Neuronal wiring diagram of an adult brain.

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1-6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10-12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Improving outcomes in emergency general surgery: Construct of a collaborative quality initiative.

BACKGROUND: Emergency general surgery conditions are common, costly, and highly morbid. The proportion of excess morbidity due to variation in health systems and processes of care is poorly understood. We constructed a collaborative quality initiative for emergency general surgery to investigate the emergency general surgery care provided and guide process improvements. METHODS: We collected data at 10 hospitals from July 2019 to December 2022. Five cohorts were defined: acute appendicitis, acute gallbladder disease, small bowel obstruction, emergency laparotomy, and overall aggregate. Processes and inpatient outcomes investigated included operative versus nonoperative management, mortality, morbidity (mortality and/or complication), readmissions, and length of stay. Multivariable risk adjustment accounted for variations in demographic, comorbid, anatomic, and disease traits. RESULTS: Of the 19,956 emergency general surgery patients, 56.8% were female and 82.8% were White, and the mean (SD) age was 53.3 (20.8) years. After accounting for patient and disease factors, the adjusted aggregate mortality rate was 3.5% (95% confidence interval [CI], 3.2-3.7), morbidity rate was 27.6% (95% CI, 27.0-28.3), and the readmission rate was 15.1% (95% CI, 14.6-15.6). Operative management varied between hospitals from 70.9% to 96.9% for acute appendicitis and 19.8% to 79.4% for small bowel obstruction. Significant differences in outcomes between hospitals were observed with high- and low-outlier performers identified after risk adjustment in the overall cohort for mortality, morbidity, and readmissions. The use of a Gastrografin challenge in patients with a small bowel obstruction ranged from 10.7% to 61.4% of patients. In patients who underwent initial nonoperative management of acute cholecystitis, 51.5% had a cholecystostomy tube placed. The cholecystostomy tube placement rate ranged from 23.5% to 62.1% across hospitals. CONCLUSION: A multihospital emergency general surgery collaborative reveals high morbidity with substantial variability in processes and outcomes among hospitals. A targeted collaborative quality improvement effort can identify outliers in emergency general surgery care and may provide a mechanism to optimize outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Petascale pipeline for precise alignment of images from serial section electron microscopy.

The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create a 3D image stack. Precise and robust alignment in the presence of image artifacts is challenging, especially as datasets are attaining the petascale. We present a computational pipeline for aligning ssEM images with several key elements. Self-supervised convolutional nets are trained via metric learning to encode and align image pairs, and they are used to initialize iterative fine-tuning of alignment. A procedure called vector voting increases robustness to image artifacts or missing image data. For speedup the series is divided into blocks that are distributed to computational workers for alignment. The blocks are aligned to each other by composing transformations with decay, which achieves a global alignment without resorting to a time-consuming global optimization. We apply our pipeline to a whole fly brain dataset, and show improved accuracy relative to prior state of the art. We also demonstrate that our pipeline scales to a cubic millimeter of mouse visual cortex. Our pipeline is publicly available through two open source Python packages.

Cell-type-specific inhibitory circuitry from a connectomic census of mouse visual cortex.

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how each cell type participates in the cortical circuit, but mapping connectivity rules at the resolution of distinct cell types remains difficult. Here, we used millimeter-scale volumetric electron microscopy1 to investigate the connectivity of all inhibitory neurons across a densely-segmented neuronal population of 1352 cells spanning all layers of mouse visual cortex, producing a wiring diagram of inhibitory connections with more than 70,000 synapses. Taking a data-driven approach inspired by classical neuroanatomy, we classified inhibitory neurons based on the relative targeting of dendritic compartments and other inhibitory cells and developed a novel classification of excitatory neurons based on the morphological and synaptic input properties. The synaptic connectivity between inhibitory cells revealed a novel class of disinhibitory specialist targeting basket cells, in addition to familiar subclasses. Analysis of the inhibitory connectivity onto excitatory neurons found widespread specificity, with many interneurons exhibiting differential targeting of certain subpopulations spatially intermingled with other potential targets. Inhibitory targeting was organized into "motif groups," diverse sets of cells that collectively target both perisomatic and dendritic compartments of the same excitatory targets. Collectively, our analysis identified new organizing principles for cortical inhibition and will serve as a foundation for linking modern multimodal neuronal atlases with the cortical wiring diagram.

Development of a Tool to Assess Surgical Resident Competence On-Call: The Western University Call Assessment Tool (WUCAT).

