Intranasal Oxytocin for Obesity.

BACKGROUND: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm2], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6. RESULTS: Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [-1036 to 1428]; visceral fat: 3.1 cm2 [-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups. CONCLUSIONS: In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.).

A resiliency intervention adapted for older women with HIV: Results from a pilot randomized controlled trial in the northeastern US.

Aging with HIV often results in psychosocial and health-related challenges for women; however, no resiliency interventions exist for older women with HIV (WWH). WWH aged ≥50 were randomized to 10 group sessions of an adapted resiliency intervention or time-matched supportive psychotherapy. Assessments were conducted at three timepoints. Feasibility and acceptability metrics were defined a priori; differences in resilience, stress coping, anxiety, and depression across timepoints were assessed. Overall, 44 WWH enrolled; participants were 58 years old on average, and 56.4% identified as Black/African American. Among those who attended any sessions, all feasibility metrics were met, and the intervention was acceptable. The interaction of study arm and time was associated with significant decreases in depression and a trend toward significant decreases in anxiety. The intervention was not associated with changes in resilience or stress coping. Adjusting delivery modality may further reduce barriers to attendance, improving feasibility and clinical outcomes.

Rates of change of pons and middle cerebellar peduncle diameters are diagnostic of multiple system atrophy of the cerebellar type.

Definitive diagnosis of multiple system atrophy of the cerebellar type (MSA-C) is challenging. We hypothesized that rates of change of pons and middle cerebellar peduncle diameters on MRI would be unique to MSA-C and serve as diagnostic biomarkers. We defined the normative data for anterior-posterior pons and transverse middle cerebellar peduncle diameters on brain MRI in healthy controls, performed diameter-volume correlations and measured intra- and inter-rater reliability. We studied an Exploratory cohort (2002-2014) of 88 MSA-C and 78 other cerebellar ataxia patients, and a Validation cohort (2015-2021) of 49 MSA-C, 13 multiple system atrophy of the parkinsonian type (MSA-P), 99 other cerebellar ataxia patients and 314 non-ataxia patients. We measured anterior-posterior pons and middle cerebellar peduncle diameters on baseline and subsequent MRIs, and correlated results with Brief Ataxia Rating Scale scores. We assessed midbrain:pons and middle cerebellar peduncle:pons ratios over time. The normative anterior-posterior pons diameter was 23.6 ± 1.6 mm, and middle cerebellar peduncle diameter 16.4 ± 1.4 mm. Pons diameter correlated with volume, r = 0.94, P < 0.0001. The anterior-posterior pons and middle cerebellar peduncle measures were smaller at first scan in MSA-C compared to all other ataxias; anterior-posterior pons diameter: Exploratory, 19.3 ± 2.6 mm versus 20.7 ± 2.6 mm, Validation, 19.9 ± 2.1 mm versus 21.1 ± 2.1 mm; middle cerebellar peduncle transverse diameter, Exploratory, 12.0 ± 2.6 mm versus 14.3 ±2.1 mm, Validation, 13.6 ± 2.1 mm versus 15.1 ± 1.8 mm, all P < 0.001. The anterior-posterior pons and middle cerebellar peduncle rates of change were faster in MSA-C than in all other ataxias; anterior-posterior pons diameter rates of change: Exploratory, -0.87 ± 0.04 mm/year versus -0.09 ± 0.02 mm/year, Validation, -0.89 ± 0.48 mm/year versus -0.10 ± 0.21 mm/year; middle cerebellar peduncle transverse diameter rates of change: Exploratory, -0.84 ± 0.05 mm/year versus -0.08 ± 0.02 mm/year, Validation, -0.94 ± 0.64 mm/year versus -0.11 ± 0.27 mm/year, all values P < 0.0001. Anterior-posterior pons and middle cerebellar peduncle diameters were indistinguishable between Possible, Probable and Definite MSA-C. The rate of anterior-posterior pons atrophy was linear, correlating with ataxia severity. Using a lower threshold anterior-posterior pons diameter decrease of -0.4 mm/year to balance sensitivity and specificity, area under the curve analysis discriminating MSA-C from other ataxias was 0.94, yielding sensitivity 0.92 and specificity 0.87. For the middle cerebellar peduncle, with threshold decline -0.5 mm/year, area under the curve was 0.90 yielding sensitivity 0.85 and specificity 0.79. The midbrain:pons ratio increased progressively in MSA-C, whereas the middle cerebellar peduncle:pons ratio was almost unchanged. Anterior-posterior pons and middle cerebellar peduncle diameters were smaller in MSA-C than in MSA-P, P < 0.001. We conclude from this 20-year longitudinal clinical and imaging study that anterior-posterior pons and middle cerebellar peduncle diameters are phenotypic imaging biomarkers of MSA-C. In the correct clinical context, an anterior-posterior pons and transverse middle cerebellar peduncle diameter decline of ∼0.8 mm/year is sufficient for and diagnostic of MSA-C.

