Male ductal carcinoma in situ: diagnosis and management of a rare disease in men.

Ductal carcinoma in situ is very rare in male patients, accounting for approximately 5%-7% of all male breast cancers. We present a case of a man in his early 70s who presented with bloody nipple discharge and gynaecomastia and was subsequently diagnosed with ductal carcinoma in situ (DCIS). We discuss his management with surgical resection and the consideration of adjuvant treatment. We also review the existing literature on the presentation, diagnosis and management of DCIS in men.

A Prospective Study Measuring Resident and Faculty Contour Concordance: A Potential Tool for Quantitative Assessment of Residents' Performance in Contouring and Target Delineation in Radiation Oncology Residency.

PURPOSE/OBJECTIVE(S): Accurate target delineation (ie, contouring) is essential for radiation treatment planning and radiotherapy efficacy. As a result, improving the quality of target delineation is an important goal in the education of radiation oncology residents. The purpose of this study was to track the concordance of radiation oncology residents' contours with those of faculty physicians over the course of 1 year to assess for patterns. MATERIALS/METHODS: Residents in postgraduate year (PGY) levels 2 to 4 were asked to contour target volumes that were then compared to the finalized, faculty physician-approved contours. Concordance between resident and faculty physician contours was determined by calculating the Jaccard concordance index (JCI), ranging from 0, meaning no agreement, to 1, meaning complete agreement. Multivariate mixed-effect models were used to assess the association of JCI to the fixed effect of PGY level and its interactions with cancer type and other baseline characteristics. Post hoc means of JCI were compared between PGY levels after accounting for multiple comparisons using Tukey's method. RESULTS: In total, 958 structures from 314 patients collected during the 2020-2021 academic year were studied. The mean JCI was 0.77, 0.75, and 0.61 for the PGY-4, PGY-3, and PGY-2 levels, respectively. The JCI score for PGY-2 was found to be lower than those for PGY-3 and PGY-4, respectively (all P < .001). No statistically significant difference of JCI score was found between the PGY-3 and PGY-4 levels. The average JCI score was lowest (0.51) for primary head and/or neck cancers, and it was highest (0.80) for gynecologic cancers. CONCLUSIONS: Tracking and comparing the concordance of resident contours with faculty physician contours is an intriguing method of assessing resident performance in contouring and target delineation and could potentially serve as a quantitative metric, which is lacking currently, in radiation oncology resident evaluation. However, additional study is necessary before this technique can be incorporated into residency assessments.

What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study's patient-level data with fidelity to the original research protocol.

OBJECTIVE: Reanalyse the patient-level data set of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with fidelity to the original research protocol and related publications. DESIGN: The study was open label and semirandomised examining the effectiveness of up to four optimised and increasingly aggressive, antidepressant therapies in depressed adults. Patients who failed to gain adequate relief from their level 1 trial on the SSRI citalopram could receive up to three additional treatment trials in levels 2-4. SETTING: 41 North American psychiatry and primary care treatment centres. PARTICIPANTS: 4041 adults screened positive for major depressive disorder. In contrast to most clinical trials, STAR*D enrolled patients seeking care (vs recruited) and included patients with a wide range of common comorbid medical and psychiatric conditions to enhance the generalisability of findings to real-world clinical practice. INTERVENTIONS: STAR*D evaluated the relative effectiveness of 13 antidepressants therapies in treatment levels 2-4 for depressed patients who failed to gain adequate benefit from their level 1 medication trial. MAIN OUTCOME MEASURES: According to the STAR*D protocol, the primary outcome was remission, defined as a score <8 on the blinded Hamilton Rating Scale for Depression (HRSD). Response was a secondary outcome defined as ≥50% reduction in HRSD scores. STAR*D's protocol specifically excluded all non-blinded clinic-administered assessments from use as research outcome measures. RESULTS: STAR*D investigators did not use the protocol-stipulated HRSD to report cumulative remission and response rates in their summary article and instead used a non-blinded clinic-administered assessment. This inflated their report of outcomes, as did their inclusion of 99 patients who scored as remitted on the HRSD at study outset as well as 125 who scored as remitted when initiating their next-level treatment. These patients should have been excluded from data analysis. In contrast to the STAR*D-reported 67% cumulative remission rate after up to four antidepressant treatment trials, the rate was 35.0% when using the protocol-stipulated HRSD and inclusion in data analysis criteria. CONCLUSION: STAR*D's cumulative remission rate was approximately half of that reported.

