Synergistic rescue of temperature-sensitive p53 mutants by hypothermia and arsenic trioxide.

The p53 tumor suppressor is inactivated by mutations in about 50% of tumors. Rescuing the transcriptional function of mutant p53 has potential therapeutic benefits. Approximately 15% of p53 mutants are temperature sensitive (TS) and regain maximal activity at 32°C. Proof of concept study showed that induction of 32°C hypothermia in mice restored TS mutant p53 activity and inhibited tumor growth. However, 32°C is the lower limit of therapeutic hypothermia procedures for humans. Higher temperatures are preferable but result in suboptimal TS p53 activation. Recently, arsenic trioxide (ATO) was shown to rescue the conformation of p53 structural mutants by stabilizing the DNA binding domain. We examined the responses of 17 frequently observed p53 TS mutants to functional rescue by temperature shift and ATO. The results showed that ATO only rescued mild p53 TS mutants with high basal activity at 37°C. Mild TS mutants showed a common feature of regaining significant activity at the semi-permissive temperature of 35°C and could be further stimulated by ATO at 35°C. TS p53 rescue by ATO was antagonized by the cellular redox mechanism and was rapidly reversible. Inhibition of glutathione (GSH) biosynthesis enhanced ATO rescue efficiency and sustained p53 activity after ATO washout. The results suggest that mild TS p53 mutants are uniquely responsive to functional rescue by ATO due to small thermostability deficits and inherent potential to regain active conformation. Combining mild hypothermia and ATO may provide an effective and safe procedure for targeting tumors with p53 TS mutations.

Post-Traumatic Stress Constrains the Dynamic Repertoire of Neural Activity.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising from exposure to a traumatic event. Although primarily defined in terms of behavioral symptoms, the global neurophysiological effects of traumatic stress are increasingly recognized as a critical facet of the human PTSD phenotype. Here we use magnetoencephalographic recordings to investigate two aspects of information processing: inter-regional communication (measured by functional connectivity) and the dynamic range of neural activity (measured in terms of local signal variability). We find that both measures differentiate soldiers diagnosed with PTSD from soldiers without PTSD, from healthy civilians, and from civilians with mild traumatic brain injury, which is commonly comorbid with PTSD. Specifically, soldiers with PTSD display inter-regional hypersynchrony at high frequencies (80-150 Hz), as well as a concomitant decrease in signal variability. The two patterns are spatially correlated and most pronounced in a left temporal subnetwork, including the hippocampus and amygdala. We hypothesize that the observed hypersynchrony may effectively constrain the expression of local dynamics, resulting in less variable activity and a reduced dynamic repertoire. Thus, the re-experiencing phenomena and affective sequelae in combat-related PTSD may result from functional networks becoming "stuck" in configurations reflecting memories, emotions, and thoughts originating from the traumatizing experience. SIGNIFICANCE STATEMENT: The present study investigates the effects of post-traumatic stress disorder (PTSD) in combat-exposed soldiers. We find that soldiers with PTSD exhibit hypersynchrony in a circuit of temporal lobe areas associated with learning and memory function. This rigid functional architecture is associated with a decrease in signal variability in the same areas, suggesting that the observed hypersynchrony may constrain the expression of local dynamics, resulting in a reduced dynamic range. Our findings suggest that the re-experiencing of traumatic events in PTSD may result from functional networks becoming locked in configurations that reflect memories, emotions, and thoughts associated with the traumatic experience.

The Associative Memory Deficit in Aging Is Related to Reduced Selectivity of Brain Activity during Encoding.

Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity or dedifferentiation has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used fMRI to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole-brain patterns of activation that predicted item versus associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared with young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory.

[MEG]PLS: A pipeline for MEG data analysis and partial least squares statistics.

