Anterior Olfactory Cortices Differentially Transform Bottom-Up Odor Signals to Produce Inverse Top-Down Outputs.

Odor information arrives first in the main olfactory bulb and is then broadcasted to the olfactory cortices and striatum. Downstream regions have unique cellular and connectivity architectures that may generate different coding patterns to the same odors. To reveal region-specific response features, tuning and decoding of single-unit populations, we recorded responses to the same odors under the same conditions across regions, namely, the main olfactory bulb (MOB), the anterior olfactory nucleus (AON), the anterior piriform cortex (aPC), and the olfactory tubercle of the ventral striatum (OT), of awake male mice. We focused on chemically closely related aldehydes that still create distinct percepts. The MOB had the highest decoding accuracy for aldehydes and was the only region encoding chemical similarity. The MOB had the highest fraction of inhibited responses and narrowly tuned odor-excited responses in terms of timing and odor selectivity. Downstream, the interconnected AON and aPC differed in their response patterns to the same stimuli. While odor-excited responses dominated the AON, the aPC had a comparably high fraction of odor-inhibited responses. Both cortices share a main output target that is the MOB. This prompted us to test if the two regions convey also different net outputs. Aldehydes activated AON terminals in the MOB as a bulk signal but inhibited those from the aPC. The differential cortical projection responses generalized to complex odors. In summary, olfactory regions reveal specialized features in their encoding with AON and aPC differing in their local computations, thereby generating inverse net centrifugal and intercortical outputs.

Visual outcomes after bevacizumab-based therapy for optic pathway glioma.

In optic pathway glioma (OPG), bevacizumab-based therapy (BBT) has promising effects on radiographic tumor burden, but the impact on vision is less clear. This single-institution study characterized visual acuity (VA) and visual field (VF) outcomes in 17 pediatric OPG patients treated with BBT. VA was stable or improved in 14 patients. Nine patients had evaluable VF data, six of whom experienced stability or improvement. Among six patients with vision deterioration as a treatment indication, stable or improved was observed for both VA and VF in five patients. In summary, BBT was associated with favorable visual outcomes in this cohort of patients with OPG.

Complex Abdominal Wall Reconstruction with Biologic Mesh for Ventral/Umbilical Hernias in Patients with Cirrhosis: Technique and Outcomes.

INTRODUCTION: Patients with cirrhosis undergoing non-liver transplant surgery have a higher risk or adverse events than those without cirrhosis. The main objectives of this study were to describe characteristics, outcomes, and outcome predictors of cirrhotic patients undergoing complex abdominal wall reconstruction (CAWR) with biologic mesh. MATERIALS AND METHODS: This study had retrospective and prospective components, including all cirrhotic patients at our center with CAWR for ventral/umbilical hernia repair with biologic mesh between December 2016 and November 2021. RESULTS: We studied 37 patients with cirrhosis. Their mean age was 57.2 years, and 64.9% were male. The median body mass index (BMI) was 28.1kg/m2. Ascites was present in 83.3% of patients. The other most common comorbidities were alcohol abuse (67.6%), hypertension (37.8%), and diabetes (24.3%). All complications in aggregate occurred in 11 patients (29.7%). Six patients (16.2%) underwent reoperation. Surgical site infections (SSIs) occurred in five patients (13.5%). Four deaths occurred within 90 days (11.2% cumulative mortality). By 120 days, there were five deaths (14.2% mortality, but none due to the operation). Seven predictor variables achieved an area under the receiver operating characteristic curve (AUROC) for SSI of 0.963, and two predictors yielded an AUROC of 0.825 for 120-day mortality. CONCLUSIONS: Our results suggest that CAWR for ventral/umbilical hernias among cirrhotic patients is feasible given a dedicated CAWR team in collaboration with transplant surgeons and a transplant hepatologist. The rates of adverse outcomes were low or at the midpoint of the range of the study-specific estimates.