Maintenance of Procedural Motor Memory across Brief Rest Periods Requires the Hippocampus.

Research on the role of the hippocampus in memory acquisition has generally focused on active learning. But to understand memory, it is at least as important to understand processes that happen offline, during both wake and sleep. In a study of patients with amnesia, we previously demonstrated that although a functional hippocampus is not necessary for the acquisition of procedural motor memory during training session, it is required for its offline consolidation during sleep. Here, we investigated whether an intact hippocampus is also required for the offline consolidation of procedural motor memory while awake. Patients with amnesia due to hippocampal damage (n = 4, all male) and demographically matched controls (n = 10, 8 males) trained on the finger tapping motor sequence task. Learning was measured as gains in typing speed and was divided into online (during task execution) and offline (during interleaved 30 s breaks) components. Amnesic patients and controls showed comparable total learning, but differed in the pattern of performance improvement. Unlike younger adults, who gain speed across breaks, both groups gained speed only while typing. Only controls retained these gains over the breaks; amnesic patients slowed down and compensated for these losses during subsequent typing. In summary, unlike their peers, whose motor performance remained stable across brief breaks in typing, amnesic patients showed evidence of impaired access to motor procedural memory. We conclude that in addition to being necessary for the offline consolidation of motor memories during sleep, the hippocampus maintains access to motor memory across brief offline periods during wake.

Mindfulness training and exercise differentially impact fear extinction neurocircuitry.

BACKGROUND: The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program. METHODS: We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27). RESULTS: The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement. CONCLUSIONS: Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.

Acupuncture for Japanese Katakori (Chronic Neck Pain): A Randomized Placebo-Controlled Double-Blind Study.

Background and Objectives: Although acupuncture is listed as a beneficial treatment for neck/shoulder stiffness, which has increased with the spread of information technology, to date, evidence of its efficacy under double-blind conditions has not been shown. This study aimed to assess whether acupuncture treatment with superficial skin piercing is superior to placebo treatment. Materials and Methods: A randomized, double-blind (practitioner-patient) placebo-controlled trial was performed at a single center with four arms (ISRCTN76896018). Four hundred patients with essential neck/shoulder stiffness were randomly assigned to penetrating needle treatment (acupuncture ritual and skin penetration), skin-touch needle treatment (acupuncture ritual and skin touch), no-touch needle treatment (acupuncture ritual alone), and no-treatment control. Each of the six acupuncturists applied a needle to each of the four acupoints in the neck/shoulder of 50 patients. Results: Each of the three treatments significantly (p = 0.01) improved neck/shoulder stiffness compared with the no-treatment control immediately and 24 h after treatment. There was a significant improvement in penetrating needle treatment over no-touch needle treatment 24 h later. However, there was no significant difference between the penetrating and skin-touch and skin-touch vs. no-touch. Conclusions: All treatments that received the ritual of acupuncture were better than the no-treatment control. Only genuine acupuncture involves the specific effects of needle insertion into the body. The acupuncture ritual had a significant impact on the subjective improvement of neck/shoulder stiffness; however, improvement with ritual alone versions of placebo acupuncture was not maintained as with superficial skin piercing. Our study provides important evidence of acupuncture efficacy and information regarding inert no-touch placebo control in acupuncture research.