The emphasis of modern neurobiological theories has recently shifted from the independent function of brain areas to their interactions in the context of whole-brain networks. As a result, neuroimaging methods and analyses have also increasingly focused on network discovery. Magnetoencephalography (MEG) is a neuroimaging modality that captures neural activity with a high degree of temporal specificity, providing detailed, time varying maps of neural activity. Partial least squares (PLS) analysis is a multivariate framework that can be used to isolate distributed spatiotemporal patterns of neural activity that differentiate groups or cognitive tasks, to relate neural activity to behavior, and to capture large-scale network interactions. Here we introduce [MEG]PLS, a MATLAB-based platform that streamlines MEG data preprocessing, source reconstruction and PLS analysis in a single unified framework. [MEG]PLS facilitates MRI preprocessing, including segmentation and coregistration, MEG preprocessing, including filtering, epoching, and artifact correction, MEG sensor analysis, in both time and frequency domains, MEG source analysis, including multiple head models and beamforming algorithms, and combines these with a suite of PLS analyses. The pipeline is open-source and modular, utilizing functions from FieldTrip (Donders, NL), AFNI (NIMH, USA), SPM8 (UCL, UK) and PLScmd (Baycrest, CAN), which are extensively supported and continually developed by their respective communities. [MEG]PLS is flexible, providing both a graphical user interface and command-line options, depending on the needs of the user. A visualization suite allows multiple types of data and analyses to be displayed and includes 4-D montage functionality. [MEG]PLS is freely available under the GNU public license (http://meg-pls.weebly.com).

Dynamic functional connectivity shapes individual differences in associative learning.

Current neuroscientific research has shown that the brain reconfigures its functional interactions at multiple timescales. Here, we sought to link transient changes in functional brain networks to individual differences in behavioral and cognitive performance by using an active learning paradigm. Participants learned associations between pairs of unrelated visual stimuli by using feedback. Interindividual behavioral variability was quantified with a learning rate measure. By using a multivariate statistical framework (partial least squares), we identified patterns of network organization across multiple temporal scales (within a trial, millisecond; across a learning session, minute) and linked these to the rate of change in behavioral performance (fast and slow). Results indicated that posterior network connectivity was present early in the trial for fast, and later in the trial for slow performers. In contrast, connectivity in an associative memory network (frontal, striatal, and medial temporal regions) occurred later in the trial for fast, and earlier for slow performers. Time-dependent changes in the posterior network were correlated with visual/spatial scores obtained from independent neuropsychological assessments, with fast learners performing better on visual/spatial subtests. No relationship was found between functional connectivity dynamics in the memory network and visual/spatial test scores indicative of cognitive skill. By using a comprehensive set of measures (behavioral, cognitive, and neurophysiological), we report that individual variations in learning-related performance change are supported by differences in cognitive ability and time-sensitive connectivity in functional neural networks. Hum Brain Mapp 37:3911-3928, 2016. © 2016 Wiley Periodicals, Inc.

Age-related changes to oscillatory dynamics in hippocampal and neocortical networks.

Recent models of hippocampal function have emphasized its role in relational binding - the ability to form lasting representations regarding the relations among distinct elements or items which can support memory performance, even over brief delays (e.g., several seconds). The present study examined the extent to which aging is associated with changes in the recruitment of oscillatory activity within hippocampal and neocortical regions to support relational binding performance on a short delay visuospatial memory task. Structural magnetic resonance imaging and MEG were used to characterize potential age-related changes in hippocampal volume, oscillatory activity, and subsequent memory performance, and the relationships among them. Participants were required to bind the relative visuospatial positions of objects that were presented singly across time. Subsequently, the objects were re-presented simultaneously, and participants were required to indicate whether the relative spatial positions among the objects had been maintained. Older and younger adults demonstrated similar task accuracy, and older adults had preserved hippocampal volumes relative to younger adults. Age-group differences were found in pre-stimulus theta (∼5Hz) and beta (∼20Hz) oscillations, and this pre-stimulus activity was related to hippocampal volumes in younger adults. Age-group differences were also found in the recruitment of oscillatory activity from the pre-stimulus period to the task. Only younger adults showed a task-related change in theta power that was predictive of memory performance. In contrast, older adults demonstrated task-related alpha (∼10Hz) oscillatory power changes that were not observed in younger adults. These findings provide novel evidence for the role of the hippocampus and functionally connected regions in relational binding that is disrupted in aging. The present findings are discussed in the context of current models regarding the cognitive neuroscience of aging.

Coordinated Information Generation and Mental Flexibility: Large-Scale Network Disruption in Children with Autism.