BACKGROUND: A central tenet of competency-based medical education is the formative assessment of trainees. There are currently no assessments designed to examine resident competence on-call, despite the on-call period being a significant component of residency, characterized by less direct supervision compared to daytime. The purpose of this study was to design a formative on-call assessment tool and collect valid evidence on its application. METHODS: Nominal group technique was used to identify critical elements of surgical resident competence on-call to inform tool development. The tool was piloted over six months in the Division of Plastic & Reconstructive Surgery at our institution. Quantitative and qualitative evidence was collected to examine tool validity. RESULTS: A ten-item tool was developed based on the consensus group results. Sixty-three assessments were completed by seven staff members on ten residents during the pilot. The tool had a reliability coefficient of 0.67 based on a generalizability study and internal item consistency was 0.92. Scores were significantly associated with years of training. We found the tool improved the quantity and structure of feedback given and that the tool was considered feasible and acceptable by both residents and staff members. CONCLUSIONS: The Western University Call Assessment Tool (WUCAT) has multiple sources of evidence supporting its use in assessing resident competence on-call.

"Winged" Eagle's syndrome: neurophysiological findings in a rare cause of spinal accessory nerve palsy. Illustrative cases.

BACKGROUND: Eagle's syndrome (ES) classically describes dysphagia, globus sensation, and otalgia from an elongated and calcified styloid process or stylohyoid ligament. Compression of the spinal accessory nerve (SAN) has not been reported as an associated feature of ES or related variants. OBSERVATIONS: The authors describe two cases of an atypical "winged" variant with SAN palsy resulting from compression by a posteriorly angulated or calcified styloid process. Both patients exhibited lateral scapular winging and atrophy of the trapezius and sternocleidomastoid muscles. Electrophysiological studies demonstrated motor unit preservation; therefore, surgical exploration, styloidectomy, and SAN decompression were performed through a transcervical approach. Postoperatively, both patients had improvements in pain and shoulder mobility, the return of muscle strength, and electrophysiological evidence of trapezius reinnervation. LESSONS: Compression of the SAN, which can be identified both clinically and on electrodiagnostic testing, is an atypical finding that can result from a posteriorly angulated or calcified styloid process. This winged variant of ES should be included in the differential for SAN palsy, and a multidisciplinary approach is recommended for assessment and management.

Gender Equality in Plastic Surgery Training: A Canadian Nationwide Cross-sectional Analysis.

Introduction: One of the important factors in achieving gender equity is ensuring equitable surgical training for all. Previous studies have shown that females get significantly lower surgical exposure than males in certain surgical specialties. Gender gap in surgical exposure has never been assessed in plastic surgery. To that end, the goal of this study was to assess if there are any differences in plastic surgery training between male and female residents. Methods: A survey was sent to all plastic surgery residency programs in Canada to assess the No. of surgeries residents operated on as a co-surgeon or primary assistant during their training. The survey also assessed career goals, level of interest in the specialty, and subjective perception of gender bias. Results: A total of 89 plastic surgery residents (59.3% participation rate) completed the survey and were included in the study. The average No. of reconstructive cases residents operated on as a co-surgeon or primary assistant was 245 ± 312 cases. There was no difference in either reconstructive or aesthetic surgery case logs between male and female residents (p > .05). However, a significantly larger proportion of females (39%) compared to males (4%) felt that their gender limited their exposure to surgical cases and led to a worsening of their overall surgical training (p < .001). Finally, a larger proportion of male residents were interested in academic careers while a larger proportion of female residents were interested in a community practice (p = .024). Conclusion: While there is no evidence of differences in the volume of logged cases between genders, female surgical residents still feel that their respective gender limits their overall surgical training. Gender inequalities in training should be addressed by residency programs.

