a prolonged post-surgical inflammatory course related to underlying uveitis regardless of surgical approach.