Autism spectrum disorder (ASD) includes deficits in social cognition, communication, and executive function. Recent neuroimaging studies suggest that ASD disrupts the structural and functional organization of brain networks and, presumably, how they generate information. Here, we relate deficits in an aspect of cognitive control to network-level disturbances in information processing. We recorded magnetoencephalography while children with ASD and typically developing controls performed a set-shifting task designed to test mental flexibility. We used multiscale entropy (MSE) to estimate the rate at which information was generated in a set of sources distributed across the brain. Multivariate partial least-squares analysis revealed 2 distributed networks, operating at fast and slow time scales, that respond completely differently to set shifting in ASD compared with control children, indicating disrupted temporal organization within these networks. Moreover, when typically developing children engaged these networks, they achieved faster reaction times. When children with ASD engaged these networks, there was no improvement in performance, suggesting that the networks were ineffective in children with ASD. Our data demonstrate that the coordination and temporal organization of large-scale neural assemblies during the performance of cognitive control tasks is disrupted in children with ASD, contributing to executive function deficits in this group.

ICA-based artifact correction improves spatial localization of adaptive spatial filters in MEG.

Beamformers are one of the most common inverse models currently used in the estimation of source activity from magnetoencephelography (MEG) data. They rely on a minimization of total power while constraining the gain in the voxel of interest, resulting in the suppression of background noise. Nonetheless, in cases where background noise is strong compared to the source of interest, or when many sources are present, the ability of the beamformer to detect and accurately localize weak sources is reduced. In visual paradigms, two main background sources can substantially impact an accurate estimation of weaker sources. Ocular artifacts are orders of magnitude higher than neural sources making it difficult for the beamformer to effectively suppress them. Primary visual activations also result in strong signals that can impede localization of weak sources. In this paper, we systematically evaluated how neural (visual) and non-neural (eye, heart) sources affect the localization accuracy of frontal and medial temporal sources in visual tasks. These sources are of tremendous interest in learning and memory studies as well as in clinical settings (Alzheimer's/epilepsy) and are typically difficult to localize robustly in MEG. Empirical data from two tasks - active learning and control - were used to evaluate our analysis techniques. Global field power calculations showed multiple time periods where active learning was significantly different from response selection with dominant sources converging to the eyes. Extensive leakage of eye activity into frontal and visual that evoked responses into parietal cortices was also observed. Contributions from ocular activity to the reconstructed time series were indiscernible from task-based recruitment of frontal sources in the original data. Removing artifacts (eye movements, cardiac, and muscular) by means of independent component analysis (ICA) led to a significant improvement in detection and localization of frontal and medial temporal sources. We verified our results by using simulations of sources placed in frontal and medial temporal regions with various types of background noise (eye, heart, and visual). We report that the detection and localization accuracy of frontal and medial temporal sources with beamformer techniques is highly dependent on the magnitude and location of background sources and that removing artifacts can substantially improve the beamformer's performance.

Targeting Cancer Metabolism to Improve Outcomes with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors have revolutionized the treatment paradigm of several cancers. However, not all patients respond to treatment. Tumor cells reprogram metabolic pathways to facilitate growth and proliferation. This shift in metabolic pathways creates fierce competition with immune cells for nutrients in the tumor microenvironment and generates by-products harmful for immune cell differentiation and growth. In this review, we discuss these metabolic alterations and the current therapeutic strategies to mitigate these alterations to metabolic pathways that can be used in combination with checkpoint blockade to offer a new path forward in cancer management.

Effectiveness of Using Nucleic Acid Amplification Test to Screen Blood Donors for Hepatitis B, Hepatitis C, and HIV: A Tertiary Care Hospital Experience From Pakistan.

Background Ensuring blood safety is the primary goal of transfusion medicine. Despite extensive serological tests and strict safety measures, the risk of transfusion-transmitted infections (TTIs) still exists. As applied to blood screening, Nucleic Acid Amplification Test (NAT) offers much higher sensitivity for detecting viral infections. It is, however, currently available to a handful of centers due to the high cost. This study aims to establish the Effectiveness of NAT by assessing the NAT yield and residual risk of transmission of Hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV with and without NAT testing. Material and method This prospective cross-sectional study recruited blood donors from January 2020 to November 2022. All donors underwent routine serologic screening. Only serologically negative donors were tested for HBV, HCV, and HIV by NAT. The NAT yield and residual risk (RR) per million donors were computed for viral infections in seronegative blood donors and calculated using the incidence/window period model. Result A total of 59708 donors were included during the study period. The overall prevalence of TTI's were: For HCV 1.7% (n = 1018), HBV 1.5% (n = 918), HIV 0.07% (n = 47), Syphilis 1.2% (n = 758) and malaria 0.3% (n = 218). Out of 57759 seronegative donors, thirty-four NAT-reactive samples were identified, with 3 cases of HCV, 31 cases of HBV, and Nil HIV cases. NAT yield of HBV was 1 in 1863 with an RR of 8.6 per million, followed by HCV with a NAT yield of 1 in 19253 and RR of 0.8 per million donations. NAT testing reduced RR for HBV by 48.9% and HCV by 94.5%. Conclusion Our study showed that NAT detected 34 out of 57759 cases initially missed by serological tests. The study suggests that the parallel use of serology and NAT screening of donated blood would be beneficial.