The EMory BrEast imaging Dataset (EMBED): A Racially Diverse, Granular Dataset of 3.4 Million Screening and Diagnostic Mammographic Images.

Supplemental material is available for this article. Keywords: Mammography, Breast, Machine Learning © RSNA, 2023.

Effectiveness and safety of monoamine oxidase inhibitor treatment for bipolar depression versus unipolar depression: An exploratory case cohort study.

OBJECTIVE: Patients with bipolar disorder spend most of their clinical lifetime in the depressive phase of their illness. However, antidepressants are discouraged in the treatment of bipolar depression due to concerns over manic induction and drug ineffectiveness. Some reports suggest that monoamine oxidase inhibitors (MAOIs) may be safe and effective compared to other antidepressants in treating bipolar depression. The present study compared the safety and effectiveness of MAOI therapy in patients with bipolar versus unipolar depression. METHODS: Data were collected from approximately 2500 clinical research charts of patients treated with MAOI therapy at a university mood disorder clinic between 1983 and 2015. A mixed-effects model was created with patient entered as the random effect. The model included the primary diagnosis (i.e., either unipolar or bipolar depression) and other clinical covariates as fixed-effect predictors. RESULTS: Patients with bipolar depression demonstrated lower post-treatment clinical global impressions/severity scores versus patients with unipolar depression (p = 0.04). Neither group demonstrated a full syndromal manic or hypomanic episode. A higher proportion of patients with bipolar depression reported myoclonic tics and tremors, which may have resulted from concomitant lithium use. Amongst the covariates, only the number of prior antidepressant trials predicted poorer outcomes from MAOI therapy. CONCLUSION: MAOIs may be more effective-and as safe-for patients with bipolar depression versus unipolar depression. Future studies should explore this possible advantage using a larger sample size.

Targeting acetyl-CoA metabolism attenuates the formation of fear memories through reduced activity-dependent histone acetylation.

Histone acetylation is a key component in the consolidation of long-term fear memories. Histone acetylation is fueled by acetyl-coenzyme A (acetyl-CoA), and recently, nuclear-localized metabolic enzymes that produce this metabolite have emerged as direct and local regulators of chromatin. In particular, acetyl-CoA synthetase 2 (ACSS2) mediates histone acetylation in the mouse hippocampus. However, whether ACSS2 regulates long-term fear memory remains to be determined. Here, we show that Acss2 knockout is well tolerated in mice, yet the Acss2-null mouse exhibits reduced acquisition of long-term fear memory. Loss of Acss2 leads to reductions in both histone acetylation and expression of critical learning and memory-related genes in the dorsal hippocampus, specifically following fear conditioning. Furthermore, systemic administration of blood-brain barrier-permeable Acss2 inhibitors during the consolidation window reduces fear-memory formation in mice and rats and reduces anxiety in a predator-scent stress paradigm. Our findings suggest that nuclear acetyl-CoA metabolism via ACSS2 plays a critical, previously unappreciated, role in the formation of fear memories.

Adult hippocampal neurogenesis and its impairment in Alzheimer's disease.

Adult neurogenesis is the creation of new neurons which integrate into the existing neural circuit of the adult brain. Recent evidence suggests that adult hippocampal neurogenesis (AHN) persists throughout life in mammals, including humans. These newborn neurons have been implicated to have a crucial role in brain functions such as learning and memory. Importantly, studies have also found that hippocampal neurogenesis is impaired in neurodegenerative and neuropsychiatric diseases. Alzheimer's disease (AD) is one of the most common forms of dementia affecting millions of people. Cognitive dysfunction is a common symptom of AD patients and progressive memory loss has been attributed to the degeneration of the hippocampus. Therefore, there has been growing interest in identifying how hippocampal neurogenesis is affected in AD. However, the link between cognitive decline and changes in hippocampal neurogenesis in AD is poorly understood. In this review, we summarized the recent literature on AHN and its impairments in AD.

High-dose-rate interstitial brachytherapy vs external beam radiation for the treatment of complex keloids.