Genetic influences of autism candidate genes on circuit wiring and olfactory decoding.

Olfaction supports a multitude of behaviors vital for social communication and interactions between conspecifics. Intact sensory processing is contingent upon proper circuit wiring. Disturbances in genetic factors controlling circuit assembly and synaptic wiring can lead to neurodevelopmental disorders, such as autism spectrum disorder (ASD), where impaired social interactions and communication are core symptoms. The variability in behavioral phenotype expression is also contingent upon the role environmental factors play in defining genetic expression. Considering the prevailing clinical diagnosis of ASD, research on therapeutic targets for autism is essential. Behavioral impairments may be identified along a range of increasingly complex social tasks. Hence, the assessment of social behavior and communication is progressing towards more ethologically relevant tasks. Garnering a more accurate understanding of social processing deficits in the sensory domain may greatly contribute to the development of therapeutic targets. With that framework, studies have found a viable link between social behaviors, circuit wiring, and altered neuronal coding related to the processing of salient social stimuli. Here, the relationship between social odor processing in rodents and humans is examined in the context of health and ASD, with special consideration for how genetic expression and neuronal connectivity may regulate behavioral phenotypes.

Successful liver transplantation in a patient recovered from COVID-19.

Transplantation in potential candidates who have recently recovered from COVID-19 is a challenge with uncertainties regarding the diagnosis, multi-organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID-19. At the time of transplant, he was SARS-CoV-2 PCR negative for 24 days and had a MELD score of 33. His post-operative course was complicated by acute rejection which responded to intense immune-suppression using T-cell depletion and steroids. He was discharged with normal end-organ function and no evidence of any active infection including COVID-19. Prospective organ transplant recipients who have recovered from COVID-19 can be considered for transplantation after careful pre-transplant evaluation, donor selection, and individualized risk-benefit analysis.

Syndapin I Loss-of-Function in Mice Leads to Schizophrenia-Like Symptoms.

Schizophrenia is associated with cognitive and behavioral dysfunctions thought to reflect imbalances in neurotransmission systems. Recent screenings suggested that lack of (functional) syndapin I (PACSIN1) may be linked to schizophrenia. We therefore studied syndapin I KO mice to address the suggested causal relationship to schizophrenia and to analyze associated molecular, cellular, and neurophysiological defects. Syndapin I knockout (KO) mice developed schizophrenia-related behaviors, such as hyperactivity, reduced anxiety, reduced response to social novelty, and an exaggerated novel object response and exhibited defects in dendritic arborization in the cortex. Neuromorphogenic deficits were also observed for a schizophrenia-associated syndapin I mutant in cultured neurons and coincided with a lack of syndapin I-mediated membrane recruitment of cytoskeletal effectors. Syndapin I KO furthermore caused glutamatergic hypofunctions. Syndapin I regulated both AMPAR and NMDAR availabilities at synapses during basal synaptic activity and during synaptic plasticity-particularly striking were a complete lack of long-term potentiation and defects in long-term depression in syndapin I KO mice. These synaptic plasticity defects coincided with alterations of postsynaptic actin dynamics, synaptic GluA1 clustering, and GluA1 mobility. Both GluA1 and GluA2 were not appropriately internalized. Summarized, syndapin I KO led to schizophrenia-like behavior, and our analyses uncovered associated molecular and cellular mechanisms.

Splenic Switch-Off for Determining the Optimal Dosage for Adenosine Stress Cardiac MR in Terms of Stress Effectiveness and Patient Safety.