Using Interdisciplinary Teams to Mitigate the Effects of Drug Shortages in Palliative Care: The Case of Lorazepam Injection.

Given the rising frequency of drug shortages in hospitals, interdisciplinary collaboration is necessary to manage medications, modify electronic medical records, and evaluate safety outcomes. One such shortage impacted lorazepam injection, a medication commonly used in palliative care to treat anxiety, agitation, and seizures. In anticipation of the lorazepam shortage in the summer of 2022, pharmacy staff collaborated with palliative care physicians to identify alternative treatment recommendations when providers were prohibited from ordering lorazepam injection. Before the shortage, lorazepam was used an average of 95 times per month on the palliative care unit. The overall use of benzodiazepines decreased substantially following the recommendation for the therapeutic alternative, midazolam, during the shortage. Once the shortage ended, use roughly returned to pre-shortage baselines. During this time, there were no patient safety events documented on the palliative care unit. Moreover, no changes to the care experience were reported by patients, family/caregivers, providers, or staff. The collaborative effort between pharmacy and palliative care specialists resulted in alternative treatments for palliative care patients during the drug shortage. This preserved the hospital's supply of lorazepam injection for a patient population with no suitable alternatives while still allowing for management of palliative patients.

The Incidence and Outcomes of Venous Thromboembolisms in Patients Admitted with Different Gastrointestinal Malignancies.

Introduction: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in cancer patients. Our study compares the mortality in hospitalized VTE patients among the four most common gastrointestinal (GI) malignancies which include esophageal, gastric, pancreatic, and colorectal cancer. Methods: A retrospective study was conducted utilizing the Nationwide Inpatient Sample database (NIS) from 2016 to 2019. Patients with VTE were identified using ICD-10 codes from all primary discharge diagnoses. Only deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered. Patients with VTE were further divided into groups: esophageal cancer, gastric cancer, pancreatic cancer, and colorectal cancer, and compared with patients who did not have these malignancies. The adjusted odds ratio (aOR) was calculated using multivariate regression analysis. Results: Among 999,559 patients discharged with a VTE diagnosis, 25,775 (2.6%) had one of the four GI malignancies. Among patients with one of the four included GI malignancy diagnosis, 18,816 (73%) patients had PE and 6,959 (27%) patients had DVT. The study shows that adults admitted to the hospitals for VTE have higher mortality when compared to patients who did not have GI malignancies, with esophageal cancer having the highest inpatient mortality with an aOR of 2.701; 95% confidence interval (CI) 1.989-3.669, p value <0.000. For the remaining GI cancers, gastric cancer had an aOR 1.576; CI: 1.094-2.269, p value 0.015, and pancreatic cancer had an aOR of 1.736; 95% CI: 1.445-2.085, p value <0.000. Patients with colorectal cancer had no significant increase in the odds of mortality with aOR of 1.213; 95% CI: 0.988-1.489, p value 0.066. Conclusions: This study demonstrates that VTE in hospitalized patients with esophageal cancer is associated with greater mortality compared to other GI malignancies.

Relationship Between Reception of Low-Dose Computed Tomography Screening, Tobacco Cessation Attempt, and Reception of Pneumococcal Vaccine.