Introduction: L'un des facteurs importants pour atteindre l'égalité des genres est d'assurer une formation chirurgicale équitable pour tous. Des études antérieures ont montré que les femmes ont une exposition significativement moindre à la chirurgie que les hommes dans certaines spécialités chirurgicales. L'écart entre genres pour l'exposition à la chirurgie n'a jamais été évalué en chirurgie plastique. À cette fin, la présente étude a eu pour objectif d'évaluer s'il y avait des différences dans la formation à la chirurgie plastique entre les résidents masculins et féminins. Méthodes: Une enquête a été envoyée à tous les programmes canadiens de résidence en chirurgie plastique pour évaluer le nombre d'interventions auxquelles les résidents ont participé en tant que co-chirurgien ou assistant principal au cours de leur formation. L'enquête a également évalué les objectifs de carrière, le niveau d'intérêt dans la spécialité et la perception subjective d'un biais lié au genre. Résultats: En tout, 89 résidents en chirurgie plastique (taux de participation de 59,3 %) ont répondu à l'enquête et ont été inclus dans l'étude. Le nombre moyen de cas de chirurgie reconstructrice au cours desquelles les résidents sont intervenus en tant que co-chirurgien ou principal assistant était de 245 ± 312 cas. Il n'y a pas eu de différence entre les journaux de cas, qu'il s'agisse de chirurgie reconstructrice ou de chirurgie esthétique entre résidents masculins et féminins (P > 0,05). Cependant, un nettement plus grand pourcentage de femmes (39 %) que d'hommes (4 %) estimait que leur genre limitait leur exposition à des cas chirurgicaux et résultait dans une aggravation de leur formation globale à la chirurgie (P < 0,001). Enfin, un plus grand pourcentage de résidents masculins était intéressé par une carrière universitaire alors qu'un plus grand pourcentage de résidentes était intéressé par une pratique dans la communauté (P = 0,024). Conclusion: Bien qu'il n'y ait pas de données probantes étayant des différences de volume des cas consignés entre les genres, les résidentes féminines en chirurgie pensent encore que leur genre limite leur formation chirurgicale. Les inégalités entre genres devraient être abordées par les programmes de résidence.

CAVE: Connectome Annotation Versioning Engine.

Advances in Electron Microscopy, image segmentation and computational infrastructure have given rise to large-scale and richly annotated connectomic datasets which are increasingly shared across communities. To enable collaboration, users need to be able to concurrently create new annotations and correct errors in the automated segmentation by proofreading. In large datasets, every proofreading edit relabels cell identities of millions of voxels and thousands of annotations like synapses. For analysis, users require immediate and reproducible access to this constantly changing and expanding data landscape. Here, we present the Connectome Annotation Versioning Engine (CAVE), a computational infrastructure for immediate and reproducible connectome analysis in up-to petascale datasets (~1mm3) while proofreading and annotating is ongoing. For segmentation, CAVE provides a distributed proofreading infrastructure for continuous versioning of large reconstructions. Annotations in CAVE are defined by locations such that they can be quickly assigned to the underlying segment which enables fast analysis queries of CAVE's data for arbitrary time points. CAVE supports schematized, extensible annotations, so that researchers can readily design novel annotation types. CAVE is already used for many connectomics datasets, including the largest datasets available to date.

Neuronal wiring diagram of an adult brain.

Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally. Here, we present the first neuronal wiring diagram of a whole adult brain, containing 5×107 chemical synapses between ~130,000 neurons reconstructed from a female Drosophila melanogaster. The resource also incorporates annotations of cell classes and types, nerves, hemilineages, and predictions of neurotransmitter identities. Data products are available by download, programmatic access, and interactive browsing and made interoperable with other fly data resources. We show how to derive a projectome, a map of projections between regions, from the connectome. We demonstrate the tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine, and descending neurons), across both hemispheres, and between the central brain and the optic lobes. Tracing from a subset of photoreceptors all the way to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviors. The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species.

NEURD: automated proofreading and feature extraction for connectomics.

We are now in the era of millimeter-scale electron microscopy (EM) volumes collected at nanometer resolution (Shapson-Coe et al., 2021; Consortium et al., 2021). Dense reconstruction of cellular compartments in these EM volumes has been enabled by recent advances in Machine Learning (ML) (Lee et al., 2017; Wu et al., 2021; Lu et al., 2021; Macrina et al., 2021). Automated segmentation methods can now yield exceptionally accurate reconstructions of cells, but despite this accuracy, laborious post-hoc proofreading is still required to generate large connectomes free of merge and split errors. The elaborate 3-D meshes of neurons produced by these segmentations contain detailed morphological information, from the diameter, shape, and branching patterns of axons and dendrites, down to the fine-scale structure of dendritic spines. However, extracting information about these features can require substantial effort to piece together existing tools into custom workflows. Building on existing open-source software for mesh manipulation, here we present "NEURD", a software package that decomposes each meshed neuron into a compact and extensively-annotated graph representation. With these feature-rich graphs, we implement workflows for state of the art automated post-hoc proofreading of merge errors, cell classification, spine detection, axon-dendritic proximities, and other features that can enable many downstream analyses of neural morphology and connectivity. NEURD can make these new massive and complex datasets more accessible to neuroscience researchers focused on a variety of scientific questions.