BACKGROUND: Adenosine stress MRI is well established for the evaluation of known and suspected coronary artery disease. However, a proportion of patients might be "under-stressed" using the standard adenosine dose. PURPOSE: To compare three different adenosine dosages for stress MRI in terms of stress adequacy based on splenic switch-off (SSO) and limiting side effects. STUDY TYPE: Prospective. POPULATION: In all, 100 patients were randomized in group 1 (33 pts), group 2 (34 pts), and group 3 (33 pts), receiving dosages of 140 µg/kg/min, 175 µg/kg/min, or 210 µg/kg/min, respectively. SSO was evaluated visually and quantitatively. SEQUENCE: Stress perfusion was performed using a 1.5T scanner in three short axes using a standard single-shot, saturation recovery gradient-echo sequence. ASSESSMENT: Three blinded experienced operators evaluated SSO on stress and rest perfusion acquisitions in the three groups. The signal intensity of the spleen and myocardium and the presence of inducible ischemia and late gadolinium enhancement were assessed. STATISTICAL ANALYSIS: T-test, analysis of variance (ANOVA), chi-squared test, and Pearson's correlation coefficient. RESULTS: SSO was present more frequently in patients receiving 175 µg/kg/min and 210 µg/kg/min (31/33 [94%] and 27/29 [93%], respectively) compared to those receiving the standard dose (19/33 [58%], P < 0.05). A positive stress result was noted in 3/33 (9%) patients receiving 140 µg/kg/min vs. 9/33 (27%) patients receiving 175 µg/kg/min and 10/31 (33%) patients receiving 210 µg/kg/min (P < 0.05 for all, P < 0.05 for group 1 vs. groups 2, 3). The relative decrease of splenic signal intensity at hyperemia vs. baseline was significantly lower in group 1 compared to groups 2 and 3 (-33% vs. -54%, -56%, respectively; P < 0.05). No adverse events during scanning were noted in groups 1 and 2, whereas in group 3 four examinations were stopped due to severe dyspnea (n = 2) and AV-blockage (n = 2). DATA CONCLUSION: A dosage of 175 µg/kg/min adenosine results in a higher proportion of SSO, which may be an indirect marker of adequate coronary vasodilatation and simultaneously offers similar safety compared to the standard 140 µg/kg/min dosage. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1732-1742.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.

Imaging of Children With Nontraumatic Headaches.

OBJECTIVE: Headache in children is a common symptom and often is worrisome for clinicians and parents because of the breadth of possible underlying significant abnormalities, including meningitis, brain neoplasms, and intracranial hemorrhage. For this reason, many children with headaches undergo neuroimaging. Most neuroimaging studies performed of children with headaches have normal findings but may lead to significant downstream effects, including unnecessary exposure to ionizing radiation or sedation, as well as unnecessary cost to the health care system. In this article, we review the current evidence and discuss the role of neuroimaging in the diagnosis and management of pediatric headaches, with a special focus on tools that may aid in increasing the rate of positive findings, such as classification systems, algorithms, and red flag criteria. CONCLUSION: Many tools exist that can help in improving the appropriateness of neuroimaging in pediatric headache. The main issues that remain to be addressed include scientific proof of safety and validity of these tools and clarity regarding the risks, benefits, and cost-effectiveness of CT versus MRI in various clinical settings and scenarios.

Are Grittier Front-Line Therapists More Likely to Implement Evidence-Based Interventions?

Substance use disorder remains a pervasive problem in the U.S. and elsewhere. Recent scholarship has explored therapist characteristics and evidence based intervention implementation in an attempt to improve client outcomes. One such construct that has received considerable attention is grit. People with high levels of grit tend to remain determined despite setbacks. This study sought to elucidate the relationship of grit to therapeutic alliance and attitudes towards evidence-based interventions in a sample of front-line therapist (n = 240). Grit was found to be positively associated with therapeutic alliance and correlated with favorable attitudes towards using proven practice. Findings suggest that gritty therapists may sustain the use of evidence based interventions in their usual services and have better client outcomes.

Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer: Evaluation of a biological-systems approach to cancer therapy (U.S. FDA IND-BB 10091; NCT 02046174, NCT 01053013).