The effects of closed-loop auditory stimulation on sleep oscillatory dynamics in relation to motor procedural memory consolidation.

STUDY OBJECTIVES: Healthy aging and many disorders show reduced sleep-dependent memory consolidation and corresponding alterations in non-rapid eye movement sleep oscillations. Yet sleep physiology remains a relatively neglected target for improving memory. We evaluated the effects of closed-loop auditory stimulation during sleep (CLASS) on slow oscillations (SOs), sleep spindles, and their coupling, all in relation to motor procedural memory consolidation. METHODS: Twenty healthy young adults had two afternoon naps: one with auditory stimulation during SO upstates and another with no stimulation. Twelve returned for a third nap with stimulation at variable times in relation to SO upstates. In all sessions, participants trained on the motor sequence task prior to napping and were tested afterward. RESULTS: Relative to epochs with no stimulation, upstate stimuli disrupted sleep and evoked SOs, spindles, and SO-coupled spindles. Stimuli that successfully evoked oscillations were delivered closer to the peak of the SO upstate and when spindle power was lower than stimuli that failed to evoke oscillations. Across conditions, participants showed similar significant post-nap performance improvement that correlated with the density of SO-coupled spindles. CONCLUSIONS: Despite its strong effects on sleep physiology, CLASS failed to enhance motor procedural memory. Our findings suggest methods to overcome this failure, including better sound calibration to preserve sleep continuity and the use of real-time predictive algorithms to more precisely target SO upstates and to avoid disrupting endogenous SO-coupled spindles and their mnemonic function. They motivate continued development of CLASS as an intervention to manipulate sleep oscillatory dynamics and improve memory.

No Differences in Auditory Steady-State Responses in Children with Autism Spectrum Disorder and Typically Developing Children.

Auditory steady-state response (ASSR) has been studied as a potential biomarker for abnormal auditory sensory processing in autism spectrum disorder (ASD), with mixed results. Motivated by prior somatosensory findings of group differences in inter-trial coherence (ITC) between ASD and typically developing (TD) individuals at twice the steady-state stimulation frequency, we examined ASSR at 25 and 50 as well as 43 and 86 Hz in response to 25-Hz and 43-Hz auditory stimuli, respectively, using magnetoencephalography. Data were recorded from 22 ASD and 31 TD children, ages 6-17 years. ITC measures showed prominent ASSRs at the stimulation and double frequencies, without significant group differences. These results do not support ASSR as a robust ASD biomarker of abnormal auditory processing in ASD. Furthermore, the previously observed atypical double-frequency somatosensory response in ASD did not generalize to the auditory modality. Thus, the hypothesis about modality-independent abnormal local connectivity in ASD was not supported.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis.

OBJECTIVE: To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies. SUMMARY BACKGROUND DATA: Identifying PC impacts prognosis and management of multiple cancer types. METHODS: Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021. Inclusion criteria were: 1) acquisition of whole-body contrast-enhanced (CE) 18F-fluorodeoxyglucose PET/MRI, 2) pathologically confirmed primary abdominopelvic malignancies. Exclusion criteria were: 1) greater than 4 weeks interval between SCI and PET/MRI, 2) unavailable follow-up. SCI consisted of whole-body CE PET/computed tomography (CT) with diagnostic quality CT, and/or CE-CT of the abdomen and pelvis, and/or CE-MRI of the abdomen±pelvis. If available, pathology or surgical findings served as the reference standard, otherwise, imaging followup was used. When SCI and PET/MRI results disagreed, medical records were checked for management changes. Follow-up data were collected until August 2021. RESULTS: One hundred sixty-four subjects were included, 85 (52%) were female, and the median age was 60 years (interquartile range 50-69). At a subject level, PET/MRI had higher sensitivity (0.97, 95% CI 0.86-1.00) than SCI (0.54, 95% CI 0.37-0.71), P < 0.001, without a difference in specificity, of 0.95 (95% CI 0.90-0.98) for PET/MRI and 0.98 (95% CI 0.93-1.00) for SCI, P » 0.250. PET/MRI and SCI results disagreed in 19 cases. In 5/19 (26%) of the discordant cases, PET/MRI findings consistent with PC missed on SCI led to management changes. CONCLUSION: PET/MRI improves detection of PC compared with SCI which frequently changes management.