Postoperative external beam radiation therapy (EBRT) with superficial X-rays or electrons and high-dose-rate brachytherapy (HDR BT) are both viable options for managing keloid scars. However, complex keloid scars are especially challenging to manage. We aim to compare the benefit and challenges between interstitial HDR BT and electron EBRT in treating the complex keloids. Three patients with 7 complex keloids: 3 jaw lines, 1 postauricular, 1 posterior neck, and 2 chest walls are included in this study. All patients are treated to 6 Gy x 3 fractions with HDR BT using the flexible interstitial catheters, and electron EBRT plans were created retrospectively for dosimetric comparison. The average D90 is 21.8 ± 8.3 Gy (1 SD) (121%) and 16.9 ± 1.9 Gy (1SD) (94%) in HDR and EBRT plans, respectively. The average treatment time was 7 minutes per patient (range: 6 - 8.5 minutes) for the HDR BT. Dosimetric comparison reveals that HDR plans provide superior coverage to the keloid scars than the EBRT plans. Clinical workflow is streamlined with HDR procedures. The cosmetic outcome with the interstitial HDR BT is satisfactory.

Mapping Female Patients' Judgments of Satisfaction to Hypothetical Changes in Depression Symptom Severity.

Within mental health, approaches to determine whether a patient experienced "meaningful" change from treatment have predominantly involved imposing thresholds on three types of metrics derived from assessments of symptom severity: end score (posttreatment score), absolute change (pre- minus posttreatment score), and proportion of change. However, none of these approaches have considered input from the consumer. This study examined correspondences between various reductions from pre- to posttreatment symptom severity levels and patients' judgments of satisfaction with change. Former or currently depressed patients were asked to provide judgments of their satisfaction reflected in vignettes that used descriptions from the Hamilton Rating Scale for Depression. Judgments from 108 female participants were fit using four metrics: end score, absolute change, proportion of change, and the combination of end score and absolute change. Akaike information criteria (AICs) and Akaike weights were used to determine the best-fitting model. Cutoffs were calculated for the five levels of satisfaction with change. Proportion of change best accounted for variation in the patients' ratings. For "slightly … ," "somewhat … ," "moderately … ," and "very … ," the proportions of reduction that corresponded with each of these ratings of satisfaction were, respectively: 17%, 39%, 62%, and 84%. Our a priori level of satisfaction (between "somewhat" and "moderately") corresponded to a 50% reduction in pretreatment severity. This study may provide services some insight into their female patients' satisfaction with change from treatment for depression using only the proportion of reduction from pretreatment severity. A similar procedure could be applied to other diagnostic groups, as well as other constructs that attend to the patient's perspective.

Synthesis and Reactivity of 1-Hydroxyherquline A.

Herein, we present the synthesis of 1-hydroxyherquline A and describe its reactivity discovered during its attempted conversion to herquline A, a long-sought natural product target in the synthetic chemical community. The strategic installation of the C1 hydroxyl group enabled the key aza-Michael addition-mediated N10-C2 bond formation and eventually access to 1-hydroxyherquline A, the most advanced herquline A congener reported to date. Our attempted reductive transformation of 1-hydroxyherquline A to herquline A was challenged by the extremely strained bowl-shaped pentacyclic structures of key precursors that prevented either radical formation at C1 or protonation (or hydrogenation) from the desired face. These discoveries regarding the innate chemical reactivities of advanced intermediates toward herquline A may prove useful in efforts toward this formidable target.

Optimizing risk-based breast cancer screening policies with reinforcement learning.

Screening programs must balance the benefit of early detection with the cost of overscreening. Here, we introduce a novel reinforcement learning-based framework for personalized screening, Tempo, and demonstrate its efficacy in the context of breast cancer. We trained our risk-based screening policies on a large screening mammography dataset from Massachusetts General Hospital (MGH; USA) and validated this dataset in held-out patients from MGH and external datasets from Emory University (Emory; USA), Karolinska Institute (Karolinska; Sweden) and Chang Gung Memorial Hospital (CGMH; Taiwan). Across all test sets, we find that the Tempo policy combined with an image-based artificial intelligence (AI) risk model is significantly more efficient than current regimens used in clinical practice in terms of simulated early detection per screen frequency. Moreover, we show that the same Tempo policy can be easily adapted to a wide range of possible screening preferences, allowing clinicians to select their desired trade-off between early detection and screening costs without training new policies. Finally, we demonstrate that Tempo policies based on AI-based risk models outperform Tempo policies based on less accurate clinical risk models. Altogether, our results show that pairing AI-based risk models with agile AI-designed screening policies has the potential to improve screening programs by advancing early detection while reducing overscreening.

Development of a Telemedicine Screening Program During the COVID-19 Pandemic.