OBJECTIVE: The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here. METHODS: Forty-eight mCRC patients (30 females; 18 males), who had failed all available, approved treatments, underwent RMB implantation (8 RMB/kg body weight) up to 4 times in phase I and phase IIa open-label trials. Physicals, labs [tumor and inflammation markers, lactate dehydrogenase (LDH)] and positron emission tomography-computed tomography (PET-CT) imaging to measure number/volume and metabolic activity of the tumors were performed pre- and 3-month-post-implantation to evaluate safety and initial efficacy (as defined by biological responses). PET-CT maximum standard uptake value (SUVmax) (baseline and d 90; SUVmax ≥2.5), LDH, and carcinoembryonic antigen (CEA) and/or cancer antigen 19-9 (CA 19-9) response (baseline, d 30 and/or d 60) were assessed and compared to OS. RESULTS: Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in 75% of patients. Fluorodeoxyglucose (FDG)-positive lesions (phase I, 39; 2a, 82) were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV (10) plus four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Responders (R) (d 0-60, 290.4-333.9), but increased steadily in Non-responders (NR) (d 0-60, 382.8-1,278.5) (d 60, P=0.050). Responders to RMBs, indicated by the changes in the above markers, correlated with OS (R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006). CONCLUSIONS: The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to mCRC. A phase III clinical trial is planned.

Reeling in the damages: Harmful algal blooms' impact on Lake Erie's recreational fishing industry.

Lake Erie is one of the most valuable natural resources in the United States, providing billions of dollars in benefits each year to recreationalists, homeowners and local governments. The ecosystem services provided by Lake Erie, however, are under threat due to harmful algal blooms. This paper provides recreational damage estimates using spatially and temporally varying algae measures and monthly fishing permit sales collected between 2011 and 2014. Results indicate that fishing license sales drop between 10% and 13% when algal conditions surpass the World Health's Organization's moderate health risk advisory threshold of 20,000 cyanobacteria cells/mL. For Lake Erie adjacent counties experiencing a large, summer-long algal bloom, this would result in approximately 3600 fewer fishing licenses issued and approximately $2.25 million to $5.58 million in lost fishing expenditures. Our results show a discrete jump in reduced angling activity upon crossing this threshold, with limited additional impacts associated with more severe algal blooms. This suggests that policies aimed at eliminating, rather than mitigating, algal levels are most beneficial to the Ohio angling industry.

Barriers and Facilitators to Implementing a Change Initiative in Long-Term Care Using the INTERACT® Quality Improvement Program.

Implementation of major organizational change initiatives presents a challenge for long-term care leadership. Implementation of the INTERACT® (Interventions to Reduce Acute Care Transfers) quality improvement program, designed to improve the management of acute changes in condition and reduce unnecessary emergency department visits and hospitalizations of nursing home residents, serves as an example to illustrate the facilitators and barriers to major change in long-term care. As part of a larger study of the impact of INTERACT® on rates of emergency department visits and hospitalizations, staff of 71 nursing homes were called monthly to follow-up on their progress and discuss successful facilitating strategies and any challenges and barriers they encountered during the yearlong implementation period. Themes related to barriers and facilitators were identified. Six major barriers to implementation were identified: the magnitude and complexity of the change (35%), instability of facility leadership (27%), competing demands (40%), stakeholder resistance (49%), scarce resources (86%), and technical problems (31%). Six facilitating strategies were also reported: organization-wide involvement (68%), leadership support (41%), use of administrative authority (14%), adequate training (66%), persistence and oversight on the part of the champion (73%), and unfolding positive results (14%). Successful introduction of a complex change such as the INTERACT® quality improvement program in a long-term care facility requires attention to the facilitators and barriers identified in this report from those at the frontline.

Imatinib Treatment of Lymphangiomatosis (Generalized Lymphatic Anomaly).