The stage at diagnosis is the single most important predictor of lung cancer outcome. Therefore, detecting lung cancer early is of utmost importance. Low-dose computed tomography (LDCT) has proven beneficial in the early detection and mortality reduction of lung cancer. Despite this, very few of the high-risk population get annual LDCT done. Patients' attitudes towards tobacco usage and preventive care can be a factor in getting LDCT. We analyzed the relationship between the willingness to undergo LDCT and a person's readiness to try tobacco cessation medication or get the pneumococcal vaccine. We also analyzed the relationship between patients who had tobacco cessation counseling and their willingness to get LDCT and pneumococcal vaccine. Medical records of high-risk patients seen in the East Tennessee State University (ETSU) clinics between January 1, 2016, and November 30, 2020, were analyzed retrospectively. In the data obtained, a total of 2,834 patients were current smokers and were included in the research. The study subjects were assessed in two ways, which from here on will be referred to as method one and method two. In the first method, patients who underwent LDCT were assessed, and the outcome investigated was tobacco cessation counseling, tobacco cessation medication prescription, and pneumococcal vaccination. In the second method, patients who had tobacco cessation counseling were assessed, and the outcome evaluated was LDCT, tobacco cessation medication prescription, and pneumococcal vaccination.  In the first method, out of 2,834 total population, 570 had undergone at least one LDCT screening during the study period. Of the 570 patients who underwent LDCT, 22.8% tried one of the tobacco cessation medications at least once during the study period (vs. 9.8% in patients who did not get the LDCT). Also, 71.5% of patients who had LDCT received at least one dose of pneumonia vaccine (vs. 35.5% in patients who did not get the LDCT). In the second method, 1,673 out of 2,834 patients received at least one tobacco cessation counseling, and out of those, 27.5% had LDCT screening (vs. 9.5% among those who never received counseling). Also, 54.9% received a pneumococcal vaccine (vs. 45.1% among those who did not receive counseling). The study demonstrates a relationship between getting LDCT and getting a pneumococcal vaccine or tobacco cessation medications. It also reveals that tobacco cessation counseling increases the odds of getting LDCT, tobacco cessation medications, and pneumococcal vaccine.

Autoimmune Hemolytic Anemia After mRNA COVID Vaccine.

Discussion of the hematologic complications of vaccination for severe acute respiratory syndrome coronavirus-2 (COVID-19) has primarily focused on the development of vaccine-associated immune thrombosis with thrombocytopenia (VITT). Other hematologic complications are uncommon. We report the case of a patient who developed immunoglobulin G (IgG)-mediated autoimmune hemolytic anemia (AIHA) after the Moderna COVID-19 messenger ribonucleic acid (mRNA) vaccine.

The interplay of cue modality and response latency in brain areas supporting crossmodal motor preparation: an event-related fMRI study.

Crossmodal (auditory, visual) motor facilitation can be defined as a cue in one sensory modality eliciting speeded responses to targets in a different sensory modality. We used event-related functional magnetic resonance imaging (fMRI) to isolate brain activity underlying crossmodal motor preparation. Our predictions were that interactions between input modality and processes underlying response selection would be indexed by distinct spatiotemporal brain dynamics. A crossmodal response selection task was designed in which a central, nonspatial cue indicated the response rule (compatible or incompatible) to a lateralized target. Cues and targets appeared in auditory and visual modalities and were separated by a lengthy delay period in which cue-related brain activity could be dissociated. We found faster reaction times to auditory compared with visual cues. Next, we correlated brain activity with behavioural performance using multivariate spatiotemporal partial least squares. We identified a distinct, significant brain-behaviour pattern in which faster reaction times to auditory cues were correlated with higher blood oxygenation level-dependent percent signal change in medial visual, frontoparietal (inferior parietal lobule, superior frontal gyrus and premotor cortex) and subcortical (thalamus and cerebellum) areas. For visual cues, quicker responses were linked to greater activity in the same frontoparietal and subcortical but not medial visual areas. Our results show that both modality-dependent and modality-independent brain areas with different brain-behaviour relationships are implicated in crossmodal motor preparation.

Rare Presentation of Atypical Hemolytic Uremic Syndrome in an Adult.

Thrombotic microangiopathies (TMA) are disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microthrombi leading to organ dysfunction. Atypical hemolytic uremic syndrome (aHUS) is a rare subtype of TMA mediated by complement dysregulation. We present a case of a 59-year-old female who presented with acute kidney injury and mild thrombocytopenia but with normal hemoglobin. We highlight the importance of prompt diagnosis of aHUS and initiating appropriate treatment with eculizumab.