Background: Telemedicine use increased during the COVID-19 pandemic due to concerns for patient and provider safety. Given the lack of testing resources initially and the large geographical range served by Augusta University (AU), a telemedicine platform with up-to-date screening guidelines was implemented for COVID-19 testing in March 2020. Our objective was to understand the level of adherence to telemedicine screening guidelines for COVID-19. Methods: The study population included health care providers and population who participated in an encounter in the AU Health Express Care virtual care program from March 22 to May 21, 2020. All encounters were intended to be for COVID-19 screening, free, and available 24 h per day, 7 days per week. Screening guidelines were developed by AU based on information from the Centers for Disease Control and Prevention and the Georgia Department of Public Health. Results: Among 17,801 total encounters, 13,600 were included in the final analysis. Overall adherence to screening guidelines was 71% in the adult population and 57% in the pediatric population. When providers did not follow guidelines, 72% determined that the patient should have a positive screen. Guidelines themselves determined that only 52% of encounters should have a positive screen. Providers' specialty significantly correlated with guideline adherence (p = 0.002). Departments with the highest adherence were psychiatry, neurology, and ophthalmology. No significant correlation was found between guideline adherence and provider degree/position. Conclusions: This study provides proof of concept of a free telehealth screening platform during an ongoing pandemic. Our screening experience was effective and different specialties participated. Our patient population lived in lower than average income zip codes, suggesting that our free telemedicine screening program successfully reached populations with higher financial barriers to health care. Early training and a posteriori knowledge of telemedicine was likely key to screening guideline adherence.

Multi-Institutional Validation of a Mammography-Based Breast Cancer Risk Model.

PURPOSE: Accurate risk assessment is essential for the success of population screening programs in breast cancer. Models with high sensitivity and specificity would enable programs to target more elaborate screening efforts to high-risk populations, while minimizing overtreatment for the rest. Artificial intelligence (AI)-based risk models have demonstrated a significant advance over risk models used today in clinical practice. However, the responsible deployment of novel AI requires careful validation across diverse populations. To this end, we validate our AI-based model, Mirai, across globally diverse screening populations. METHODS: We collected screening mammograms and pathology-confirmed breast cancer outcomes from Massachusetts General Hospital, USA; Novant, USA; Emory, USA; Maccabi-Assuta, Israel; Karolinska, Sweden; Chang Gung Memorial Hospital, Taiwan; and Barretos, Brazil. We evaluated Uno's concordance index for Mirai in predicting risk of breast cancer at one to five years from the mammogram. RESULTS: A total of 128,793 mammograms from 62,185 patients were collected across the seven sites, of which 3,815 were followed by a cancer diagnosis within 5 years. Mirai obtained concordance indices of 0.75 (95% CI, 0.72 to 0.78), 0.75 (95% CI, 0.70 to 0.80), 0.77 (95% CI, 0.75 to 0.79), 0.77 (95% CI, 0.73 to 0.81), 0.81 (95% CI, 0.79 to 0.82), 0.79 (95% CI, 0.76 to 0.83), and 0.84 (95% CI, 0.81 to 0.88) at Massachusetts General Hospital, Novant, Emory, Maccabi-Assuta, Karolinska, Chang Gung Memorial Hospital, and Barretos, respectively. CONCLUSION: Mirai, a mammography-based risk model, maintained its accuracy across globally diverse test sets from seven hospitals across five countries. This is the broadest validation to date of an AI-based breast cancer model and suggests that the technology can offer broad and equitable improvements in care.

Patients' judgments of the importance of treatment-induced reductions in symptoms of depression: The role of specific symptoms, magnitudes of change, and post-treatment levels.

Objective: An implicit assumption in the use of depressive severity measures to assess change during treatment, such as the Hamilton Rating Scale for Depression (HRSD), is that reductions from pre- to post-treatment that are equal to each other are of equal value. However, stakeholders' valuations of changes might depart substantially from this assumption. Method: Vignettes were constructed that reflected the six possible 1, 2, and 3-point reductions on five cognitive and four somatic symptoms derived from the HRSD. Former or currently depressed patients provided judgments of the importance of the symptom reductions. Mean importance ratings were modeled using symptom category and the pre/post-treatment combination. Differences were explored using the Tukey method. Results: Results indicated that mean ratings, from most to least important, were: Anxiety, Suicide, Depressed Mood, Work, and Guilt (the cognitive symptoms) followed by Somatic, Sleep, Appetite & Weight, and Retardation (the somatic symptoms). Participants valued reductions that resulted in posttreatment scores of zero more than expected, given the magnitude of the reductions. Conclusions: The value of reductions in symptoms captured by the HRSD, as judged by patients, appears to differ as a function of symptom category and the post-treatment score. Similar patterns might characterize other measures of depression severity.