Lymphangiomatosis (eg, generalized lymphatic anomaly) is an abnormal proliferation of lymphatic endothelial cells. It is often a childhood disease, but it may present in adulthood by infiltrating organs and cause obstruction, bleeding, or disruption of lymphatic flow. Pulmonary involvement may be mild or cause diffuse interstitial lung disease, airway obstruction, hemoptysis, chylothorax, chylopericardium, and culminate in respiratory failure. Treatment has been limited to surgical resection or drainage procedures because there is no accepted effective systemic therapy. This report presents a patient with lymphangiomatosis and life-threatening hemoptysis in whom positive immunostaining forc-KITsuggested upregulation of tyrosine kinase and whose disease was controlled with imatinib.

Impact of Cardiovascular Risk Factors on Long-Term Mortality After Liver Transplantation.

Immunosuppression with calcineurin inhibitors has contributed to an increased prevalence of hypertension, diabetes, and hypercholesterolemia in patients receiving liver transplantation. This study evaluated the prevalence of cardiovascular risk factors, their management, and long-term mortality after liver transplantation. Medical records were reviewed in 333 adult patients who underwent orthotopic liver transplantation. Data were collected on medical diagnoses before and after transplantation, medication use, and on long-term mortality. The 333 patients in the study included 223 men and 110 women, mean age 59 ± 10 years. The mean follow-up was 50 ± 28 months. After transplantation, there was a high prevalence of hypertension (67%), hypercholesterolemia (46%), diabetes mellitus (42%), and chronic kidney disease (45%). Out of 333 patients in the study, 96 patients (29%) died during follow-up. Stepwise logistic regression was performed to identify the risk factors that might influence long-term mortality outcomes. Based on pretransplant characteristics, positive independent risk factors that increased mortality were age at transplant and hepatitis C. After transplantation, positive predictive factors were diabetes mellitus and cancer. A negative predictive risk factor for mortality was hypercholesterolemia. Analysis of medication after transplantation showed that positive predictive factors were the use of insulin, steroids, and antibiotics. Negative predictors for mortality were tacrolimus and mycophenolate. Our data suggest that diabetes mellitus and hepatitis C play an important role in worsening posttransplant mortality.

The management of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal tract. No medication at present is approved by the Food and drug administration of United States for the treatment of EG. The rarity of the disease limits our experience with the different management options. It also limits the ability to conduct randomized controlled trials that could clearly delineate the efficacy of new therapeutic agents. This review assesses the various management options that have been tried on patients with EG.

High Frequency Sampling of TTL Pulses on a Raspberry Pi for Diffuse Correlation Spectroscopy Applications.

Diffuse Correlation Spectroscopy (DCS) is a well-established optical technique that has been used for non-invasive measurement of blood flow in tissues. Instrumentation for DCS includes a correlation device that computes the temporal intensity autocorrelation of a coherent laser source after it has undergone diffuse scattering through a turbid medium. Typically, the signal acquisition and its autocorrelation are performed by a correlation board. These boards have dedicated hardware to acquire and compute intensity autocorrelations of rapidly varying input signal and usually are quite expensive. Here we show that a Raspberry Pi minicomputer can acquire and store a rapidly varying time-signal with high fidelity. We show that this signal collected by a Raspberry Pi device can be processed numerically to yield intensity autocorrelations well suited for DCS applications. DCS measurements made using the Raspberry Pi device were compared to those acquired using a commercial hardware autocorrelation board to investigate the stability, performance, and accuracy of the data acquired in controlled experiments. This paper represents a first step toward lowering the instrumentation cost of a DCS system and may offer the potential to make DCS become more widely used in biomedical applications.

Motivational interviewing in permanent supportive housing: the role of organizational culture.

This study evaluated motivational interviewing (MI) in a permanent supportive housing agency. The agency's contradictory social service and business missions resulted in an incompatible organizational culture theorized to diminish MI's effectiveness. A combination of observational, interview, and archival data collected over 3 years were used to examine MI implementation within an incompatible supportive housing agency. Two major themes arose: how MI is used to categorize and change clients in permanent supportive housing and how worker-worker relationships affect MI implementation. The results suggest that within incompatible organizational environments, key elements of effective MI implementation are greatly weakened.