Intimate Partner Violence-Related Brain Injury Among Colombian Women.

OBJECTIVE: The aim of this study was to assess the prevalence of brain injury (BI) and its relationship to cognitive and psychological outcomes in women survivors of intimate partner violence (IPV) in Colombia, South America. SETTING: Women's shelters and organizations in Barranquilla, Colombia. PARTICIPANTS: Seventy women from the city of Barranquilla, Colombia, who experienced any form of IPV. DESIGN: Cross-sectional, retrospective. MAIN MEASURES: Participants were administered the computerized EMBRACED neuropsychological battery to assess learning, working and long-term memory, cognitive flexibility, and processing speed. Participants also completed measures of psychological symptoms. Partner violence severity was assessed with a semistructured interview for survivors of domestic violence. Presence and severity of IPV-related BI were assessed using the Brain Injury Severity Assessment (BISA). RESULTS: Thirty-one percent of women sustained at least one BI during an abusive relationship, and 10% sustained repetitive BIs. Furthermore, BI was negatively associated with measures of long-term and working memory, cognitive flexibility, as well as a trending ( P = .05) positive association with depression. With the exception of the relationship between BI and cognitive flexibility, which was substantially reduced and no longer significant, all of these relationships were nearly identical in strength when controlling for abuse severity, socioeconomic status, and educational level. CONCLUSION: These data are the first to specifically examine IPV-related BI in relation to cognitive and psychological functioning in a sample of Colombian women. These data add cross-cultural knowledge to the limited work in this area that has largely focused on women in North America.

Associations among acute and chronic musculoskeletal pain, sleep duration, and C-reactive protein (CRP): A cross-sectional study of the UK biobank dataset.

Both musculoskeletal pain and sleep disturbances are major health problems worldwide. Literature suggests that the two are reciprocally related and both may be associated with changes in C-reactive protein (CRP) levels. However, the relationships among musculoskeletal pain, sleep duration, and CRP remain unclear. In this cross-sectional study, we investigated the relationship between acute and chronic musculoskeletal pain, sleep, and inflammation using the data from the initial visit of the UK Biobank. 17,642 individuals with chronic musculoskeletal pain, 11,962 individuals with acute musculoskeletal pain, and 29,604 pain-free controls were included in the analysis. In addition, we validated the findings using data from the second visit assessment of the UK Biobank. We found that 1) chronic pain was associated with higher CRP levels compared to both acute pain and the pain-free controls; 2) chronic pain was associated with a lower sleep score (a measurement of sleep patterns), compared to acute pain and the pain-free controls; and acute pain was associated with lower sleep scores compared to the controls; 3) there was a significant negative association between the sleep score and CRP; 4) CRP may partially mediate the association between chronic pain and decreased sleep score. However, the effect size of the mediation was rather small, and the pathophysiological significance remains uncertain. Further validation is needed. These findings were partly replicated in the UK Biobank second visit assessment cohort with a smaller sample size. Our findings, which are based on the large UK Biobank dataset, support the interplay between musculoskeletal pain, sleep patterns, and the potential mediating role of CRP on this reciprocal relationship.

Mortality related to the use of stapler devices and clip appliers: Analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience database.