The Nature, Timing, and Symptom Trajectories of Dropout From Transdiagnostic and Single-Diagnosis Cognitive-Behavioral Therapy for Anxiety Disorders.

Dropout from psychotherapy is common and can have negative effects for patients, providers, and researchers. A better understanding of when and why patients stop treatment early, as well as actionable factors contributing to dropout, has the potential to prevent it. Here, we examined dropout from a large randomized controlled trial of transdiagnostic versus single-diagnosis cognitive-behavioral treatment (CBT) for patients with anxiety disorders (n = 179; Barlow et al., 2017). We aimed to characterize the timing of and reasons for dropout and test whether participants who dropped out had different symptom trajectories than those who completed treatment. Results indicated that overall, the greatest risk of dropout was prior to the first treatment session. In single-diagnosis CBT, dropout risk was particularly elevated before the first session and after other early sessions, whereas in transdiagnostic CBT, dropout risk was low and stable before and during treatment. Participants most often dropped out due to failure to comply with study procedures or dissatisfaction with or desiring alternative treatment. Results from multilevel models showed that trajectories of anxiety symptoms did not significantly differ between dropouts and completers. These findings suggest that there may be specific time windows for targeted and timely interventions to prevent dropout from CBT.

Broad-Spectrum Antibiotic Use and Disease Progression in Early-Stage Melanoma Patients: A Retrospective Cohort Study.

Animal studies and a few clinical studies have reported mixed findings on the association between antibiotics and cancer incidence. Antibiotics may inhibit tumor cell growth, but could also alter the gut-microbiome-modulated immune system and increase the risk of cancer. Studies that assess how antibiotics affect the progression of cancer are limited. We evaluated the association between broad-spectrum antibiotic use and melanoma progression. We conducted a retrospective cohort study using IQVIA PharMetrics® Plus data (2008-2018). We identified patients with malignant melanoma who underwent wide local excision or Mohs micrographic surgery within 90 days of first diagnosis. Surgery date was the index date. Patients were excluded if they had any other cancer diagnosis or autoimmune disorders in 1 year before the index date ("baseline"). Exposure to broad-spectrum antibiotics was identified in three time windows using three cohorts: 3 months prior to the index date, 1 month after the index date, and 3 months after the index date. The covariates were patients' demographic and clinical characteristics identified in the 1-year baseline period. The patients were followed from the index date until cancer progression, loss of enrollment, or the end of 2 years after the index date. Progression was defined as: (i) any hospice care after surgery, (ii) a new round of treatment for melanoma (surgery, chemotherapy, immunotherapy, targeted therapy, or radiotherapy) 180 days after prior treatment, or (iii) a metastasis diagnosis or a diagnosis of a new nonmelanoma primary cancer at least 180 days after first melanoma diagnosis or prior treatment. A high-dimensional propensity score approach with inverse weighting was used to adjust for the patients' baseline differences. Cox proportional hazard regression was used for estimating the association. The final samples included 3930, 3831, and 3587 patients (mean age: 56 years). Exposure to antibiotics was 16% in the prior-3-months, 22% in the post-1-month, and 22% in the post-3-months. In the pre-3-months analysis, 9% of the exposed group and 9% of the unexposed group had progressed. Antibiotic use was not associated with melanoma progression (HR: 0.81; 95% CI: 0.57-1.14). However, antibiotic use in subsequent 1 month and subsequent 3 months was associated with 31% reduction (HR: 0.69; 95% CI: 0.51-0.92) and 32% reduction (HR: 0.68; 95% CI: 0.51-0.91) in progression, respectively. In this cohort of patients with likely early-stage melanoma cancer, antibiotic use in 1 month and 3 months after melanoma surgery was associated with a lower risk of melanoma progression. Future studies are warranted to validate the findings.

Synthesis of Pentacyclic Framework of Herquline A.

The highly strained bowl-shaped pentacyclic structure of herquline A has rendered it one of the most difficult problems in organic synthesis yet to be solved. The challenges associated with the synthesis of herquline A have been well documented in four Ph.D. dissertations and in multiple reports regarding syntheses of its structurally simpler congeners. Herein, we report the construction of the pentacyclic core of herquline A that contains both N10-C2 and C3-C3' bonds. The key for success was the development of the tandem aza-Michael addition/enolate capture protocol that set the stage for subsequent palladium catalyzed C3(sp2 )-C3'(sp2 ) coupling reaction. Ensuing oxidative dearomatization of the left aryl ring allowed the formation of the pentacyclic diketone core of herquline A.