Functional connectomics reveals general wiring rule in mouse visual cortex.

To understand how the brain computes, it is important to unravel the relationship between circuit connectivity and function. Previous research has shown that excitatory neurons in layer 2/3 of the primary visual cortex of mice with similar response properties are more likely to form connections. However, technical challenges of combining synaptic connectivity and functional measurements have limited these studies to few, highly local connections. Utilizing the millimeter scale and nanometer resolution of the MICrONS dataset, we studied the connectivity-function relationship in excitatory neurons of the mouse visual cortex across interlaminar and interarea projections, assessing connection selectivity at the coarse axon trajectory and fine synaptic formation levels. A digital twin model of this mouse, that accurately predicted responses to arbitrary video stimuli, enabled a comprehensive characterization of the function of neurons. We found that neurons with highly correlated responses to natural videos tended to be connected with each other, not only within the same cortical area but also across multiple layers and visual areas, including feedforward and feedback connections, whereas we did not find that orientation preference predicted connectivity. The digital twin model separated each neuron's tuning into a feature component (what the neuron responds to) and a spatial component (where the neuron's receptive field is located). We show that the feature, but not the spatial component, predicted which neurons were connected at the fine synaptic scale. Together, our results demonstrate the "like-to-like" connectivity rule generalizes to multiple connection types, and the rich MICrONS dataset is suitable to further refine a mechanistic understanding of circuit structure and function.

Strength Comparison of Fibrin Glue and Suture Constructs in Upper Extremity Peripheral Nerve Coaptations: An In Vitro Study.

PURPOSE: To compare in vitro failure loads of nerve coaptations using fibrin glue alone, a suture alone, and a combination of fibrin glue and a suture. METHODS: The median, radial, and ulnar nerves of 15 fresh-frozen cadaveric upper extremity specimens (45 nerves in total) were dissected in vitro and transected 5 cm proximal to the wrist crease to simulate an injury requiring coaptation. Three coaptation techniques were used: fibrin glue alone, a suture alone, and a suture augmented with fibrin glue. The load to failure of each repair was measured using a linear servo-actuator with an in-line force sensor. The results were analyzed using 2-way repeated measures analysis of variance tests and pairwise comparisons with Bonferroni correction. RESULTS: Both the nerve coaptation technique and the specific nerve that was repaired had a significant effect on failure load. Suture-glue repair had the highest load to failure, 11.2 ± 2.9 N, and significantly increased the load to failure by 2.9 ± 1.7 N compared with glue repair alone. There was no significant difference between suture-glue repair and suture repair alone or between glue repair alone and suture repair alone. CONCLUSIONS: In this in vitro cadaveric model, nerve injury coaptation using both a suture and fibrin glue resulted in the strongest repair. The addition of fibrin glue may provide some benefit when used to augment suture repair, but when used in isolation, it is inferior to combined suture-and-glue constructs. CLINICAL RELEVANCE: Combined suture-and-glue nerve coaptations might be useful in the early postoperative period in increasing nerve repair strength and potentially reducing rupture rates.

The Effect of Flexor Digitorum Profundus Repair Position Relative to Camper Chiasm on Tendon Biomechanics.

PURPOSE: The purpose of this study was to investigate the impact of repairing a zone II flexor digitorum profundus (FDP) laceration anatomically versus extra-anatomically on tendon loads and work of flexion (WOF). METHODS: Twenty digits from 5 cadaveric specimens were tested using an in vitro active finger motion simulator under 2 FDP tendon repair conditions: anatomic and extra-anatomic. Tensile loads in FDP and flexor digitorum superficialis (FDS), WOF, and total active finger range of motion (ROM) were measured using in-line load cells and electromagnetic tracking, respectively. RESULTS: The anatomic repairs had no effect on tendon loads or WOF for either FDP or FDS. The extra-anatomic repairs increased FDP loads by 32% and decreased FDS loads by 9% compared with those in the intact condition. This pattern was similar for WOF following extra-anatomic repairs, which increased FDP WOF by 31% and decreased FDS WOF by 18%. Comparing the 2 repairs, FDP loads and WOF were 25% and 22% greater, respectively, with extra-anatomic repairs compared with anatomic repairs, with no significant change in FDS. Total active ROM was not affected by either repair. CONCLUSIONS: In this in vitro cadaveric model, extra-anatomic repairs of FDP increased tendon loads and WOF compared with anatomic repairs. CLINICAL RELEVANCE: On the basis of this study, reconstitution of the anatomic relationship of FDP and FDS at the Camper chiasm during the repair of zone II flexor tendon lacerations is recommended.