BACKGROUND: Surgical staplers and clip appliers are commonly used and have a potential to malfunction, which may result in serious injury or death. These events are self-reported to the Food and Drug Administration and compiled in the Food and Drug Administration's Manufacturer and User Facility Device Experience database. This study characterizes mortality related to surgical stapler and clip applier failure reported in the Food and Drug Administration's Manufacturer and User Facility Device Experience database. METHODS: The Food and Drug Administration's Manufacturer and User Facility Device Experience database was reviewed between 1992 and 2016 for medical device reports related to surgical staplers and clip appliers filed under the following product codes: GAG, FZP, GDO, GDW, KOG, and GCJ. Adverse events including death and the type of device failure were reviewed. Temporal trends in reported deaths related to device failure were analyzed and the Healthcare Cost and Utilization Project database was used to adjust for annual surgical case volume using linear regression analysis. RESULTS: A total of 75,415 malfunctions, 21,115 injuries, and 676 deaths were associated with the use of surgical stapler and clip applier devices. Most deaths occurred postoperatively (N = 516, 76.3%) and were due to infection/sepsis (N = 89, 17.2%) or vascular injuries (N = 110, 21.3%). Intraoperative mortality (N = 79, 11.7%) was primarily due to vascular injuries (N = 73, 92.4%). Device failures resulting in death were noted both intraoperatively (N = 268, 39.6%) and postoperatively (N = 325, 48.1%). In post hoc root cause analysis, a surgical stapler and clip applier device problem was the most common attributed cause of death (N = 238, 65.4%). In the linear regression analysis, there was a significant increase in the mortality from device failure in the study period after adjusting for annual surgical volume (P < .01). CONCLUSION: Mortality related to the use of surgical staplers and clip appliers is increasing. Most deaths occurred postoperatively, and an increased awareness of potential life-threatening complications is warranted when these devices are used.

Network hub centrality and working memory performance in schizophrenia.

Cognitive impairment, and working memory deficits in particular, are debilitating, treatment-resistant aspects of schizophrenia. Dysfunction of brain network hubs, putatively related to altered neurodevelopment, is thought to underlie the cognitive symptoms associated with this illness. Here, we used weighted degree, a robust graph theory metric representing the number of weighted connections to a node, to quantify centrality in cortical hubs in 29 patients with schizophrenia and 29 age- and gender-matched healthy controls and identify the critical nodes that underlie working memory performance. In both patients and controls, elevated weighted degree in the default mode network (DMN) was generally associated with poorer performance (accuracy and reaction time). Higher degree in the ventral attention network (VAN) nodes in the right superior temporal cortex was associated with better performance (accuracy) in patients. Degree in several prefrontal and parietal areas was associated with cognitive performance only in patients. In regions that are critical for sustained attention, these correlations were primarily driven by between-network connectivity in patients. Moreover, a cross-validated prediction analysis showed that a linear model using a summary degree score can be used to predict an individual's working memory accuracy (r = 0.35). Our results suggest that schizophrenia is associated with dysfunctional hubs in the cortical systems supporting internal and external cognition and highlight the importance of topological network analysis in the search of biomarkers for cognitive deficits in schizophrenia.

A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods.

BACKGROUND: Obesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity. METHODS: We report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18-45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to <35, 35 to <40, ≥40 kg/m2). We investigate the efficacy, safety, and mechanisms of oxytocin administration in reducing body weight. Secondary endpoints include changes in resting energy expenditure, body composition, caloric intake, metabolic profile, and brain activation via functional magnetic resonance imaging in response to food images and during an impulse control task. Safety and tolerability (e.g., review of adverse events, vital signs, electrocardiogram, comprehensive metabolic panel) are assessed throughout the study and six weeks after treatment completion. RESULTS: Sixty-one male and female participants aged 18-45 years were randomized (mean age 34 years, mean BMI 37 kg/m2). The study sample is diverse with 38% identifying as non-White and 20% Hispanic. CONCLUSION: Investigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae.