SCU-Net: A deep learning method for segmentation and quantification of breast arterial calcifications on mammograms.

PURPOSE: Measurements of breast arterial calcifications (BAC) can offer a personalized, non-invasive approach to risk-stratify women for cardiovascular diseases such as heart attack and stroke. We aim to detect and segment breast arterial calcifications in mammograms accurately and suggest novel measurements to quantify detected BAC for future clinical applications. METHODS: To separate BAC in mammograms, we propose a lightweight fine vessel segmentation method Simple Context U-Net (SCU-Net). Due to the large image size of mammograms, we adopt a patch-based way to train SCU-Net and obtain the final whole-image-size results by stitching patchwise results together. To further quantify calcifications, we test five quantitative metrics to inspect the progression of BAC for subjects: sum of mask probability metric ( P M ), sum of mask area metric ( A M ), sum of mask intensity metric ( S I M ), sum of mask area with threshold intensity metric T A M X , and sum of mask intensity with threshold X metric T S I M X . Finally, we demonstrate the ability of the metrics to longitudinally measure calcifications in a group of 26 subjects and evaluate our quantification metrics compared with calcified voxels and calcium mass on breast CT for 10 subjects. RESULTS: Our segmentation results are compared with state-of-the-art network architectures based on recall, precision, accuracy, F1 score/Dice score, and Jaccard index evaluation metrics and achieve corresponding values of 0.789, 0.708, 0.997, 0.729, and 0.581 for whole-image-size results. The quantification results all show >95% correlation between quantification measures on predicted masks of SCU-Net as compared to the groundtruth and measurement of calcification on breast CT. For the calcification quantification measurement, our calcification volume (voxels) results yield R2 -correlation values of 0.834, 0.843, 0.832, 0.798, and 0.800 for the P M , A M , S I M , T A M 100 , T S I M 100 metrics, respectively; our calcium mass results yield comparable R2 -correlation values of 0.866, 0.873, 0.840, 0.774, and 0.798 for the same metrics. CONCLUSIONS: Simple Context U-Net is a simple method to accurately segment arterial calcification retrospectively on routine mammograms. Quantification of the calcifications based on this segmentation in the retrospective cohort study has sufficient sensitivity to detect the normal progression over time and should be useful for future research and clinical applications.

Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease.

Dopamine (DA) is a behaviorally and clinically diverse neuromodulator that controls CNS function. DA plays major roles in many behaviors including locomotion, learning, habit formation, perception, and memory processing. Reflecting this, DA dysregulation produces a wide variety of cognitive symptoms seen in neuropsychiatric diseases such as Parkinson's, Schizophrenia, addiction, and Alzheimer's disease. Here, we review recent advances in the DA systems neuroscience field and explore the advancing hypothesis that DA's behavioral function is linked to disease deficits in a neural circuit-dependent manner. We survey different brain areas including the basal ganglia's dorsomedial/dorsolateral striatum, the ventral striatum, the auditory striatum, and the hippocampus in rodent models. Each of these regions have different reported functions and, correspondingly, DA's reflecting role in each of these regions also has support for being different. We then focus on DA dysregulation states in Parkinson's disease, addiction, and Alzheimer's Disease, emphasizing how these afflictions are linked to different DA pathways. We draw upon ideas such as selective vulnerability and region-dependent physiology. These bodies of work suggest that different channels of DA may be dysregulated in different sets of disease. While these are great advances, the fine and definitive segregation of such pathways in behavior and disease remains to be seen. Future studies will be required to define DA's necessity and contribution to the functional plasticity of different striatal regions.

The interplay of neurovasculature and adult hippocampal neurogenesis.

The subgranular zone of the dentate gyrus provides a local microenvironment (niche) for neural stem cells. In the adult brain, it has been established that the vascular compartment of such niches has a significant role in regulating adult hippocampal neurogenesis. More recently, evidence showed that neurovascular coupling, the relationship between blood flow and neuronal activity, also regulates hippocampal neurogenesis. Here, we review the most recent articles on addressing the intricate relationship between neurovasculature and adult hippocampal neurogenesis and a novel pathway where functional hyperemia enhances hippocampal neurogenesis. In the end, we have further reviewed recent research showing that impaired neurovascular coupling may cause declined neurogenesis and contribute to brain damage in neurodegenerative diseases.