Medullary Carcinoma of the Colon: A Histopathologic Challenge.

Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer. It is commonly associated with deficient mismatch repair proteins and has a strong association with Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here, we discuss an interesting case of MC of the colon that was metastatic on presentation and constituted a diagnostic challenge.

The Association of Rural-Urban Inhabitation With Gastric Adenocarcinoma Mortality and Treatment: A Surveillance, Epidemiology, and End Results (SEER)-Based Study.

Background Gastric cancer is one of the most prevalent cancers in the world and the third most common cause of death from cancer. The diagnosis and treatment are often complex and require a multifaceted approach. Hence, appropriate and timely management is essential for better patient outcomes. Our aim was to determine if rural inhabitation affects the mortality of patients with gastric adenocarcinoma. If such an association exists, we propose to ascertain whether this is related to delayed diagnosis, differing tumor characteristics, or treatment inequalities. Methods The Cox model was applied to gastric adenocarcinoma cases diagnosed during 2004-2011 in American residents aged 20+ years in the Surveillance, Epidemiology, and End Results (SEER) program to determine the impact of rurality on mortality. Binary logistic regression was used to compare the odds of not receiving surgical treatment for localized tumors between rural and urban areas. It was also used to measure the association of rurality with stage at diagnosis (non-metastatic vs. metastatic). Results There was a significant association of rurality on 5-year mortality [HR 1.14 (1.09-1.20), p < 0.01]. No significant association was observed between rural-urban residency and stage at diagnosis, with an odds ratio (OR) of 0.95 (0.87-1.03), p = 0.21. The median time from diagnosis to any first-course treatment was one month for both rural and urban counties. Rural residents were far more likely not to receive surgical treatment for localized tumors than their urban counterparts [OR 1.70 (1.41-2.05), p < 0.01]. A greater percentage of rural inhabitants had cardia tumors as compared to urban ones, 39.8% vs. 33.8% respectively. Non-cardia tumors were far less likely not to receive surgical treatment (i.e., more likely to receive surgical treatment) than cardia tumors [OR 0.35 (0.30-0.41), p < 0.01]. Conclusions Rurality is associated with worse gastric adenocarcinoma mortality. This may be due to a lesser probability of receiving surgical treatment for early-stage disease and differences in the primary site of the tumor between rural and urban counties, but not due to differences in stage at presentation. Future research should focus on improving health care access in rural communities.

Functional connectivity-based subtypes of individuals with and without autism spectrum disorder.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder, characterized by impairments in social communication and restricted, repetitive behaviors. Neuroimaging studies have shown complex patterns and functional connectivity (FC) in ASD, with no clear consensus on brain-behavior relationships or shared patterns of FC with typically developing controls. Here, we used a dimensional approach to characterize two distinct clusters of FC patterns across both ASD participants and controls using k-means clustering. Using multivariate statistical analyses, a categorical approach was taken to characterize differences in FC between subtypes and between diagnostic groups. One subtype was defined by increased FC within resting-state networks and decreased FC across networks compared with the other subtype. A separate FC pattern distinguished ASD from controls, particularly within default mode, cingulo-opercular, sensorimotor, and occipital networks. There was no significant interaction between subtypes and diagnostic groups. Finally, a dimensional analysis of FC patterns with behavioral measures of IQ, social responsiveness, and ASD severity showed unique brain-behavior relations in each subtype and a continuum of brain-behavior relations from ASD to controls within one subtype. These results demonstrate that distinct clusters of FC patterns exist across ASD and controls, and that FC subtypes can reveal unique information about brain-behavior relationships.

A Case of Anti-glomerular Basement Disease Without Pulmonary Involvement.

Anti-glomerular basement membrane disease is a rare but classic example of an antibody-mediated disease. The scale of injury that it entails depends on the site where the antibodies are deposited, with some patients presenting with a composite of pulmonary and renal damage. In other scenarios, the renal system is the main site of affliction with patients deteriorating to a status of acute renal failure within days of diagnosis. Due to the paucity of its incidence, we present our findings of anti-glomerular basement disease with pulmonary sparing. Herein, we also review the array of different physical findings, different forms of perpetrating antibodies, the diagnostic tools at our disposal, and the treatment modalities utilized to prevent catastrophic tissue injuries.