Cognitive deficits, clinical variables, and white matter microstructure in schizophrenia: a multisite harmonization study.

Cognitive deficits are among the best predictors of real-world functioning in schizophrenia. However, our understanding of how cognitive deficits relate to neuropathology and clinical presentation over the disease lifespan is limited. Here, we combine multi-site, harmonized cognitive, imaging, demographic, and clinical data from over 900 individuals to characterize a) cognitive deficits across the schizophrenia lifespan and b) the association between cognitive deficits, clinical presentation, and white matter (WM) microstructure. Multimodal harmonization was accomplished using T-scores for cognitive data, previously reported standardization methods for demographic and clinical data, and an established harmonization method for imaging data. We applied t-tests and correlation analysis to describe cognitive deficits in individuals with schizophrenia. We then calculated whole-brain WM fractional anisotropy (FA) and utilized regression-mediation analyses to model the association between diagnosis, FA, and cognitive deficits. We observed pronounced cognitive deficits in individuals with schizophrenia (p < 0.006), associated with more positive symptoms and medication dosage. Regression-mediation analyses showed that WM microstructure mediated the association between schizophrenia and language/processing speed/working memory/non-verbal memory. In addition, processing speed mediated the influence of diagnosis and WM microstructure on the other cognitive domains. Our study highlights the critical role of cognitive deficits in schizophrenia. We further show that WM is crucial when trying to understand the role of cognitive deficits, given that it explains the association between schizophrenia and cognitive deficits (directly and via processing speed).

The Impaired Subcortical Pathway From Superior Colliculus to the Amygdala in Boys With Autism Spectrum Disorder.

Objective: Increasing evidence suggests that a subcortical pathway from the superior colliculus (SC) through the pulvinar to the amygdala plays a crucial role in mediating non-conscious processing in response to emotional visual stimuli. Given the atypical eye gaze and response patterns to visual affective stimuli in autism, we examined the functional and white matter structural difference of the pathway in boys with autism spectrum disorder (ASD) and typically developing (TD) boys. Methods: A total of 38 boys with ASD and 38 TD boys were included. We reconstructed the SC-pulvinar-amygdala pathway in boys with ASD and TD using tractography and analyzed tract-specific measurements to compare the white matter difference between the two groups. A region of interest-based functional analysis was also applied among the key nodes of the pathway to explore the functional connectivity network. Results: Diffusion tensor imaging analysis showed decreased fractional anisotropy (FA) in pathways for boys with ASD compared to TD. The FA change was significantly associated with the atypical communication pattern in boys with ASD. In addition, compared to TD, we found that the ASD group was associated with increased functional connectivity between the right pulvinar and the left SC. Conclusion: Our results indicated that the functional and white matter microstructure of the subcortical route to the amygdala might be altered in individuals with autism. This atypical structural change of the SC-pulvinar-amygdala pathway may be related to the abnormal communication patterns in boys with ASD.

Restoration of Vision in Severe, Cicatricial, Ocular Surface Disease With the Boston Keratoprosthesis Type II.