The Evaluation of a Flexor Digitorum Profundus-to-Volar Plate Zone I Repair Versus Button Repair: An In vitro Biomechanics Study.

PURPOSE: The purpose of the study was to evaluate joint kinematics and tendon work of flexion (WOF) following a flexor digitorum profundus (FDP)-to-volar plate (VP) repair technique relative to a pullout button for zone I flexor tendon injuries. METHODS: Fourteen digits were tested using an in vitro active finger motion simulator under 3 repaired conditions following a simulated zone I avulsion: button, FDP-VP, and "no slack" FDP-VP (corrected for additional VP length). Outcome metrics included active joint range of motion (ROM), fingertip strength, FDP and flexor digitorum superficialis tensile loads, and WOF. RESULTS: The button and FDP-VP techniques restored WOF to the intact condition for FDP and flexor digitorum superficialis. All repairs restored distal interphalangeal joint ROM and kinematics to the intact condition. Similarly, all repairs restored WOF; however, the "no slack" FDP-VP significantly increased WOF by 10% to 12% over the simple FDP-VP repair. The button technique had similar fingertip strength to the intact condition, whereas the FDP-VP repairs significantly reduced peak fingertip strength from intact, albeit only 1-2 N compared with the button repair. CONCLUSION: In this in vitro cadaveric model, the button and FDP-VP techniques restored WOF and ROM to within intact levels, with no difference between these repairs in all measured outcome metrics. CLINICAL RELEVANCE: Based on its initial strength and its equal biomechanical performance compared with the button repair, the FDP-VP technique may be a viable option for treating FDP avulsions.

FlyWire: online community for whole-brain connectomics.

Due to advances in automated image acquisition and analysis, whole-brain connectomes with 100,000 or more neurons are on the horizon. Proofreading of whole-brain automated reconstructions will require many person-years of effort, due to the huge volumes of data involved. Here we present FlyWire, an online community for proofreading neural circuits in a Drosophila melanogaster brain and explain how its computational and social structures are organized to scale up to whole-brain connectomics. Browser-based three-dimensional interactive segmentation by collaborative editing of a spatially chunked supervoxel graph makes it possible to distribute proofreading to individuals located virtually anywhere in the world. Information in the edit history is programmatically accessible for a variety of uses such as estimating proofreading accuracy or building incentive systems. An open community accelerates proofreading by recruiting more participants and accelerates scientific discovery by requiring information sharing. We demonstrate how FlyWire enables circuit analysis by reconstructing and analyzing the connectome of mechanosensory neurons.

In Vivo Non-Thermal, Selective Cancer Treatment With High-Frequency Medium-Intensity Focused Ultrasound.

Focused ultrasound (FUS) has proven its efficacy in non-invasive, radiation-free cancer treatment. However, the commonly used low-frequency high-intensity focused ultrasound (HIFU) destroys both cancerous and healthy tissues non-specifically through extreme heat and inertial cavitation with low spatial resolution. To address this issue, we evaluate the therapeutic effects of pulsed (60 Hz pulse repetition frequency, 1.45 ms pulse width) high-frequency (20.7 MHz) medium-intensity (spatial-peak pulse-average intensity ISPPA < 279.1 W/cm2, spatial-peak temporal-average intensity ISPTA < 24.3 W/cm2) focused ultrasound (pHFMIFU) for selective cancer treatment without thermal damage and with low risk of inertial cavitation (mechanical index < 0.66), in an in vivo subcutaneous B16F10 melanoma tumor growth model in mice. The pHFMIFU with 104 µm focal diameter is generated by a microfabricated self-focusing acoustic transducer (SFAT) with a Fresnel acoustic lens. A three-axis positioning system has been developed for automatic scanning of the transducer to cover a larger treatment volume, while a water-cooling system is custom-built for dissipating non-acoustic heat from the transducer surface. Initial testing revealed that pHFMIFU treatment can be applied to a living animal while maintaining skin temperature under 35.6 °C without damaging normal skin and tissue. After eleven days of treatment with pHFMIFU, the treated tumors were significantly smaller with large areas of necrosis and apoptosis in the treatment field compared to untreated controls. Potential mechanisms of this selective, non-thermal killing effect, as well as possible causes of and solutions to the variation in treatment results, have been analyzed and proposed. The pHFMIFU could potentially be used as a new therapeutic modality for safer cancer treatment especially in critical body regions, due to its cancer-specific effects and high spatial resolution.

Hoarding and obsessive-compulsive behaviours in frontotemporal dementia: Clinical and neuroanatomic associations.

BACKGROUND: Hoarding and obsessive-compulsive behaviours (OCB) are well documented symptoms in frontotemporal dementia (FTD). While contemporary models consider hoarding and obsessive-compulsive disorder distinct, the related behaviours have not been separately examined in patients with FTD, and the neuroanatomical correlates of hoarding in patients with FTD have not been previously examined (American Psychiatric Association, 2013; Grisham and Baldwin, 2015; Mataix-Cols et al., 2010). METHODS: Patients with FTD who were evaluated between 2004 and 2018 at our centre were included. Cortical thickness and subcortical volumetric analyses were completed on available T1 high resolution anatomic scans using FreeSurfer. RESULTS: Eighty-seven patients met inclusion criteria, and 49 had scans available for quantitative MRI volumetric analysis. New hoarding behaviours were present in 29% of patients and were more common in the semantic variant subtype of FTD, while 49% of individuals had new or increased OCB. Hoarding behaviours were associated with decreased thickness in a factor comprised of left temporal, insular and anterior cingulate cortices. The presence of OCB was predicted by reduced cortical thickness and volumes in a factor comprised of the anterior cingulate and subcortical volumes in the bilateral amygdala and hippocampus. OCB were associated with greater right temporal cortical thickness in comparison to patients with hoarding. DISCUSSION: The association of the semantic variant with hoarding, together with the observed associations between left temporal atrophy and hoarding indicate that degeneration of the left temporal lobe has a role in the emergence of hoarding in FTD. As in current models of Hoarding disorder and Obsessive-Compulsive disorder, our results suggest that in patients with FTD, hoarding and OCB are clinically and anatomically partially dissociable phenomenon. The results may also help to further elucidate the cognitive processes and neural networks contributing to Hoarding disorder and Obsessive-Compulsive disorder in persons without dementia.

Esophagectomy in Patients with Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome: A Viable Option.

The objective of this study was to assess the outcomes for patients with human immunodeficiency virus (HIV) and acquired immune deficiency virus (AIDS) who had esophagectomy done for both benign and malignant conditions. A retrospective chart review of patients with HIV and AIDS undergoing esophagectomy at a rural referral hospital was done for the period of 2009-2014. Patient postoperative complications, outcomes, and follow-up data were charted. All procedures were done by a single lead surgeon. Nine patients met the study criteria, 7 of whom had esophageal cancer, and 2 with strictures. Four patients had received nutritional self-expanding metal stent preoperatively. The mean stent duration was 61 days. Three patients had been on antiretroviral therapy before surgery. Preoperative CD4 counts were available in 7 patients. Eight patients underwent a 3-field esophagectomy and 1 was unresectable. Seven of these patients had successful outcomes, with varying follow-up times. One patient died post procedure while in the hospital. Complications included stricture and anastomotic leak. Although HIV-positive patients face increased risk during surgical procedures, this status should not be a firm contraindication to surgery. Quality nutritional status, antiretroviral use, and overall CD4 count levels remain important parameters in considering surgical treatment for these patients. With careful patient evaluation and planning, esophagectomy in an HIV and AIDS setting is feasible with successful outcomes.

Alu repeats as transcriptional regulatory platforms in macrophage responses to M. tuberculosis infection.

To understand the epigenetic regulation of transcriptional response of macrophages during early-stage M. tuberculosis (Mtb) infection, we performed ChIPseq analysis of H3K4 monomethylation (H3K4me1), a marker of poised or active enhancers. De novo H3K4me1 peaks in infected cells were associated with genes implicated in host defenses and apoptosis. Our analysis revealed that 40% of de novo regions contained human/primate-specific Alu transposable elements, enriched in the AluJ and S subtypes. These contained several transcription factor binding sites, including those for members of the MEF2 and ATF families, and LXR and RAR nuclear receptors, all of which have been implicated in macrophage differentiation, survival, and responses to stress and infection. Combining bioinformatics, molecular genetics, and biochemical approaches, we linked genes adjacent to H3K4me1-associated Alu repeats to macrophage metabolic responses against Mtb infection. In particular, we show that LXRα signaling, which reduced Mtb viability 18-fold by altering cholesterol metabolism and enhancing macrophage apoptosis, can be initiated at response elements present in Alu repeats. These studies decipher the mechanism of early macrophage transcriptional responses to Mtb, highlighting the role of Alu element transposition in shaping human transcription programs during innate immunity.