PURPOSE: To assess clinical outcomes of patients with severe, cicatricial ocular surface disease (OSD) implanted with the currently marketed design of the Boston keratoprosthesis type II (BK2). DESIGN: Retrospective cohort study. METHODS: Records of consecutive patients undergoing BK2 implantation from June 2009 to March 2021 were assessed for postoperative visual acuity, postoperative complications, device replacement, and additional surgeries. RESULTS: Fifty-six eyes of 53 patients with a mean follow-up of 45.8 months (range, 0.2-134.7 months) were included. Stevens-Johnson syndrome/toxic epidermal necrolysis was the most common indication (49.1%), followed by mucous membrane pemphigoid (39.6%) and other OSD (11.3%). Visual acuity improved from logMAR 2.2 ± 0.5 preoperatively to 1.5 ± 1.2 at final follow-up. Of 56 eyes, 50 saw ≥20/200 at some point postoperatively. Of the eyes with a follow-up of more than 5 years, 50.0% retained a visual acuity of ≥20/200 at their final follow-up. The most common complications over the entire postoperative course (mean ∼4 years) were de novo or worsening glaucoma (41.1%), choroidal effusions (30.3%), retinal detachment (25.0%), and end-stage glaucoma (25.0%). In a univariate analysis, patients who experienced irreversible loss of ≥20/200 visual acuity were more likely to have been previously implanted with an older design of BK2, less likely to be on preoperative systemic immunosuppressive therapy, and less likely to have undergone concurrent glaucoma tube implantation, compared to patients who retained ≥20/200 acuity (P < .04 for all). CONCLUSIONS: Advances in device design and postoperative care have made implantation of BK2 a viable option for corneal blindness in the setting of severe cicatricial OSD.

Remediating Desmoplasia with EGFR-Targeted Photoactivable Multi-Inhibitor Liposomes Doubles Overall Survival in Pancreatic Cancer.

Desmoplasia is characteristic of pancreatic ductal adenocarcinoma (PDAC), which exhibits 5-year survival rates of 3%. Desmoplasia presents physical and biochemical barriers that contribute to treatment resistance, yet depleting the stroma alone is unsuccessful and even detrimental to patient outcomes. This study is the first demonstration of targeted photoactivable multi-inhibitor liposomes (TPMILs) that induce both photodynamic and chemotherapeutic tumor insult, while simultaneously remediating desmoplasia in orthotopic PDAC. TPMILs targeted with cetuximab (anti-EGFR mAb) contain lipidated benzoporphyrin derivative (BPD-PC) photosensitizer and irinotecan. The desmoplastic tumors comprise human PDAC cells and patient-derived cancer-associated fibroblasts. Upon photoactivation, the TPMILs induce 90% tumor growth inhibition at only 8.1% of the patient equivalent dose of nanoliposomal irinotecan (nal-IRI). Without EGFR targeting, PMIL photoactivation is ineffective. TPMIL photoactivation is also sixfold more effective at inhibiting tumor growth than a cocktail of Visudyne-photodynamic therapy (PDT) and nal-IRI, and also doubles survival and extends progression-free survival by greater than fivefold. Second harmonic generation imaging reveals that TPMIL photoactivation reduces collagen density by >90% and increases collagen nonalignment by >103 -fold. Collagen nonalignment correlates with a reduction in tumor burden and survival. This single-construct phototoxic, chemotherapeutic, and desmoplasia-remediating regimen offers unprecedented opportunities to substantially extend survival in patients with otherwise dismal prognoses.

Different Eye Tracking Patterns in Autism Spectrum Disorder in Toddler and Preschool Children.

Background: Children with autism spectrum disorder (ASD) have been observed to be associated with fixation abnormality as measured eye tracking, but the dynamics behind fixation patterns across age remain unclear. Materials and Methods: In this study, we investigated gaze patterns between toddlers and preschoolers with and without ASD while they viewed video clips and still images (i.e., mouth-moving face, biological motion, mouthing face vs. moving object, still face picture vs. objects, and moving toys). Results: We found that the fixation time percentage of children with ASD showed significant decrease compared with that of TD children in almost all areas of interest (AOI) except for moving toy (helicopter). We also observed a diagnostic group (ASD vs. TD) and chronological age (Toddlers vs. preschooler) interaction for the eye AOI during the mouth-moving video clip. Support vector machine analysis showed that the classifier could discriminate ASD from TD in toddlers with an accuracy of 80% and could discriminate ASD from TD in preschoolers with an accuracy of 71%. Conclusion: Our results suggest that toddlers and preschoolers may be associated with both common and distinct fixation patterns. A combination of eye tracking and machine learning methods has the potential to shed light on the development of new early screening/diagnosis methods for ASD.